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Examining Cognitive Decline Across Black and White Participants in the Harvard Aging Brain Study.

ABSTRACT: BACKGROUND:Black Americans are approximately twice as likely to develop dementia as compared to White Americans and the magnitude of this disparity is often attributed to a variety of factors that include psychosocial and vascular risk factors. However, less is known about the potential contribution of Alzheimer's disease pathological differences. OBJECTIVE:To examine potential differences incross-sectional and longitudinal cognitive performance in black and white participants who were clinically normal at baseline. METHODS:296 participants (48 African-American/black participants) underwent MRI and amyloid PET at baseline. Linear mixed models were used to examine the main effects of race, years of education, reading ability, Framingham Heart Study cardiovascular risk score (FHS-CVD), white matter hyperintensities (WMH), and amyloid (A?) burden on the Preclinical Alzheimer Cognitive Composite-5 (PACC5). RESULTS:Lower levels of educationalattainment and reading ability were found for blacks compared to whites. By contrast, no differences in FHS-CVD, WMH, or A? were found by racial group. Baseline differences in PACC5 score were attenuated after adjusting for educationalfactors, vascular factors, and A?, but remained lower for blacks compared to whites (?=?-0.24, p?=?0.014). Further, blacks demonstrated a faster rate of PACC5 decline longitudinally compared to whites (? ?=?-0.055, p?=?0.025) after adjusting for covariates. CONCLUSION:Accounting for educationalfactors, vascular factors, and A? burden diminished, but did not eliminate, racial differences in PACC5 performance longitudinally. Understanding potential differences in longitudinal cognitive outcomes by race may be important for upcoming secondary prevention trials.

SUBMITTER: Amariglio RE

PROVIDER: S-EPMC7397774 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Examining Cognitive Decline Across Black and White Participants in the Harvard Aging Brain Study.

Amariglio Rebecca E RE Buckley Rachel F RF Rabin Jennifer S JS Papp Kathryn V KV Quiroz Yakeel T YT Mormino Elizabeth C EC Sparks Kathryn P KP Johnson Keith A KA Rentz Dorene M DM Sperling Reisa A RA

Journal of Alzheimer's disease : JAD 20200101 4

<h4>Background</h4>Black Americans are approximately twice as likely to develop dementia as compared to White Americans and the magnitude of this disparity is often attributed to a variety of factors that include psychosocial and vascular risk factors. However, less is known about the potential contribution of Alzheimer's disease pathological differences.<h4>Objective</h4>To examine potential differences incross-sectional and longitudinal cognitive performance in black and white participants who ...[more]

PMID: 32417775

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Project description:This study undertakes a systematic and comprehensive analysis of brain gene expression profiles of immune/inflammation-related genes in aging and Alzheimer's disease (AD).In a well-powered microarray study of young (20 to 59 years), aged (60 to 99 years), and AD (74 to 95 years) cases, gene responses were assessed in the hippocampus, entorhinal cortex, superior frontal gyrus, and post-central gyrus.Several novel concepts emerge. First, immune/inflammation-related genes showed major changes in gene expression over the course of cognitively normal aging, with the extent of gene response far greater in aging than in AD. Of the 759 immune-related probesets interrogated on the microarray, approximately 40% were significantly altered in the SFG, PCG and HC with increasing age, with the majority upregulated (64 to 86%). In contrast, far fewer immune/inflammation genes were significantly changed in the transition to AD (approximately 6% of immune-related probesets), with gene responses primarily restricted to the SFG and HC. Second, relatively few significant changes in immune/inflammation genes were detected in the EC either in aging or AD, although many genes in the EC showed similar trends in responses as in the other brain regions. Third, immune/inflammation genes undergo gender-specific patterns of response in aging and AD, with the most pronounced differences emerging in aging. Finally, there was widespread upregulation of genes reflecting activation of microglia and perivascular macrophages in the aging brain, coupled with a downregulation of select factors (TOLLIP, fractalkine) that when present curtail microglial/macrophage activation. Notably, essentially all pathways of the innate immune system were upregulated in aging, including numerous complement components, genes involved in toll-like receptor signaling and inflammasome signaling, as well as genes coding for immunoglobulin (Fc) receptors and human leukocyte antigens I and II.Unexpectedly, the extent of innate immune gene upregulation in AD was modest relative to the robust response apparent in the aged brain, consistent with the emerging idea of a critical involvement of inflammation in the earliest stages, perhaps even in the preclinical stage, of AD. Ultimately, our data suggest that an important strategy to maintain cognitive health and resilience involves reducing chronic innate immune activation that should be initiated in late midlife.

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Dataset Information

Examining Cognitive Decline Across Black and White Participants in the Harvard Aging Brain Study.

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Examining Cognitive Decline Across Black and White Participants in the Harvard Aging Brain Study.

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