Link between cortisol and lower brain volume stronger in women High serum cortisol levels were tied to reduced brain volumes and lower cognitive performance among adults in their 40s, a cross-sectional analysis of the Framingham Heart Study third generation cohort found. Higher morning cortisol was associated with worse memory and lower total cerebral brain and regional gray matter volumes in young to middle-aged adults, reported Justin Echouffo-Tcheugui, MD, PhD, formerly of Harvard Medical School in Boston and now at Johns Hopkins University in Baltimore, and colleagues in Neurology. "Before the study, we knew that that chronic elevation in circulating cortisol levels adversely impacted brain structure and function in animals and patients with certain conditions," Echouffo-Tcheugui told MedPage Today. "Our study provides evidence that a similar relation may exist among individuals without dementia in the general population." Prior studies have focused on older people, have not always excluded confounding conditions like dementia, and have been small studies that rarely examined multiple brain regions. "The relationship between cortisol and brain structure and function has been subject to some controversy, due largely to small sample size," said James Herman, PhD, of the University of Cincinnati Neurobiology Research Center. "The authors leverage the large sample size afforded by the Framingham study to perhaps put to rest some of this controversy, showing a negative relationship between morning cortisol, cognition, and cerebral volume," Herman, who was not involved with the study, told MedPage Today. Echouffo-Tcheugui and colleagues examined dementia-free Framingham Heart Study third generation participants who underwent cognitive testing (n=2,231) and brain MRI (n=2,018). Participants also provided a fasting morning blood sample. The group had an average age of 48.5, and 46.8% were male. The researchers stratified participants into low, middle, and high tertiles with those in the middle (referent) group having cortisol levels between 10.8 and 15.8 µg/dL (n=740). After adjustment for potential confounders, higher cortisol (highest vs middle tertile) was linked to worse performance on visual perception, executive function, and attention tasks. Higher cortisol was tied to lower total cerebral brain volume (beta = −0.38, P=0.008), parietal gray matter volume (beta = −0.06, P=0.046), and frontal gray matter volume (beta = −0.12, P=0.006). It also was associated with multiple areas of microstructural changes shown by decreased regional fractional anisotropy, especially in the splenium and body of the corpus callosum region and the posterior part of the corona radiata. The association of cortisol with total cerebral brain volume varied by sex (P=0.048 for interaction). Higher cortisol was inversely tied to cerebral brain volume in women (P=0.001), but not in men (P=0.717). The lowest tertile of cortisol was not associated with any brain volume or cognitive measures. "This study supports work performed in rodents and non-human primates, and demonstrates that excessive stress hormone secretion can be linked to functional and structural impairments in brain," Herman observed. "It adds to an emerging body of data indicating that where stress hormones are concerned, sex matters." Study limitations included the fact that cortisol levels were measured only once and may not represent long-term exposure to the hormone. Framingham Heart Study participants were mostly middle-aged with European ancestry, and results do not reflect the population as a whole. Source
