Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages: individual participant meta-analysis of five cohorts

Sci Rep. 2019 Mar 14;9(1):4555. doi: 10.1038/s41598-019-40566-x.

Abstract

Evidence on the association between functioning of the hypothalamic pituitary adrenal (HPA) axis and cognitive capability at older ages is mixed. We undertook a systematic review (until October 2016) and individual participant data (IPD) meta-analysis to test if dysregulation of the HPA axis is associated with worse cognitive capability. Five cohort studies were included in the IPD meta-analysis of diurnal cortisol patterns with crystallised and fluid cognitive ability. Higher night time cortisol was associated with worse fluid ability (standardised coefficient per SD increase -0.063, 95% CI -0.124, -0.002, P = 0.04; I2 = 79.9%; age and gender adjusted). A larger diurnal drop was associated with better fluid ability (standardised coefficient per SD increase 0.037, 95% CI 0.008, 0.065, P = 0.01; I2 = 49.2%; age and gender adjusted). A bigger cortisol awakening response (CAR) was weakly associated with better fluid (P = 0.09; I2 = 0.0%; age and gender adjusted) and crystallised (P = 0.10; I2 = 0.0%; age and gender adjusted) ability. There is weak evidence that a greater diurnal decline of the HPA axis and a larger CAR are associated with improvements in cognition at older ages. As associations are cross-sectional, we cannot rule out reverse causation.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging*
  • Circadian Rhythm
  • Cognition Disorders / physiopathology*
  • Cohort Studies
  • Female
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology*