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

Background: 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.

Methods: 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.

Results: 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; I = 48.5 %), saliva (g = 0.540, P < 0.001; I = 13.6 %), and cerebrospinal fluids (g = 0.565, P = 0.003; I = 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; I = 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.

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