Concurrent frailty + depression likely boost dementia risk in older people: Study

Previously published research has primarily focused on the individual associations between physical frailty or depression and dementia risk, despite the fact that both have physiological and pathological factors in common, they explain.

To explore the potential interaction between these two factors on dementia risk in older adults, the researchers tracked the diagnosis of any type of dementia in 220,947 participants (average age: 64; 53% women) from 3 large study groups.

These were the UK Biobank, the English Longitudinal Study of Ageing (ELSA), and the Health and Retirement Study.

Physical frailty was assessed using modified versions of the Fried frailty criteria, in which a person is considered to be frail if they have 3 or more of the following indicators: unintentional weight loss; self-reported exhaustion; low physical activity; slow walking speed; and weak grip strength.

Depression was evaluated through responses to mental health questionnaires or combined with hospital admission records.

Compared with those in good physical health, frail participants across all 3 groups were older, more likely to be female, weigh more, have more long term conditions and lower educational attainment.

During an average tracking period of nearly 13 years, 9088 people (7605 in the UK Biobank, 1207 in the Health Retirement Study and 276 in the ELSA) were diagnosed with dementia of any type.

Analysis of the data revealed that compared with those in good physical health, those who were frail were more than 2.5 times as likely to be diagnosed with dementia, while depression was associated with a 59% heightened risk.

And participants who were both physically frail and depressed were more than 3 times as likely to be diagnosed with dementia as those in good physical and mental health.

What’s more, a significant additional interaction between physical frailty and depression was observed, with around 17% of the overall dementia risk attributable to these two factors combined.

“These results underscore the complex relationship between frailty, depression, and cognitive function,” write the researchers.

“Lower levels of frailty may allow the health system to partially offset the cognitive burden of depression and, similarly, lower levels of depression may enable the system to mitigate the burden of frailty,” they suggest.

“However, once both factors exceed a certain threshold, this compensatory ability may be compromised, leading to a sharp increase in the risk of dementia,” they add.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers sound a note of caution in the interpretation of the findings, primarily because the definitions of physical frailty, depression, and dementia varied across the three cohorts.

Nevertheless, the researchers conclude: “Given that physical frailty and depression are modifiable, concurrent interventions targeting these conditions could significantly reduce dementia risk.”

Reference:

Ding Y, Duan M, Shen J, Xu L, Ma Y, He D, et al. Associations of physical frailty, depression and their interaction with incident all-cause dementia among older adults: evidence from three prospective cohorts. General Psychiatry. 2025;38:e102172. https://doi.org/10.1136/gpsych-2025-102172