Worse cardiovascular function is known to correlate with risk of neurodegenerative conditions. Evidence points to a range of mechanisms that include reduced cerebral blood flow, hypertension, atherosclerosis, and a dysfunctional blood-brain barrier. Here researchers use an aging clock based on analysis of brain imaging to compare the aging of the brain, as assessed this way, with various aspects of health and lifestyle. As might be expected, risk factors for cardiovascular disease are also correlated with accelerated brain aging.
This study investigated the associations of brain age gap (BAG) – a biological marker of brain resilience – with life exposures, neuroimaging measures, biological processes, and cognitive function. In this population-based cross-sectional study of septuagenarians, findings highlight that physical inactivity, diabetes, and stroke or transient ischemic attack (TIA) were independently associated with higher BAG, reflecting older-appearing brains. Conversely, prediabetes was associated with younger-appearing brains (lower BAG), but this became statistically not significant after adjustment for all risk factors simultaneously. Regular physical activity moderated the obesity-BAG relationship, yielding the lowest BAG in individuals with obesity who were physically active.
Greater cortical thickness, particularly in AD- and resilience-related regions, was linked to lower BAG. Conversely, a higher burden of small vessel disease, white-matter microstructural alterations, systemic inflammation, and high blood glucose levels were associated with a greater BAG, highlighting their influence on brain health in late life. Greater BAG was also related to poorer cognitive outcomes, particularly attention/speed and visuospatial abilities. Notably, sex-specific associations emerged, suggesting distinct pathological and resilience pathways to cognitive disorders between females and males. Together, these findings confirm that vascular-related lifestyles and health factors likely contribute to shaping the appearance of the brain during the aging process. The interplay between vascular brain injury, inflammation, and insulin-related dysregulations may be the key to understanding the neurobiological underpinnings of BAG, therefore, of resilience mechanisms in aging.
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