Association between falls and dementia risk: Evidence from three cohort studies

Abstract Background and Objectives The relationship between falls and dementia risk remains unclear. This study aims to investigate this association and assess the impact of genetic risk on this relationship. Methods We included 265,416, 5,506, and 948 participants from the United Kingdom (UK) Biobank, China Health and Retirement Longitudinal Study (CHARLS), and Xuanwu cognitive cohort. A Cox model and logistic regression analysis were used to estimate the relationship between falls and dementia risk. Results Falls showed significant associations with an elevated risk of dementia in both UK Biobank (single falls: Hazard Ratio [HR] 1.22, 95% Confidence Interval [CI]: 1.13-1.31; multiple falls: HR 1.73, 95% CI: 1.58-1.89), CHARLS cohorts (falls: HR 1.29, 95% CI: 1.11-1.50) and Xuanwu cognitive cohort (single falls: OR 1.72, 95% CI: 1.18-2.50; multiple falls: OR 1.89, 95% CI: 1.17-3.02). In addition, the results showed that falls were associated with cognitive decline during follow-up. Those who experienced single falls demonstrated reduced whole-brain gray matter volume (β = −1276.031, P = 0.029) and parahippocampal gyrus volume (β left = −22.410, P = 0.011; β right = −31.570, P = 0.001), whereas those experienced multiple falls, in addition to these findings, demonstrated increased deep white matter hyperintensities (β = 123.146, P = 0.004) and decreased gray matter volume in the hippocampus (β left = −18.440, P = 0.002; β right = −20.599, P = 0.001) and parahippocampal gyrus volume (β left = −48.805, P < 0.001; β right = −58.263, P < 0.001). Furthermore, falls and polygenic risk scores (PRSs) showed a significant interaction ( P = 0.001), with higher dementia risk observed in individuals with multiple falls and high genetic risk. Conclusions Falls are an early sign of dementia risk, and genetic susceptibility facilitates this association. Falls indicate potential atrophy in cognition-related brain regions. Falls are a simple and easily observable sign for dementia screening.