Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis

Michael P Gardner,Stafford Lightman,Avan Aihie Sayer,Cyrus Cooper,Rachel Cooper,Dorly Deeg,Shah Ebrahim,John Gallacher,Mika Kivimaki,Meena Kumari,Diana Kuh,Richard M Martin,Geeske Peeters,Yoav Ben-Shlomo

doi:10.1016/j.psyneuen.2012.04.016

Abstract

SummaryThe association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.

Highlights

The hypothalamic pituitary adrenal (HPA) axis is one of several plausible candidate pathways contributing to biological ageing
Of the nine UK cohort studies involved in HALCyon, four have data on both cortisol and physical performance: the Boyd Orr cohort (Martin et al, 2005); the Caerphilly Prospective Study (CaPS) (Smith et al, 2005); the Hertfordshire Cohort Study (HCS) (Syddall et al, 2005); and the MRC National Survey of Health and Development (NSHD) (Wadsworth et al, 2006; Kuh et al, 2011)
Mean chair rise time ranged from 12.7 Æ 4.7 SD s for five chair rises in Longitudinal Aging Study Amsterdam (LASA) to 24.8 Æ 7.3 SD s for ten chair rises in NSHD

Summary

Introduction

The hypothalamic pituitary adrenal (HPA) axis is one of several plausible candidate pathways contributing to biological ageing It activates the secretion of glucocorticoids (cortisol in man) in response to stressful stimuli and exhibits a marked circadian rhythm so that in humans cortisol levels are higher in the morning and decline over the day. In the WHII study (Kumari et al, 2010) and Caerphilly Prospective Study (CaPS) (Gardner et al, 2011) individuals with less diurnal variability had slower walking speed, whilst in LASA there were gender differences so that women with higher cortisol levels showed worse performance on a standing balance test and men with higher cortisol levels were slower in walking and chair rises (Peeters et al, 2007). In a longitudinal analysis of LASA, higher cortisol was associated with higher risk of a loss of grip strength over four-years (Peeters et al, 2008)

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