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2. Association of neighborhood disadvantage with cognitive function and cortical disorganization in an unimpaired cohort

Author

Safai, Apoorva, Jonaitis, Erin, Langhough, Rebecca E, Buckingham, William R, Johnson, Sterling C., Powell, W. Ryan, Kind, Amy J. H., Bendlin, Barbara B., and Tiwari, Pallavi

Subjects
Quantitative Biology - Neurons and Cognition, Statistics - Applications
Abstract

Neighborhood disadvantage is associated with worse health and cognitive outcomes. Morphological similarity network (MSN) is a promising approach to elucidate cortical network patterns underlying complex cognitive functions. We hypothesized that MSNs could capture changes in cortical patterns related to neighborhood disadvantage and cognitive function. This cross-sectional study included cognitively unimpaired participants from two large Alzheimers studies at University of Wisconsin-Madison. Neighborhood disadvantage status was obtained using the Area Deprivation Index (ADI). Cognitive performance was assessed on memory, processing speed and executive function. Morphological Similarity Networks (MSN) were constructed for each participant based on the similarity in distribution of cortical thickness of brain regions, followed by computation of local and global network features. Association of ADI with cognitive scores and MSN features were examined using linear regression and mediation analysis. ADI showed negative association with category fluency,implicit learning speed, story recall and modified pre-clinical Alzheimers cognitive composite scores, indicating worse cognitive function among those living in more disadvantaged neighborhoods. Local network features of frontal and temporal regions differed based on ADI status. Centrality of left lateral orbitofrontal region showed a partial mediating effect between association of neighborhood disadvantage and story recall performance. Our preliminary findings suggest differences in local cortical organization by neighborhood disadvantage, which partially mediated the relationship between ADI and cognitive performance, providing a possible network-based mechanism to, in-part, explain the risk for poor cognitive functioning associated with disadvantaged neighborhoods.

Published
2024

3. Author Correction: Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease

Author

Martinelli, Filippo, Heinken, Almut, Henning, Ann-Kristin, Ulmer, Maria A., Hensen, Tim, González, Antonio, Arnold, Matthias, Asthana, Sanjay, Budde, Kathrin, Engelman, Corinne D., Estaki, Mehrbod, Grabe, Hans-Jörgen, Heston, Margo B., Johnson, Sterling, Kastenmüller, Gabi, Martino, Cameron, McDonald, Daniel, Rey, Federico E., Kilimann, Ingo, Peters, Olive, Wang, Xiao, Spruth, Eike Jakob, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Hansen, Niels, WenzelGlanz, Buerger, Katharina, Janowitz, Daniel, Laske, Christoph, Munk, Matthias H., Spottke, Annika, Roy, Nina, Nauck, Matthias, Teipel, Stefan, Knight, Rob, Kaddurah-Daouk, Rima F., Bendlin, Barbara B., Hertel, Johannes, and Thiele, Ines

Published
2024
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4. Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer’s disease

Author

Martinelli, Filippo, Heinken, Almut, Henning, Ann-Kristin, Ulmer, Maria A., Hensen, Tim, González, Antonio, Arnold, Matthias, Asthana, Sanjay, Budde, Kathrin, Engelman, Corinne D., Estaki, Mehrbod, Grabe, Hans-Jörgen, Heston, Margo B., Johnson, Sterling, Kastenmüller, Gabi, Martino, Cameron, McDonald, Daniel, Rey, Federico E., Kilimann, Ingo, Peters, Olive, Wang, Xiao, Spruth, Eike Jakob, Schneider, Anja, Fliessbach, Klaus, Wiltfang, Jens, Hansen, Niels, Glanz, Wenzel, Buerger, Katharina, Janowitz, Daniel, Laske, Christoph, Munk, Matthias H., Spottke, Annika, Roy, Nina, Nauck, Matthias, Teipel, Stefan, Knight, Rob, Kaddurah-Daouk, Rima F., Bendlin, Barbara B., Hertel, Johannes, and Thiele, Ines

Published
2024
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9. Vitamin E Intake Is Associated with Lower Brain Volume in Haptoglobin 1-1 Elderly with Type 2 Diabetes

Author

Livny, Abigail, primary, Schnaider Beeri, Michal, additional, Heymann, Anthony, additional, Moshier, Erin, additional, Berman, Yuval, additional, Mamistalov, Mary, additional, Shahar, Danit-Rivka, additional, Tsarfaty, Galia, additional, Leroith, Derek, additional, Preiss, Rachel, additional, Soleimani, Laili, additional, Silverman, Jeremy M., additional, Bendlin, Barbara B., additional, Levy, Andrew, additional, and Ravona-Springer, Ramit, additional

Published
2024
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10. Inflammation, tau pathology, and synaptic integrity associated with sleep spindles and memory prior to β-amyloid positivity.

Author

Mander, Bryce A, Dave, Abhishek, Lui, Kitty K, Sprecher, Katherine E, Berisha, Destiny, Chappel-Farley, Miranda G, Chen, Ivy Y, Riedner, Brady A, Heston, Margo, Suridjan, Ivonne, Kollmorgen, Gwendlyn, Zetterberg, Henrik, Blennow, Kaj, Carlsson, Cynthia M, Okonkwo, Ozioma C, Asthana, Sanjay, Johnson, Sterling C, Bendlin, Barbara B, and Benca, Ruth M

Subjects
Aging, Neurodegenerative, Alzheimer's Disease, Acquired Cognitive Impairment, Genetics, Neurosciences, Sleep Research, Dementia, Brain Disorders, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Cognitive Dysfunction, Female, Humans, Inflammation, Male, Middle Aged, Peptide Fragments, Sleep, tau Proteins, Alzheimer's disease, sleep spindles, tau phosphorylation, inflammation, neurodegeneration, memory, Alzheimer’s disease, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Study objectivesFast frequency sleep spindles are reduced in aging and Alzheimer's disease (AD), but the mechanisms and functional relevance of these deficits remain unclear. The study objective was to identify AD biomarkers associated with fast sleep spindle deficits in cognitively unimpaired older adults at risk for AD.MethodsFifty-eight cognitively unimpaired, β-amyloid-negative, older adults (mean ± SD; 61.4 ± 6.3 years, 38 female) enriched with parental history of AD (77.6%) and apolipoprotein E (APOE) ε4 positivity (25.9%) completed the study. Cerebrospinal fluid (CSF) biomarkers of central nervous system inflammation, β-amyloid and tau proteins, and neurodegeneration were combined with polysomnography (PSG) using high-density electroencephalography and assessment of overnight memory retention. Parallelized serial mediation models were used to assess indirect effects of age on fast frequency (13 to

Published
2022

13. Associations between recall of proper names in story recall and CSF amyloid and tau in adults without cognitive impairment

Author

Hale, Madeline R., Langhough, Rebecca, Du, Lianlian, Hermann, Bruce P., Van Hulle, Carol A., Carboni, Margherita, Kollmorgen, Gwendlyn, Basche, Kristin E., Bruno, Davide, Sanson-Miles, Leah, Jonaitis, Erin M., Chin, Nathaniel A., Okonkwo, Ozioma C., Bendlin, Barbara B., Carlsson, Cynthia M., Zetterberg, Henrik, Blennow, Kaj, Betthauser, Tobey J., Johnson, Sterling C., and Mueller, Kimberly D.

Published
2024
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14. Dilated Convolutional Neural Networks for Sequential Manifold-valued Data

Author

Zhen, Xingjian, Chakraborty, Rudrasis, Vogt, Nicholas, Bendlin, Barbara B., and Singh, Vikas

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Efforts are underway to study ways via which the power of deep neural networks can be extended to non-standard data types such as structured data (e.g., graphs) or manifold-valued data (e.g., unit vectors or special matrices). Often, sizable empirical improvements are possible when the geometry of such data spaces are incorporated into the design of the model, architecture, and the algorithms. Motivated by neuroimaging applications, we study formulations where the data are {\em sequential manifold-valued measurements}. This case is common in brain imaging, where the samples correspond to symmetric positive definite matrices or orientation distribution functions. Instead of a recurrent model which poses computational/technical issues, and inspired by recent results showing the viability of dilated convolutional models for sequence prediction, we develop a dilated convolutional neural network architecture for this task. On the technical side, we show how the modules needed in our network can be derived while explicitly taking the Riemannian manifold structure into account. We show how the operations needed can leverage known results for calculating the weighted Fr\'{e}chet Mean (wFM). Finally, we present scientific results for group difference analysis in Alzheimer's disease (AD) where the groups are derived using AD pathology load: here the model finds several brain fiber bundles that are related to AD even when the subjects are all still cognitively healthy.

Published
2019

15. Gut inflammation associated with age and Alzheimer’s disease pathology: a human cohort study

Author

Heston, Margo B., Hanslik, Kendra L., Zarbock, Katie R., Harding, Sandra J., Davenport-Sis, Nancy J., Kerby, Robert L., Chin, Nathaniel, Sun, Yi, Hoeft, Ana, Deming, Yuetiva, Vogt, Nicholas M., Betthauser, Tobey J., Johnson, Sterling C., Asthana, Sanjay, Kollmorgen, Gwendlyn, Suridjan, Ivonne, Wild, Norbert, Zetterberg, Henrik, Blennow, Kaj, Rey, Federico E., Bendlin, Barbara B., and Ulland, Tyler K.

Published
2023
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16. Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status

Author

Gallagher, Rigina L., Koscik, Rebecca Langhough, Moody, Jason F., Vogt, Nicholas M., Adluru, Nagesh, Kecskemeti, Steven R., Van Hulle, Carol A., Chin, Nathaniel A., Asthana, Sanjay, Kollmorgen, Gwendlyn, Suridjan, Ivonne, Carlsson, Cynthia M., Johnson, Sterling C., Dean, III, Douglas C., Zetterberg, Henrik, Blennow, Kaj, Alexander, Andrew L., and Bendlin, Barbara B.

Published
2023
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18. Tractography passes the test: Results from the diffusion-simulated connectivity (disco) challenge

Author

Girard, Gabriel, Rafael-Patiño, Jonathan, Truffet, Raphaël, Aydogan, Dogu Baran, Adluru, Nagesh, Nair, Veena A., Prabhakaran, Vivek, Bendlin, Barbara B., Alexander, Andrew L., Bosticardo, Sara, Gabusi, Ilaria, Ocampo-Pineda, Mario, Battocchio, Matteo, Piskorova, Zuzana, Bontempi, Pietro, Schiavi, Simona, Daducci, Alessandro, Stafiej, Aleksandra, Ciupek, Dominika, Bogusz, Fabian, Pieciak, Tomasz, Frigo, Matteo, Sedlar, Sara, Deslauriers-Gauthier, Samuel, Kojčić, Ivana, Zucchelli, Mauro, Laghrissi, Hiba, Ji, Yang, Deriche, Rachid, Schilling, Kurt G, Landman, Bennett A., Cacciola, Alberto, Basile, Gianpaolo Antonio, Bertino, Salvatore, Newlin, Nancy, Kanakaraj, Praitayini, Rheault, Francois, Filipiak, Patryk, Shepherd, Timothy M., Lin, Ying-Chia, Placantonakis, Dimitris G., Boada, Fernando E., Baete, Steven H., Hernández-Gutiérrez, Erick, Ramírez-Manzanares, Alonso, Coronado-Leija, Ricardo, Stack-Sánchez, Pablo, Concha, Luis, Descoteaux, Maxime, Mansour L．, Sina, Seguin, Caio, Zalesky, Andrew, Marshall, Kenji, Canales-Rodríguez, Erick J., Wu, Ye, Ahmad, Sahar, Yap, Pew-Thian, Théberge, Antoine, Gagnon, Florence, Massi, Frédéric, Fischi-Gomez, Elda, Gardier, Rémy, Haro, Juan Luis Villarreal, Pizzolato, Marco, Caruyer, Emmanuel, and Thiran, Jean-Philippe

Published
2023
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19. Insights from the IronTract challenge: Optimal methods for mapping brain pathways from multi-shell diffusion MRI

Author

Maffei, Chiara, Girard, Gabriel, Schilling, Kurt G., Aydogan, Dogu Baran, Adluru, Nagesh, Zhylka, Andrey, Wu, Ye, Mancini, Matteo, Hamamci, Andac, Sarica, Alessia, Teillac, Achille, Baete, Steven H., Karimi, Davood, Yeh, Fang-Cheng, Yildiz, Mert E., Gholipour, Ali, Bihan-Poudec, Yann, Hiba, Bassem, Quattrone, Andrea, Quattrone, Aldo, Boshkovski, Tommy, Stikov, Nikola, Yap, Pew-Thian, de Luca, Alberto, Pluim, Josien, Leemans, Alexander, Prabhakaran, Vivek, Bendlin, Barbara B., Alexander, Andrew L., Landman, Bennett A., Canales-Rodríguez, Erick J., Barakovic, Muhamed, Rafael-Patino, Jonathan, Yu, Thomas, Rensonnet, Gaëtan, Schiavi, Simona, Daducci, Alessandro, Pizzolato, Marco, Fischi-Gomez, Elda, Thiran, Jean-Philippe, Dai, George, Grisot, Giorgia, Lazovski, Nikola, Puch, Santi, Ramos, Marc, Rodrigues, Paulo, Prčkovska, Vesna, Jones, Robert, Lehman, Julia, Haber, Suzanne N., and Yendiki, Anastasia

Published
2022
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21. Age-related differences in white matter microstructure measured by advanced diffusion MRI in healthy older adults at risk for Alzheimer’s disease

Author

Motovylyak, Alice, Vogt, Nicholas M., Adluru, Nagesh, Ma, Yue, Wang, Rui, Oh, Jennifer M., Kecskemeti, Steven R., Alexander, Andrew L., Dean, Douglas C., Gallagher, Catherine L., Sager, Mark A., Hermann, Bruce P., Rowley, Howard A., Johnson, Sterling C., Asthana, Sanjay, Bendlin, Barbara B., and Okonkwo, Ozioma C.

Published
2022
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24. Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers

Author

Casaletto, Kaitlin B, Elahi, Fanny M, Bettcher, Brianne M, Neuhaus, John, Bendlin, Barbara B, Asthana, Sanjay, Johnson, Sterling C, Yaffe, Kristine, Carlsson, Cynthia, Blennow, Kaj, Zetterberg, Henrik, and Kramer, Joel H

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Neurodegenerative, Behavioral and Social Science, Acquired Cognitive Impairment, Brain Disorders, Dementia, Clinical Research, Alzheimer's Disease, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoproteins E, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Hippocampus, Humans, Imaging, Three-Dimensional, Independent Living, Magnetic Resonance Imaging, Male, Memory Disorders, Mental Recall, Middle Aged, Neurogranin, Neuropsychological Tests, Peptide Fragments, tau Proteins, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveTo determine the association between synaptic functioning as measured via neurogranin in CSF and cognition relative to established Alzheimer disease (AD) biomarkers in neurologically healthy older adults.MethodsWe analyzed CSF concentrations of neurogranin, β-amyloid (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau) among 132 neurologically normal older adults (mean 64.5, range 55-85), along with bilateral hippocampal volumes and a measure of episodic memory (Auditory Verbal Learning Test, delayed recall). Univariable analyses examined the relationship between neurogranin and the other AD-related biomarkers. Multivariable regression models examined the relationship between neurogranin and delayed recall, adjusting for age and sex, and interaction terms (neurogranin × AD biomarkers).ResultsHigher neurogranin concentrations were associated with older age (ρ = 0.20, p = 0.02), lower levels of p-tau and t-tau, and smaller hippocampal volumes (p < 0.03), but not with CSF Aβ42 (p = 0.18). In addition, CSF neurogranin demonstrated a significant relationship with memory performance independent of the AD-related biomarkers; individuals with the lowest CSF neurogranin concentrations performed better on delayed recall than those with medium or high CSF neurogranin concentrations (p < 0.01). Notably, CSF p-tau, t-tau, and Aβ42 and hippocampal volumes were not significantly associated with delayed recall scores (p > 0.40), and did not interact with neurogranin to predict memory (p > 0.10).ConclusionsSynaptic dysfunction (assessed via neurogranin) may be an early pathologic process in age-related neurodegeneration, and a sensitive marker of age-related cognitive abilities, potentially preceding or even acting independently from AD pathogenesis. Synaptic functioning may be a useful early marker of cognitive aging and possibly a target for future brain aging interventions.

Published
2017

25. Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults

Author

Sprecher, Kate E, Koscik, Rebecca L, Carlsson, Cynthia M, Zetterberg, Henrik, Blennow, Kaj, Okonkwo, Ozioma C, Sager, Mark A, Asthana, Sanjay, Johnson, Sterling C, Benca, Ruth M, and Bendlin, Barbara B

Subjects
Acquired Cognitive Impairment, Sleep Research, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Prevention, Clinical Research, Dementia, Aging, Alzheimer's Disease, Brain Disorders, Neurodegenerative, Neurological, Amyloid beta-Peptides, Biomarkers, Chemokine CCL2, Chitinase-3-Like Protein 1, Female, Humans, Longitudinal Studies, Male, Mental Status Schedule, Middle Aged, Neurofilament Proteins, Nuclear Proteins, Peptide Fragments, Phosphorylation, RNA-Binding Proteins, Self Report, Sleep, Sleep Wake Disorders, tau Proteins, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract

ObjectiveTo determine the relationship between sleep quality and CSF markers of Alzheimer disease (AD) pathology in late midlife.MethodsWe investigated the relationship between sleep quality and CSF AD biomarkers in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention. A total of 101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal. Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 [Aβ42]), tau pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation (monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein 1 [YKL-40]), and synaptic dysfunction/degeneration (neurogranin). To adjust for individual differences in total amyloid production, Aβ42 was expressed relative to Aβ40. To assess cumulative pathology, CSF biomarkers were expressed in ratio to Aβ42. Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.ResultsWorse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42. There were no significant associations between sleep and NFL or neurogranin.ConclusionsSelf-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.

Published
2017

28. Alzheimer's disease APOE neuropathology‐based score, amyloid, and ptau polygenic scores' association with amyloid PET positivity.

Author

Hammad, Yazan, Deming, Yuetiva, Morse, Jacob, Grover, Ethan, Bendlin, Barbara B., and Betthauser, Tobey J.

Abstract

Background: APOE is the greatest genetic risk factor for AD, however, other smaller genetic effects are often ignored. In this work, endophenotype‐informed polygenic scores (PGS) that exclude the APOE region were tested along with a separate, previously published, APOE neuropathology‐based score (APOEscore). The APOEscore serves as a more nuanced quantification of APOE genetic risk that considers the effects of the different haplotypes. PGS and APOEscore were compared to amyloid positivity, determined via PET imaging, which is used as a measure for AD risk and progression. Methods: Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with genetic data and Florbetapir (18F‐AV‐45) amyloid PET summary SUVR (whole cerebellum reference region) values were included in analyses. Amyloid positivity (A+) was defined as SUVR > 1.11. PGS were calculated using the weights from genome‐wide association studies (GWAS) of CSF Aβ42 (amyloid‐PGS) or ptau181 (ptau‐PGS), after excluding the APOE region (±500kb). APOE effects were accounted for using the APOEscore that was calculated following Deming et al (2023). Results: 1094 participants (618 A+) were included in the analyses (Table 1). The APOEscore was significantly associated with A+ after accounting for sex and age at scan (OR = 2.931, P = 6.38e‐45; Table 2). The amyloid‐PGS was also significantly associated with A+ (OR = 0.492, P = 0.026), whereas the ptau‐PGS did not quite reach significance (OR = 3.218, P = 0.054). After adding the APOEscore, the effect of amyloid‐PGS on A+ remained but did not quite reach significance (OR = 0.515, P = 0.072) and ptau‐PGS was not significant (OR = 1.845, P = 0.375). Conclusion: These results validate the utility of the APOEscore with PET amyloid as well as the potential value of including non‐APOE genes in quantifying the genetic risk for amyloid accumulation and AD. The significant association between amyloid‐PGS and A+, and near significance after adding the APOEscore, demonstrates the existence of additional genetic effects outside of APOE that have an impact on amyloid accumulation. While the ptau‐PGS did not reach significance, possibly due to sample size, the OR (3.218) was greater in magnitude than the amyloid‐PGS (1/OR = 2.033). Future work will explore these relationships in other cohorts and with other PET AD biomarkers. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Older adults at greater risk for Alzheimer’s disease show stronger associations between sleep apnea severity in REM sleep and verbal memory

Author

Lui, Kitty K., primary, Dave, Abhishek, additional, Sprecher, Kate E., additional, Chappel-Farley, Miranda G., additional, Riedner, Brady A., additional, Heston, Margo B., additional, Taylor, Chase E., additional, Carlsson, Cynthia M., additional, Okonkwo, Ozioma C., additional, Asthana, Sanjay, additional, Johnson, Sterling C., additional, Bendlin, Barbara B., additional, Mander, Bryce A., additional, and Benca, Ruth M., additional

Published
2024
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30. Brain aging in temporal lobe epilepsy: Chronological, structural, and functional

Author

Hwang, Gyujoon, Hermann, Bruce, Nair, Veena A., Conant, Lisa L., Dabbs, Kevin, Mathis, Jed, Cook, Cole J., Rivera-Bonet, Charlene N., Mohanty, Rosaleena, Zhao, Gengyan, Almane, Dace N., Nencka, Andrew, Felton, Elizabeth, Struck, Aaron F., Birn, Rasmus, Maganti, Rama, Humphries, Colin J., Raghavan, Manoj, DeYoe, Edgar A., Bendlin, Barbara B., Prabhakaran, Vivek, Binder, Jeffrey R., and Meyerand, Mary E.

Published
2020
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32. Melatonin : A potential nighttime guardian against Alzheimer's.

Author

Zhang, Zefan, Xue, Pei, Bendlin, Barbara B, Zetterberg, Henrik, De Felice, Fernanda, Tan, Xiao, Benedict, Christian, Zhang, Zefan, Xue, Pei, Bendlin, Barbara B, Zetterberg, Henrik, De Felice, Fernanda, Tan, Xiao, and Benedict, Christian

Abstract

In the context of the escalating global health challenge posed by Alzheimer's disease (AD), this comprehensive review considers the potential of melatonin in both preventive and therapeutic capacities. As a naturally occurring hormone and robust antioxidant, accumulating evidence suggests melatonin is a compelling candidate to consider in the context of AD-related pathologies. The review considers several mechanisms, including potential effects on amyloid-beta and pathologic tau burden, antioxidant defense, immune modulation, and regulation of circadian rhythms. Despite its promise, several gaps need to be addressed prior to clinical translation. These include conducting additional randomized clinical trials in patients with or at risk for AD dementia, determining optimal dosage and timing, and further determining potential side effects, particularly of long-term use. This review consolidates existing knowledge, identifies gaps, and suggests directions for future research to better understand the potential of melatonin for neuroprotection and disease mitigation within the landscape of AD.

Published
2024
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34. Fitness, independent of physical activity is associated with cerebral blood flow in adults at risk for Alzheimer’s disease

Author

Dougherty, Ryan J., Boots, Elizabeth A., Lindheimer, Jacob B., Stegner, Aaron J., Van Riper, Stephanie, Edwards, Dorothy F., Gallagher, Catherine L., Carlsson, Cynthia M., Rowley, Howard A., Bendlin, Barbara B., Asthana, Sanjay, Hermann, Bruce P., Sager, Mark A., Johnson, Sterling C., Okonkwo, Ozioma C., and Cook, Dane B.

Published
2020
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35. Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults

Author

Sprecher, Kate E, Bendlin, Barbara B, Racine, Annie M, Okonkwo, Ozioma C, Christian, Bradley T, Koscik, Rebecca L, Sager, Mark A, Asthana, Sanjay, Johnson, Sterling C, and Benca, Ruth M

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Psychology, Neurodegenerative, Brain Disorders, Aging, Neurosciences, Sleep Research, Alzheimer's Disease, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Dementia, Acquired Cognitive Impairment, Clinical Research, Prevention, Behavioral and Social Science, Neurological, Aged, Alzheimer Disease, Amyloid beta-Peptides, Aniline Compounds, Apolipoproteins E, Cerebral Cortex, Cohort Studies, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Positron-Emission Tomography, Radiography, Self Report, Sleep Wake Disorders, Statistics as Topic, Thiazoles, Alzheimer's disease, Amyloid, Midlife, PET, Self-report, Sleep, Clinical Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Midlife may be an ideal window for intervention in Alzheimer's disease (AD). To determine whether sleep is associated with early signs of AD neuropathology (amyloid deposition) in late midlife, we imaged brain amyloid deposits using positron emission tomography with [C-11]Pittsburgh Compound B (PiB), and assessed sleep with the Epworth Sleepiness Scale and the Medical Outcomes Study Sleep Scale in 98 cognitively healthy adults (aged 62.4 ± 5.7 years) from the Wisconsin Registry for Alzheimer's Prevention. We used multiple regressions to test the extent to which sleep scores predicted regional amyloid burden. Participants reporting less adequate sleep, more sleep problems, and greater somnolence on the Medical Outcomes Study had greater amyloid burden in AD-sensitive brain regions (angular gyrus, frontal medial orbital cortex, cingulate gyrus, and precuneus). Amyloid was not associated with reported sleep amount, symptoms of sleep-disordered breathing, trouble falling asleep, or Epworth Sleepiness Scale. Poor sleep may be a risk factor for AD and a potential early marker of AD or target for preventative interventions in midlife.

Published
2015

36. Diffeomorphic Metric Mapping and Probabilistic Atlas Generation of Hybrid Diffusion Imaging based on BFOR Signal Basis

Author

Du, Jia, Hosseinbor, A. Pasha, Chung, Moo K., Bendlin, Barbara B., Suryawanshi, Gaurav, Alexander, Andrew L., and Qiu, Anqi

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

We propose a large deformation diffeomorphic metric mapping algorithm to align multiple b-value diffusion weighted imaging (mDWI) data, specifically acquired via hybrid diffusion imaging (HYDI), denoted as LDDMM-HYDI. We then propose a Bayesian model for estimating the white matter atlas from HYDIs. We adopt the work given in Hosseinbor et al. (2012) and represent the q-space diffusion signal with the Bessel Fourier orientation reconstruction (BFOR) signal basis. The BFOR framework provides the representation of mDWI in the q-space and thus reduces memory requirement. In addition, since the BFOR signal basis is orthonormal, the L2 norm that quantifies the differences in the q-space signals of any two mDWI datasets can be easily computed as the sum of the squared differences in the BFOR expansion coefficients. In this work, we show that the reorientation of the $q$-space signal due to spatial transformation can be easily defined on the BFOR signal basis. We incorporate the BFOR signal basis into the LDDMM framework and derive the gradient descent algorithm for LDDMM-HYDI with explicit orientation optimization. Additionally, we extend the previous Bayesian atlas estimation framework for scalar-valued images to HYDIs and derive the expectation-maximization algorithm for solving the HYDI atlas estimation problem. Using real HYDI datasets, we show the Bayesian model generates the white matter atlas with anatomical details. Moreover, we show that it is important to consider the variation of mDWI reorientation due to a small change in diffeomorphic transformation in the LDDMM-HYDI optimization and to incorporate the full information of HYDI for aligning mDWI.

Published
2013

37. Measuring longitudinal cognition: Individual tests versus composites

Author

Jonaitis, Erin M., Koscik, Rebecca L., Clark, Lindsay R., Ma, Yue, Betthauser, Tobey J., Berman, Sara E., Allison, Samantha L., Mueller, Kimberly D., Hermann, Bruce P., Van Hulle, Carol A., Christian, Bradley T., Bendlin, Barbara B., Blennow, Kaj, Zetterberg, Henrik, Carlsson, Cynthia M., Asthana, Sanjay, and Johnson, Sterling C.

Published
2019
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39. CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges

Author

Jonaitis, Erin M, primary, Jeffers, Beckie, additional, VandenLangenberg, Monica, additional, Ma, Yue, additional, Van Hulle, Carol, additional, Langhough, Rebecca, additional, Du, Lianlian, additional, Chin, Nathaniel A, additional, Przybelski, Robert J, additional, Hogan, Kirk J, additional, Christian, Bradley T, additional, Betthauser, Tobey J, additional, Okonkwo, Ozioma C, additional, Bendlin, Barbara B, additional, Asthana, Sanjay, additional, Carlsson, Cynthia M, additional, and Johnson, Sterling C, additional

Published
2024
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40. Abdominal fat depots are related to lower cognitive functioning and brain volumes in middle‐aged males at high Alzheimer's risk

Author

Golan Shekhtman, Sapir, primary, Boccara, Ethel, additional, Ravona‐Springer, Ramit, additional, Inbar, Yael, additional, Zelicha, Hila, additional, Livny, Abigail, additional, Bendlin, Barbara B., additional, Lesman‐Segev, Orit, additional, Yore, Iscka, additional, Heymann, Anthony, additional, Sano, Mary, additional, Mardor, Yael, additional, Azuri, Joseph, additional, and Schnaider Beeri, Michal, additional

Published
2024
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42. Poor self‐rated health is associated with faster cognitive decline and greater small vessel disease in older adults with type 2 diabetes

Author

Ramsingh, Nadia, primary, Lin, Hung‐Mo, additional, Ouyang, Yuxia, additional, Ravona‐Springer, Ramit, additional, Livny, Abigail, additional, Soleimani, Laili, additional, Bendlin, Barbara B., additional, Meir, Mery Ben, additional, Heymann, Anthony, additional, Sano, Mary, additional, Azuri, Joseph, additional, and Beeri, Michal Schnaider, additional

Published
2024
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45. KLOTHO KL‐VS heterozygosity is associated with diminished age‐related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults.

Author

Driscoll, Ira Frahmand, Lose, Sarah, Ma, Yue, Bendlin, Barbara B., Gallagher, Catherine, Johnson, Sterling C., Asthana, Sanjay, Hermann, Bruce, Sager, Mark A., Blennow, Kaj, Zetterberg, Henrik, Carlsson, Cynthia, Kollmorgen, Gwendlyn, Quijano‐Rubio, Clara, Dubal, Dena, and Okonkwo, Ozioma C.

Abstract

INTRODUCTION: We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL‐VS variant (KL‐VS heterozygosity [KL‐VSHET]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin‐6 [IL‐6], S100 calcium‐binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase‐3‐like protein 1 [YKL‐40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total α‐synuclein [α‐Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]). METHODS: This Alzheimer disease risk‐enriched cohort consisted of 454 cognitively unimpaired adults (Mage = 61.5 ± 7.75). Covariate‐adjusted multivariate regression examined relationships between age (mean‐split[age ≥ 62]) and CSF biomarkers (Roche/NeuroToolKit), and whether they differed between KL‐VSHET (N = 122) and non‐carriers (KL‐VSNC; N = 332). RESULTS: Older age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age‐stratified analyses, KL‐VSNC exhibited this same pattern (Ps ≤ 0.05) which was not significant for IL‐6, S100B, Ng, and α‐Syn (Ps ≥ 0.13) in KL‐VSHET. Although age‐related differences in GFAP, sTREM2, and YKL‐40 were evident for both groups (Ps ≤ 0.01), the effect magnitude was markedly stronger for KL‐VSNC. DISCUSSION: Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL‐VSHET. Highlights: Older age was associated with poorer profiles across all cerebrospinal fluid biomarkers of neuroinflammation, neurodegeneration, and synaptic dysfunction.KLOTHO KL‐VS non‐carriers exhibit this same pattern, which is does not significantly differ between younger and older KL‐VS heterozygotes for interleukin‐6, S100 calcium‐binding protein B, neurogranin, and total α‐synuclein.Although age‐related differences in glial fibrillary acidic protein, triggering receptor expressed on myeloid cells, and chitinase‐3‐like protein 1 are evident for both KL‐VS groups, the magnitude of the effect is markedly stronger for KL‐VS non‐carriers.Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults are attenuated in KL‐VS heterozygotes. [ABSTRACT FROM AUTHOR]

Published
2024
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