Low plasma cortisol and large hippocampal volume are associated with reduced risk of clinical progression in MCI

Abstract

AbstractBackgroundHigh cortisol concentration, a biomarker of hypothalamic‐pituitary‐adrenal (HPA) axis activation, and low hippocampal volume have been linked to increased risk for Alzheimer’s disease (AD). This longitudinal study evaluates the impact of baseline plasma cortisol levels on hippocampal atrophy and on clinical progression in patients with mild cognitive impairment (MCI).MethodParticipants with mild cognitive impairment (MCI, n=305) were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) based on measures of plasma cortisol (at baseline) and hippocampal volume. We assessed relationships between plasma cortisol levels, hippocampal volume, and risk of progression to clinical AD over a variable study period of up to 100 months.ResultHigher plasma cortisol levels were related to greater decline in hippocampal volume in MCI patients, adjusting for baseline volume (Figure 1, left). Hippocampal volume at baseline predicted progression to clinical AD, while plasma cortisol alone did not. Plasma cortisol interacted with hippocampal volume (Figure 1, right), such that MCI patients with relatively large hippocampal volumes and low plasma cortisol levels at baseline were less likely to progress to clinical AD.ConclusionThis study demonstrates the involvement of plasma cortisol in hippocampal degeneration and risk of clinical progression in MCI patients. Our findings suggest that regulation of HPA axis activation may be protective against neural degradation and clinical decline in these high‐risk individuals.