Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study.
Level 4 - case-series / case-control
Cross-sectional observational study within a prospective cohort
PubMed 30355700 · doi:10.1212/WNL.0000000000006549
What was done
Researchers evaluated dementia-free Framingham Heart Study (generation 3) participants (mean age 48.5 years, 46.8% men) to determine associations between early morning serum cortisol and both cognitive function (n = 2,231) and structural brain MRI measures (n = 2,018). Cognitive testing assessed memory, abstract reasoning, visual perception, attention, and executive function. MRI measures included total white matter, lobar gray matter, white matter hyperintensities, covert infarcts, cerebral microbleeds, and fractional anisotropy. Linear and logistic regression models compared cortisol tertiles (middle tertile as referent), adjusting for age, sex, APOE genotype, and vascular risk factors.
What was found
Participants in the highest cortisol tertile had worse memory and visual perception, as well as lower total cerebral brain volume and lower occipital and frontal lobar gray matter volumes compared to the middle tertile. Higher cortisol was also associated with microstructural white matter changes (decreased regional fractional anisotropy), especially in the splenium of the corpus callosum and posterior corona radiata. An interaction with sex was observed for total cerebral brain volume (p = 0.048), where higher cortisol was inversely associated with cerebral volume in women (p = 0.001) but not in men (p = 0.717). APOE4 genotype did not modify these associations. Exact numerical effect sizes and confidence intervals were not provided in the abstract.
Why it matters
These findings suggest that elevated systemic cortisol levels are linked to subclinical structural brain alterations and cognitive deficits in middle-aged adults, well before clinical dementia onset.
Limits
The study is cross-sectional and cannot demonstrate causality or chronological precedence. Cortisol was measured from a single morning blood draw rather than 24-hour diurnal profiling, and precise effect estimates were not reported in the abstract.
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