EXPOSURE TO AIR POLLUTION AND COGNITIVE PERFORMANCE OF HEALTHY INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

AbstractIntroductionVolumetric estimates of subcortical and cortical structures, extracted from T1-weighted MRIs, are widely used in many clinical and research applications. Here, we investigate the impact of the presence of white matter hyperintensities (WMHs) on FreeSurfer grey matter (GM) structure volumes and its possible bias on functional relationships.MethodsT1-weighted images from 1077 participants (4321 timepoints) from the Alzheimer’s Disease Neuroimaging Initiative were processed with FreeSurfer version 6.0.0. WMHs were segmented using a previously validated algorithm on either T2-weighted or Fluid-attenuated inversion recovery (FLAIR) images. Mixed effects models were used to assess the relationships between overlapping WMHs and GM structure volumes and overal WMH burden, as well as to investigate whether such overlaps impact associations with age, diagnosis, and cognitive performance.ResultsParticipants with higher WMH volumes had higher overalps with GM volumes of bilateral caudate, cerebral cortex, putamen, thalamus, pallidum, and accumbens areas (P < 0.0001). When not corrected for WMHs, caudate volumes increased with age (P < 0.0001) and were not different between cognitively healthy individuals and age-matched probable Alzheimer’s disease patients. After correcting for WMHs, caudate volumes decreased with age (P < 0.0001), and Alzheimer’s disease patients had lower caudate volumes than cognitively healthy individuals (P < 0.01). Uncorrected caudate volume was not associated with ADAS13 scores, whereas corrected lower caudate volumes were significantly associated with poorer cognitive performance (P < 0.0001).ConclusionsPresence of WMHs leads to systematic inaccuracies in GM segmentations, particularly for the caudate, which can also change clinical associations. While specifically measured for the Freesurfer toolkit, this problem likely affects other algorithms.

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Acculturation moderates cognitive performance in adults at risk of autosomal dominant Alzheimer's Disease

Innovation in Aging ◽

10.1093/geroni/igab046.3654 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 1031-1031

Author(s):

Kayla Tureson ◽

Christopher Beam ◽

John Ringman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Cognitive Functioning ◽

Cognitive Ability ◽

Cognitive Performance ◽

Mexican Americans ◽

Autosomal Dominant ◽

General Cognitive Ability ◽

The Impact

Abstract Acculturative processes via persistent exposure to a set of cultural practices and behaviors can influence cognitive functioning (Park & Huang, 2010). The impact of acculturation on populations at risk for Alzheimer’s disease (AD), however, remains understudied. Persons with or at-risk for early-onset autosomal dominant AD (ADAD) offer a known AD pathogenesis and the opportunity to study whether acculturation moderates their cognitive performance. The present study used a latent variable model to test whether effects of latent cognitive ability on observable cognitive performance depend on acculturation. Participants included 119 adults with or at-risk for ADAD, the majority of whom were of Mexican origin with various levels of U.S. acculturation. Participants completed the Cognitive Abilities Screening Instrument (CASI) and the Acculturation Rating Scale for Mexican Americans-II (ARSMA-II). Confirmatory factor analysis was used to estimate a latent general cognitive ability factor from nine domains (e.g., attention, abstraction and judgment). The ARSMA-II was used to test whether factor loadings depended on level of acculturation, covarying for mutation status. Results revealed ARSMA-II scores nearly significantly moderated the effects of general cognitive ability on abstraction and judgment (λ = 0.20, SE = 0.11, p = .070). Individual differences in general cognitive ability at lower levels of acculturation likely predict lower abstraction and judgment performance. Cognitive assessments may not equally represent true cognitive ability in Mexican-Americans. Although the CASI was developed as a cross-cultural measure of cognitive functioning, caution should be exercised in inferring true cognitive functioning in Mexican-Americans who may not be acculturated to the U.S.

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Therapeutic Potential of TNF-α Inhibition for Alzheimer’s Disease Prevention

Journal of Alzheimer s Disease ◽

10.3233/jad-200711 ◽

2020 ◽

Vol 78 (2) ◽

pp. 619-626

Author(s):

Noel Torres-Acosta ◽

James H. O’Keefe ◽

Evan L. O’Keefe ◽

Richard Isaacson ◽

Gary Small

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

At Risk ◽

Cognitive Performance ◽

Therapeutic Potential ◽

Amyloid Β ◽

Blocking Agents ◽

Populations At Risk ◽

Tnf Α ◽

Factor Α

Background: Alzheimer’s disease (AD) is increasingly prevalent and over 99% of drugs developed for AD have failed in clinical trials. A growing body of literature suggests that potent inhibitors of tumor necrosis factor-α (TNF-α) have potential to improve cognitive performance. Objective: In this review, we summarize the evidence regarding the potential for TNF-α inhibition to prevent AD and improve cognitive function in people at risk for dementia. Methods: We conducted a literature review in PubMed, screening all articles published before July 7, 2019 related to TNF blocking agents and curcumin (another TNF-α inhibitor) in the context of AD pathology. The keywords in the search included: AD, dementia, memory, cognition, TNF-α, TNF inhibitors, etanercept, infliximab, adalimumab, golimumab, and curcumin. Results: Three large epidemiology studies reported etanercept treated patients had 60 to 70% lower odds ratio (OR) of developing AD. Two small-randomized control trials (RCTs) demonstrated an improvement in cognitive performance for AD patients treated with etanercept. Studies using animal models of dementia also reported similar findings with TNF blocking agents (etanercept, infliximab, adalimumab, Theracurmin), which appeared to improve cognition. A small human RCT using Theracurmin, a well-absorbed form of curcumin that lowers TNF-α, showed enhanced cognitive performance and decreased brain levels of amyloid-β plaque and tau tangles. Conclusion: TNF-α targeted therapy is a biologically plausible approach to the preservation of cognition, and warrants larger prospective RCTs to further investigate potential benefits in populations at risk of developing AD.

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