Highest risk seen for those with both physical frailty and depression; significant additive interaction also seen
THURSDAY, Dec. 18, 2025 (HealthDay News) — Individuals with physical frailty and depression have increased risk of dementia, with the highest risk for those with both, according to a study published online Dec. 16 in General Psychiatry.
Yihong Ding, from the Zhejiang University School of Medicine in China, and colleagues examined the joint effect and interaction of physical frailty and depression on the risk of all-cause dementia in prospective analyses among participants aged ≥60 years from the U.K. Biobank, the English Longitudinal Study of Ageing, and the Health and Retirement Study. The analyses included 220,947 participants.
The researchers found that 9,088 participants developed incident all-cause dementia over 2,832,696 person-years of follow-up. Frail individuals had a significantly increased risk of dementia compared with robust individuals (pooled hazard ratio, 2.55). In addition, a 1.59-fold excess risk for dementia was conferred by depression (pooled hazard ratio, 1.59). Prediction accuracy was significantly improved by adding physical frailty and depression to a traditional dementia risk model. The highest dementia risk was exhibited by participants with both physical frailty and depression (pooled hazard ratio, 3.23) compared to those without physical frailty and depression. A significant additive interaction was seen between physical frailty and depression (pooled relative excess risk due to interaction, 0.38), with 17.1 percent of dementia risk attributed to their interactive effects.
“Given that physical frailty and depression are modifiable, concurrent interventions targeting these conditions could significantly reduce dementia risk,” the authors write.
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