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Characterizing the Molecular Architecture of Cortical Regions Associated with High Educational Attainment in Older Individuals.

ABSTRACT: Neuroimaging investigations have revealed interindividual variations in anatomy, metabolism, activity, and connectivity of specific cortical association areas through which years of education (YoE), as a common proxy of cognitive reserve, may operate in the face of age- or pathology-associated brain changes. However, the associated molecular properties of YoE-related brain regions and the biological pathways involved remain poorly understood. In the present study we first identified brain areas that showed an association between cortical thickness and YoE among 122 cognitively healthy older human individuals (87 female). We subsequently characterized molecular properties of these regions by studying brain-wide microarray measurements of regional gene expression. In accordance with previous studies, we observed that YoE were associated with higher cortical thickness in medial prefrontal, anterior cingulate, and orbitofrontal areas. Compared with the rest of the cortex, these regions exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in ionotropic and metabotropic neurotransmission as well as activation of immune response. Our genome-wide expression profile analysis of YoE-related brain regions points to distinct molecular pathways that may underlie a higher capacity for plastic changes in response to lifetime intellectual enrichment and potentially also a higher resilience to age-related pathologic brain changes.SIGNIFICANCE STATEMENT We combined a neuroimaging-based analysis with a transcriptome-wide gene expression approach to investigate the molecular-functional properties of cortical regions associated with educational attainment, as a commonly used proxy for cognitive reserve, in older individuals. The strongest association with education was observed in specific areas of the medial prefrontal cortex, and these areas exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in neurotransmission and immune responses. These findings complement previous neuroimaging studies in the field and point to novel biological pathways that may mediate the beneficial effects of high educational attainment on adaptability to cope with, or prevent, age-related brain changes. The identified genes and pathways now warrant further exploration in mechanistic studies.

SUBMITTER: Bartres-Faz D

PROVIDER: S-EPMC6554631 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Project description:Older adults' psychosocial outcomes during the COVID-19 pandemic have been inequitable by socio-economic status (SES). However, studies have focused solely on own SES, ignoring emerging evidence of the relationship between adult child SES and late-life health. We evaluated whether adult child educational attainment - a core marker of SES - is associated with older parents' psychosocial outcomes during the pandemic. We used data from the Survey of Health, Aging, and Retirement in Europe (SHARE) 2004-2018 and the SHARE Corona Surveys (SCS) 2020 and 2021. We included 40,392 respondents ≥ 65 years who had pre-pandemic information on adult child educational attainment and self-reported psychosocial outcomes during the pandemic, including self-assessments of worsened psychosocial outcomes compared to the pre-pandemic period. We used generalized estimating equations with a Poisson distribution and a log link, adjusted for respondent and family-level characteristics, including respondents' own educational attainment. Older adults whose adult children averaged levels of educational attainment at or above (vs. below) their country-specific mean had a lower prevalence of feeling nervous (Prevalence Ratio [PR]: 0.94, 95% Confidence Interval [CI]: 0.90, 0.97), sad or depressed (PR: 0.94, 95% CI: 0.91, 0.98), and having sleep problems (PR: 0.94, 95% CI: 0.90, 0.97) during the pandemic. Additionally, higher adult child educational attainment was associated with a lower risk of perceiving worsened feelings of nervousness (PR: 0.95, 95% CI: 0.90, 1.01) and worsened sleep problems (PR: 0.91, 95% CI: 0.82, 1.01) as compared to the pre-pandemic. In stratified models, protective associations were observed only in countries experiencing "high" levels of COVID-19 intensity at the time of the survey. All of these results are derived from adjusted models. Adult child SES may have "upward" spillover effects on the psychosocial wellbeing of older parents during periods of societal duress like the pandemic.

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Characterizing the Molecular Architecture of Cortical Regions Associated with High Educational Attainment in Older Individuals.

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