Potential causal relationship seen between physical frailty and dementia in forward MR analysis, but null association seen in reverse MR
By Elana Gotkine HealthDay Reporter
WEDNESDAY, Sept. 24, 2025 (HealthDay News) — Physical frailty may contribute to the development of dementia, according to a study published online Sept. 17 in Neurology.
Xiangying Suo, from the School of Public Health of Zhengzhou University in China, and colleagues conducted a prospective cohort study based on U.K. Biobank participants without dementia to examine the link between physical frailty and dementia. Five criteria were used to define physical frailty (weight loss, exhaustion, physical inactivity, slow walking speed, and low grip strength).
A total of 8,900 dementia cases were documented during a median follow-up of 13.58 years among 489,573 participants. The researchers found that the risk for dementia was significantly higher in those with prefrailty and frailty compared with nonfrail individuals (hazard ratios, 1.50 and 2.82, respectively). Compared with those with low genetic risk and nonfrailty, the highest risk for dementia was seen for participants with frailty and high genetic risk (hazard ratio, 3.87 for high polygenic risk score; 8.45 for APOE-ε carriers). A potential causal relationship was seen between physical frailty and dementia in the forward Mendelian randomization (MR) analysis (odds ratio, 1.79), while a null causal association was suggested in the reverse MR. Potential underlying mechanisms linking physical frailty to dementia include genetic background and neurologic and immunometabolic function.
“These findings reinforce the importance of identifying and managing frailty as a strategy for preventing dementia,” coauthor Yacong Bo, Ph.D., from Zhengzhou University, said in a statement.
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