Association of cognitive frailty with subsequent all-cause mortality among middle-aged and older adults in 17 countries

Objectives
Cognitive frailty refers to the co-occurrence of cognitive impairment and frailty without concurrent Alzheimer's disease or dementia. Studies of cognitive frailty and mortality have been limited to single country or older people. However, frailty and cognitive decline may occur much earlier. We aimed to examine the association between different cognitive frailty status and subsequent all-cause mortality among middle-aged and older people in 17 countries.

Methods
Participants aged 50 and over were drawn from six prospective cohorts of aging. We classified participants according to their cognitive impairment and frailty status into the following groups: none, only cognitive impairment, only frailty and cognitive frailty. Competing-risks regression models were used to evaluate the association of different cognitive frailty status at baseline with subsequent all-cause mortality.

Results
The cognitive frailty group had a higher mortality risk compared to those without cognitive impairment and frailty groups. Meta-analysis results showed participants with cognitive frailty (pooled subhazard ratio [SHR]=2.34, 95% confidence interval [CI]: 2.01-2.72, I2=68.0%) had a higher mortality risk compared with those with only cognitive impairment status (pooled SHR=1.36, 95% CI: 1.25-1.48, I2=3.0%) or only frailty status (pooled SHR=1.83, 95% CI: 1.72-1.95, I2=31.0%). The association between cognitive frailty and mortality were stronger among those who were aged 70 years and older, males, single and non-consumers of alcohol.

Conclusions
Cognitive frailty, frailty or cognitive impairment alone, is associated with an increased risk of all-cause mortality in Asian, European and American countries. Physical and cognitive function screening should be conducted as early as possible in middle-aged and older people, and targeted intervention approaches should be developed to reduce the incidence of adverse health outcomes.