The fall-dementia connection: Synergistic effects of falls with genetic and health risk factors

Abstract

Background

Few studies have examined the inverse relationship between dementia and falls, i.e., whether falls before dementia are a herald of dementia.

Objective

We aimed to explore the relationship between fall experiences and risk of dementia, assessing how factors like APOE ε4 allele, family history of dementia, comorbidities, traumatic brain injury (TBI), and frailty modify this association.

Methods

We used data from the UK Biobank. We used Cox proportional hazards models to estimate the HRs and 95% CIs for the association between falls and all-cause dementia, Alzheimer's disease (AD), vascular dementia (VaD), and non-Alzheimer/non-vascular dementia (NAVD). The synergistic effects of fall experiences and APOE, dementia family history, cardiovascular disease (CVD), diabetes, TBI, frailty on dementia were also investigated.

Results

Totally, 403,502 participants were included. 99,832 people experienced at least one fall, and 4143 dementia cases were observed. People who experienced falls had a higher risk of all-cause dementia, AD, VaD, and NAVD, with HRs (95% CIs) of 1.71(1.61, 1.83), 1.33 (1.20, 1.47), 2.00 (1.74, 2.29), and 2.03 (1.84, 2.24), respectively. The risk of dementia increased with the number of falls and with falls occurring later in life (after age 60). Fall experiences had a synergistic effect with dementia risk factors (APOE ε4 allele, family history of dementia and comorbidities), TBI, and frailty, collectively increasing the risk of dementia.

Conclusions

Falls before dementia were linked to a higher risk of dementia. The risk escalated with more falls and falls after age 60. Combining falls with risk factors further amplified dementia risk.