Data from: Circulating cortisol and cognitive and structural brain measures in a middle-aged cohort: the Framingham Heart Study

Objective: To assess the association of early morning serum cortisol with
cognitive performance and brain structural integrity in community-dwelling
young and middle-aged adults without dementia. Methods: We evaluated
dementia-free Framingham Study (Generation 3) participants (mean age 48.5
years; 46.8% men), who underwent cognitive testing for memory, abstract
reasoning, visual perception, attention, and executive function (n= 2231),
and brain MRI (n=2018) to assess total white matter, lobar gray matter,
and white matter hyperintensity volumes and fractional anisotropy (FA)
measures. We used linear and logistic regression to assess the relations
of cortisol (categorized in tertiles, with the middle tertile as referent)
to measures of cognition, MRI volumes, presence of covert brain infarcts
(CBI) and cerebral microbleeds (CMB), and voxel-based microstructural
white matter integrity and gray matter density, adjusting for age, sex,
APOE and vascular risk factors. Results: Higher cortisol (highest tertile
vs. middle tertile) was associated with worse memory and visual
perception, as well as lower total cerebral brain, occipital and frontal
lobar gray matter volumes. Higher cortisol was associated with multiple
areas of microstructural changes (decreased regional FA), especially in
the splenium of corpus callosum and the posterior corona radiata. The
association of cortisol with total cerebral brain volume varied by sex (p
interaction=0.048); higher cortisol was inversely associated with cerebral
brain volume in women [p=0.001] but not in men [p=0.717]). There was no
effect modification by the apoE4 genotype of the relations of cortisol and
cognition or imaging traits. Conclusions: Higher serum cortisol was
associated with lower brain volumes and impaired memory in asymptomatic
younger to middle-aged adults, with the association being evident
particularly in women.