Frailty is a Risk Factor for Dementia

Age-related frailty is characterized by physical weakness and chronic inflammation, but this is the visible tip of the iceberg. Chronic inflammation accelerates much of the dysfunction of aging. As researchers note here, this includes neurodegenerative processes that lead to dementia. Reducing frailty in the population will therefore likely lead to a reduction in dementia incidence. The most plausibly useful lines of work on frailty therapies at present focus on ways to reduce the chronic inflammation of aging, from elimination of senescent cells and their pro-inflammatory secretions to ways to selectively suppress inflammatory signaling.

Researchers worked with data from more than 196,000 adults aged over 60 in the UK Biobank. They calculated participants' genetic risk and used a previously-developed score for frailty, which reflects the accumulation of age-related symptoms, signs, disabilities and diseases. They analysed this alongside a score on healthy lifestyle behaviours, and who went on to develop dementia. "We're seeing increasing evidence that taking meaningful action during life can significantly reduce dementia risk. Our research is a major step forward in understanding how reducing frailty could help to dramatically improve a person's chances of avoiding dementia, regardless of their genetic predisposition to the condition. This is exciting because we believe that some of the underlying causes of frailty are in themselves preventable. In our study, this looked to be possible partly through engaging in healthy lifestyle behaviours."

Over the 10-year UK Biobank study period, dementia was detected via hospital admission records in 1,762 of the participants - and these people were much more likely to have a high degree of frailty before their diagnosis compared with those who did not develop dementia. The importance of preventing or reducing frailty was highlighted when the researchers examined the impact of genetic risk in people with different degrees of frailty. Genetic risk factors exerted their expected effect on risk of dementia in study participants who were healthy, but genes were progressively less important in study participants who were the most frail. In those frail study participants, risk of dementia was high regardless of their genes.

Compared with study participants with a low degree of frailty, risk of dementia was more than 2.5 times higher (268 per cent) among study participants who had a high degree of frailty - even after controlling for numerous genetic determinants of dementia. Study participants who reported more engagement in healthy lifestyle behaviours were less likely to develop dementia, partly because they had a lower degree of frailty.