Abstract
INTRODUCTION: Psychological distress has been linked with cognitive impairment. However, whether the relationship is causal, reflects preclinical dementia neuropathology, or confounding by common causes remains unclear. METHODS: In five UK longitudinal studies, we examined associations of psychological distress with subsequent cognition using linear and mixed effects models, and dementia using logistic regression. We examined variation by age-at-assessment, severity, and distress persistence, combining study-specific estimates using two-stage individual participant data meta-analysis. RESULTS: Pooling across studies (N = 24,564), greater baseline psychological distress was associated with lower subsequent cognitive level (β = -0.03 [95% confidence interval [CI]: -0.06; -0.01]; I(2) = 70%), and dementia (odd ratio [OR] = 1.1 [1.0; 1.2]; I(2) = 0%), but not cognitive change. Associations were found for clinically significant, persistent and intermittent distress. Dementia was associated with distress assessed at ages 65-75, and 55-64, but not 45-54 years. DISCUSSION: Findings highlight the relevance of psychological distress in later cognitive outcomes, with potential future implications for dementia prevention and identifying high-risk groups.