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1. White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases

Author: Miracle Ozzoude, Brenda Varriano, Derek Beaton, Joel Ramirez, Sabrina Adamo, Melissa F. Holmes, Christopher J. M. Scott, Fuqiang Gao, Kelly M. Sunderland, Paula McLaughlin, Maged Goubran, Donna Kwan, Angela Roberts, Robert Bartha, Sean Symons, Brian Tan, Richard H. Swartz, Agessandro Abrahao, Gustavo Saposnik, Mario Masellis, Anthony E. Lang, Connie Marras, Lorne Zinman, Christen Shoesmith, Michael Borrie, Corinne E. Fischer, Andrew Frank, Morris Freedman, Manuel Montero-Odasso, Sanjeev Kumar, Stephen Pasternak, Stephen C. Strother, Bruce G. Pollock, Tarek K. Rajji, Dallas Seitz, David F. Tang-Wai, John Turnbull, Dar Dowlatshahi, Ayman Hassan, Leanne Casaubon, Jennifer Mandzia, Demetrios Sahlas, David P. Breen, David Grimes, Mandar Jog, Thomas D. L. Steeves, Stephen R. Arnott, Sandra E. Black, Elizabeth Finger, Jennifer Rabin, ONDRI Investigators, and Maria Carmela Tartaglia
Subjects: White matter hyperintensities, Cortical thickness, Neuropsychiatric symptoms, Neurodegenerative disease, Cerebrovascular disease, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. Methods Five hundred thirteen participants with one of these conditions, i.e. Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. Results Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson’s disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. Conclusions In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.
Published: 2023
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2. Associations between MRI-visible perivascular spaces, brain atrophy, white matter hyperintensities, and speeded executive function, in neurodegenerative and cerebrovascular diseases.

Author: Daniela Andriuta, Joel Ramirez, Fuqiang Gao, Jennifer Rabin, Madeline E Wood, Paula M McLaughlin, Christopher JM Scott, Miracle Ozzoude, Allison A Dilliott, Robert A Hegele, Maria C Tartaglia, David Tang-Wai, Richard H Swartz, Leanne Casaubon, Sanjeev Kumar, Dar Dowlatshahi, Jennifer Mandzia, Demetrios Sahlas, Gustavo Saposnik, Corinne Fischer, Michael Borrie, Ayman Hassan, Malcolm A Binns, Morris Freedman, Elizabeth Finger, Andrew Frank, Robert Bartha, Sean Symons, Mario Masellis, and Sandra E Black
Subjects: Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Introduction: MRI-visible perivascular spaces (PVS) are a neuroimaging feature of cerebral small vessel disease and are commonly observed in patients with cerebrovascular and neurodegenerative disease. However, it is unclear whether PVS burden is associated with cognition. The aim of this study was to investigate the potential associations between PVS volumes, brain atrophy, white matter hyperintensities (WMH), and speeded executive function, in patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Methods: ONDRI participants (n=333) clinically diagnosed with Alzheimer's disease/mild cognitive impairment (ADMCI), frontotemporal dementia (FTD), and cerebrovascular diseases (CVD), with clinical, neuropsychological, MRI, plasma biomarkers (glial fibrillary acidic protein (GFAP); neurofilament light, (NfL); p-tau181; Aβ42/40), and available apolipoprotein E epsilon 4 (APOE E4) status, were included in this analysis. MRI-based measurements for brain parenchymal fraction (BPF), lacunes, PVS and WMH were extracted using the ONDRI imaging pipeline. The neuropsychological test scores were standardized (z-transformed), speeded executive function z- scores were computed as the mean of digit symbol modalities test and trail making test part B timed z-scores. The variables selected in bivariate analysis (p
Published: 2024
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3. Standing middle cerebral artery velocity predict cognitive performance on working memory tasks in adults with varying levels of cognitive abilities

Author: Laura Fitzgibbon-Collins, J. Kevin Shoemaker, Michael Borrie, and Jaspreet Bhangu
Subjects: Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Introduction: The pathophysiology of dementia is multifactorial and reduced cerebral blood flow (CBF) is a predictor of cognitive impairment. The majority of research on CBF and dementia has been completed in the supine position, however during upright-posture the vascular system must counter gravitational forces and the redistribution of blood volume to the working muscles to maintain CBF. Aim: Determine if diastolic middle cerebral artery velocity (MCAdv) during standing is associated with lower performance on a working memory task (WMT, 1-back or 2-back) in older adults. Methods: Fifty-three participants (73±6yrs, 17-females: 14 cognitively intact, 30 mild cognitive impairment, 9 dementia) were analyzed. MCAdv profiles the lowest level of flow within a cardiac cycle. Beat-by-beat MCAdv (transcranial Doppler ultrasound) and mean arterial pressure (MAP, plethysmography) were averaged for 30-sec during supine-rest and standing (figure 1). K-means algorithms identified three homogeneous groups (increased-MCAdv, maintained-MCAdv, and reduced-MCAdv) from standing MCAdv (figure 2). Participants completed a 90-second WMT and a performance-based signal detection variable was calculated [sensitivity-A’=0.5+((hit rate−false alarm rate) × (1+hit rate−false alarm rate))/(4 × hit rate × (1−false alarm rate))], and a speed versus accuracy exchange was calculated [sensitivity-A’ score=100xsensitivity-A’/target reaction time(ms)x100]. ANCOVA (covariate: age), and post-hoc analyses were completed on standing MCAdv and WMT. Multiple linear regressions were completed for WMT with age and either MAP or MCAdv (supine and standing), and simple linear regressions were also completed. Significance was set to p≤0.05. Results: The reduced-MCAdv group had lower WMT scores (p
Published: 2024
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4. EFFECTS OF VASCULAR BURDEN ON COGNITION ARE MEDIATED BY ATROPHY, AMYLOID, AND GLUCOSE METABOLISM: A MULTI-CENTRE MIXED COHORT OF SMALL VESSEL DISEASE AND ALZHEIMER'S PATHOLOGY

Author: Julie Ottoy, LC Campbell, Miracle Ozzoude, LC Campbell, Katherine Zukotynski, LC Campbell, Sabrina Adamo, LC Campbell, Christopher Scott, LC Campbell, Vincent Gaudet, Joel Ramirez, LC Campbell, Walter Swardfager, Hugo Cogo-Moreira, LC Campbell, Benjamin Lam, LC Campbell, Aparna Bhan, LC Campbell, Parisa Mojiri, LC Campbell, Min Su Kang, Jennifer Rabin, LC Campbell, Alex Kiss, Stephen Strother, Christian Bocti, Michael Borrie, Howard Chertkow, Richard Frayne, Robin Hsiung, Robert Laforce, Jr., Michael D. Noseworthy, Frank S. Prato, Demetrios J. Sahlas, Eric E. Smith, Phillip H. Kuo, Vesna Sossi, Alexander Thiel, Jean-Paul Soucy, Jean-Claude Tardif, Sandra E. Black, LC Campbell, and Maged Goubran, LC Campbell
Subjects: Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2024
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5. Standing middle cerebral artery velocity predicts cognitive function and gait speed in older adults with cognitive impairment, and is impacted by sex differences

Author: Laura K Fitzgibbon-Collins, Geoff B Coombs, Mamiko Noguchi, Shashankdhwaj Parihar, Richard L Hughson, Michael Borrie, Sue Peters, J Kevin Shoemaker, and Jaspreet Bhangu
Subjects: Transcranial doppler, Cerebral perfusion, Sex differences, Supine to stand, Pulsatility index, Montreal cognitive assessment, Specialties of internal medicine, RC581-951, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Upright posture challenges the cerebrovascular system, leading to changes in middle cerebral artery velocity (MCAv) dynamics which are less evident at supine rest. Chronic alterations in MCAv have been linked to hypoperfusion states and the effect that this may have on cognition remains unclear. This study aimed to determine if MCAv and oscillatory metrics of MCAv (ex. pulsatility index, PI) during upright posture are i) associated with cognitive function and gait speed (GS) to a greater extent than during supine rest, and ii) are different between sexes.Beat-by-beat MCAv (transcranial Doppler ultrasound) and mean arterial pressure (MAP, plethysmography) were averaged for 30-seconds during supine-rest through a transition to standing for 53 participants (73±6yrs, 17 females). While controlling for age, multiple linear regressions predicting MoCA scores and GS from age, supine MCAv metrics, and standing MCAv metrics, were completed. Simple linear regressions predicting Montreal Cognitive Assessment (MoCA) score and GS from MCAv metrics were performed separately for females and males. Significance was set to p
Published: 2024
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6. Using co-creation focus groups to customise a remote multidomain programme designed to increase dementia literacy

Author: Aravind Ganesh, Teresa Liu-Ambrose, Natalie Phillips, Kenneth Rockwood, Edeltraut Kröger, Nathan Herrmann, Guangyong Zou, Paul Mick, Serge Gauthier, Walter Wittich, Marie-Céline Lorenzini, Danielle Laurin, Gillian Einstein, Jennifer Bethell, Eric Smith, Karen Messer, Caroline Duchaine, Andrew Hamilton, Heather Keller, Barry Greenberg, Lesley Miller, Susan Marzolini, Robin Hsiung, Jennifer Campos, Jennifer Walker, Catherine Hughes, Nicole Gervais, Andrew Centen, Louis Bherer, Brigitte Gilbert, Amanda Wagner, Katherine Siminovitch, Laura Middleton, Carol Thomas, Andrew Lim, Nicole Anderson, Quincy Almeida, Ron Postuma, Nadia Gosselin, Howard Feldman, Alan Evans, Howard Chertkow, Nellie Kamkar, Manuel Montero-Odasso, Mark Speechley, Bill McIlroy, Richard Camicioli, Roger Marple, Raed Joundi, Chris McGibbon, Linda Yetman, Bryn Robinson, Sylvie Belleville, Haakon Nygaard, Danielle Alcock, Sarah Banks, Paul Brewster, Senny Chan, Marc Cuesta, Samir Das, Carol Evans, Guylaine Ferland, Scott Hofer, Inbal Itzhak, Diane Jacobs, Jody-Lynn Lupo, Zia Mohades, Carolyn Revta, Julie Robillard, Penny Slack, Kayla Regan, Gabrielle Aubin, Asma Fadhlaoui, Nicole D Anderson, Nouha Ben Gaied, Joyla Furlano, Pamela Jarrett, Michael Borrie, January Durant, Tatiana Herold, Yanina Sarquis-Adamson, Penelope Slack, Amal Trigui, Shahnaz Winer, Fatim Ajwani, Anas Alrohimi, Gabrielle Aubin Geneviève Arsenault-Lapierre, Maude Bouchard, Mark Boulos, Jacqueline Burt, Asif Javed Butt, Julie Carrier, Alison Chasteen, Rachel A. Crockett, Danielle D’Amico, Véronique Daneault, Thanh Dang-Vu, Alex Desautels, Caroline Desrosiers, Shirley Dumassais, Emily Dwosh, Margaret Fahnestok, Ryan Stanley Falck, Alexandra Fiocco, Christine Gagnon, Jean-François Gagnon, Liisa Galea, Catherine-Alexandra Grégoire, Stephanie Huang, Inbal Itzak, Elizaveta Klekovkina, Kim Lasnier-Le Quang, Dominique Lorrain, Kaljani Mahalingam, Sarantia Samantha Maltezos, Brooklyn Mankasingh, Samira Mehrabi, Tatiyana Mollayeva, Annabelle Moore, Aline Moussard, Reanne Mundadan, Kelly Murphy, Leigh-Anne M. Noltie, JB Orange, Emilie Parolin, Kathy Pichora-Fuller, Lori Piquette, Jason Plaks, Avery Pratt, Maria Natasha Rajah, Helli Raptis, Anne Julien-Rocheleau, Marie Y. Savundranayagam, Kylie Sullivan, Munira Sultana, Fatima Tangkhpanya, Talar Tcherkezian, Anne-Julie Tessier, Lynn Valeyry Verty, Stephanie Yamin, Anthonio Zadra, Rolando Acosta, Camille Beaudoin, Charlie Henri-Bellamare, Jessica Callegaro, Milad Heshmati, Pierre Pac Soo, Krista Lanctot, Joanne McLaurin, Paul Territo, Donald Weaver, Cheryl Wellington, Rida Abou-Haidar, Sarah Best, Korbin Blue, Isabella Celotto, Lauren Cole, Roger Dixon, Hiroko Dodge, Nada Elhayek, Thalia Field, Jason Haassenstab, Josée Hachee, Lisa Madlesnky, Lauren Moniz, Hanin Omar, Chris Pauley, Jenna Sands Ève Samson, Andrew Sexton, Sheetal Shajan, Sachie Sharma, Mariam Sidrak, Julia Truemner, François Boutin, Yves Boutot, Lise Daigle, Nita Goldband, Elaine Harris, Janet Finkelstein, Kateri Marchand, and Lloyd Schneider
Subjects: Medicine
Abstract: Objectives To adapt the content and functionalities of Brain Health PRO, a web-based multidomain program designed to increase dementia literacy, to the context and needs of users, providers and community organisations across Québec, Canada.Design Five consecutive qualitative co-creation focus group sessions 30–90 min in duration each, exploring potential barriers and facilitators to usability, accessibility, comprehensibility, participant recruitment and retention.Setting Virtual meetings.Participants A 15-member team based in Québec and Ontario, Canada, consisting of 9 researchers (including a graduate student and the project coordinator), representing occupational therapy, sensory rehabilitation, neuropsychology, psychology, health science and research methods, 3 informal caregivers of older adults living with cognitive decline and 3 members of the Federation of Quebec Alzheimer Societies.Data analysis Session recordings were summarised through both qualitative description and thematic analysis.Results The synthesised recommendations included adjustments around diversity, the complexity and presentation styles of the materials, suggestions on refining the web interface and the measurement approaches; it influenced aspects of participant recruitment, retention efforts and engagement with the content of Brain Health PRO.Conclusions Co-creation in dementia prevention research is important because it involves collaboration between researchers, community support and service providers, and persons with lived experience as care providers, in the design and implementation of clinical studies. This approach helps to ensure that the content and presentation of educational material is relevant and meaningful to the target population and those involved in its delivery, and it leads to a greater understanding of their needs and perspectives.
Published: 2023
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7. Contribution of rare variant associations to neurodegenerative disease presentation

Author: Allison A. Dilliott, Abdalla Abdelhady, Kelly M. Sunderland, Sali M. K. Farhan, Agessandro Abrahao, Malcolm A. Binns, Sandra E. Black, Michael Borrie, Leanne K. Casaubon, Dar Dowlatshahi, Elizabeth Finger, Corinne E. Fischer, Andrew Frank, Morris Freedman, David Grimes, Ayman Hassan, Mandar Jog, Sanjeev Kumar, Donna Kwan, Anthony E. Lang, Jennifer Mandzia, Mario Masellis, Adam D. McIntyre, Stephen H. Pasternak, Bruce G. Pollock, Tarek K. Rajji, Ekaterina Rogaeva, Demetrios J. Sahlas, Gustavo Saposnik, Christine Sato, Dallas Seitz, Christen Shoesmith, Thomas D. L. Steeves, Richard H. Swartz, Brian Tan, David F. Tang-Wai, Maria C. Tartaglia, John Turnbull, Lorne Zinman, ONDRI Investigators, and Robert A. Hegele
Subjects: Medicine, Genetics, QH426-470
Abstract: Abstract Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson’s disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.
Published: 2021
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8. Targeted copy number variant identification across the neurodegenerative disease spectrum

Author: Allison A. Dilliott, Kristina K. Zhang, Jian Wang, Agessandro Abrahao, Malcolm A. Binns, Sandra E. Black, Michael Borrie, Dar Dowlatshahi, Elizabeth Finger, Corinne E. Fischer, Andrew Frank, Morris Freedman, David Grimes, Ayman Hassan, Mandar Jog, Sanjeev Kumar, Anthony E. Lang, Jennifer Mandzia, Mario Masellis, Stephen H. Pasternak, Bruce G. Pollock, Tarek K. Rajji, Ekaterina Rogaeva, Demetrios J. Sahlas, Gustavo Saposnik, Christine Sato, Dallas Seitz, Christen Shoesmith, Thomas D. L. Steeves, Richard H. Swartz, Brian Tan, David F. Tang‐Wai, Maria C. Tartaglia, John Turnbull, Lorne Zinman, ONDRI Investigators, and Robert A. Hegele
Subjects: cerebrovascular disease, copy number variants, neurodegenerative disease, next‐generation sequencing, Genetics, QH426-470
Abstract: Abstract Background Although genetic factors are known to contribute to neurodegenerative disease susceptibility, there remains a large amount of heritability unaccounted for across the diagnoses. Copy number variants (CNVs) contribute to these phenotypes, but their presence and influence on disease state remains relatively understudied. Methods Here, we applied a depth of coverage approach to detect CNVs in 80 genes previously associated with neurodegenerative disease within participants of the Ontario Neurodegenerative Disease Research Initiative (n = 519). Results In total, we identified and validated four CNVs in the cohort, including: (1) a heterozygous deletion of exon 5 in OPTN in an Alzheimer's disease participant; (2) a duplication of exons 1–5 in PARK7 in an amyotrophic lateral sclerosis participant; (3) a duplication of >3 Mb, which encompassed ABCC6, in a cerebrovascular disease (CVD) participant; and (4) a duplication of exons 7–11 in SAMHD1 in a mild cognitive impairment participant. We also identified 43 additional CNVs that may be candidates for future replication studies. Conclusion The identification of the CNVs suggests a portion of the apparent missing heritability of the phenotypes may be due to these structural variants, and their assessment is imperative for a thorough understanding of the genetic spectrum of neurodegeneration.
Published: 2022
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9. Non-Binary Approaches for Classification of Amyloid Brain PET.

Author: Katherine Zukotvnski, Vincent C. Gaudet, Phillip Kuo, Sabrina Adamo, Maged Goubran, Christian Bocti, Michael Borrie, Howard Chertkow, Richard Frayne, Robin Hsiung, Robert Laforce Jr., Michael D. Noseworthy, Frank S. Prato, Jim D. Sahlas, Christopher Scott, Eric E. Smith, Vesna Sossi, Alexander Thiel, Jean-Paul Soucy, Jean-Claude Tardif, and Sandra E. Black
Published: 2019
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10. Sex Modulates the Pathological Aging Effect on Caudate Functional Connectivity in Mild Cognitive Impairment

Author: Zhengshi Yang, Jessica Z. K. Caldwell, Jeffrey L. Cummings, Aaron Ritter, Jefferson W. Kinney, Dietmar Cordes, The Alzheimer's Disease Neuroimaging Initiative (ADNI), Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Enchi Liu, Tom Montine, Anthony Gamst, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Danielle Harvey, John Kornak, Anders Dale, Matthew Bernstein, Joel Felmlee, Nick Fox, Paul Thompson, Norbert Schuff, Gene Alexander, Charles DeCArli, Dan Bandy, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Nigel J. Cairns, Lisa Taylor-Reinwald, J. Q. Trojanowki, Les Shaw, Virginia M.Y. Lee, Magdalena Korecka, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Zaven Khachaturian, Richard Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Joseph Quinn, Betty Lind, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Bryan M. Spann, James Brewer, Helen Vanderswag, Judith L. Heidebrink, Joanne L. Lord, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Munir Chowdhury, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, John C. Morris, Beau Ances, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy Schneider, Daniel Marson, Randall Griffith, David Clark, Hillel Grossman, Effie Mitsis, Aliza Romirowsky, Leyla deToledo-Morrell, Raj C. Shah, Ranjan Duara, Daniel Varon, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Stephanie Kielb, Henry Rusinek, Mony J de Leon, Lidia Glodzik, P. Murali Doraiswamy, Jeffrey R. Petrella, Edward R. Coleman, Steven E. Arnold, Jason H. Karlawish, David Wolk, Charles D. Smith, Greg Jicha, Peter Hardy, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Ruth A. Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Ramon Diaz-Arrastia, Kristen Martin-Cook, Michael DeVous, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Heather S Anderson, Russell H. Swerdlow, Liana Apostolova, Po H. Lu, George Bartzokis, Daniel H.S. Silverman, Neill R Graff-Radford, Francine Parfitt, Heather Johnson, Martin Farlow, Scott Herring, Ann M. Hake, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Michele Assaly, Andrew KertesZ, John Rogers, Dick Trost, Charles Bernick, Donna Munic, Diana Kerwin, Marek-Marsel Mesulam, Kristine Lipowski, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Walter Martinez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Meghan Frey, Allyson Rosen, Jared Tinklenberg, Marwan Sabbagh, Christine Belden, Sandra Jacobson, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Salome K. Bwayo, Alan Lerner, Leon Hudson, Paula Ogrocki, Evan Fletcher, Owen Carmichael, John Olichney, Charles DeCarli, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Steven G. Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Barry A. Hendin, Douglas W. Scharre, Maria Kataki, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Robert B. Santulli, Eben S. Schwartz, Kaycee M. Sink, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, Jacobo Mintzer, Crystal Flynn Longmire, and Kenneth Spicer
Subjects: aging effect, caudate, mild cognitive impairment, functional connectivity, Alzheimer's Disease, sex difference, Psychiatry, RC435-571
Abstract: PurposeTo assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process.Materials and MethodsTwo hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI.ResultsThe MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P = 6.23 × 10−7, right: P = 3.37 × 10−8), but not for men (P > 0.3 for bilateral caudate nuclei). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI.ConclusionSex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.
Published: 2022
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11. Magnetic Resonance Imaging Sequence Identification Using a Metadata Learning Approach

Author: Shuai Liang, Derek Beaton, Stephen R. Arnott, Tom Gee, Mojdeh Zamyadi, Robert Bartha, Sean Symons, Glenda M. MacQueen, Stefanie Hassel, Jason P. Lerch, Evdokia Anagnostou, Raymond W. Lam, Benicio N. Frey, Roumen Milev, Daniel J. Müller, Sidney H. Kennedy, Christopher J. M. Scott, The ONDRI Investigators, Stephen C. Strother, Angela Troyer, Anthony E. Lang, Barry Greenberg, Chris Hudson, Dale Corbett, David A. Grimes, David G. Munoz, Douglas P. Munoz, Elizabeth Finger, J. B. Orange, Lorne Zinman, Manuel Montero-Odasso, Maria Carmela Tartaglia, Mario Masellis, Michael Borrie, Michael J. Strong, Morris Freedman, Paula M. McLaughlin, Richard H. Swartz, Robert A. Hegele, Sandra E. Black, and William E. McIlroy
Subjects: health data, MRI sequence naming standardization, data share and exchange, machine learning, metadata learning, AI-assisted data management, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Despite the wide application of the magnetic resonance imaging (MRI) technique, there are no widely used standards on naming and describing MRI sequences. The absence of consistent naming conventions presents a major challenge in automating image processing since most MRI software require a priori knowledge of the type of the MRI sequences to be processed. This issue becomes increasingly critical with the current efforts toward open-sharing of MRI data in the neuroscience community. This manuscript reports an MRI sequence detection method using imaging metadata and a supervised machine learning technique. Three datasets from the Brain Center for Ontario Data Exploration (Brain-CODE) data platform, each involving MRI data from multiple research institutes, are used to build and test our model. The preliminary results show that a random forest model can be trained to accurately identify MRI sequence types, and to recognize MRI scans that do not belong to any of the known sequence types. Therefore the proposed approach can be used to automate processing of MRI data that involves a large number of variations in sequence names, and to help standardize sequence naming in ongoing data collections. This study highlights the potential of the machine learning approaches in helping manage health data.
Published: 2021
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12. Correction to: The Toronto cognitive assessment (TorCA): normative data and validation to detect amnestic mild cognitive impairment

Author: Morris Freedman, Larry Leach, M. Carmela Tartaglia, Kathryn A. Stokes, Yael Goldberg, Robyn Spring, Nima Nourhaghighi, Tom Gee, Stephen C. Strother, Mohammad O. Alhaj, Michael Borrie, Sultan Darvesh, Alita Fernandez, Corinne E. Fischer, Jennifer Fogarty, Barry D. Greenberg, Michelle Gyenes, Nathan Herrmann, Ron Keren, Josh Kirstein, Sanjeev Kumar, Benjamin Lam, Suvendrini Lena, Mary Pat McAndrews, Gary Naglie, Robert Partridge, Tarek K. Rajji, William Reichmann, M. Uri Wolf, Nicolaas P. L. G. Verhoeff, Jordana L. Waserman, Sandra E. Black, and David F. Tang-Wai
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Upon publication of this article [1], it was brought to our attention that one of the 303 participants in the normative study should have been deleted from the database.
Published: 2018
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13. Healthy Cognitive Aging: A Hybrid Random Vector Functional-Link Model for the Analysis of Alzheimer's Disease.

Author: Peng Dai 0002, Femida Gwadry-Sridhar, Michael Bauer 0003, Michael Borrie, and Xue Teng
Published: 2017
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14. The Toronto Cognitive Assessment (TorCA): normative data and validation to detect amnestic mild cognitive impairment

Author: Morris Freedman, Larry Leach, M. Carmela Tartaglia, Kathryn A. Stokes, Yael Goldberg, Robyn Spring, Nima Nourhaghighi, Tom Gee, Stephen C. Strother, Mohammad O. Alhaj, Michael Borrie, Sultan Darvesh, Alita Fernandez, Corinne E. Fischer, Jennifer Fogarty, Barry D. Greenberg, Michelle Gyenes, Nathan Herrmann, Ron Keren, Josh Kirstein, Sanjeev Kumar, Benjamin Lam, Suvendrini Lena, Mary Pat McAndrews, Gary Naglie, Robert Partridge, Tarek K. Rajji, William Reichmann, M. Uri Wolf, Nicolaas P. L. G. Verhoeff, Jordana L. Waserman, Sandra E. Black, and David F. Tang-Wai
Subjects: Toronto Cognitive Assessment, TorCA, Mild cognitive impairment, Cognitive assessment, Diagnosis, Validation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract: Abstract Background A need exists for easily administered assessment tools to detect mild cognitive changes that are more comprehensive than screening tests but shorter than a neuropsychological battery and that can be administered by physicians, as well as any health care professional or trained assistant in any medical setting. The Toronto Cognitive Assessment (TorCA) was developed to achieve these goals. Methods We obtained normative data on the TorCA (n = 303), determined test reliability, developed an iPad version, and validated the TorCA against neuropsychological assessment for detecting amnestic mild cognitive impairment (aMCI) (n = 50/57, aMCI/normal cognition). For the normative study, healthy volunteers were recruited from the Rotman Research Institute registry. For the validation study, the sample was comprised of participants with aMCI or normal cognition based on neuropsychological assessment. Cognitively normal participants were recruited from both healthy volunteers in the normative study sample and the community. Results The TorCA provides a stable assessment of multiple cognitive domains. The total score correctly classified 79% of participants (sensitivity 80%; specificity 79%). In an exploratory logistic regression analysis, indices of Immediate Verbal Recall, Delayed Verbal and Visual Recall, Visuospatial Function, and Working Memory/Attention/Executive Control, a subset of the domains assessed by the TorCA, correctly classified 92% of participants (sensitivity 92%; specificity 91%). Paper and iPad version scores were equivalent. Conclusions The TorCA can improve resource utilization by identifying patients with aMCI who may not require more resource-intensive neuropsychological assessment. Future studies will focus on cross-validating the TorCA for aMCI, and validation for disorders other than aMCI.
Published: 2018
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15. Bagging Ensembles for the Diagnosis and Prognostication of Alzheimer's Disease.

Author: Peng Dai 0002, Femida Gwadry-Sridhar, Michael Bauer 0003, and Michael Borrie
Published: 2016
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16. Vascular burden and cognition: Mediating roles of neurodegeneration and amyloid PET

Author: Julie, Ottoy, Miracle, Ozzoude, Katherine, Zukotynski, Sabrina, Adamo, Christopher, Scott, Vincent, Gaudet, Joel, Ramirez, Walter, Swardfager, Hugo, Cogo-Moreira, Benjamin, Lam, Aparna, Bhan, Parisa, Mojiri, Min Su, Kang, Jennifer S, Rabin, Alex, Kiss, Stephen, Strother, Christian, Bocti, Michael, Borrie, Howard, Chertkow, Richard, Frayne, Robin, Hsiung, Robert Jr, Laforce, Michael D, Noseworthy, Frank S, Prato, Demetrios J, Sahlas, Eric E, Smith, Phillip H, Kuo, Vesna, Sossi, Alexander, Thiel, Jean-Paul, Soucy, Jean-Claude, Tardif, Sandra E, Black, and Maged, Goubran
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, mental disorders, Neurology (clinical), Geriatrics and Gerontology
Abstract: INTRODUCTIONIt remains unclear to which extent vascular burden promotes neurodegeneration and cognitive dysfunction in a cohort spanning low-to-severe small vessel disease (SVD) and amyloid-beta pathology.METHODSIn 120 subjects, we investigated 1) whether vascular burden, quantified as total or lobar white matter hyperintensity (WMH) volumes, is associated with different cognitive domains; and 2) whether the total WMH effect on cognition is mediated by amyloid (18F-AV45-PET), glucose metabolism (18F-FDG-PET), and/or cortical atrophy.RESULTSIncreased total WMH volume was associated with poorer performance in all cognitive domains tested, with the strongest effects observed for semantic fluency. These relationships were mediated mainly through cortical atrophy, particularly in the temporal lobe, and to a lesser extent through amyloid and metabolism. WMH volumes differentially impacted cognition depending on lobar location and amyloid status.DISCUSSIONOur study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive impairment through temporal lobe atrophy.
Published: 2022

17. Prediction and Classification of Alzheimer’s Disease Based on Combined Features From Apolipoprotein-E Genotype, Cerebrospinal Fluid, MR, and FDG-PET Imaging Biomarkers

Author: Yubraj Gupta, Ramesh Kumar Lama, Goo-Rak Kwon, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: Alzheimer's disease, MCIs (MCI stable), MCIc (MCI converted), sMRI, FDG-PET, CSF, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.
Published: 2019
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18. The Influence of Cerebrospinal Fluid Abnormalities and APOE 4 on PHF-Tau Protein: Evidence From Voxel Analysis and Graph Theory

Author: Yuan Li, Zhijun Yao, Yue Yu, Yu Fu, Ying Zou, Bin Hu, for the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine, Gustavo Jimenez, Michael Donohue, Devon Gessert, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Sarah Walter, Lindsey Hergesheimer, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Joseph Quinn, Lisa C. Silbert, Betty Lind, Jeffrey A. Kaye, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Jaimie Ziolkowski, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Javier Villanueva-Meyer, Valory Pavlik, Nathaniel Pacini, Ashley Lamb, Joseph S. Kass, Rachelle S. Doody, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Randy Yeh, Beau Ances, David Winkfield, Maria Carroll, Angela Oliver, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Hillel Grossman, Effie Mitsis, Raj C. Shah, Melissa Lamar, Patricia Samuels, Ranjan Duara, Maria T. Greig-Custo, Rosemarie Rodriguez, Chiadi Onyike, Daniel D’Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Jamika Singleton-Garvin, Anaztasia Ulysse, Mrunalini Gaikwad, P. Murali Doraiswamy, Jeffrey R. Petrella, Olga James, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Jason H. Karlawish, David A. Wolk, Sanjeev Vaishnavi, Christopher M. Clark, Steven E. Arnold, Charles D. Smith, Greg Jicha, Peter Hardy, Riham El Khouli, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Kim Martin, Nancy Kowalksi, Melanie Keltz, Bonnie S. Goldstein, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Gaby Thai, Aimee Pierce, Beatriz Yanez, Elizabeth Sosa, Megan Witbracht, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Ellen Woo, Daniel H.S. Silverman, Edmond Teng, Sarah Kremen, Liana Apostolova, Kathleen Tingus, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Chris (Chinthaka) Heyn, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, William Pavlosky, Irina Rachinsky, Dick Drost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad A. Marshall, Jerome Yesavage, Joy L. Taylor, Steven Chao, Barton Lane, Allyson Rosen, Jared Tinklenberg, Edward Zamrini, Christine M. Belden, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Ntekim E. Oyonumo, Joanne Allard, Olu Ogunlana, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Joel Hetelle, Kathryn DeMarco, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Rawan Tarawneh, Earl A. Zimmerman, Dzintra Celmins, David Hart, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Mia Yang, Akiva Mintz, Rhode Island, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Courtney Bodge, Stephen Salloway, Paul Malloy, Stephen Correia, Athena Lee, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, John Rogers, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Delwyn D. Miller, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Susan K. Schultz, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Christi Leach, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Lindsey Hergesheimen, Jacqueline Hayes, Shannon Finley, Susan Landau, Erin Householder, Karl Friedl, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Bonnie Goldstein, Kimberly S. Martin, Steven G. Potkin, Adrian Preda, Dana Nguyen, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Gad Marshall, Marwan N. Sabbagh, Sandra A. Jacobson, Saba Wolday, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: PHF-Tau, graph theory, network properties, APOE 4, CSF-Tau, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Mild cognitive impairment (MCI) is a transitional state between the cognitive changes in normal aging and Alzheimer’s disease (AD), which induces abnormalities in specific brain regions. Previous studies showed that paired helical filaments Tau (PHF-Tau) protein is a potential pathogenic protein which may cause abnormal brain function and structure in MCI and AD patients. However, the understanding of the PHF-Tau protein network in MCI patients is limited. In this study, 225 subjects with PHF-Tau Positron Emission Tomography (PET) images were divided into four groups based on whether they carried Apolipoprotein E ε4 (APOE 4) or abnormal cerebrospinal fluid Total-Tau (CSF T-Tau). They are two important pathogenic factors that might cause cognitive function impairment. The four groups were: individuals harboring CSF T-Tau pathology but no APOE 4 (APOE 4−T+); APOE 4 carriers with normal CSF T-Tau (APOE 4+T−); APOE 4 carriers with abnormal CSF T-Tau (APOE 4+T+); and APOE 4 noncarriers with abnormal CSF T-Tau (APOE 4−T−). We explored the topological organization of PHF-Tau networks in these four groups and calculated five kinds of network properties: clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Our findings showed that compared with APOE 4−T− group, the other three groups showed different alterations in the clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Simultaneously, voxel-level analysis was conducted and the results showed that compared with APOE 4−T− group, the other three groups were found increased PHF-Tau distribution in some brain regions. For APOE 4+T+ group, positive correlation was found between the value of PHF-Tau distribution in altered regions and Functional Assessment Questionnaire (FAQ) score. Our results indicated that the effects of APOE 4 and abnormal CSF T-Tau may induce abnormalities of PHF-Tau protein and APOE 4 has a greater impact on PHF-Tau than abnormal CSF T-Tau. Our results may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI patients.
Published: 2019
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19. New Perspective for Non-invasive Brain Stimulation Site Selection in Mild Cognitive Impairment: Based on Meta- and Functional Connectivity Analyses

Author: Jiao Liu, Binlong Zhang, Georgia Wilson, Jian Kong, the Alzheimer’s Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
Subjects: mild cognitive impairment, non-invasive brain stimulation, stimulation site, meta-analysis, resting state functional connectivity, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: BackgroundNon-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.ObjectiveTo explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.MethodsThe meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.ResultsWe found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.ConclusionOur results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.
Published: 2019
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20. Performing Sparse Regularization and Dimension Reduction Simultaneously in Multimodal Data Fusion

Author: Zhengshi Yang, Xiaowei Zhuang, Christopher Bird, Karthik Sreenivasan, Virendra Mishra, Sarah Banks, Dietmar Cordes, the Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: sparse principal component analysis, PCA, canonical correlation analysis, CCA, data fusion, mild cognitive impairment, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.
Published: 2019
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21. Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Author: Qian Zhao, Min Liu, Lingxia Ha, Yun Zhou, Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, Steven Chao, Scott Mackin, Rema Raman, Erin Drake, Mike Donohue, Gustavo Jimenez, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Lindsey Hergesheimer, Elizabeth Shaffer, Craig Nelson, David Bickford, Meryl Butters, Michelle Zmuda, Denise Reyes, Kelley M. Faber, Kelly N. Nudelman, Yiu Ho Au, Kelly Scherer, Daniel Catalinotto, Samuel Stark, Elise Ong, and Dariella Fernandez
Subjects: 18F-AV1451, Tau PET, cognitively normal, mild cognition impairment, Alzheimer's disease, Neurology. Diseases of the nervous system, RC346-429
Abstract: Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification.
Published: 2019
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22. Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort

Author: Kelly M, Sunderland, Derek, Beaton, Stephen R, Arnott, Peter, Kleinstiver, Donna, Kwan, Jane M, Lawrence-Dewar, Joel, Ramirez, Brian, Tan, Robert, Bartha, Sandra E, Black, Michael, Borrie, Donald, Brien, Leanne K, Casaubon, Brian C, Coe, Benjamin, Cornish, Allison A, Dilliott, Dar, Dowlatshahi, Elizabeth, Finger, Corinne, Fischer, Andrew, Frank, Julia, Fraser, Morris, Freedman, Barry, Greenberg, David A, Grimes, Ayman, Hassan, Wendy, Hatch, Robert A, Hegele, Christopher, Hudson, Mandar, Jog, Sanjeev, Kumar, Anthony, Lang, Brian, Levine, Wendy, Lou, Jennifer, Mandzia, Connie, Marras, William, McIlroy, Manuel, Montero-Odasso, David G, Munoz, Douglas P, Munoz, Joseph B, Orange, David S, Park, Stephen H, Pasternak, Frederico, Pieruccini-Faria, Tarek K, Rajji, Angela C, Roberts, John F, Robinson, Ekaterina, Rogaeva, Demetrios J, Sahlas, Gustavo, Saposnik, Christopher J M, Scott, Dallas, Seitz, Christen, Shoesmith, Thomas D L, Steeves, Michael J, Strong, Stephen C, Strother, Richard H, Swartz, Sean, Symons, David F, Tang-Wai, Maria Carmela, Tartaglia, Angela K, Troyer, John, Turnbull, Lorne, Zinman, Paula M, McLaughlin, Mario, Masellis, Malcolm A, Binns, and Guangyong, Zou
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Abstract: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap.This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes.We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation.Data will be shared with the global scientific community. Within-disease and disease-agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.
Published: 2022

23. Consensus Statement Regarding the Application of Biogen to Health Canada for Approval of Aducanumab

Author: Christian Bocti, Shabbir Amanullah, Robin Hsiung, Howard Chertkow, Howard Feldman, Manuel Montero-Odasso, Haakon B. Nygaard, Andrew Kirk, Kenneth Rockwood, David B. Hogan, Michael Borrie, Sandra E. Black, Morris Freedman, Mario Masellis, Natalie A. Phillips, Louis Verret, and Tarek K. Rajji
Subjects: Geriatrics, medicine.medical_specialty, Statement (logic), business.industry, aducanumab, Disease, medicine.disease, drug therapy, Food and drug administration, CCNA, Commentaries, Family medicine, medicine, Dementia, Aducanumab, Geriatrics and Gerontology, business, Alzheimer’s disease, Gerontology, Administration (government)
Abstract: Alzheimer’s disease is a major cause of morbidity and mortality. Currently, there are no disease-modifying pharmacotherapies for this condition. Aducanumab, an amyloid beta-directed monoclonal antibody that targets aggregated forms of amyloid-beta in the brains of people with Alzheimer’s disease, has raised hopes that such a therapy has been discovered, but its approval by the US Food and Drug Administration has engendered a good deal of controversy. A similar application for approval has been submitted to Health Canada. In response to this, a group of Canadian clinical dementia experts representing a number of organizations, including the Canadian Geriatrics Society, was convened by the Canadian Consortium on Neurodegeneration in Aging (CCNA) to discuss the evidence currently available on this agent and seek consensus on what advice they would offer Health Canada on the application. There was wide-spread agreement that it would be premature for aducanumab to receive approval for the treatment of Alzheimer’s disease. It was also noted that the Canadian health-care system is poorly prepared at this time to deal with a disease-modifying therapeutic with targeting, administration, and monitoring characteristics like aducanumab. In this paper, the consensus reached is presented along with its underlying rationale.
Published: 2021

24. Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke

Author: Di Yu, Nuanyi Liang, Julia Zebarth, Qing Shen, Miracle Ozzoude, Maged Goubran, Jennifer S. Rabin, Joel Ramirez, Christopher J. M. Scott, Fuqiang Gao, Robert Bartha, Sean Symons, Seyyed Mohammad Hassan Haddad, Courtney Berezuk, Brian Tan, Donna Kwan, Robert A. Hegele, Allison A. Dilliott, Nuwan D. Nanayakkara, Malcolm A. Binns, Derek Beaton, Stephen R. Arnott, Jane M. Lawrence‐Dewar, Ayman Hassan, Dar Dowlatshahi, Jennifer Mandzia, Demetrios Sahlas, Leanne Casaubon, Gustavo Saposnik, Yurika Otoki, Krista L. Lanctôt, Mario Masellis, Sandra E. Black, Richard H. Swartz, Ameer Y. Taha, Walter Swardfager, Natalie Rashkovan, Agessandro Abrahao, Lorne Zinman, Alisia Bonnick, Christopher Scott, Melissa Holmes, Sabrina Adamo, Morris Freedman, Mojdeh Zamyadi, Stephen Arnott, Malcolm Binns, Pradeep Raamana, Stephen Strother, Kelly Sunderland, Athena Theyers, Abiramy Uthirakumaran, Brian Levine, Angela Troyer, Michael Strong, Peter Kleinstiver, Michael Borrie, Elizabeth Finger, Christen Shoesmith, Frederico Faria, Manuel Montero‐Odasso, Yanina Sarquis‐Adamson, Alanna Black, Allison Ann Dilliott, Rob Hegele, John Robinson, Sali Farhan, Rob Bartha, Hassan Haddad, Nuwan Nanayakkara, Guangyong Zou, Stephen Pasternak, JB Orange, Angela Roberts, Mandar Jog, Dallas Seitz, Don Brien, Ying Chen, Brian Coe, Doug Munoz, Paula McLaughlin, Alicia Peltsch, Susan Bronskill, Wendy Lou, Sanjeev Kumar, Bruce Pollock, Tarek Rajji, David Tang‐Wai, Carmela Tartaglia, Brenda Varriano, Marvin Chum, John Turnbull, Jane Lawrence‐Dewar, Julia Fraser, Bill McIlroy, Ben Cornish, Karen Van Ooteghem, Chris Hudson, Elena Leontieva, Wendy Hatch, Faryan Tayyari, Sherif Defrawy, Edward Margolin, Efrem Mandelcorn, Barry Greenberg, Anthony Lang, Connie Marras, Andrew Frank, David Grimes, Dennis Bulman, John Woulfe, Mahdi Ghani, Tom Steeves, David Munoz, Corinne Fischer, Ekaterina Rogaeva, Sujeevini Sujanthan, David Breen, and Roger A. Dixon
Subjects: Epoxide Hydrolases, small vessel disease, white matter hyperintensity, Neurosciences, Water, lacunar stroke, soluble epoxide hydrolase, Cardiorespiratory Medicine and Haematology, oxylipin, Magnetic Resonance Imaging, Brain Disorders, Linoleic Acid, Stroke, Cerebral Small Vessel Diseases, Humans, Biomedical Imaging, Oxylipins, Atrophy, Cardiology and Cardiovascular Medicine, ONDRI Investigators [Link]
Abstract: Background Cerebral small vessel disease is associated with higher ratios of soluble‐epoxide hydrolase derived linoleic acid diols (12,13‐dihydroxyoctadecenoic acid [DiHOME] and 9,10‐DiHOME) to their parent epoxides (12(13)‐epoxyoctadecenoic acid [EpOME] and 9(10)‐EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra‐high‐performance liquid chromatography–mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13‐DiHOME/12(13)‐EpOME ratio (β=0.251, P =0.023). The 12,13‐DiHOME/12(13)‐EpOME ratio was associated with more lacunes (β=0.266, P =0.028) but not with large vessel stroke volumes. Ratios of 12,13‐DiHOME/12(13)‐EpOME and 9,10‐DiHOME/9(10)‐EpOME were associated with greater volumes of white matter hyperintensities (β=0.364, P P P =0.011; β=0.314, P =0.006). In small vessel stroke, the 12,13‐DiHOME/12(13)‐EpOME ratio was associated with higher white matter free water diffusion (β=0.439, P =0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10‐DiHOME/9(10)‐EpOME ratio was associated with temporal lobe atrophy (β=−0.277, P =0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble‐epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular‐glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.
Published: 2022

25. Smoking Gun? Effect of smoking history on cognition in AD and MCI

Author: Lucas M Crawford‐Holland, Jennifer S. Rabin, Luis R Fornazzari, Tom A. Schweizer, Corinne E. Fischer, David G. Munoz, Sanjeev Kumar, Sandra E. Black, Morris Freedman, Michael Borrie, Andrew R Frank, Stephen H Pasternak, Bruce G. Pollock, Tarek K. Rajji, Dallas Seitz, David F. Tang‐Wai, Carmela Tartaglia, Donna Kwan, and Brian Tan
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022

26. White Matter Hyperintensities and Cortical Atrophy are associated with Neuropsychiatric Symptoms in Neurodegenerative and Cerebrovascular Diseases

Author: Miracle Ozzoude, Brenda Varriano, Derek Beaton, Joel Ramirez, Sabrina Adamo, Melissa F. Holmes, Christopher J.M. Scott, Fuqiang Gao, Kelly M. Sunderland, Paula McLaughlin, Maged Goubran, Donna Kwan, Angela Roberts, Robert Bartha, Sean Symons, Brian Tan, Richard H. Swartz, Agessandro Abrahao, Gustavo Saposnik, Mario Masellis, Anthony E. Lang, Connie Marras, Lorne Zinman, Christen Shoesmith, Michael Borrie, Corinne E. Fischer, Andrew Frank, Morris Freedman, Manuel Montero-Odasso, Sanjeev Kumar, Stephen Pasternak, Stephen C. Strother, Bruce G. Pollock, Tarek K. Rajji, Dallas Seitz, David F. Tang-Wai, John Turnbull, Dar Dowlatshahi, Ayman Hassan, Leanne Casaubon, Jennifer Mandzia, Demetrios Sahlas, David P. Breen, David Grimes, Mandar Jog, Thomas D.L. Steeves, Stephen R. Arnott, Sandra E. Black, Elizabeth Finger, Jennifer Rabin, ONDRI Investigators, and Maria Carmela Tartaglia
Abstract: Background: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical atrophy to NPS in participants across neurodegenerative and cerebrovascular diseases. Methods: 513 participants with one of these conditions, i.e. Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson’s Disease, or Cerebrovascular Disease were included in the study. NPS were assessed using the Neuropsychiatric Inventory – Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter atrophy. Results: Although NPS were frequent across the five disease groups, participants with Frontotemporal Dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both Frontotemporal Dementia and Parkinson’s Disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. Conclusions: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that increased cortical atrophy and white matter hyperintensities burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.
Published: 2022

27. A hybrid manifold learning algorithm for the diagnosis and prognostication of Alzheimer's disease.

Author: Peng Dai 0002, Femida Gwadry-Sridhar, Michael Bauer 0003, and Michael Borrie
Published: 2015

28. Corrigendum: Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Author: Shengwen Guo, Chunren Lai, Congling Wu, Guiyin Cen, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
Subjects: mild cognitive impairment, conversion, cortical feature, sparse-constrained regression, feature reduction, classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2017
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29. Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Author: Shengwen Guo, Chunren Lai, Congling Wu, Guiyin Cen, The Alzheimer's Disease Neuroimaging Initiative, Michael W. Weiner, Paul Aisen, Michael Weiner, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Archana B. Balasubramanian, Jennifer Mason, Iris Sim, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C. Morris, Nigel J. Cairns, Erin Franklin, Lisa Taylor-Reinwald, Virginia Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Lean Thal, Leon Thal, Neil Buckholtz, Peter J. Snyder, Marilyn Albert, Richard Frank, John Hsiao, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne L. Lord, Sara S. Mason, Colleen S. Albers, David Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva-Meyer, Valory Pavlik, Victoria Shibley, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau Ances, Maria Carroll, Mary L. Creech, Mark A. Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, David Geldmacher, Marissa Natelson Love, Randall Griffith, David Clark, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Raj C. Shah, Leyla deToledo-Morrell, Ranjan Duara, Maria T. Greig-Custo, Warren Barker, Chiadi Onyike, Daniel D'Agostino, Stephanie Kielb, Martin Sadowski, Mohammed O. Sheikh, Ulysse Anaztasia, Gaikwad Mrunalini, P. Murali Doraiswamy, Jeffrey R. Petrella, Salvador Borges-Neto, Terence Z. Wong, Edward Coleman, Steven E. Arnold, Jason H. Karlawish, David A. Wolk, Christopher M. Clark, Charles D. Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L. Lopez, MaryAnn Oakley, Donna M. Simpson, Anton P. Porsteinsson, Bonnie S. Goldstein, Kim Martin, Kelly M. Makino, M. Saleem Ismail, Connie Brand, Steven G. Potkin, Adrian Preda, Dana Nguyen, Kyle Womack, Dana Mathews, Mary Quiceno, Allan I. Levey, James J. Lah, Janet S. Cellar, Jeffrey M. Burns, Russell H. Swerdlow, William M. Brooks, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H.S. Silverman, Po H. Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Kim Poki-Walker, Martin R. Farlow, Ann Marie Hake, Brandy R. Matthews, Jared R. Brosch, Scott Herring, Christopher H. van Dyck, Richard E. Carson, Martha G. MacAvoy, Pradeep Varma, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Benita Mudge, Vesna Sossi, Howard Feldman, Michele Assaly, Elizabeth Finger, Stephen Pasternack, Irina Rachisky, Dick Trost, Andrew Kertesz, Charles Bernick, Donna Munic, Marek-Marsel Mesulam, Emily Rogalski, Kristine Lipowski, Sandra Weintraub, Borna Bonakdarpour, Diana Kerwin, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A. Sperling, Keith A. Johnson, Gad Marshall, Jerome Yesavage, Joy L. Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N. Sabbagh, Christine M. Belden, Sandra A. Jacobson, Sherye A. Sirrel, Neil Kowall, Ronald Killiany, Andrew E. Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O. Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Curtis Tatsuoka, Parianne Fatica, Evan Fletcher, Pauline Maillard, John Olichney, Charles DeCarli, Owen Carmichael, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M. Carlsson, Pierre Tariot, Anna Burke, Ann Marie Milliken, Nadira Trncic, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W. Scharre, Maria Kataki, Brendan Kelley, Earl A. Zimmerman, Dzintra Celmins, Alice D. Brown, Godfrey D. Pearlson, Karen Blank, Karen Anderson, Laura A. Flashman, Marc Seltzer, Mary L. Hynes, Robert B. Santulli, Kaycee M. Sink, Gordineer Leslie, Jeff D. Williamson, Pradeep Garg, Franklin Watkins, Brian R. Ott, Geoffrey Tremont, Lori A. Daiello, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J. Rosen, Bruce L. Miller, David Perry, Jacobo Mintzer, Kenneth Spicer, David Bachman, Stephen Pasternak, Irina Rachinsky, John Rogers, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K. Schultz, Karen Ekstam Smith, Hristina Koleva, Ki Won Nam, Hyungsub Shim, Norman Relkin, Gloria Chiang, Michael Lin, Lisa Ravdin, Amanda Smith, Balebail Ashok Raj, Kristin Fargher, Thomas Neylan, Jordan Grafman, Gessert Devon, Davis Melissa, Rosemary Morrison, Hayes Jacqueline, Finley Shannon, Kantarci Kejal, Ward Chad, Erin Householder, Crawford Karen, Neu Scott, Friedl Karl, Becerra Mauricio, Debra Fleischman, Konstantinos Arfanakis, Daniel Varon, Maria T Greig, Olga James, Bonnie Goldstein, Kimberly S. Martin, Dino Massoglia, Olga Brawman-Mintzer, Walter Martinez, Howard Rosen, Kelly Behan, Sterling C. Johnson, J. Jay Fruehling, Sandra Harding, Elaine R. Peskind, Eric C. Petrie, Gail Li, Jerome A. Yesavage, Ansgar J. Furst, and Steven Chao
Subjects: mild cognitive impairment, conversion, cortical feature, sparse-constrained regression, feature reduction, classification, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.
Published: 2017
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30. Vascular Contributions to Neurodegeneration: Protocol of the COMPASS-ND Study

Author: Cheryl R. McCreary, Serge Gauthier, Richard Frayne, Michael Borrie, Sandra E. Black, Simon Duchesne, Eric E. Smith, Richard Camicioli, Victor Whitehead, Fuqiang Gao, and Feryal Saad
Subjects: Canada, medicine.medical_specialty, Disease, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Alzheimer Disease, Internal medicine, medicine, Humans, Dementia, Cognitive Dysfunction, Longitudinal Studies, Prospective Studies, Vascular dementia, Aged, 030304 developmental biology, 0303 health sciences, Lewy body, medicine.diagnostic_test, business.industry, Vascular disease, Leukoaraiosis, Reproducibility of Results, Magnetic resonance imaging, General Medicine, medicine.disease, Magnetic Resonance Imaging, Neurology, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: To describe the neuroimaging and other methods for assessing vascular contributions to neurodegeneration in the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study, a Canadian multi-center, prospective longitudinal cohort study, including reliability and feasibility in the first 200 participants. Methods: COMPASS-ND includes persons with Alzheimer’s disease (AD; n = 150), Parkinson’s disease (PD) and Lewy body dementias (LBDs) (200), mixed dementia (200), mild cognitive impairment (MCI; 400), subcortical ischemic vascular MCI (V-MCI; 200), subjective cognitive impairment (SCI; 300), and cognitively intact elderly controls (660). Magnetic resonance imaging (MRI) was acquired according to the validated Canadian Dementia Imaging Protocol and visually reviewed by either of two experienced readers blinded to clinical characteristics. Other relevant assessments include history of vascular disease and risk factors, blood pressure, height and weight, cholesterol, glucose, and hemoglobin A1c. Results: Analyzable data were obtained in 197/200 of whom 18 of whom were clinically diagnosed with V-MCI or mixed dementia. The overall prevalence of infarcts was 24.9%, microbleeds was 24.6%, and high white matter hyperintensity (WMH) was 31.0%. MRI evidence of a potential vascular contribution to neurodegeneration was seen in 12.9%–40.0% of participants clinically diagnosed with another condition such as AD. Inter-rater reliability was good to excellent. Conclusion: COMPASS-ND will be a useful platform to study vascular brain injury and its association with risk factors, biomarkers, and cognitive and functional decline across multiple age-related neurodegenerative diseases. Initial findings show that MRI-defined vascular brain injury is common in all cognitive syndromes and is under-recognized clinically.
Published: 2021

31. Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative

Author: Derek Beaton, Paula M. McLaughlin, Joseph B. Orange, Douglas P. Munoz, Jennifer Mandzia, Agessandro Abrahao, Malcolm A. Binns, Sandra E. Black, Michael Borrie, Dar Dowlatshahi, Morris Freedman, Corinne E. Fischer, Elizabeth C. Finger, Andrew Frank, David Grimes, Ayman Hassan, Sanjeev Kumar, Anthony Edward Lang, Brian Levine, Connie Marras, Mario Masellis, Bruce G. Pollock, Tarek K. Rajji, Joel Ramirez, Demetrios J. Sahlas, Gustavo Saposnik, Christopher J. M. Scott, Dallas P. Seitz, Stephen C. Strother, Kelly M. Sunderland, Brian Tan, David F. Tang‐Wai, Angela K. Troyer, John Turnbull, Lorne Zinman, Richard H. Swartz, Maria Carmela Tartaglia, David P. Breen, Donna Kwan, Angela C. Roberts, and null the ONDRI Investigators
Subjects: Ontario, Neurodegenerative Diseases, correspondence analysis, Cerebrovascular Disorders, Psychiatry and Mental health, Caregivers, neurodegenerative disorders, Frontotemporal Dementia, Activities of Daily Living, Humans, neuropsychiatric symptoms, Geriatrics and Gerontology, activities of daily living, Zarit's burden interview
Abstract: Objectives: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders?. Methods/Design: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. Results: We found three components in the ZBI. The first was “overall burden” and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = −0.566, basic ADLs r = −0.43), (2) moderately related to cognition (MoCA r = −0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. Conclusions: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.
Published: 2022

32. Ontario Geriatric Specialist Physician Resources 2018

Author: Monisha Basu, Jeanette C. Prorok, Kelly Kay, Tracy Cooper, Michael Borrie, and Dallas Seitz
Subjects: Ontario, Geriatrics, care of the elderly physicians, education.field_of_study, medicine.medical_specialty, business.industry, Population, geriatricians, Geriatric specialist, physician human resources, Care of the elderly, Family medicine, Narrative/Systemic Review, Medicine, Christian ministry, Geriatrics and Gerontology, specialized geriatric services, business, education, Gerontology, Geriatric psychiatry, Health needs
Abstract: Background The number of older adults with complex health needs in Ontario is growing. The Ministry of Health and Long-Term Care requested a resource mapping project to assess the current 2018 and projected 2025 number of specialist physician resources. Methods Geriatric specialist physicians were defined as geriatricians, geriatric psychiatrists, and Care of the Elderly (COE) physicians. We determined the current number of geriatricians, geriatric psychiatrists, and COEs and clinical full-time-equivalent complement (CFTE) for geriatric medicine and geriatric psychiatry specialists. We projected the number of new trainees expected to enter practice and the number of physicians expected to retire by 2025. We compared these numbers and projections against established specialist/population ratios for geriatricians and geriatric psychiatrists. Results There was a deficit of geriatricians and geriatric psychiatrists (geriatricians: CFTE deficit of 150.5; geriatric psychiatrists: CFTE deficit of 116.3). In 2025, the projected CFTE deficit of geriatricians will increase to at least 210.35 and geriatric psychiatrists to 194.6. Only about 30% of COE physicians work in direct support of specialized services for the elderly. Conclusions There is significant current and anticipated undersupply in the required number of geriatricians, geriatric psychiatrists, and COE physicians to meet anticipated population demand.
Published: 2020

33. Dual decline in gait speed and cognition is associated with future dementia: evidence for a phenotype

Author: Frederico Pieruccini-Faria, Susan W. Muir-Hunter, Amit X. Garg, Jennie Wells, Michael Borrie, Louis Bherer, Yanina Sarquis-Adamson, Manuel Montero-Odasso, Richard Camicioli, Nick W. Bray, Mark Speechley, Qu Tian, Vladimir Hachinski, Joel Mahon, Stephanie Cullen, Josh Titus, and Luigi Ferrucci
Subjects: Male, Gerontology, Aging, 03 medical and health sciences, Cognition, 0302 clinical medicine, medicine, Humans, Dementia, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Gait, Aged, Proportional hazards model, business.industry, General Medicine, medicine.disease, Explained variation, Walking Speed, Preferred walking speed, Phenotype, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Dyslipidemia, Cohort study
Abstract: Background concurrent declines in gait speed and cognition have been associated with future dementia. However, the clinical profile of ‘dual decliners’, those with concomitant decline in both gait speed and cognition, has not been yet described. We aimed to describe the phenotype and the risk for incident dementia of those who present with dual decline in comparison with non-dual decliners. Methods prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants’ gait speed, cognition, medical status, functionality, incidence of adverse events and dementia, biannually over 7 years. Gait speed was assessed with a 6-m electronic walkway and global cognition using the MoCA test. We compared characteristics between dual decliners and non-dual decliners using t-test, chi-square and hierarchical regression models. We estimated incident dementia using Cox models. Results among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual decliners had a 3-fold risk (HR: 3.12, 95%CI: 1.23–7.93, P = 0.017) of progression to dementia compared with non-dual decliners. Dual decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (P = 0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual decliners group. Adding hypertension and dyslipidemia increased the explained variation by 8 and 10%, respectively. The risk of becoming a dual decliner was 4-fold higher if hypertension was present. Conclusion older adults with a concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. Older adults with dual decline have a distinct phenotype with a higher prevalence of hypertension, a treatable condition.
Published: 2020

34. Structural Brain Magnetic Resonance Imaging to Rule Out Comorbid Pathology in the Assessment of Alzheimer’s Disease Dementia: Findings from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study and Clinical Trials Over the Past 10 Years

Author: Sara Mitchell, Fuqiang Gao, Tarek K. Rajji, Michael Borrie, Robert Bartha, Morris Freedman, Christopher J.M. Scott, Joel Ramirez, Sean P. Symons, Maria Carmela Tartaglia, Ondri Investigators, Corinne E. Fischer, Bruce G. Pollock, Michael Uri Wolf, Miracle Ozzoude, David F. Tang-Wai, Sanjeev Kumar, Richard H. Swartz, Dallas Seitz, Stephen H. Pasternak, Sandra E. Black, Gary Naglie, Nathan Herrmann, Elizabeth Finger, Andrew Frank, Arunima Kapoor, Jennifer Mandzia, William E. Reichman, Mario Masellis, and Nicolaas Paul L.G. Verhoeff
Subjects: 0301 basic medicine, Male, Pathology, medicine.medical_specialty, Neuroimaging, Disease, Comorbidity, Cohort Studies, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Medicine, Dementia, Humans, Brain magnetic resonance imaging, Cognitive Dysfunction, Aged, Aged, 80 and over, Ontario, Clinical Trials as Topic, business.industry, General Neuroscience, Incidence (epidemiology), Dementia, Vascular, Incidence, Brain, Neurodegenerative Diseases, General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Clinical trial, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Cohort, Medical Biophysics, Observational study, Female, Geriatrics and Gerontology, business, Tomography, X-Ray Computed, 030217 neurology & neurosurgery, Research Article
Abstract: Background/Objective: Structural brain magnetic resonance imaging (MRI) is not mandatory in Alzheimer's disease (AD) research or clinical guidelines. We aimed to explore the use of structural brain MRI in AD/mild cognitive impairment (MCI) trials over the past 10 years and determine the frequency with which inclusion of standardized structural MRI acquisitions detects comorbid vascular and non-vascular pathologies. Methods: We systematically searched ClinicalTrials.gov for AD clinical trials to determine their neuroimaging criteria and then used data from an AD/MCI cohort who underwent standardized MRI protocols, to determine type and incidence of clinically relevant comorbid pathologies. Results: Of 210 AD clinical trials, 105 (50%) included structural brain imaging in their eligibility criteria. Only 58 (27.6%) required MRI. 16,479 of 53,755 (30.7%) AD participants were in trials requiring MRI. In the observational AD/MCI cohort, 141 patients met clinical criteria; 22 (15.6%) had relevant MRI findings, of which 15 (10.6%) were exclusionary for the study. Discussion: In AD clinical trials over the last 10 years, over two-thirds of participants could have been enrolled without brain MRI and half without even a brain CT. In a study sample, relevant comorbid pathology was found in 15% of participants, despite careful screening. Standardized structural MRI should be incorporated into NIA-AA diagnostic guidelines (when available) and research frameworks routinely to reduce diagnostic heterogeneity.
Published: 2020

35. Comparison of neuronal activity profiles in Alzheimer’s disease and frontotemporal dementia measured by resting‐state fMRI

Author: Seyyed Mohammad Hassan Haddad, Christopher J.M. Scott, Stephen R. Arnott, Miracle Ozzoude, Stephen C. Strother, Sandra E. Black, Michael Borrie, Elizabeth Finger, Maria Carmela Trataglia, Donna Kwan, Derek Beaton, Sean Symons, Andrea Soddu, Ravi S. Menon, Manuel Montero‐Odasso, and Robert Bartha
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021

36. Amyloid‐independent vascular contributions to cortical atrophy and cognition in a multi‐center mixed cohort with low to severe small vessel disease

Author: Julie Ottoy, Miracle Ozzoude, Katherine Zukotynski, Sabrina M. Adamo, Christopher J. M. Scott, Vincent Gaudet, Joel Ramirez, Walter Swardfager, Benjamin Lam, Aparna Bhan, Alex Kiss, Stephen C. Strother, Christian Bocti, Michael Borrie, Howard Chertkow, Richard Frayne, Ging‐Yuek Robin Hsiung, Robert Laforce, Michael D. Noseworthy, Frank S. Prato, Demetrios J. Sahlas, Eric E. Smith, Vesna Sossi, Alexander Thiel, Jean‐Paul Soucy, Jean‐Claude Tardif, Maged Goubran, and Sandra E. Black
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2021

37. Contribution of rare variant associations to neurodegenerative disease presentation

Author: Ekaterina Rogaeva, Leanne K. Casaubon, David F. Tang-Wai, Corinne E. Fischer, Michael Borrie, Morris Freedman, Christen Shoesmith, Donna Kwan, Elizabeth Finger, Brian Tan, Maria Carmela Tartaglia, Gustavo Saposnik, Sanjeev Kumar, Malcolm A. Binns, Dallas Seitz, Sandra E. Black, Mandar Jog, Richard H. Swartz, Sali M K Farhan, John Turnbull, Andrew Frank, Abdalla Abdelhady, Bruce G. Pollock, Kelly M Sunderland, Robert A. Hegele, David Grimes, Agessandro Abrahao, Stephen H. Pasternak, Thomas Steeves, Demetrios J. Sahlas, Dar Dowlatshahi, Christine Sato, Ayman Hassan, Anthony E. Lang, Lorne Zinman, Ondri Investigators, Mario Masellis, Adam D. McIntyre, Allison A Dilliott, Tarek K. Rajji, and Jennifer Mandzia
Subjects: Nonsynonymous substitution, Genetics, Neurodegenerative diseases, Neurodegeneration, Disease, QH426-470, Targeted resequencing, Biology, medicine.disease, Article, Disease Presentation, medicine, Medicine, Amyotrophic lateral sclerosis, Molecular Biology, Genetics (clinical), Loss function, Genetic association study, Genetic association, Frontotemporal dementia
Abstract: Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson’s disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.
Published: 2021

38. Updated Inventory and Projected Requirements for Specialist Physicians in Geriatrics

Author: José A. Morais, Michael Borrie, Kelly Kay, Robert E. Lam, Tracy Cooper, Frank Molnar, David B. Hogan, and Monisha Basu
Subjects: medicine.medical_specialty, Canada, geriatric specialist, Resource planning, Population, physician human resources, care of the elderly, Resource (project management), medicine, Population growth, education, specialized geriatric services, Original Research, Geriatrics, education.field_of_study, workforce projection, business.industry, Care of the elderly, geriatrician, Physician supply, inventory, Family medicine, Geriatrics and Gerontology, business, Specialist Physician, Gerontology
Abstract: Background The predicted growth of Canadians aged 65+ and the resultant rise in the demand for specialized geriatric services (SGS) requires physician resource planning. We updated the 2011 Canadian Geriatrics Society physician resource inventory and created projections for 2025 and 2030. Methods The number and full-time equivalents (FTEs) of geriatricians and Care of the Elderly (COE) physicians working in SGS were determined. FTE counts for 2025 and 2030 were estimated by accounting for retirements and trainees. A ratio of 1.25/10,000 population 65+ was used to predict physician resource requirements. Results Between 2011 and 2019 the number of geriatricians and COE physicians increased from 276 (235.8 FTEs) and 128 (89.9 FTEs), respectively, to 376 (319.6 FTEs) and 354 (115.5 FTEs). This increase did not keep pace with the 65+ population growth. The current gap between supply and need is expected to increase. Discussion The physician supply gap is projected to widen in 2025 and 2030. Increased recruitment and interdisciplinary team-based care, supported by enhanced funding models, and full integration of COE physicians in SGS could reduce this increasing gap. In contrast to pediatrician supply in Canada, the specialist physician resources available to the population 65+ reflect a disparity.
Published: 2021

39. Determining whether Sex and Zygosity modulates the association between ApoE4 and Psychosis in Neurodegenerative Disease Cohorts using the ONDRI platform

Author: Mila Valcic, Sandra Black, Morris Freedman, Michael Borrie, Andrew Frank, Sanjeev Kumar, Stephen Pasternak, Bruce Pollock, Tarek Rajji, Dallas Seitz, David Tang-Wai, Carmela Tartaglia, Mario Masellis, Anthony Lang, David Breen, David Grimes, Mandar Jog, Connie Marras, Rick Swartz, Gustavo Saposnik, Donna Kwan, Brian Tan, Rob Hegele, Allison A. Dilliott, John Robinson, Ekaterina Rogaeva, Sali Farhan, Paula McLaughlin, Stephen Strother, Malcolm Binns, Thomas Steeves, Pawel Kostyrko, Komal Talib, Luis Fornazzari, Nathan Churchill, Tom A. Schweizer, David G. Munoz, and Corinne E. Fischer
Subjects: Psychiatry and Mental health, Geriatrics and Gerontology
Published: 2022

40. Investigating the Contribution of White Matter Hyperintensities and Cortical Thickness to Empathy in Neurodegenerative and Cerebrovascular Diseases

Author: Jennifer Mandzia, David Grimes, John Turnbull, Brenda Varriano, Corinne E. Fischer, Ondri Investigators, Derek Beaton, Angela Roberts, Christopher J.M. Scott, Maged Goubran, Mario Masellis, Demetrios J. Sahlas, Ayman Hassan, Donna Kwan, Dallas Seitz, David P. Breen, Andrew Frank, Richard H. Swartz, Sean P. Symons, Connie Marras, Carmela Tartaglia, Fuqiang Gao, Gustavo Saposnik, Leanne K. Casaubon, Michael Borrie, Morris Freedman, Manuel Montero-Odasso, Thomas Steeves, Joel Ramirez, Paula M. McLaughlin, Marvin Chum, Kelly M Sunderland, Brian Tan, Mandar Jog, David F. Tang-Wai, Stephen R. Arnott, Bruce G. Pollock, Jennifer S. Rabin, Robert Bartha, Anthony E. Lang, Agessandro Abrahao, Miracle Ozzoude, Lorne Zinman, Sanjeev Kumar, Christen Shoesmith, Elizabeth Finger, Stephen H. Pasternak, Dar Dowlatshahi, Sandra E. Black, Stephen C. Strother, Tarek K. Rajji, and Melissa F. Holmes
Subjects: medicine.medical_specialty, business.industry, media_common.quotation_subject, Empathy, Disease, Audiology, medicine.disease, behavioral disciplines and activities, Hyperintensity, Atrophy, mental disorders, Interpersonal Reactivity Index, medicine, Alzheimer's disease, Amyotrophic lateral sclerosis, business, Frontotemporal dementia, media_common
Abstract: Introduction: Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases.Methods: 513 participants with Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia (FTD), Parkinson’s Disease, or Cerebrovascular Disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness.Results: A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex(female), global cognition, and right parietal and occipital WMH.Conclusions: Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.
Published: 2021

41. The Use of Random Forests to Classify Amyloid Brain PET

Author: Jean-Paul Soucy, Alexander Thiel, Howard Chertkow, Robert Laforce, Katherine Zukotynski, Vincent Gaudet, Robin Hsiung, Vesna Sossi, Maged Goubran, Eric E. Smith, Sandra E. Black, Demetrios J. Sahlas, Christian Bocti, Michael Borrie, Frank S. Prato, Sabrina Adamo, Jean-Claude Tardif, Richard Frayne, Michael D. Noseworthy, Christopher J.M. Scott, and Phillip H. Kuo
Subjects: Male, Amyloid, Neuroimaging, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, mental disorders, Image Processing, Computer-Assisted, Humans, Medicine, Cognitive Dysfunction, Radiology, Nuclear Medicine and imaging, Prospective Studies, Aged, Aged, 80 and over, Aniline Compounds, business.industry, Brain, Pattern recognition, General Medicine, Middle Aged, Random forest, Data set, Amyloid deposition, Positron-Emission Tomography, 030220 oncology & carcinogenesis, Ethylene Glycols, Female, Supervised Machine Learning, Artificial intelligence, business
Abstract: To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification.The data set included 57 baseline F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with severe white matter disease, presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter, and clinically read by 2 nuclear medicine physicians with interpretation based on consensus (35 negative, 22 positive). SUV ratio data and clinical reads were used for supervised training of an RF classifier programmed in MATLAB.A 10,000-tree RF, each tree using 15 randomly selected cases and 20 randomly selected features (SUV ratio per region of interest), with 37 cases for training and 20 cases for testing, had sensitivity = 86% (95% confidence interval [CI], 42%-100%), specificity = 92% (CI, 64%-100%), and classification accuracy = 90% (CI, 68%-99%). The most common features at the root node (key regions for stratification) were (1) left posterior cingulate (1039 trees), (2) left middle frontal gyrus (1038 trees), (3) left precuneus (857 trees), (4) right anterior cingulate gyrus (655 trees), and (5) right posterior cingulate (588 trees).Random forests can classify brain PET as positive or negative for amyloid deposition and suggest key clinically relevant, regional features for classification.
Published: 2019

42. Correction to: The Toronto cognitive assessment (TorCA): normative data and validation to detect amnestic mild cognitive impairment

Author: Nathan Herrmann, Benjamin Lam, Jennifer Fogarty, Tarek K. Rajji, Larry Leach, David F. Tang-Wai, Josh Kirstein, Sanjeev Kumar, Jordana L. Waserman, Mary Pat McAndrews, M. Uri Wolf, Barry D. Greenberg, Gary Naglie, Kathryn A. Stokes, Michelle Gyenes, M. Carmela Tartaglia, Yael Goldberg, Nicolaas Paul L.G. Verhoeff, Nima Nourhaghighi, Michael Borrie, Morris Freedman, Mohammad Alhaj, Tom Gee, Sandra E. Black, Corinne E. Fischer, Robert Partridge, Stephen C. Strother, Alita Fernandez, William Reichmann, Ron Keren, Sultan Darvesh, Suvendrini Lena, and Robyn Spring
Subjects: 0301 basic medicine, medicine.medical_specialty, Normative study, Neurology, Geriatrics gerontology, Cognitive Neuroscience, lcsh:RC346-429, lcsh:RC321-571, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine, Normative, Neurology (clinical), Cognitive Assessment System, Cognitive impairment, Psychology, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, 030217 neurology & neurosurgery, Geriatric psychiatry, lcsh:Neurology. Diseases of the nervous system, Clinical psychology
Abstract: Upon publication of this article [1], it was brought to our attention that one of the 303 participants in the normative study should have been deleted from the database.
Published: 2018

43. MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease

Author: Joel Ramirez, Melissa F. Holmes, Courtney Berezuk, Donna Kwan, Brian Tan, Derek Beaton, Christopher J.M. Scott, Miracle Ozzoude, Fuqiang Gao, Di Yu, Walter Swardfager, Jane Lawrence-Dewar, Dar Dowlatshahi, Gustavo Saposnik, Mark I. Boulos, Brian J. Murray, Sean Symons, Robert Bartha, Sandra E. Black, Richard H. Swartz, Andrew Lim, Michael Strong, Peter Kleinstiver, Natalie Rashkovan, Susan Bronskill, Michael Borrie, Elizabeth Finger, Corinne Fischer, Andrew Frank, Morris Freedman, Sanjeev Kumar, Stephen Pasternak, Bruce Pollock, Tarek Rajji, Dallas Seitz, David Tang-Wai, Carmela Tartaglia, Brenda Varriano, Agessandro Abrahao, Marvin Chum, Christen Shoesmith, John Turnbull, Lorne Zinman, Julia Fraser, Bill McIlroy, Ben Cornish, Karen Van Ooteghem, Frederico Faria, Manuel Montero-Odasso, Yanina Sarquis-Adamson, Alanna Black, Barry Greenberg, Wendy Hatch, Chris Hudson, Elena Leontieva, Ed Margolin, Efrem Mandelcorn, Faryan Tayyari, Sherif Defrawy, Don Brien, Ying Chen, Brian Coe, Doug Munoz, Alisia Bonnick, Leanne Casaubon, Ayman Hassan, Jennifer Mandzia, Demetrios Sahlas, David Breen, David Grimes, Mandar Jog, Anthony Lang, Connie Marras, Mario Masellis, Tom Steeves, Dennis Bulman, Allison Ann Dilliott, Mahdi Ghani, Rob Hegele, John Robinson, Ekaterina Rogaeva, Sali Farhan, Rob Bartha, Hassan Haddad, Nuwan Nanayakkara, Christopher Scott, Melissa Holmes, Sabrina Adamo, Mojdeh Zamyadi, Stephen Arnott, Malcolm Binns, Wendy Lou, Pradeep Raamana, Stephen Strother, Kelly Sunderland, Athena Theyers, Abiramy Uthirakumaran, Guangyong (GY) Zou, Sujeevini Sujanthan, David Munoz, Roger A. Dixon, John Woulfe, Brian Levine, Paula McLaughlin, J.B. Orange, Alicia Peltsch, Angela Roberts, and Angela Troyer
Subjects: Adult, medicine.medical_specialty, Perivascular spaces, Disease, Pittsburgh Sleep Quality Index, Internal medicine, Basal ganglia, medicine, Animals, Humans, Perivascular space, Depression (differential diagnoses), Ontario, business.industry, Sleep apnea, Neurodegenerative Diseases, General Medicine, Sleep quality, medicine.disease, Sleep in non-human animals, Magnetic Resonance Imaging, Small vessel disease, Cerebrovascular Disorders, medicine.anatomical_structure, Virchow-Robin, Cerebral Small Vessel Diseases, cardiovascular system, Cardiology, Glymphatic system, Vascular cognitive impairment, business, Sleep, Glymphatic System
Abstract: Objectives Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior. Methods We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index. Results Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38–22.26, p = 0.018). Conclusions Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.
Published: 2021

44. Reduced neuronal activity in Alzheimer’s disease and mild cognitive impairment measured by resting state fMRI

Author: Ravi S. Menon, Christopher J.M. Scott, Seyyed M. H. Haddad, Michael Borrie, Derek Beaton, Donna Kwan, Sandra E. Black, Stephen R. Arnott, Sean P. Symons, Manuel Montero-Odasso, Andrea Soddu, Stephen C. Strother, Elizabeth Finger, Robert Bartha, Maria Carmela Tartaglia, and Miracle Ozzoude
Subjects: Resting state fMRI, Epidemiology, business.industry, Health Policy, Early detection, Disease, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Neuroimaging, Medicine, Premovement neuronal activity, Neurology (clinical), Geriatrics and Gerontology, Cognitive impairment, business, Neuroscience
Published: 2020

45. Abnormal brain structure mediates the association between ApoE4 and slow gait among patients with pathological cognitive impairment: Results from the Ontario Neurodegenerative Research Initiative

Author: Derek Beaton, Paula M. McLaughlin, Robert A. Hegele, Frederico Faria-Pieruccini, Kelly M Sunderland, Malcolm A. Binns, Ryota Sakurai, Michael Borrie, Morris Freedman, Carmela Tartaglia, Ben Cornish, Anthony E. Lang, Bill McIlroy, Sean P. Symons, Angela Roberts, Brian Tan, Korbin Blue, Robert Bartha, Donna Kwan, Sandra E. Black, Richard H. Swartz, Stephen C. Strother, Allison A Dilliott, Stephen H. Pasternak, Seyyed M. H. Haddad, Joel Ramirez, Manuel Montero-Odasso, Douglas P. Munoz, and Mario Masellis
Subjects: medicine.medical_specialty, Epidemiology, Behavioral neurology, business.industry, Health Policy, Neuropsychiatry, medicine.disease, Research initiative, Gait, Psychiatry and Mental health, Cellular and Molecular Neuroscience, Physical medicine and rehabilitation, Developmental Neuroscience, medicine, Dementia, Neurology (clinical), Geriatrics and Gerontology, Cognitive impairment, Association (psychology), business, Pathological
Published: 2020

46. The Ontario Neurodegenerative Disease Research Initiative

Author: Lorne Zinman, Michael J. Strong, Paula M. McLaughlin, Julia Fraser, Andrew Frank, Stephen H. Pasternak, Malcolm A. Binns, Angela Roberts, Mandar Jog, Dar Dowlatshahi, Demetrios J. Sahlas, Ayman Hassan, Jennifer Mandzia, Robert A. Hegele, Sandra E. Black, Leanne K. Casaubon, Angela K. Troyer, David G. Munoz, Thomas Steeves, Frederico Pieruccini-Faria, Wendy Lou, Joel Ramirez, Kelly M Sunderland, Ondri Investigators, Manuel Montero-Odasso, Connie Marras, Robert Bartha, Christopher Hudson, Christen Shoesmith, Michael Borrie, Donna Kwan, Morris Freedman, Maria Carmela Tartaglia, David F. Tang-Wai, David S. Park, Allison A Dilliott, Benjamin Cornish, Ekaterina Rogaeva, Donald C. Brien, Tarek K. Rajji, Stephen C. Strother, Sean P. Symons, Stephen R. Arnott, Mario Masellis, David Grimes, Sanjeev Kumar, John Turnbull, Wendy Hatch, Anthony E. Lang, Brian C. Coe, Douglas P. Munoz, Brian Levine, Elizabeth Finger, Peter W. Kleinstiver, Corinne E. Fischer, Brian Tan, Christopher J.M. Scott, Jane M. Lawrence-Dewar, William E. McIlroy, Dallas Seitz, Derek Beaton, Richard H. Swartz, Joseph B. Orange, John F. Robinson, Barry D. Greenberg, and Gustavo Saposnik
Subjects: Gerontology, business.industry, Cohort, medicine, Neuropsychology, Montreal Cognitive Assessment, Cognition, Disease, Amyotrophic lateral sclerosis, medicine.disease, business, Frontotemporal dementia, Cohort study
Abstract: ObjectiveIn individuals over the age of 65, concomitant neurodegenerative pathologies contribute to cognitive and/or motor decline and can be aggravated by cerebrovascular disease, but our understanding of how these pathologies synergize to produce the decline represents an important knowledge gap. The Ontario Neurodegenerative Disease Research Initiative (ONDRI), a multi-site, longitudinal, observational cohort study, recruited participants across multiple prevalent neurodegenerative diseases and cerebrovascular disease, collecting a wide array of data and thus allowing for deep investigation into common and unique phenotypes. This paper describes baseline features of the ONDRI cohort, understanding of which is essential when conducting analyses or interpreting results.MethodsFive disease cohorts were recruited: Alzheimer’s disease/amnestic mild cognitive impairment (AD/MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Parkinson’s disease (PD), and cerebrovascular disease (CVD). Assessment platforms included clinical, neuropsychology, eye tracking, gait and balance, neuroimaging, retinal imaging, genomics, and pathology. We describe recruitment, data collection, and data curation protocols, and provide a summary of ONDRI baseline characteristics.Results520 participants were enrolled. Most participants were in the early stages of disease progression. Participants had a median age of 69 years, a median Montreal Cognitive Assessment score of 25, a median percent of independence of 100 for basic activities of daily living, and a median of 93 for instrumental activities. Variation between disease cohorts existed for age, level of cognition, and geographic location.ConclusionONDRI data will enable exploration into unique and shared pathological mechanisms contributing to cognitive and motor decline across the spectrum of neurodegenerative diseases.
Published: 2020

47. Brain Health: A Concept Analysis

Author: Michael Borrie, Boniface Harerimana, Julie Walsh, Cheryl Forchuk, and Jennifer Fogarty
Subjects: 03 medical and health sciences, 0302 clinical medicine, 030504 nursing, Concept Formation, Formal concept analysis, Brain, Humans, Pshychiatric Mental Health, 0305 other medical science, Psychology, Construct (philosophy), 030227 psychiatry, Cognitive psychology
Abstract: The concept of brain health has been inconsistently used across disciplines. This concept analysis sought to clarify brain health and construct a unified definition that may lead to consistent use of this concept. The analysis used Walker and Avant's framework to identify scholarly reports on the concept of brain health from various electronic databases. Building on the identified data sources, brain health can be understood as the brain's ability to optimally adapt to internal and external human conditions through cognitive and emotional responses across one's lifespan, which result in sustainable positive changes in brain structures and functional features. This analysis emphasized that maintaining brain health has positive implications on an individual's lifelong quality of health, independence, and delaying cognitive decline. By clarifying uses and definitions of the concept of brain health, this concept analysis may enable researchers and clinicians to evaluate and interpret the concept related data consistently.
Published: 2020

48. Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario Neurodegenerative Disease Research Initiative

Author: Stephen C. Strother, Michael Borrie, Morris Freedman, David Grimes, Joseph B. Orange, Sanjeev Kumar, Tarek K. Rajji, Gustavo Saposnik, Demetrios J. Sahlas, Malcolm A. Binns, Elizabeth Finger, Paula M. McLaughlin, Douglas P. Munoz, Lorne Zinman, Carmela Tartaglia, Corinne E. Fischer, Jennifer Mandzia, Derek Beaton, Joel Ramirez, Kelly M Sunderland, Richard H. Swartz, Angela Roberts, Ayman Hassan, Connie Marras, Dallas Seitz, Lang Ae, Sandra E. Black, Dariush Dowlatshahi, Bruce G. Pollock, Agessandro Abrahao, Mario Masellis, Kwan D, Tan B, Angela K. Troyer, John Turnbull, Christopher J.M. Scott, Brian Levine, David F. Tang-Wai, David P. Breen, and Andrew Frank
Subjects: Gerontology, Text mining, business.industry, Psychology, business
Abstract: Objectives: In the Ontario Neurodegenerative Disease Research Initiative (ONDRI), we aimed to ask and answer: (1) How many and what types of burdens are captured by the Zarit’s Burden Interview (ZBI)? (2) Do we see categorical or spectrum-like effects for burden(s)? and (3) Which if any demographic, clinical, and cognitive measures are related to burden(s)?Methods: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer’s disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson’s disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI, then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery.Results: We found three components in the ZBI. The first was “overall burden” and was (1) strongly related to increased neuropsychiatric symptoms and decreased independence in activities of daily living, (2) moderately related to cognition, and (3) showed little-to-no differences between disorders. The second and third components showed four types of caregiving concerns: current care of patient, future care of patient, personal concerns of study partner, and social concerns of study partner. Discussion: Caregiving concerns are individual experiences and emphasize the importance of support for management of activities of daily living and neuropsychiatric symptoms, and underscore individualized needs for caregiving assessment and education.
Published: 2020

49. Delaying Transition Into Long-Term Care for Persons Living With Dementia: Multispecialty Interprofessional Team Memory Clinics

Author: Michael Borrie, Jo-Anne Clarke, Linda Lee, Tejal Patel, Loretta M. Hillier, and Frank Molnar
Subjects: Patient Care Team, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Health Policy, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Interprofessional Relations, General Medicine, medicine.disease, Long-Term Care, Article, Long-term care, Memory, Family medicine, medicine, Dementia, Interprofessional teamwork, Humans, Geriatrics and Gerontology, business, General Nursing
Published: 2020

50. Dual-task gait speed assessments with an electronic walkway and a stopwatch in older adults. A reliability study

Author: J. Mahon, Mark Speechley, Michael Borrie, Josh Titus, Louis Bherer, Frederico Pieruccini-Faria, Nick W. Bray, Manuel Montero-Odasso, Nellie Kamkar, Richard Camicioli, Yanina Sarquis-Adamson, and Stephanie Cullen
Subjects: 0301 basic medicine, Male, Aging, medicine.medical_specialty, Canada, Validity, Walking, Biochemistry, law.invention, Task (project management), 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Gait (human), Physical medicine and rehabilitation, law, Reliability study, London, Genetics, Medicine, Humans, Cognitive decline, Molecular Biology, Gait, Stopwatch, Reliability (statistics), Aged, business.industry, Reproducibility of Results, Cell Biology, Gait speed, Walking Speed, 030104 developmental biology, Cross-Sectional Studies, Female, Electronics, business, human activities, 030217 neurology & neurosurgery
Abstract: Slow gait speed prospectively predicts elevated risk of adverse events such as falls, morbidity, and mortality. Additionally, gait speed under a cognitively demanding challenge (dual-task gait) predicts further cognitive decline and dementia incidence. This evidence has been mostly collected using electronic walkways; however, not all clinical set ups have an electronic walkway and comparability with simple manual dual-gait speed testing, like a stopwatch, has not yet been examined. Our main objective was to assess concurrent-validity and reliability of gait speed assessments during dual-tasking using a stopwatch and electronic walkway in older adults with mild and subjective cognitive impairment (MCI and SCI).Cross-sectional, reliability study.Clinic based laboratory at an academic hospital in London, ON, Canada.237 walk tests from 34 community-dwelling participants (mean age 71.84 SD 5.38; 21 female - 62%, 13 male - 38%) with SCI and MCI. were included from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) study.Each participant performed seven walk tests: three single gait walks at their normal pace, three dual-task walks (walking and counting backwards by one, by sevens, and naming animals), and one fast walk.Gait speed (cm/s) for each walk was measured simultaneously with an electronic walkway (Zeno Mat®) and a handheld stopwatch (Ultrak chronometer®). Dual-task cost (DTC) was calculated for the three individual dual-task walks as [((single gait speed - dual-task gait speed) / single gait speed) ∗ 100]. Level of agreement between the two measurement methods was analyzed using Pearson correlations, paired t-tests, and Bland-Altman plots.Gait speed was consistently lower when measured with the stopwatch than with the electronic walkway (mean speed difference: 10.6 cm/s ± 5.1, p 0.001). Calculating DTC, however, yielded very similar results with both methods (mean DTC difference: 0.19 ± 1.18, p = 0.872). The higher the DTC, the closer the measurement between methods.Assessing and calculating DTC with a stopwatch is simple, accessible and reliable. Its validity and reliability were high in this clinical sample of community older adults with SCI and MCI.
Published: 2020

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