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Signs of frailty may signal future dementia more than a decade before cognitive symptoms appear, new findings that could provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.
Results from an international study assessing the trajectory of frailty found that levels of frailty increased significantly in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurements were taken before that accelerated period, frailty was still positively associated with dementia risk, the investigators noted.
“We found that with every four to five additional health problems, the risk of developing dementia increased by an average of 40%, whereas the risk was lower for those who were physically fit,” study investigator David Ward, PhD, of the Center for Health Services Research, University of Queensland, Brisbane, Australia, told Medscape Medical News.
Photo by David Ward PhD David Ward, PhD The results were published online Nov. 11 in JAMA Neurology.
A Promising Biomarker An accessible biomarker for both biological age and dementia risk is essential to advance dementia prevention and treatment strategies, the investigators noted, noting that growing evidence suggests that frailty may be a promising candidate for this role.
To learn more about the relationship between frailty and dementia, Ward and his team analyzed data from 29,849 participants aged 60 years and older (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Ageing Project (MAP; n = 1451), and the National Alzheimer's Coordinating Centre (NACC; n = 12,582).
The primary outcome was overall dementia. Depending on the cohort, dementia diagnoses were determined by cognitive testing, self- or family-report of physician diagnosis, or diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.
Investigators retrospectively determined frailty index scores by collecting health and functional outcome data for participants from each group. Only participants with frailty data on at least 30 deficits were included.
Deficits commonly included included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and financial management challenges.
Investigators conducted follow-up visits with participants until they developed dementia or the study ended, with follow-up duration varying across groups.
After adjusting for potential confounders, frailty scores were modeled using a backward time scale.
Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, 18.5% higher in women on the ELSA, 20.9% higher in the HRS, and 16.2% higher in the MAP than in men. There were no gender differences in frailty scores in the NACC cohort.
When measured over a timeline, frailty scores were significantly and consistently higher in the dementia group 8–20 years before dementia onset compared with those who did not develop dementia (20 years in the HRS; 13 in the MAP; 12 in the ELSA; 8 in the NACC).
The increase in frailty index scores began to accelerate 4–9 years before dementia onset for the different groups, the investigators noted.
In all four groups, each 0.1 increase in frailty score was positively associated with dementia risk.
Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, showing the strongest association.
Among participants whose baseline frailty measurements were conducted before the onset of the predementia acceleration period, the association between frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.
‘Four Pillars of Prevention’ The good news, the investigators said, is that the long trajectory of frailty symptoms before dementia onset offers ample opportunity for intervention.
To slow the development of frailty, Ward recommends adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.
Ward recommends that neurologists track their patients' frailty and points to a recent article focused on helping neurologists use frailty measures to influence care planning.
Limitations of the study include the potential for reverse efficacy and the fact that investigators were unable to adjust for genetic risk for dementia.
Commenting on the findings in Obscure Pathway Medscape Medical News, Lysia Newman, PhD, senior director of health services research at the Alzheimer's Association, said: