Elevated plasma cortisol associated with larger ventricles and smaller hippocampal volumes – a study in 2 independent elderly cohorts

Cortisol is considered the most fundamental stress hormone and is elevated in stress and multiple neuropsychiatric conditions. Prior studies have shown associations of plasma cortisol levels with total cerebral and hippocampal volumes and less consistently with the amygdala. Here, we extend our hypothesis to test associations of plasma cortisol with 1) ventricular 2) hippocampal and 3) amygdalar volumes, in two independent elderly cohorts across a broad cognitive spectrum ranging from normal cognition to Alzheimer’s disease. We demonstrate elevated cortisol to be associated with larger lateral ventricular volumes and smaller hippocampal volumes, predominantly in the right cerebral hemisphere, regardless of age, sex or cognitive status. We noted a non-significant trend of smaller amygdalar volumes with elevated cortisol. Our findings support smaller brain parenchyma volumes seen with elevated cortisol and may encourage effective strategies reducing cortisol and stress. They may also serve as imaging biomarkers for assessing therapeutic benefits of stress and cortisol lowering interventions aiming to halt or reverse the brain volume alterations and theoretically improve cognition and quality of life. Highlights Elevated cortisol associated with larger ventricular volumes and smaller hippocampal volumes Associations are predominantly noted in the right cerebral hemisphere. Similar non-significant trends noted in amygdalar volumes Cortisol and stress reducing strategies may halt brain changes and improve quality of life Imaging biomarkers may help assess efficacy of cortisol-lowering therapeutic interventions