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1. Considerations for widespread implementation of blood-based biomarkers of Alzheimers disease.

Author

Mielke, Michelle, Anderson, Matthew, Ashford, J, Jeromin, Andreas, Lin, Pei-Jung, Rosen, Allyson, Tyrone, Jamie, Vandevrede, Lawren, Willis, Deanna, Hansson, Oskar, Khachaturian, Ara, Schindler, Suzanne, Weiss, Joan, Batrla, Richard, Bozeat, Sasha, Dwyer, John, Holzapfel, Drew, Jones, Daryl, Murray, James, Partrick, Katherine, Scholler, Emily, Vradenburg, George, Young, Dylan, Braunstein, Joel, Burnham, Samantha, de Oliveira, Fabricio, Hu, Yan, Mattke, Soeren, Merali, Zul, Monane, Mark, Sabbagh, Marwan, Shobin, Eli, Weiner, Michael, and Udeh-Momoh, Chinedu

Subjects
Alzheimers disease, amyloid, biomarker, blood‐based biomarkers, clinical implementation, clinical practice, cognitive impairment, disease‐modifying treatment, ethics, patient journey, primary care, secondary care, Humans, Alzheimer Disease, Biomarkers, United States, Early Diagnosis
Abstract

Diagnosing Alzheimers disease (AD) poses significant challenges to health care, often resulting in delayed or inadequate patient care. The clinical integration of blood-based biomarkers (BBMs) for AD holds promise in enabling early detection of pathology and timely intervention. However, several critical considerations, such as the lack of consistent guidelines for assessing cognition, limited understanding of BBM test characteristics, insufficient evidence on BBM performance across diverse populations, and the ethical management of test results, must be addressed for widespread clinical implementation of BBMs in the United States. The Global CEO Initiative on Alzheimers Disease BBM Workgroup convened to address these challenges and provide recommendations that underscore the importance of evidence-based guidelines, improved training for health-care professionals, patient empowerment through informed decision making, and the necessity of community-based studies to understand BBM performance in real-world populations. Multi-stakeholder engagement is essential to implement these recommendations and ensure credible guidance and education are accessible to all stakeholders.

Published
2024

2. Recommendations for clinical implementation of blood-based biomarkers for Alzheimers disease.

Author

Mielke, Michelle, Anderson, Matthew, Ashford, J, Jeromin, Andreas, Lin, Pei-Jung, Rosen, Allyson, Tyrone, Jamie, Vandevrede, Lawren, Willis, Deanna, Hansson, Oskar, Khachaturian, Ara, Schindler, Suzanne, Weiss, Joan, Batrla, Richard, Bozeat, Sasha, Dwyer, John, Holzapfel, Drew, Jones, Daryl, Murray, James, Partrick, Katherine, Scholler, Emily, Vradenburg, George, Young, Dylan, Braunstein, Joel, Burnham, Samantha, de Oliveira, Fabricio, Hu, Yan, Mattke, Soeren, Merali, Zul, Monane, Mark, Sabbagh, Marwan, Shobin, Eli, Weiner, Michael, and Udeh-Momoh, Chinedu

Subjects
Alzheimers disease, amyloid, biomarker, blood‐based biomarkers, clinical implementation, clinical practice, cognitive impairment, disease‐modifying treatment, patient journey, primary care, secondary care, Alzheimer Disease, Humans, Biomarkers, Positron-Emission Tomography
Abstract

Blood-based biomarkers (BBM) for Alzheimers disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimers Disease convened a BBM Workgroup to provide recommendations for two clinical implementational pathways for BBMs: one for current use for triaging and another for future use to confirm amyloid pathology. These pathways provide a standardized diagnostic approach with guidance on interpreting BBM test results. Integrating BBMs into clinical practice will simplify the diagnostic process and facilitate timely access to DMTs for eligible patients.

Published
2024

3. Dynamic proportional loss of functional connectivity revealed change of left superior frontal gyrus in subjective cognitive decline: an explanatory study based on Chinese and Western cohorts

Author

Wang, Luyao, Hu, Wenjing, Dong, Fan, Sheng, Can, Wu, Jinglong, Han, Ying, Jiang, Jiehui, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jagust, William, Trojanowski, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Saykin, Andrew J., Morris, John, Shaw, Leslie M., Khachaturian, Zaven, Sorensen, Greg, Kuller, Lew, Raichle, Marcus, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, Marek M., Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Thomas, Ronald G., Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Bernstein, Matthew, Thompson, Paul, Schuff, Norbert, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A., Foster, Norm, Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Taylor-Reinwald, Lisa, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M., Potkin, Steven G., Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Thal, Leon, Buckholtz, Neil, Albert, Marylyn, Frank, Richard, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Schneider, Lon S., Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M., Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L., Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Doody, Rachelle S., Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Bell, Karen L., Ances, Beau, Carroll, Maria, Leon, Sue, Mintun, Mark A., Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, de Toledo-Morrell, Leyla, Shah, Raj C., Duara, Ranjan, Varon, Daniel, Greig, Maria T., Roberts, Peggy, Onyike, Chiadi, D’Agostino, Daniel, Kielb, Stephanie, Galvin, James E., Cerbone, Brittany, Michel, Christina A., Rusinek, Henry, de Leon, Mony J., Glodzik, Lidia, De Santi, Susan, Doraiswamy, PMurali, Petrella, Jeffrey R., Wong, Terence Z., Arnold, Steven E., Karlawish, Jason H., Wolk, David, Smith, Charles D., Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Goldstein, Bonnie S., Martin, Kim, Makino, Kelly M., Ismail, MSaleem, Brand, Connie, Mulnard, Ruth A., Thai, Gaby, McAdams-Ortiz, Catherine, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I., Lah, James J., Cellar, Janet S., Burns, Jeffrey M., Anderson, Heather S., Swerdlow, Russell H., Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H. S., Lu, Po H., Bartzokis, George, Graff-Radford, Neill R., Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H., Carson, Richard E., MacAvoy, Martha G., Chertkow, Howard, Bergman, Howard, Hosein, Chris, Hsiung, Ging-Yuek Robin, Feldman, Howard, Mudge, Benita, Assaly, Michele, Bernick, Charles, Munic, Donna, Kertesz, Andrew, Rogers, John, Trost, Dick, Kerwin, Diana, Lipowski, Kristine, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad, Frey, Meghan, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N., Belden, Christine M., Jacobson, Sandra A., Sirrel, Sherye A., Kowall, Neil, Killiany, Ronald, Budson, Andrew E., Norbash, Alexander, Johnson, Patricia Lynn, Allard, Joanne, Lerner, Alan, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichae, Owen, Olichney, John, DeCarli, Charles, Kittur, Smita, Borrie, Michael, Lee, T.-Y., Bartha, Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W., Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A., Celmins, Dzintra, Brown, Alice D., Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Santulli, Robert B., Kitzmiller, Tamar J., Schwartz, Eben S., Sink, Kaycee M., Williamson, Jeff D., Garg, Pradeep, Watkins, Franklin, Ott, Brian R., Querfurth, Henry, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J., Miller, Bruce L., Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K., Ponto, Laura L. Boles, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Neylan, Thomas, Grafman, Jordan, Davis, Melissa, Morrison, Rosemary, Hayes, Jacqueline, Finley, Shannon, Friedl, Karl, Fleischman, Debra, Arfanakis, Konstantinos, James, Olga, Massoglia, Dino, Fruehling, JJay, Harding, Sandra, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Yesavage, Jerome A., Taylor, Joy L., and Furst, Ansgar J.

Published
2025
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5. Genetic associations with dementia‐related proteinopathy: Application of item response theory

Author

Katsumata, Yuriko, Fardo, David W, Shade, Lincoln MP, Wu, Xian, Karanth, Shama D, Hohman, Timothy J, Schneider, Julie A, Bennett, David A, Farfel, Jose M, Gauthreaux, Kathryn, Mock, Charles, Kukull, Walter A, Abner, Erin L, Nelson, Peter T, Carrillo, Maria, Reiman, Eric M, Chen, Kewei, Masterman, Donna, Green, Robert C, Ho, Carole, Fleisher, Adam, Saykin, Andrew J, Nho, Kwangsik, Apostolova, Liana G, Risacher, Shannon L, Jackson, Jonathan, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jack, Clifford R, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Petersen, Ronald, Hsiao, John K, Potter, William, Masliah, Eliezer, Ryan, Laurie, Bernard, Marie, Silverberg, Nina, Kormos, Adrienne, Conti, Cat, Veitch, Dallas, Flenniken, Derek, Sacrey, Diana Truran, Choe, Mark, Ashford, Miriam, Chen, Stephanie Rossi, Faber, Kelley, Nudelman, Kelly, Wilme, Kristi, Foroud, Tatiana M, Trojanowki, John Q, Shaw, Leslie M, Korecka, Magdalena, Figurski, Michal, Khachaturian, Zaven, Barnes, Lisa, Malone, Ian, Fox, Nick C, Beckett, Laurel, Weiner, Michael W, Jagust, William, Landau, Susan, Knaack, Alexander, DeCarli, Charles, Harvey, Danielle, Fletcher, Evan, González, Hector, Jin, Chengshi, Tosun‐Turgut, Duygu, Neuhaus, John, Fockler, Juliet, Nosheny, Rachel, Koeppe, Robert A, Yushkevich, Paul A, Das, Sandhitsu, Mathis, Chet, Toga, Arthur W, Zimmerman, Caileigh, Gessert, Devon, Shcrer, Elizabeth, Miller, Garrett, Coker, Godfrey, Jimenez, Gustavo, Salazar, Jennifer, Pizzola, Jeremy, Crawford, Karen, Hergesheimer, Lindsey, Donohue, Michael, and Rafii, Michael

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Acquired Cognitive Impairment, Genetics, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Alzheimer's Disease, Lewy Body Dementia, Aging, Prevention, Neurodegenerative, 2.1 Biological and endogenous factors, Neurological, Humans, alpha-Synuclein, TDP-43 Proteinopathies, Proteostasis Deficiencies, DNA-Binding Proteins, Biological Products, Alzheimer Disease, Membrane Proteins, Nerve Tissue Proteins, Alzheimer's Disease Neuroimaging Initiative, National Alzheimer's Coordinating Center, ARHGEF28, Alzheimer's Coordinating Center, Alzheimer's Disease Sequencing Project, Alzheimer's disease neuropathologic changes, Item response theory, Lewy, RGNEF, Religious Orders Study, Rush Memory and Aging Project, SDHAF1, TMEM68, neuropathology, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.MethodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.ResultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility.DiscussionA novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies.HighlightsLatent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors.

Published
2024

7. Acceptable performance of blood biomarker tests of amyloid pathology — recommendations from the Global CEO Initiative on Alzheimer’s Disease

Author

Schindler, Suzanne E., Galasko, Douglas, Pereira, Ana C., Rabinovici, Gil D., Salloway, Stephen, Suárez-Calvet, Marc, Khachaturian, Ara S., Mielke, Michelle M., Udeh-Momoh, Chi, Weiss, Joan, Batrla, Richard, Bozeat, Sasha, Dwyer, John R., Holzapfel, Drew, Jones, Daryl Rhys, Murray, James F., Partrick, Katherine A., Scholler, Emily, Vradenburg, George, Young, Dylan, Algeciras-Schimnich, Alicia, Aubrecht, Jiri, Braunstein, Joel B., Hendrix, James, Hu, Yan Helen, Mattke, Soeren, Monane, Mark, Reilly, David, Somers, Elizabeth, Teunissen, Charlotte E., Shobin, Eli, Vanderstichele, Hugo, Weiner, Michael W., Wilson, David, and Hansson, Oskar

Published
2024
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8. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Arnold, Matthias, Meikle, Peter J, Giles, Corey, Kaddurah-Daouk, Rima, Saykin, Andrew J, Nho, Kwangsik, Kueider-Paisley, Alexandra, Doraiswamy, P Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Risacher, Shannon L, Kastenmüller, Gabi, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Morris, John C, Perrin, Richard J, Shaw, Leslie M, Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K, Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, and Ryan, Laurie

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Acquired Cognitive Impairment, Neurodegenerative, Networking and Information Technology R&D (NITRD), Machine Learning and Artificial Intelligence, Dementia, Alzheimer's Disease, Brain Disorders, Neurological, Humans, Aged, Magnetic Resonance Imaging, Deep Learning, Alzheimer Disease, Neuroimaging, Metabolome, Lipids, Cognitive Dysfunction, Alzheimer's Disease Metabolomics Consortium, Alzheimer's Disease Neuroimaging Initiative, Alzheimer's disease, Deep learning, Lipidomics, Machine learning, Metabolomics, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundDeep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. This study introduces the Circular-Sliding Window Association Test (c-SWAT) to improve the classification accuracy in predicting AD using serum-based metabolomics data, specifically lipidomics.MethodsThe c-SWAT methodology builds upon the existing Sliding Window Association Test (SWAT) and utilizes a three-step approach: feature correlation analysis, feature selection, and classification. Data from 997 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) served as the basis for model training and validation. Feature correlations were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA), and Convolutional Neural Networks (CNN) were employed for feature selection. Random Forest was used for the final classification.FindingsThe application of c-SWAT resulted in a classification accuracy of up to 80.8% and an AUC of 0.808 for distinguishing AD from cognitively normal older adults. This marks a 9.4% improvement in accuracy and a 0.169 increase in AUC compared to methods without c-SWAT. These results were statistically significant, with a p-value of 1.04 × 10ˆ-4. The approach also identified key lipids associated with AD, such as Cer(d16:1/22:0) and PI(37:6).InterpretationOur results indicate that c-SWAT is effective in improving classification accuracy and in identifying potential lipid biomarkers for AD. These identified lipids offer new avenues for understanding AD and warrant further investigation.FundingThe specific funding of this article is provided in the acknowledgements section.

Published
2023

9. Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis

Author

Bocancea, Diana I, Svenningsson, Anna L, van Loenhoud, Anna C, Groot, Colin, Barkhof, Frederik, Strandberg, Olof, Smith, Ruben, Weiner, Michael W, Aisen, Paul, Petersen, Ronald, Jack, Clifford R, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John C, Perrin, Richard J, Shaw, Leslie M, Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, González, Hector, Ho, Carole, Hsiao, John K, Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormo, Adrienne, Montine, Tom, Conti, Cat B, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C, Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I, Nir, Talia M, Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, and Crawfor, Karen

Subjects
Health Sciences, Dementia, Brain Disorders, Cerebrovascular, Aging, Neurosciences, Alzheimer's Disease Related Dementias (ADRD), Neurodegenerative, Biomedical Imaging, Vascular Cognitive Impairment/Dementia, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Behavioral and Social Science, Clinical Research, Acquired Cognitive Impairment, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Mental health, Neurological, Humans, Alzheimer Disease, Longitudinal Studies, tau Proteins, Cross-Sectional Studies, Cerebral Cortical Thinning, Positron-Emission Tomography, Brain, Cognition, Apolipoproteins E, Alzheimer's disease, tau, resilience, cognition, PET, MRI, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Mechanisms of resilience against tau pathology in individuals across the Alzheimer's disease spectrum are insufficiently understood. Longitudinal data are necessary to reveal which factors relate to preserved cognition (i.e. cognitive resilience) and brain structure (i.e. brain resilience) despite abundant tau pathology, and to clarify whether these associations are cross-sectional or longitudinal. We used a longitudinal study design to investigate the role of several demographic, biological and brain structural factors in yielding cognitive and brain resilience to tau pathology as measured with PET. In this multicentre study, we included 366 amyloid-β-positive individuals with mild cognitive impairment or Alzheimer's disease dementia with baseline 18F-flortaucipir-PET and longitudinal cognitive assessments. A subset (n = 200) additionally underwent longitudinal structural MRI. We used linear mixed-effects models with global cognition and cortical thickness as dependent variables to investigate determinants of cognitive resilience and brain resilience, respectively. Models assessed whether age, sex, years of education, APOE-ε4 status, intracranial volume (and cortical thickness for cognitive resilience models) modified the association of tau pathology with cognitive decline or cortical thinning. We found that the association between higher baseline tau-PET levels (quantified in a temporal meta-region of interest) and rate of cognitive decline (measured with repeated Mini-Mental State Examination) was adversely modified by older age (Stβinteraction = -0.062, P = 0.032), higher education level (Stβinteraction = -0.072, P = 0.011) and higher intracranial volume (Stβinteraction = -0.07, P = 0.016). Younger age, higher education and greater cortical thickness were associated with better cognitive performance at baseline. Greater cortical thickness was furthermore associated with slower cognitive decline independent of tau burden. Higher education also modified the negative impact of tau-PET on cortical thinning, while older age was associated with higher baseline cortical thickness and slower rate of cortical thinning independent of tau. Our analyses revealed no (cross-sectional or longitudinal) associations for sex and APOE-ε4 status on cognition and cortical thickness. In this longitudinal study of clinically impaired individuals with underlying Alzheimer's disease neuropathological changes, we identified education as the most robust determinant of both cognitive and brain resilience against tau pathology. The observed interaction with tau burden on cognitive decline suggests that education may be protective against cognitive decline and brain atrophy at lower levels of tau pathology, with a potential depletion of resilience resources with advancing pathology. Finally, we did not find major contributions of sex to brain nor cognitive resilience, suggesting that previous links between sex and resilience might be mainly driven by cross-sectional differences.

Published
2023

10. Perspectives of old-age and dementia researchers on communication with policymakers and public research funding decision-makers: an international cross-sectional survey

Author

Peter Fusdahl, Miguel Germán Borda, Jonathan Patricio Baldera, Dag Aarsland, Ara Khachaturian, and Geir Sverre Braut

Subjects
Alzheimer’s disease, old age medicine, brain health, public health care research, health care management, dementia, Medicine (General), R5-920
Abstract

IntroductionSociety commonly believes that research knowledge is complementary to public decision-making. This study aimed to understand the perspectives and implications of dementia researchers communicating with policymakers and public research decision-makers (public officials).MethodsThis study uses 24 questions from an anonymous, online survey, which was received by 392 members of nine European, Latin American, and United States medical researcher associations/networks in the fields of age-related neurological degeneration and dementia medicine. The data were analyzed via crosstab analysis, two group comparison analyses, and a logistic regression model.ResultsIn total, 91 (23.2%) respondents completed the questionnaire. Eight independent variables were related to researchers’ research discipline, research remuneration, experience, authorship, H-index, and research grants. The statistically significant variables determining whether the respondents had contact with public officials were “Years of research experience” (p = 0.004), “Number of articles first-authored in the last 5 years” (p = 0.007), and “Average H-index in the last 5 years” (p = 0.048) [median (IQR)]; 47% of the surveyed researchers had been in contact with public officials in the last 12 months. The most frequently communicated topics were the importance of their own research to society (61%) and their own funding (60%); 87% (n = 79) of the researchers did not believe that public officials had a very good understanding of their dementia research.ConclusionLess than half (47%) of dementia researchers communicate with public officials, and they communicate mostly about the importance of their own research and funding their own research. Nine of 10 researchers do not believe that public officials understand their research well.

Published
2024
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13. Large-Scale Crosstalk-Corrected Thermo-Optic Phase Shifter Arrays in Silicon Photonics

Author

Gurses, Volkan, Fatemi, Reza, Khachaturian, Aroutin, and Hajimiri, Ali

Subjects
Physics - Optics, Electrical Engineering and Systems Science - Systems and Control, Physics - Applied Physics
Abstract

We introduce a thermo-optic phase shifter (TOPS) array architecture with independent phase control of each phase shifter for large-scale and high-density photonic integrated circuits with two different control schemes: pulse amplitude modulation (PAM) and pulse width modulation (PWM). We realize a compact spiral TOPS and a 288-element high-density row-column TOPS array with this architecture and drive TOPS with waveforms of both control schemes and of different array sizes. We present a thermal excitation model and a finite difference method-based simulation to simulate large-scale TOPS arrays and compare both schemes experimentally and theoretically. We also analyze the effects of thermal crosstalk in the realized TOPS array and implement a thermal crosstalk correction algorithm with the developed model. The high-density TOPS array architecture and the thermal crosstalk correction algorithm pave the way for high-density TOPS arrays with independent phase control in large-scale photonic integrated circuits interfaced with electronics limited in voltage swing and bandwidth., Comment: 12 pages and 19 figures

Published
2022
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14. Using Semicircular Sampling to Increase Sea Water/Ice Discrimination Altitude

Author

Alexey Nekrasov, Alena Khachaturian, and Colin Fidge

Subjects
uav, remote sensing, airborne scatterometer, radar backscatter, sea water/ice discrimination., Technology (General), T1-995, Social sciences (General), H1-99
Abstract

The rapid development of aircraft and unmanned aerial vehicles (UAV) increases their use, including in polar areas, which are characterized by their remoteness and rather harsh conditions. The dominant trends in airborne radar development are expanding their functionality and increasing the altitude of their applicability. Our study focuses on the functionality enhancement of airborne high-altitude conical scanning radars currently used for circular clouds and precipitation observations as well as for sea wind measurements. Recently, we showed how a semicircular observation scheme, instead of a circular one, can double the maximum applicable altitude of sea wind measurements made with such radars. Here we apply this approach to show how an airborne high-altitude conical scanning radar’s functionality can also be expanded for sea water/ice discrimination within a semicircular observation scheme, again doubling the maximum discrimination altitude compared to circular observations. The discrimination is performed in scatterometer mode using the minimum statistical distance of the measured normalized radar cross sections (NRCSs) to the geophysical model functions (GMFs) of the sea water and ice underlying surfaces. However, as no sea ice GMF is available for the considered horizontal transmit and receive polarization at the Ku band, we instead used a substitute sea ice GMF having the same azimuth isotropic property setting for its NRCSs as the averaged value of the measured azimuth NRCSs within the semicircular observations scheme. Our analysis found that incidence angles of 30°, 45°, and 60° are well suited to our sea water/ice discrimination method, and that incidence angles higher than 30° are preferable as they provide a higher difference in the statistical distance of the measured NRCSs to the sea ice and water GMFs, whereas an incidence angle of 30° provides the highest applicable altitude for sea water/ice discrimination and wind retrieval. We also demonstrated the ability of the sea water/ice discrimination procedure’s implementation for any airborne wind scatterometer or multimode radar operated in scatterometer mode over freezing seas to avoid entirely erroneous sea wind measurement results when a sea ice surface is observed. The obtained results can also be used for enhancing aircraft and UAV radars and for developing new remote sensing systems. Doi: 10.28991/ESJ-2024-08-02-07 Full Text: PDF

Published
2024
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15. The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores

Author

Weiner, MW, Aisen, P, Petersen, R, Jack, CR, Jagust, W, Trojanowki, JQ, Toga, AW, Beckett, L, Green, RC, Saykin, AJ, Morris, JC, Perrin, RJ, Shaw, LM, Khachaturian, Z, Carrillo, M, Potter, W, Barnes, L, Bernard, M, González, H, Ho, C, Hsiao, JK, Jackson, J, Masliah, E, Masterman, D, Okonkwo, O, Perrin, R, Ryan, L, Silverberg, N, Fleisher, A, Sacrey, DT, Fockler, J, Conti, C, Veitch, D, Neuhaus, J, Jin, C, Nosheny, R, Ashford, M, Flenniken, D, Kormos, A, Monine, T, Rafii, M, Raman, R, Jimenez, G, Donohue, M, Gessert, D, Salazar, J, Zimmerman, C, Cabrera, Y, Walter, S, Miller, G, Coker, G, Clanton, T, Hergesheimer, L, Smith, S, Adegoke, O, Mahboubi, P, Moore, S, Pizzola, J, Shaffer, E, Sloan, B, Harvey, D, Forghanian-Arani, A, Borowski, B, Ward, C, Schwarz, C, Jones, D, Gunter, J, Kantarci, K, Senjem, M, Vemuri, P, Reid, R, Fox, NC, Malone, I, Thompson, P, Thomopoulos, SI, Nir, TM, Jahanshad, N, DeCarli, C, Knaack, A, Fletcher, E, Tosun-Turgut, D, Chen, SR, Choe, M, Crawford, K, Yushkevich, PA, Das, S, Koeppe, RA, Reiman, EM, Chen, K, Mathis, C, Landau, S, Cairns, NJ, Householder, E, Franklin, E, Bernhardt, H, Taylor-Reinwald, L, Tojanowki, JQ, Korecka, M, and Figurski, M

Subjects
Biological Sciences, Genetics, Prevention, Human Genome, 2.1 Biological and endogenous factors, Good Health and Well Being, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Knowledge Bases, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, Alzheimer’s Disease Neuroimaging Initiative, Biological sciences, Biomedical and clinical sciences
Abstract

The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu ) or via a command-line interface. We report study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. We introduce a streamlined analysis tool and web interface to calculate and contextualize polygenic risk scores across various studies, which we anticipate will facilitate a wider adaptation of polygenic risk scores in future disease research.

Published
2022

16. The neurophysiological brain-fingerprint of Parkinson’s diseaseResearch in context

Author

Jason da Silva Castanheira, Alex I. Wiesman, Justine Y. Hansen, Bratislav Misic, Sylvain Baillet, John Breitner, Judes Poirier, Pierre Bellec, Véronique Bohbot, Mallar Chakravarty, Louis Collins, Pierre Etienne, Alan Evans, Serge Gauthier, Rick Hoge, Yasser Ituria-Medina, Gerhard Multhaup, Lisa-Marie Münter, Natasha Rajah, Pedro Rosa-Neto, Jean-Paul Soucy, Etienne Vachon-Presseau, Sylvia Villeneuve, Philippe Amouyel, Melissa Appleby, Nicholas Ashton, Daniel Auld, Gülebru Ayranci, Christophe Bedetti, Marie-Lise Beland, Kaj Blennow, Ann Brinkmalm Westman, Claudio Cuello, Mahsa Dadar, Leslie-Ann Daoust, Samir Das, Marina Dauar-Tedeschi, Louis De Beaumont, Doris Dea, Maxime Descoteaux, Marianne Dufour, Sarah Farzin, Fabiola Ferdinand, Vladimir Fonov, Julie Gonneaud, Justin Kat, Christina Kazazian, Anne Labonté, Marie-Elyse Lafaille-Magnan, Marc Lalancette, Jean-Charles Lambert, Jeannie-Marie Leoutsakos, Laura Mahar, Axel Mathieu, Melissa McSweeney, Pierre-François Meyer, Justin Miron, Jamie Near, Holly NewboldFox, Nathalie Nilsson, Pierre Orban, Cynthia Picard, Alexa Pichet Binette, Jean-Baptiste Poline, Sheida Rabipour, Alyssa Salaciak, Matthew Settimi, Sivaniya Subramaniapillai, Angela Tam, Christine Tardif, Louise Théroux, Jennifer Tremblay-Mercier, Stephanie Tullo, Irem Ulku, Isabelle Vallée, Henrik Zetterberg, Vasavan Nair, Jens Pruessner, Paul Aisen, Elena Anthal, Alan Barkun, Thomas Beaudry, Fatiha Benbouhoud, Jason Brandt, Leopoldina Carmo, Charles Edouard Carrier, Laksanun Cheewakriengkrai, Blandine Courcot, Doris Couture, Suzanne Craft, Christian Dansereau, Clément Debacker, René Desautels, Sylvie Dubuc, Guerda Duclair, Mark Eisenberg, Rana El-Khoury, Anne-Marie Faubert, David Fontaine, Josée Frappier, Joanne Frenette, Guylaine Gagné, Valérie Gervais, Renuka Giles, Renee Gordon, Clifford Jack, Benoit Jutras, Zaven Khachaturian, David Knopman, Penelope Kostopoulos, Félix Lapalme, Tanya Lee, Claude Lepage, Illana Leppert, Cécile Madjar, David Maillet, Jean-Robert Maltais, Sulantha Mathotaarachchi, Ginette Mayrand, Diane Michaud, Thomas Montine, John Morris, Véronique Pagé, Tharick Pascoal, Sandra Peillieux, Mirela Petkova, Galina Pogossova, Pierre Rioux, Mark Sager, Eunice Farah Saint-Fort, Mélissa Savard, Reisa Sperling, Shirin Tabrizi, Pierre Tariot, Eduard Teigner, Ronald Thomas, Paule-Joanne Toussaint, Miranda Tuwaig, Vinod Venugopalan, Sander Verfaillie, Jacob Vogel, Karen Wan, Seqian Wang, Elsa Yu, Isabelle Beaulieu-Boire, Pierre Blanchet, Sarah Bogard, Manon Bouchard, Sylvain Chouinard, Francesca Cicchetti, Martin Cloutier, Alain Dagher, Clotilde Degroot, Alex Desautels, Marie Hélène Dion, Janelle Drouin-Ouellet, Anne-Marie Dufresne, Nicolas Dupré, Antoine Duquette, Thomas Durcan, Lesley K. Fellows, Edward Fon, Jean-François Gagnon, Ziv Gan-Or, Angela Genge, Nicolas Jodoin, Jason Karamchandani, Anne-Louise Lafontaine, Mélanie Langlois, Etienne Leveille, Martin Lévesque, Calvin Melmed, Oury Monchi, Jacques Montplaisir, Michel Panisset, Martin Parent, Minh-Thy Pham-An, Ronald Postuma, Emmanuelle Pourcher, Trisha Rao, Jean Rivest, Guy Rouleau, Madeleine Sharp, Valérie Soland, Michael Sidel, Sonia Lai Wing Sun, Alexander Thiel, and Paolo Vitali

Subjects
Movement disorders, Parkinson’s disease, Neural dynamics, Oscillations, Arrhythmic brain activity, Magnetoencephalography, Medicine, Medicine (General), R5-920
Abstract

Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Published
2024
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17. Discretization of Annular-Ring Diffraction Pattern for Large-Scale Photonics Beamforming

Author

Khachaturian, Aroutin, Fatemi, Reza, Darbinian, Artsroun, and Hajimiri, Ali

Subjects
Physics - Optics, Electrical Engineering and Systems Science - Systems and Control, Physics - Applied Physics
Abstract

A solid-state active beamformer based on the annular-ring diffraction pattern is proposed for an integrated photonic platform. Such a circularly symmetric annular-ring aperture achieves radiating element limited FOV. Furthermore, it is demonstrated that a multi-annular-ring aperture with a fixed linear density of elements maintains the beam efficiency for larger apertures while reducing the beamwidth and side-lobe-level (SLL). A 255-element multi-annular-ring OPA with active beamforming is implemented in a standard photonics process. 510 phase and amplitude modulators enable beamforming and beam steering using this aperture. A row-column drive methodology reduces the required electrical drivers by more than a factor of 5., Comment: 12 pages and 9 figures submitted to OSA for publication

Published
2021

20. IQ Photonic Receiver for Coherent Imaging with a Scalable Aperture

Author

Khachaturian, Aroutin, Fatemi, Reza, and Hajimiri, Ali

Subjects
Electrical Engineering and Systems Science - Signal Processing, Electrical Engineering and Systems Science - Systems and Control, Physics - Optics
Abstract

Silicon photonics (SiP) integrated coherent image sensors offer higher sensitivity and improved range-resolution-product compared to direct detection image sensors such as CCD and CMOS devices. Previous generation of SiP coherent imagers suffer from relative optical phase fluctuations between the signal and reference paths, which results in random phase and amplitude fluctuations in the output signal. This limitation negatively impacts the SNR and signal acquisition times. Here we present a coherent imager system that suppresses the optical carrier signal and removes non-idealities from the relative optical path using a photonic in-phase (I) and quadrature (Q) receiver via a $90^\circ$ hybrid detector. Furthermore, we incorporate row-column read-out and row-column addressing schemes to address the electro-optical interconnect density challenge. Our novel row-column read-out architecture for the sensor array requires only $2N$ interconnects for $N^2$ sensors. An $8\times8$ IQ sensor array is presented as a proof-of-concept demonstration with $1.2\times 10^{-5}$ resolution over range accuracy. Free-space FMCW ranging with 250um resolution at 1m distance has been demonstrated using this sensor array., Comment: 8 pages, 15 figures, submitted to IEEE for publication

Published
2021

21. Achieving Full Grating-Lobe-Free Field-of-View with Low-Complexity Co-prime Photonic Beamforming Transceivers

Author

Khachaturian, Aroutin, Fatemi, Reza, and Hajimiri, Ali

Subjects
Electrical Engineering and Systems Science - Signal Processing, Physics - Optics
Abstract

Integrated photonic active beamforming can significantly reduce the size and cost of coherent imagers for LiDAR and medical imaging applications. In current architectures, the complexity of photonic and electronic circuitry linearly increases with the desired imaging resolution. We propose a novel photonic transceiver architecture based on co-prime sampling techniques that breaks this trade-off and achieves the full (radiating-element-limited) field-of-view (FOV) for a 2D aperture with a single-frequency laser. Using only order-of-N radiating elements, this architecture achieves beamwidth and side-lobe level (SLL) performance equivalent to a transceiver with order-of-N-squared elements with half-wavelength spacing. Furthermore, we incorporate a pulse amplitude modulation (PAM) row-column drive methodology to reduce the number of required electrical drivers for this architecture from order of N to order of square root of N. A silicon photonics implementation of this architecture using two 64-element apertures, one for transmitting and one for receiving, requires only 34 PAM electrical drivers and achieves a transceiver SLL of -11.3dB with 1026 total resolvable spots, and 0.6 degree beamwidth within a 23x16.3 degree FOV., Comment: 9 pages, 6 figures, submitted to OSA for publications

Published
2021

22. 'Big Data' of the Digital Archive: A Dialogue with a Raster Manuscript

Author

Lyubov V. Khachaturian

Subjects
ego-documentary heritage, archival materials, digital archive, russian literature of the 20th century, handwritten heritage, big data, data mining, Literature (General), PN1-6790
Abstract

The article reflects the current trends in working with the digital heritage of Russian literature, examines the process of forming virtual archives as a gradual accumulation of the “big data” of scientific research, i. e. unrecognized information array of raster documents containing tens of thousands of images. The research analyzes the specifics of scientific work in the field of ego-documentary heritage that arose at the turn of the 20th – 21st centuries (a corpus of diary entries, workbooks, notebooks, correspondence), the principles of publication and modern standards of digitization of archival heritage. The study and practicing of the three most promising virtual resources on the history of Russian literature of the mid-19th – first half of the 20th centuries allows to formulate specific tasks and methods of visualization of a large corpus of raster images of archival documents, as well as previously untapped possibilities of search engine automation. Much attention is paid to the transition from the graphical elements of the raster image of the manuscript to semantic ones, which allow the use of data mining elements for an unrecognized data array.

Published
2023
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23. Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data

Author

Kaddurah-Daouk, Rima, Kueider-Paisley, Alexandra, Doraiswamy, P. Murali, Blach, Colette, Moseley, Arthur, Thompson, Will, St John-Williams, Lisa, Mahmoudiandehkhordi, Siamak, Tenenbaum, Jessica, Welsh-Balmer, Kathleen, Plassman, Brenda, Saykin, Andrew J., Nho, Kwangsik, Risacher, Shannon L., Kastenmüller, Gabi, Arnold, Matthias, Han, Xianlin, Baillie, Rebecca, Knight, Rob, Dorrestein, Pieter, Brewer, James, Mayer, Emeran, Labus, Jennifer, Baldi, Pierre, Gupta, Arpana, Fiehn, Oliver, Barupal, Dinesh, Meikle, Peter, Mazmanian, Sarkis, Rader, Dan, Kling, Mitchel, Shaw, Leslie, Trojanowski, John, van Duijin, Cornelia, Nevado-Holgado, Alejo, Bennett, David, Krishnan, Ranga, Keshavarzian, Ali, Vogt, Robin, Ikram, Arfan, Hankemeier, Thomas, Thiele, Ines, Price, Nathan, Funk, Cory, Baloni, Priyanka, Jia, Wei, Wishart, David, Brinton, Roberta, Chang, Rui, Farrer, Lindsay, Au, Rhoda, Qiu, Wendy, Würtz, Peter, Koal, Therese, Mangravite, Lara, Krumsiek, Jan, Suhre, Karsten, Newman, John, Moreno, Herman, Foroud, Tatania, Sacks, Frank, Jansson, Janet, Weiner, Michael W., Aisen, Paul, Petersen, Ronald, Jack, Clifford R., Jr., Jagust, William, Trojanowki, John Q., Toga, Arthur W., Beckett, Laurel, Green, Robert C., Morris, John C., Perrin, Richard J., Shaw, Leslie M., Khachaturian, Zaven, Carrillo, Maria, Potter, William, Barnes, Lisa, Bernard, Marie, Gonzalez, Hector, Ho, Carole, Hsiao, John K., Jackson, Jonathan, Masliah, Eliezer, Masterman, Donna, Okonkwo, Ozioma, Perrin, Richard, Ryan, Laurie, Silverberg, Nina, Fleisher, Adam, Sacrey, Diana Truran, Fockler, Juliet, Conti, Cat, Veitch, Dallas, Neuhaus, John, Jin, Chengshi, Nosheny, Rachel, Ashford, Miriam, Flenniken, Derek, Kormos, Adrienne, Montine, Tom, Rafii, Michael, Raman, Rema, Jimenez, Gustavo, Donohue, Michael, Gessert, Devon, Salazar, Jennifer, Zimmerman, Caileigh, Cabrera, Yuliana, Walter, Sarah, Miller, Garrett, Coker, Godfrey, Clanton, Taylor, Hergesheimer, Lindsey, Smith, Stephanie, Adegoke, Olusegun, Mahboubi, Payam, Moore, Shelley, Pizzola, Jeremy, Shaffer, Elizabeth, Sloan, Brittany, Harvey, Danielle, Forghanian-Arani, Arvin, Borowski, Bret, Ward, Chad, Schwarz, Christopher, Jones, David, Gunter, Jeff, Kantarci, Kejal, Senjem, Matthew, Vemuri, Prashanthi, Reid, Robert, Fox, Nick C., Malone, Ian, Thompson, Paul, Thomopoulos, Sophia I., Nir, Talia M., Jahanshad, Neda, DeCarli, Charles, Knaack, Alexander, Fletcher, Evan, Tosun-Turgut, Duygu, Chen, Stephanie Rossi, Choe, Mark, Crawford, Karen, Yushkevich, Paul A., Das, Sandhitsu, Koeppe, Robert A., Reiman, Eric M., Chen, Kewei, Mathis, Chet, Landau, Susan, Cairns, Nigel J., Householder, Erin, Franklin, Erin, Bernhardt, Haley, Taylor-Reinwald, Lisa, Korecka, Magdalena, Figurski, Michal, Neu, Scott, Apostolova, Liana G., Shen, Li, Foroud, Tatiana M., Nudelman, Kelly, Faber, Kelley, Wilmes, Kristi, Thal, Leon, Silbert, Lisa C., Lind, Betty, Crissey, Rachel, Kaye, Jeffrey A., Carter, Raina, Dolen, Sara, Quinn, Joseph, Schneider, Lon S., Pawluczyk, Sonia, Becerra, Mauricio, Teodoro, Liberty, Dagerman, Karen, Spann, Bryan M., Vanderswag, Helen, Ziolkowski, Jaimie, Heidebrink, Judith L., Zbizek-Nulph, Lisa, Lord, Joanne L., Mason, Sara S., Albers, Colleen S., Knopman, David, Johnson, Kris, Villanueva-Meyer, Javier, Pavlik, Valory, Pacini, Nathaniel, Lamb, Ashley, Kass, Joseph S., Doody, Rachelle S., Shibley, Victoria, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Honig, Lawrence S., Mintz, Akiva, Ances, Beau, Winkfield, David, Carroll, Maria, Stobbs-Cucchi, Georgia, Oliver, Angela, Creech, Mary L., Mintun, Mark A., Schneider, Stacy, Geldmacher, David, Love, Marissa Natelson, Griffith, Randall, Clark, David, Brockington, John, Marson, Daniel, Grossman, Hillel, Goldstein, Martin A., Greenberg, Jonathan, Mitsis, Effie, Shah, Raj C., Lamar, Melissa, Samuels, Patricia, Duara, Ranjan, Greig-Custo, Maria T., Rodriguez, Rosemarie, Albert, Marilyn, Onyike, Chiadi, Farrington, Leonie, Rudow, Scott, Brichko, Rottislav, Kielb, Stephanie, Smith, Amanda, Raj, Balebail Ashok, Fargher, Kristin, Sadowski, Martin, Wisniewski, Thomas, Shulman, Melanie, Faustin, Arline, Rao, Julia, Castro, Karen M., Ulysse, Anaztasia, Chen, Shannon, Sheikh, Mohammed O., Singleton-Garvin, Jamika, Petrella, JeffreyR., James, Olga, Wong, Terence Z., Borges-Neto, Salvador, Karlawish, Jason H., Wolk, David A., Vaishnavi, Sanjeev, Clark, Christopher M., Arnold, Steven E., Smith, Charles D., Jicha, Gregory A., Raslau, Flavius D., Lopez, Oscar L., Oakley, MaryAnn, Simpson, Donna M., Porsteinsson, Anton P., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. Saleem, Brand, Connie, Thai, Gaby, Pierce, Aimee, Yanez, Beatriz, Sosa, Elizabeth, Witbracht, Megan, Kelley, Brendan, Nguyen, Trung, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Levey, Allan I., Lah, James J., Hajjar, Ihab, Cellar, Janet S., Burns, Jeffrey M., Swerdlow, Russell H., Brooks, William M., Silverman, Daniel H.S., Kremen, Sarah, Apostolova, Liana, Tingus, Kathleen, Lu, Po H., Bartzokis, George, Woo, Ellen, Teng, Edmond, Graff-Radford, Neill R., Parfitt, Francine, Poki-Walker, Kim, Farlow, Martin R., Hake, Ann Marie, Matthews, Brandy R., Brosch, Jared R., Herring, Scott, van, Christopher H., Mecca, Adam P., Good, Susan P., MacAvoy, Martha G., Carson, Richard E., Varma, Pradeep, Chertkow, Howard, Vaitekunis, Susan, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Heyn, Chris (Chinthaka), Robin Hsiung, Ging-Yuek, Kim, Ellen, Mudge, Benita, Sossi, Vesna, Feldman, Howard, Assaly, Michele, Finger, Elizabeth, Pasternak, Stephen, Rachinsky, Irina, Kertesz, Andrew, Drost, Dick, Rogers, John, Grant, Ian, Muse, Brittanie, Rogalski, Emily, Robson, Jordan, Mesulam, M.-Marsel, Kerwin, Diana, Wu, Chuang-Kuo, Johnson, Nancy, Lipowski, Kristine, Weintraub, Sandra, Bonakdarpour, Borna, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Rosen, Howard J., Miller, Bruce L., Perry, David, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, MCCann, Kelly, Poe, Jessica, Sperling, Reisa A., Johnson, Keith A., Marshall, Gad A., Yesavage, Jerome, Taylor, Joy L., Chao, Steven, Coleman, Jaila, White, Jessica D., Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Belden, Christine M., Atri, Alireza, Clark, Kelly A., Zamrini, Edward, Sabbagh, Marwan, Killiany, Ronald, Stern, Robert, Mez, Jesse, Kowall, Neil, Budson, Andrew E., Obisesan, Thomas O., Ntekim, Oyonumo E., Wolday, Saba, Khan, Javed I., Nwulia, Evaristus, Nadarajah, Sheeba, Lerner, Alan, Ogrocki, Paula, Tatsuoka, Curtis, Fatica, Parianne, Maillard, Pauline, Olichney, John, Carmichael, Owen, Bates, Vernice, Capote, Horacio, Rainka, Michelle, Borrie, Michael, Lee, T.-Y., Bartha, Dr Rob, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M., Perrin, Allison, Burke, Anna, Scharre, Douglas W., Kataki, Maria, Tarawneh, Rawan, Hart, David, Zimmerman, Earl A., Celmins, Dzintra, Miller, Delwyn D., BolesPonto, Laura L., Smith, Karen Ekstam, Koleva, Hristina, Shim, Hyungsub, Nam, Ki Won, Schultz, Susan K., Williamson, Jeff D., Craft, Suzanne, Cleveland, Jo, Yang, Mia, Sink, Kaycee M., Ott, Brian R., Drake, Jonathan, Tremont, Geoffrey, Daiello, Lori A., Drake, Jonathan D., Ritter, Aaron, Bernick, Charles, Munic, Donna, O'Connelll, Abigail, Mintzer, Jacobo, Wiliams, Arthur, Masdeu, Joseph, Shi, Jiong, Garcia, Angelica, Newhouse, Paul, Potkin, Steven, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Kittur, Smita, Pearlson, Godfrey D., Blank, Karen, Anderson, Karen, Flashman, Laura A., Seltzer, Marc, Hynes, Mary L., Santulli, Robert B., Relkin, Norman, Chiang, Gloria, Lee, Athena, Lin, Michael, Ravdin, Lisa, Petersen, Ron, Neylan, Thomas, Grafman, Jordan, Danowski, Sarah, Nguyen-Barrera, Catherine, Hayes, Jacqueline, Finley, Shannon, Bernstein, Matthew, Senjem, Matt, Foster, Norm, Kim, Sungeun, Sood, Ajay, Blanchard, Kimberly S., Fleischman, Debra, Arfanakis, Konstantinos, Varon, Daniel, Greig, Maria T., Petrella, Jeffrey R., Goldstein, Bonnie, Martin, Kimberly S., Reist, Christopher, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Rosen, Howard, Marshall, Gad, Peskind, Elaine R., Petrie, Eric C., Li, Gail, Mackin, Scott, Jimenez-Maggiora, Gustavo, Drake, Erin, Donohue, Mike, Nelson, Craig, Bickford, David, Butters, Meryl, Zmuda, Michelle, Reyes, Denise, Faber, Kelley M., Nudelman, Kelly N., Au, Yiu Ho, Scherer, Kelly, Catalinotto, Daniel, Stark, Samuel, Ong, Elise, Fernandez, Dariella, Jo, Taeho, Kim, Junpyo, Bice, Paula, Huynh, Kevin, Wang, Tingting, Meikle, Peter J., and Giles, Corey

Published
2023
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26. Real-world diagnostic, referral, and treatment patterns in early Alzheimer's disease among community-based practices in the United States.

Author

Juday, Timothy R, Holub, Ashley, Mattke, Soeren, Betts, Keith A, Kitchen, Sophie A, Liu, Hongjiao, Batrla, Richard, Frech, Feride H, and Khachaturian, Ara S

Subjects
ALZHEIMER'S disease, MILD cognitive impairment, LANDSCAPE changes, PHYSICIANS, MEDICAL records
Abstract

Background: Over 90% of individuals with mild cognitive impairment (MCI) may not receive a timely diagnosis. Understanding community-based practice patterns, where most individuals are seen, is critical to improving patient care. Objective: To understand how patients with MCI and mild dementia due to Alzheimer's disease (AD) are diagnosed and managed in community-based settings, including the use of clinical and cognitive assessments, referrals to dementia-related specialties, and receipt of treatment. Methods: This observational study recruited community-based primary care physicians (PCPs) (N = 177) and neurologists (N = 147) in August-September 2023, through a verified physician panel with broad geographic representation across the US. Physicians abstracted medical chart data from patients diagnosed with MCI or mild AD within the previous two years. Data collected included use of neurocognitive assessments, biomarker and structural imagine tests, referrals, and treatments. Descriptive statistics were used. Results: Medical records for 817 MCI and 467 mild AD patients were abstracted. The mean age was 70.2 years, 56.4% were female, and 67.2% were White. Symptoms were commonly reported by a family member (67.2%). Nearly 1 in 6 patients did not receive any neurocognitive assessments (16.1%), and nearly 1 in 4 did not receive a structural imaging or AD-specific biomarker test (23.7%). AD-specific biomarker tests were more common among patients aged ≥65 (87.1% versus 75.3%; p < 0.05). Less than 1 in 4 patients were referred for cognitive/behavioral concerns. Conclusions: As the diagnostic and treatment landscape changes, education on symptom recognition, and physician training on new technologies may facilitate timely diagnoses and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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27. Foundry-fabricated grating coupler demultiplexer inverse-designed via fast integral methods

Author

Constantine Sideris, Aroutin Khachaturian, Alexander D. White, Oscar P. Bruno, and Ali Hajimiri

Subjects
Astrophysics, QB460-466, Physics, QC1-999
Abstract

Wavelength division multiplexing is a key method for boosting the data transfer rate of photonic devices, typically requiring multiple on-chip elements to achieve. Here, a combined grating coupler demultiplexer is developed by inverse-design methods and fabricated with standard Si foundry processes.

Published
2022
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28. 18F-florbetapir Positron Emission Tomography–determined Cerebral &bgr;-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery

Author

Klinger, Rebecca Y, James, Olga G, Borges-Neto, Salvador, Bisanar, Tiffany, Li, Yi-Ju, Qi, Wenjing, Berger, Miles, Terrando, Niccolò, Newman, Mark F, Doraiswamy, P Murali, Mathew, Joseph P, Weiner, Michael W, Aisen, Paul, Weiner, Michael, Petersen, Ronald, Jack, Clifford R, Jagust, William, Trojanowki, John Q, Toga, Arthur W, Beckett, Laurel, Green, Robert C, Saykin, Andrew J, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, David, Mesulam, M Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Balasubramanian, Archana B, Mason, Jennifer, Sim, Iris, Harvey, Danielle, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCArli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Landau, Susan, Morris, John C, Cairns, Louis Nigel J, Franklin, Erin, Taylor-Reinwald, Lisa, Lee, Virginia, Korecka, Magdalena, Figurski, Michal, Crawford, Karen, Neu, Scott, Foroud, Tatiana M, Potkin, Steven, Shen, Li, Faber, Kelley, Kim, Sungeun, Nho, Kwangsik, Thal, Lean, Thal, Leon, and Buckholtz, Neil

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Brain Disorders, Neurodegenerative, Behavioral and Social Science, Dementia, Neurosciences, Acquired Cognitive Impairment, Biomedical Imaging, Clinical Research, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Mental Health, 2.1 Biological and endogenous factors, Neurological, Aged, Amyloid beta-Peptides, Aniline Compounds, Brain, Cardiac Surgical Procedures, Cognitive Dysfunction, Ethylene Glycols, Female, Fluorine Radioisotopes, Humans, Male, Mental Status and Dementia Tests, Middle Aged, Positron-Emission Tomography, Postoperative Complications, Prospective Studies, Alzheimer’s Disease Neuroimaging Initiative (ADNI) Study Group, Neurologic Outcomes Research Group, Anesthesiology, Clinical sciences
Abstract

BackgroundAmyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively.MethodsAmyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype.ResultsThe authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls.ConclusionsIn this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.

Published
2018

32. Khachaturian piano works.

Author

Khachaturi͡an, Aram, 1903-1978, composer., McLachlan, Murray, 1965- instrumentalist., Khachaturi͡an, Aram, 1903-1978. Toccata, piano., Khachaturi͡an, Aram, 1903-1978. Poėma., Khachaturi͡an, Aram, 1903-1978. Pieces, piano., Khachaturi͡an, Aram, 1903-1978. Detskiĭ alʹbom., Khachaturi͡an, Aram, 1903-1978. Sonatas, piano., Khachaturi͡an, Aram, 1903-1978. Sonatina, piano., and Khachaturi͡an, Aram, 1903-1978. Maskarad. Valʹs; arranged.

Published
2011

33. Concerto for cello ; Concerto-rhapsody for cello & orchestra

Author

Khachaturi͡an, Aram, 1903-1978, composer., Gosudarstvennyĭ simfonicheskiĭ orkestr SSSR., Tarasova, Marina, instrumentalist., Dudarova, Veronika, 1916-2009, conductor., Khachaturi͡an, Aram, 1903-1978. Concertos, cello, orchestra., and Khachaturi͡an, Aram, 1903-1978. Kont͡sert-rapsodii͡a, cello, orchestra.

Published
2011

34. Famous ballet suites : Spartacus, Gayaneh, Maskarade

Author

Khachaturi͡an, Aram, 1903-1978, composer., Royal Philharmonic Orchestra., Simonov, I͡Uriĭ, 1941- conductor., Khachaturi͡an, Aram, 1903-1978. Gai͡anė. Selections., Khachaturi͡an, Aram, 1903-1978. Spartak. Selections., and Khachaturi͡an, Aram, 1903-1978. Maskarad. Selections. Suite.

Published
2010

35. Suites and dances

Author

Khachaturi͡an, Aram, 1903-1978, composer., Hayastani Petakan Simfonik Nvagakhumb., Tjeknavorian, Loris, conductor., Khachaturi͡an, Aram, 1903-1978. Maskarad., Khachaturi͡an, Aram, 1903-1978. Valensianskai͡a vdova. Suite., Khachaturi͡an, Aram, 1903-1978. Tant͡sevalʹnai͡a si͡uita., and Khachaturi͡an, Aram, 1903-1978. Stalingradskai͡a bitva. Suite.

Published
2007

36. Khachaturian, Gayane ; Spartacus ; Masquerade.

Author

Khachaturi︠a︡n, Aram, 1903-1978, composer., Royal Philharmonic Orchestra, performer., Container of (expression): Khachaturi︠a︡n, Aram, 1903-1978. Gai︠a︡nė. Selections; arranged., Container of (work): Khachaturi︠a︡n, Aram, 1903-1978. Spartak. no. 1. Suite,, Container of (work): Khachaturi︠a︡n, Aram, 1903-1978. Spartak. no. 2. Suite,, Container of (work): Khachaturi︠a︡n, Aram, 1903-1978. Maskarad. Suite., and Simonov, I︠U︡riĭ, 1941- conductor.

Published
2009

37. Violin concerto ; Cello concerto

Author

Khachaturi͡an, Aram, 1903-1978, composer., London Philharmonic Orchestra, instrumentalist., Royal Scottish National Orchestra, instrumentalist., Mordkovitch, Lydia, instrumentalist., Järvi, Neeme, conductor., Thomson, Bryden, conductor., Wallfisch, Raphael, 1953- instrumentalist., Container of (work): Khachaturi͡an, Aram, 1903-1978. Concertos, violin, orchestra,, and Container of (work): Khachaturi͡an, Aram, 1903-1978. Concertos, cello, orchestra.

Published
2002

38. Ode to joy

Author

Khachaturian, Aram Il'ich, 1903-1978., Armenian Philharmonic Chorus. Performer, Hayastani Petakan Simfonik Nvagakhumb. Performer, Amirkhanian, Mourad. Performer, Hatsagortsian, Hasmik. Performer, Khachatrian, Vardouhi. Performer, Khachaturian, Aram Il'ich, 1903-1978. Ballada o rodine., Khachaturian, Aram Il'ich, 1903-1978. Konëtìsertnye arii., Khachaturian, Aram Il'ich, 1903-1978. Oda radosti., Khachaturian, Aram Il'ich, 1903-1978. Poéma., Khachaturian, Aram Il'ich, 1903-1978. Zangezur. Marsh., and Tjeknavorian, Loris. Conductor

Published
2000

39. Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis

Author

Zhou, Xiaopu, Chen, Yu, Mok, Kin Y, Zhao, Qianhua, Chen, Keliang, Chen, Yuewen, Hardy, John, Li, Yun, Fu, Amy KY, Guo, Qihao, Ip, Nancy Y, Saykin, Andrew J, Toga, Arthur W, Borowski, Bret, Ward, Chad, DeCarli, Charles, Mathis, Chet, Jack, Clifford R, Harvey, Danielle, Holtzman, David, Jones, David, Gessert, Devon, Lilly, Eli, Reiman, Eric M, Franklin, Erin, Hefti, Franz, Sorensen, Greg, Jimenez, Gustavo, Fillit, Howard, Gunter, Jeff, Salazar, Jennifer, Hsiao, John, Morris, John, Trojanowki, John Q, Neu, Karen Crawford Scott, Kantarci, Kejal, Faber, Kelley, Harless, Kelly, Chen, Kewei, Nho, Kwangsik, Beckett, Laurel, Thal, Lean, Thal, Leon, Shaw, Leslie M, Kuller, Lew, Shen, Li, Hergesheimer, Lindsey, Taylor-Reinwald, Lisa, Mesulam, M Marcel, Korecka, Magdalena, Raichle, Marc, Carrillo, Maria, Albert, Marilyn, Senjem, Matt, Bernstein, Matthew, Donohue, Michael, Weiner, Michael, Figurski, Michal, Buckholtz, Neil, Fox, Nick, Cairns, Nigel J, Schuff, Norbert, Foster, Norm, Aisen, Paul, Thompson, Paul, Davies, Peter, Snyder, Peter J, Snyder, Peter, Vemuri, Prashanthi, Frank, Richard, Koeppe, Robert A, Green, Robert C, Petersen, Ronald, Walter, Sarah, Paul, Steven, Potkin, Steven, Kim, Sungeun, Foroud, Tatiana M, Montine, Tom, Lee, Virginia, Jagust, William, Potter, William, Cabrera, Yuliana, Khachaturian, Zaven, Fleisher, Adam, Pierce, Aimee, Mintz, Akiva, Lerner, Alan, Norbash, Alexander, Levey, Allan I, Rosen, Allyson, Smith, Amanda, Ulysse, Anaztasia, Budson, Andrew E, Kertesz, Andrew, Oliver, Angela, Hake, Ann Marie, Burke, Anna, Sarrael, Antero, and Porsteinsson, Anton P

Subjects
Biological Sciences, Genetics, Alzheimer's Disease, Clinical Research, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Human Genome, Neurosciences, Dementia, Acquired Cognitive Impairment, Brain Disorders, Prevention, Neurodegenerative, Aging, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Good Health and Well Being, Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Asian People, China, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Immune System, Male, Middle Aged, Potassium Channels, Inwardly Rectifying, Risk Factors, Alzheimer’s Disease Neuroimaging Initiative, Alzheimer’s disease, GWAS, immune, risk variant, whole-genome sequencing
Abstract

Alzheimer's disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10-14), two common variants, GCH1 (rs72713460, P = 4.36 × 10-5) and KCNJ15 (rs928771, P = 3.60 × 10-6), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype-phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE, GCH1, and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system.

Published
2018

41. Spartacus : ballet suites 1-3

Author

Khachaturi͡an, Aram, 1903-1978, composer., Royal Scottish National Orchestra, performer., Järvi, Neeme, conductor., Container of (work): Khachaturi͡an, Aram, 1903-1978. Spartak. no. 1. Suite,, Container of (work): Khachaturi͡an, Aram, 1903-1978. Spartak. no. 2. Suite,, and Container of (work): Khachaturi͡an, Aram, 1903-1978. Spartak. no. 3. Suite,

Published
1991

42. Piano concerto ; Gayaneh ballet suite ; Masquerade suite

Author

Khachaturi͡an, Aram, 1903-1978, composer., Scottish National Orchestra, performer., Järvi, Neeme, conductor., Orbelian, Constantine, instrumentalist., Container of (work): Khachaturi͡an, Aram, 1903-1978. Concertos, piano, orchestra,, Container of (work): Khachaturi͡an, Aram, 1903-1978. Maskarad. Suite., and Container of (work): Khachaturi͡an, Aram, 1903-1978. Gai͡anė. Selections.

Published
1987

43. Spartacus : Gayaneh ; Masquerade

Author

Khachaturi͡an, Aram Ilʹich, 1903-1978., Hayastani Petakan Simfonik Nvagakhumb. Performer, Tjeknavorian, Loris. Conductor, Ippolitov-Ivanov, Mikhail Mikha?lovich, 1859-1935. Kavkazskie çeskizy., Khachaturian, Aram Il'ich, 1903-1978. Maskarad. Suite., and Khachaturian, Aram Il'ich, 1903-1978. Spartak. Selections.

Published
1991

44. Piano concerto : dance suite; waltz; polka

Author

Khachaturian, Aram Il'ich, 1903-1978., Hayastani Petakan Simfonik Nvagakhumb. Performer, Khachaturian, Aram Il'ich, 1903-1978. Concertos, piano, orchestra,, Khachaturian, Aram Il'ich, 1903-1978. Maskarad. Val's., Khachaturian, Aram Il'ich, 1903-1978. Tant?sevalʹnai?a si?uita., and Tjeknavorian, Loris. Conductor

Published
1995

46. Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer’s Disease

Author

Allegri, Ricardo, Amtashar, Fatima, Bateman, Randy, Benzinger, Tammie, Berman, Sarah, Bodge, Courtney, Brandon, Susan, Brooks, William (Bill), Buck, Jill, Buckles, Virginia, Chea, Sochenda, Chhatwal, Jasmeer, Chrem, Patricio, Chui, Helena, Cinco, Jake, Clifford, Jack, Cruchaga, Carlos, D‘Mello, Mirelle, Donahue, Tamara, Douglas, Jane, Edigo, Noelia, Erekin-Taner, Nilufer, Fagan, Anne, Farlow, Marty, Farrar, Angela, Feldman, Howard, Flynn, Gigi, Fox, Nick, Franklin, Erin, Fujii, Hisako, Gant, Cortaiga, Gardener, Samantha, Ghetti, Bernardino, Goate, Alison, Goldman, Jill, Gordon, Brian, Graff-Radford, Neill, Gray, Julia, Gurney, Jenny, Hassenstab, Jason, Hirohara, Mie, Holtzman, David, Hornbeck, Russ, DiBari, Siri Houeland, Ikeuchi, Takeshi, Ikonomovic, Snezana, Jerome, Gina, Jucker, Mathias, Karch, Celeste, Kasuga, Kensaku, Kawarabayashi, Takeshi, Klunk, William (Bill), Koeppe, Robert, Kuder-Buletta, Elke, Laske, Christoph, Lee, Jae-Hong, Levin, Johannes, Marcus, Daniel, Martins, Ralph, Mason, Neal Scott, Masters, Colin, Maue-Dreyfus, Denise, McDade, Eric, Montoya, Lucy, Mori, Hiroshi, Morris, John, Nagamatsu, Akem, Neimeyer, Katie, Noble, James, Norton, Joanne, Perrin, Richard, Raichle, Marc, Ringman, John, Roh, Jee Hoon, Salloway, Stephen, Schofield, Peter, Shimada, Hiroyuki, Shiroto, Tomoyo, Shoji, Mikio, Sigurdson, Wendy, Sohrabi, Hamid, Sparks, Paige, Suzuki, Kazushi, Swisher, Laura, Taddei, Kevin, Wang, Jen, Wang, Peter, Weiner, Mike, Wolfsberger, Mary, Xiong, Chengjie, Xu, Xiong, Tam, Angela, Labonté, Anne, Pichet Binette, Alexa, Faubert, Anne-Marie, Mathieu, Axel, Madjar, Cécile, Carrier, Charles Edouard, Dansereau, Christian, Kazazian, Christina, Lepage, Claude, Picard, Cynthia, Maillet, David, Michaud, Diane, Couture, Doris, Dea, Doris, Cuello, Claudio, Barkun, Alan, Evans, Alan, Courcot, Blandine, Tardif, Christine, Debacker, Clément, Jack, Clifford R., Fontaine, David, Knopman, David S., Maultaup, Gerhard, Near, Jamie, Leoutsakos, Jeannie-Marie, Maltais, Jean-Robert, Brandt, Jason, Pruessner, Jens, Morris, John C., Breitner, John C.S., Poirier, Judes, Cheewakriengkrai, Laksanun, Münter, Lisa-Marie, Collins, Louis, Chakravarty, Mallar, Sager, Mark A., Dauar-Tedeschi, Marina, Eisenberg, Mark, Rajah, Natasha, Aisen, Paul, Toussaint, Joanne, Rosa-Neto, Pedro, Bellec, Pierre, Kostopoulos, Penelope, Etienne, Pierre, Tariot, Pierre N., Orban, Pierre, Sperling, Reisa A., Hoge, Rick, Thomas, Ronald G., Gauthier, Serge, Craft, Suzanne, Villeneuve, Sylvia, Montine, Thomas J., Nair, Vasavan, Bohbot, Véronique, Venugopalan, Vinod, Fonov, Vladimir, Ituria-Medina, Yasser, Khachaturian, Zaven S., Teigner, Eduard, Anthal, Elena, Yu, Elsa, Ferdinand, Fabiola, Pogossova, Galina, Mayrand, Ginette, Duclair, Guerda, Gagné, Guylaine, Newbold-Fox, Holly, Leppert, Illana, Vallée, Isabelle, Vogel, Jacob W., Tremblay-Mercier, Jennifer, Frenette, Joanne, Frappier, Josée, Kat, Justin, Miron, Justin, Wan, Karen, Mahar, Laura, Carmo, Leopoldina, Théroux, Louise, Dadar, Mahsa, Dufour, Marianne, Lafaille-Magnan, Marie-Elyse, Appleby, Melissa, Savard, Mélissa, Tuwaig, Miranda, Petkova, Mirela, Rioux, Pierre, Meyer, Pierre-François, El-Khoury, Rana, Gordon, Renee, Giles, Renuka, Das, Samir, Wang, Seqian, Tabrizi, Shirin, Mathotaarachchi, Sulantha, Dubuc, Sylvie, Lee, Tanya, Beaudry, Thomas, Gervais, Valérie, Pagé, Véronique, Gonneaud, Julie, Ayranci, Gülebru, Pascoal, Tharick A., Desautels, René, Benbouhoud, Fatiha, Saint-Fort, Eunice Farah, Verfaillie, Sander C.J., Farzin, Sarah, Salaciak, Alyssa, Tullo, Stephanie, Vachon-Presseau, Etienne, Daoust, Leslie-Ann, Köbe, Theresa, Spreng, Nathan, McSweeney, Melissa, Nilsson, Nathalie, Pishnamazi, Morteza, Bedetti, Christophe, Vachon-Presseau, Étienne, Bateman, Randall, and Collins, D. Louis

Published
2021
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48. The Platform of Information and Economic Security of the Russian Industrial Enterprises

Author

Khachaturian, Harutyun H., Ponomareva, Svetlana V., Melnikova, Anna S., Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Bogoviz, Aleksei V., editor, and Ragulina, Yulia V., editor

Published
2020
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49. The Main Areas of Integrated Digitalization of the Strategic Management of Competitiveness of Enterprises from the Russian Industrial High-Tech Branches

Author

Kandybko, Natalia V., Ryazanov, Alexander A., Khachaturian, Suren A., Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Bogoviz, Aleksei V., editor, and Ragulina, Yulia V., editor

Published
2020
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50. The role of the Alzheimer's Association in the genesis of Alzheimer's Disease Neuroimaging Initiative.

Author

Carrillo, Maria C., Mahinrad, Simin, Snyder, Heather M., and Khachaturian, Zaven

Abstract

Here we highlight the Alzheimer's Association's role since its inception, as a strategic collaborator with National Institutes of Health–National Institute on Aging in the development of the modern era of the Alzheimer's Movement and in making Alzheimer's disease (AD) a national priority in the United States by developing several initiatives to advance knowledge about the cause, diagnosis, and treatment of dementia. Among these collaborative undertakings, the Alzheimer's Disease Neuroimaging Initiative (ADNI) is an exemplary case, launched with groundwork by the Neuroimaging Working Group sponsored by the Association's Ronald and Nancy Reagan Research Institute on AD. The unique contribution of the Association to the development of ADNI includes participation as a member of ADNI's Private Partner Scientific Board and involvement in developing an AD biomarker standardization and validation subproject, which has led to a conceptual shift in the field to define AD based on its underlying biology. Furthermore, the creation of Worldwide ADNI (WW‐ADNI) is highlighted, underscoring the global impact of these efforts. Highlights: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a keystone undertaking in the evolving landscape of Alzheimer's disease (AD) research, and is now in its fourth iteration.The Alzheimer's Association has partnered with ADNI since its inception.ADNI 4 and the Association continue to collaborate, ensuring representation within the study population. [ABSTRACT FROM AUTHOR]

Published
2024
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