High Early-Morning Cortisol Related to Impaired Memory, Lower Brain Volume

Cortisol glucocorticoid hormone
Cortisol glucocorticoid hormone
Researchers investigated a link between higher levels of the stress hormone cortisol and deficient memory skills in people without dementia.

In dementia-free young and middle-aged adults, higher early morning serum cortisol is associated with impaired memory and lower brain volume, which suggests that cortisol may be a predictive biomarker for future dementia risk, according to results from the Framingham Heart Study published in Neurology.

Researchers identified dementia-free individuals from generation 3 of the Framingham Heart Study with a mean age of 48.5 years. All participants underwent cognitive assessment for abstract reasoning, visual perception, memory, executive function, and attention (N=2231), and a subset underwent brain magnetic resonance imaging for assessment of total white matter, white matter hyperintensity volumes, lobar gray matter, and fractional anisotropy measures (n=2018). In addition, all individuals included in the analysis had serum cortisol concentrations measured. The researchers evaluated the association between cortisol and measures of magnetic resonance imaging volumes, cognition, presence of cerebral microbleeds and brain infarcts, white matter integrity, and gray matter density.

The median serum cortisol level in the overall population was 12.92 μg/dL (25th-75th percentile, 9.82-17.58 μg/dL). Compared with the median tertile, the highest cortisol tertile was associated with lower total cerebral brain volume (P =.008), parietal gray matter volume (P =.046), and frontal gray matter volume (P =.006). In adjusted analysis, the highest cortisol tertile vs the median cortisol tertile was associated with worse global cognition (P =.001) and poorer performance on the Hooper Visual Organization Test (P =.002) and the Trails A and Trails B (P =.001). The researchers also found that women were more likely than men to have lower cerebral brain volume if they also scored in the highest cortisol tertile (P =.001 vs P =.717, respectively).

Limitations of the analysis include its cross-sectional design and the assessment of cortisol levels only once per day.

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“It is important to point out that our study reflects a community-based sample and is not directly comparable to the examination of participants in a research setting to diagnose hypercortisolism or hypocortisolism,” the researchers added. “Our community-based study does not characterize people with extreme phenotypes related to blood cortisol levels because we did not carry out further screening or diagnostic testing beyond the assessment of serum cortisol.”


Echouffo-Tcheugui JB, Conner SC, Himali JJ, et al. Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology. 2018;91(21):e1961-e1970.