Cortisol hypersecretion and the risk of Alzheimer's disease: A systematic review and meta-analysis

Morning cortisol levels have been reported to be elevated among patients with Alzheimer's disease (AD); yet no meta-analysis has been conducted to confirm the existence and magnitude of this association. It also remains unclear whether hypercortisolism is a risk factor for AD.

PubMed, EMBASE, and PsycINFO were systematically searched for eligible studies. Cross-sectional data were pooled using random-effects meta-analyses; the differences in morning cortisol levels between patients and cognitively normal controls were quantified. Longitudinal studies were qualitatively synthesised due to methodological heterogeneity.

17,245 participants from 57 cross-sectional studies and 19 prospective cohort studies were included. Compared with cognitively normal controls, AD patients had moderately increased morning cortisol in blood (g = 0.422, P < 0.001; I² = 48.5 %), saliva (g = 0.540, P < 0.001; I² = 13.6 %), and cerebrospinal fluids (g = 0.565, P = 0.003; I² = 75.3 %). A moderate elevation of morning cortisol was also detected in cerebrospinal fluids from patients with mild cognitive impairment (MCI) versus controls (g = 0.309, P = 0.001; I² = 0.0 %). Cohort studies suggested that higher morning cortisol may accelerate cognitive decline in MCI or mild AD patients, but the results in cognitively healthy adults were inconsistent.

Morning cortisol was confirmed to be moderately elevated in AD patients and may have diagnostic and prognostic values for AD.