Medicine and Health Sciences Commons^™

Examining The Effects Of Formal Education Level On The Montreal Cognitive Assessment, Renee S. White, Justin M. Barber, Jordan P. Harp, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Background: Brief, global assessments such as the Montreal Cognitive Assessment (MoCA) are widely used in primary care for assessing cognition in older adults. Like other neuropsychological instruments, lower formal education can influence MoCA interpretation.

Methods: Data from 2 large studies of cognitive aging were used—Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC). Both use comprehensive examinations to determine cognitive status and have brain amyloid status for many participants. Mixed models were used to account for random variation due to data source.

Results: Cognitively intact participants with lower education (≤12 years) were more likely than …

Expanding The Horizon Of Research Into The Pathogenesis Of The White Matter Diseases Proceedings Of The 2021 Annual Workshop Of The Albert Research Institute For White Matter And Cognition, Shawn N. Whitehead, Askiel Bruno, Jeffrey M. Burns, S. Thomas Carmichael, Anna Csiszar, Jodi D. Edwards, Fanny Elahi, Giuseppe Faraco, Douglas B. Goulding, Deborah R. Gustafson, Vladimir Hachinski, Gary A. Rosenberg, Farzaneh A. Sorond, Andy Y. Shih, Kai Hei Tse, Zoltan Ungvari, Donna M. Wilcock, Kristen L. Zuloaga, Frank C. Barone

Sanders-Brown Center on Aging Faculty Publications

White matter pathologies are critically involved in the etiology of vascular cognitive impairment–dementia (VCID), Alzheimer’s disease (AD), and Alzheimer’s disease and related diseases (ADRD), and therefore need to be considered a treatable target (Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793–4, [1]. To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of “The Albert Research Institute for White Matter and Cognition” in 2020. The first annual “Institute” meeting …

Arginase 1 Insufficiency Precipitates Amyloid-Β Deposition And Hastens Behavioral Impairment In A Mouse Model Of Amyloidosis, Chao Ma, Jerry B. Hunt, Maj-Linda B. Selenica, Awa Sanneh, Leslie A. Sandusky-Beltran, Mallory Watler, Rana Daas, Andrii Kovalenko, Huimin Liang, Devon Placides, Chuanhai Cao, Xiaoyang Lin, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Alzheimer’s disease (AD) includes several hallmarks comprised of amyloid-β (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines. However, currently, it remains unknown if the reduction of arginase 1 (Arg1) in myeloid cell impacts amyloidosis. Herein, we produced haploinsufficiency of Arg1 by the hemizygous deletion in myeloid cells using Arg1 …

Assessing General Cognitive And Adaptive Abilities In Adults With Down Syndrome: A Systematic Review, Sarah Hamburg, Bryony Lowe, Carla Marie Startin, Concepcion Padilla, Antonia Coppus, Wayne Silverman, Juan Fortea, Shahid Zaman, Elizabeth Head, Benjamin L. Handen, Ira Lott, Weihong Song, André Strydom

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Measures of general cognitive and adaptive ability in adults with Down syndrome (DS) used by previous studies vary substantially. This review summarises the different ability measures used previously, focusing on tests of intelligence quotient (IQ) and adaptive behaviour (AB), and where possible examines floor effects and differences between DS subpopulations. We aimed to use information regarding existing measures to provide recommendations for individual researchers and the DS research community.

RESULTS: Nineteen studies reporting IQ test data met inclusion for this review, with 17 different IQ tests used. Twelve of these IQ tests were used in only one study while …

White Matter Hyperintensity Regression: Comparison Of Brain Atrophy And Cognitive Profiles With Progression And Stable Groups, Omar M. Al-Janabi, Christopher E. Bauer, Larry B. Goldstein, Richard R. Murphy, Ahmed A. Bahrani, Charles D. Smith, Donna M. Wilcock, Brian T. Gold, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and …

Age Drives Distortion Of Brain Metabolic, Vascular And Cognitive Functions, And The Gut Microbiome, Jared D. Hoffman, Ishita Parikh, Stefan J. Green, George Chlipala, Robert P. Mohney, Mignon Keaton, Bjoern Bauer, Anika M. S. Hartz, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in …

Diabetes Is Associated With Cerebrovascular But Not Alzheimer's Disease Neuropathology, Erin L. Abner, Peter T. Nelson, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Randall L. Woltjer, Nigel J. Cairns, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Kamal Masaki, Suzanne L. Tyas, David A. Bennett, Julie A. Schneider, Zoe Arvanitakis

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood.

METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression.

RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone.

DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to …

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …