Older people who are both physically frail and living with depression may face a sharply higher risk of developing dementia, according to a major international study involving more than 200,000 participants in the UK and the United States.
The research, published in open access journal General Psychiatry, found that while frailty and depression each increase dementia risk on their own, the combination of the two is particularly dangerous. Older adults who were both frail and depressed were more than three times as likely to develop dementia as those in good physical and mental health.
Researchers also estimated that the interaction between frailty and depression accounted for around 17% of overall dementia risk in the population studied.
Globally, about 57 million people are currently living with dementia, a number expected to triple by 2050. In Australia, data from the Australian Bureau of Statistics has revealed dementia has surpassed ischaemic heart disease as the country’s leading cause of death.
Despite this growing burden, most previous research has examined physical frailty and depression separately, even though the two conditions share overlapping biological and pathological pathways.
Researchers analysed data from 220,947 adults with an average age of 64. Participants were drawn from three large studies: the UK Biobank, the English Longitudinal Study of Ageing (ELSA), and the US-based Health and Retirement Study, with women making up just over half of the participant pool.
Physical frailty was assessed using modified versions of the widely used Fried frailty criteria. Participants were considered frail if they met three or more indicators, including unintentional weight loss, exhaustion, low physical activity, slow walking speed and weak grip strength. Depression was identified through mental health questionnaires and hospital admission records.
During an average follow-up period of almost 13 years, 9,088 participants were diagnosed with dementia of any type.
The analysis showed that frail participants were more than two-and-a-half times as likely to develop dementia compared with those in good physical health. Depression alone was linked to a 59% increase in dementia risk. But the highest risk was seen among those who had both conditions.
The researchers also found a significant interaction between frailty and depression, suggesting the two conditions together have a greater impact than either alone.
“These results underscore the complex relationship between frailty, depression and cognitive function,” the authors wrote.
They suggested that when frailty or depression is mild, the health system may be able to compensate for some of the cognitive burden. However, once both conditions reach a certain level, this compensatory capacity may be overwhelmed, leading to a steep rise in dementia risk.
While cautioning that the study was observational, meaning it cannot prove cause and effect, they also noted that definitions of frailty, depression and dementia differed slightly across the three study groups.
Even so, the report said its findings have important implications for prevention. Because both physical frailty and depression are potentially modifiable, the researchers argue that routinely assessing and treating both conditions in older adults could help reduce the risk of dementia.
“Given that physical frailty and depression are modifiable, concurrent interventions targeting these conditions could significantly reduce dementia risk,” they concluded.
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