Age-Related Differences in Brain Morphology and the Modifiers in Middle-Aged and Older Adults

Abstract

Brain structural morphology differs with age. This study examined age-differences in surface-based morphometric measures of cortical thickness, volume, and surface area in a well-defined sample of 8137 generally healthy UK Biobank participants aged 45–79 years. We illustrate that the complexity of age-related brain morphological differences may be related to the laminar organization and regional evolutionary history of the cortex, and age of about 60 is a break point for increasing negative associations between age and brain morphology in Alzheimer’s disease (AD)-prone areas. We also report novel relationships of age-related cortical differences with individual factors of sex, cognitive functions of fluid intelligence, reaction time and prospective memory, cigarette smoking, alcohol consumption, sleep disruption, genetic markers of apolipoprotein E, brain-derived neurotrophic factor, catechol-O-methyltransferase, and several genome-wide association study loci for AD and further reveal joint effects of cognitive functions, lifestyle behaviors, and education on age-related cortical differences. These findings provide one of the most extensive characterizations of age associations with major brain morphological measures and improve our understanding of normal structural brain aging and its potential modifiers.

Association between exposure to air pollution and thalamus volume in adults: A cross-sectional study

“…Furthermore, we investigated separate interaction effects between age, sex, educational attainment, and overall self-rated health in the association between each air pollutant and thalamic volume by adding an interaction term (e.g., age by PM 2.5 ) to the adjusted linear-regression models. We investigated these interactions because of prior work suggests that increased susceptibility to air pollution might be associated with age [2,28], that age may interact with modifiers of brain morphology [29], that sex differences in brain morphology exist [30] and may interact with air-pollution-related injury, and that air pollution might affect women and men differently [31]. Because education has been associated with both brain volume [32] and risk for neurodegenerative disease [33], there could potentially be an interaction with education since educational attainment appears to be protective in both cognitive aging and in response to brain pathology [34].…”

An epigenetic predictor of death captures multi-modal measures of brain health

“…There was also some heterogeneity in the associations with regional cortical volume, whereby effects were strongest in frontal and temporal regions. These regions also exhibit the largest annual decrease in middle and older age [55], and are most informative for predicting chronological age (albeit using cortical thickness rather than volume; [56]). White matter hyperintensities, which associate with DNAm GrimAge, have also been linked to cortical loss in temporal and lateral frontal regions [57].…”

An epigenetic predictor of death captures multi-modal measures of brain health

“…There was also some heterogeneity in the associations with regional cortical volume, whereby effects were strongest in frontal (superior lateral and medial) and temporal regions. These regions also exhibit the largest annual decrease in middle and older age [54], and are most informative for predicting chronological age (albeit using cortical thickness rather than volume; [55]). White matter hyperintensities, which associate with DNAm GrimAge, have also been linked to cortical loss in temporal and lateral frontal regions [56].…”