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Brain microstructure mediates sex-specific patterns of cognitive aging.

ABSTRACT: Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). Gray and white matter microstructure correlated with global cognition, executive function, visuospatial memory, episodic memory, and logical memory, with the strongest associations for restricted, hindered and free isotropic diffusion. Associations were stronger for women than for men, a difference likely due to greater age-related variability in cognitive scores and microstructure in women. Isotropic diffusion mediated effects of age on cognition for both sexes, though distinct mediation patterns were present for women and men. For women, hippocampal and corpus callosum microstructure mediated age effects on verbal and visuospatial memory, respectively, whereas for men fiber microstructure (mainly fornix and corpus callosum) mediated age effects on executive function and visuospatial memory. These findings implicate sex-specific pathways by which changing brain cytoarchitecture contributes to cognitive aging, and suggest that RSI may be useful for evaluating risk for cognitive decline or monitoring efficacy of interventions to preserve brain health in later life.

SUBMITTER: Reas ET

PROVIDER: S-EPMC7906181 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Brain microstructure mediates sex-specific patterns of cognitive aging.

Reas Emilie T ET Hagler Donald J DJ Zhong Allison J AJ Lee Roland R RR Dale Anders M AM McEvoy Linda K LK

Aging 20210128 3

Normal brain aging is characterized by declining neuronal integrity, yet it remains unclear how microstructural injury influences cognitive aging and whether such mechanisms differ between sexes. Using restriction spectrum imaging (RSI), we examined sex differences in associations between brain microstructure and cognitive function in 147 community-dwelling older men and women (56-99 years). Gray and white matter microstructure correlated with global cognition, executive function, visuospatial m ...[more]

PMID: 33510046

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Project description:BackgroundSexual minority (SM) older adults experience mental health disparities. Psychiatric disorders and neuropsychiatric symptoms (NPS) are risk factors for cognitive decline. Although older people in same-sex (SSR) compared to mixed-sex relationships (MSR) perform more poorly on cognitive screening tests, prior studies found no differences in rates of dementia diagnosis or neuropsychological profiles. We sought to explore the role of NPS on neurocognitive outcomes for SM populations. We compared cognitive performance and structural brain parameters of older adults in SSR and MSR.MethodsData were originally collected at Alzheimer's Disease Research Centers (ADRCs). Inclusion criteria were: age of 55+ years, a study partner identified as a spouse/partner, and availability of T1-MRI brain volumes/thickness. Participants were labeled as either SSR or MSR based on their/their co-participant's reported sex. We identified 1,073 participants (1,037 MSR-555 cognitively unimpaired [CU]; 36 SSR-23 CU) with structural MRI data, Mini-Mental State Exam (MMSE), and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores. A subset of the overall sample completed comprehensive neuropsychological assessment (n = 939; 908 MSR-494 CU; 31 SSR-22 CU). Covariates included in statistical models were age, sex, education, total intracranial volume, and apolipoprotein E genotype.ResultsMultivariate general linear models showed significant diagnosis-by-relationship interaction effects on the left parahippocampal gyrus volume. After stratification by relationship group, only cognitively impaired (CI) MSR had significantly smaller left parahippocampal volumes than MSR-CU. The SSR group showed better episodic memory performance. Severity of neuropsychiatric symptoms was negatively associated with volume/thickness of bilateral fronto-temporal areas and with MMSE scores, predominantly in the MSR group.ConclusionIn our study, MSR participants presented with a more compromised cognitive profile than SSR participants. MSR-CI participants showed significantly smaller left medio-temporal volumes, a neural signature of AD. Neuropsychiatric symptoms predicted smaller fronto-temporal volumes in the MSR more consistently than in the SSR group. These findings may be due to unexplored protective factors against cognitive decline in SM elders. Indeed, social support has been proposed as a protective factor warranting future investigation.

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Brain microstructure mediates sex-specific patterns of cognitive aging.

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Brain microstructure mediates sex-specific patterns of cognitive aging.

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