Modifiable Risk Factors for Dementia by Frailty: Application of Population Intervention Effects

Abstract

BackgroundSeveral modifiable risk factors for dementia have been identified. Rising interests focus on how frailty captures heterogeneous treatment and prevention effects. This study aimed to examine the association between modifiable risk factors and all-cause dementia among middle-aged and older adults and compare population-level intervention effects across frailty status.MethodsParticipants from UK Biobank without dementia and with available data on frailty and modifiable risk factors at baseline were included. Dementia was ascertained from inpatient records. Frailty was defined by a modified version of physical frailty phenotype and classified as non-frail, pre-frail and frail. Thirteen socioeconomic, life-style, environmental, and medical risk factors were included. We used Logistic regression to examine their association with 10-year dementia. Population intervention effects were also estimated by parametric G-computation.ResultsOf 381, 419 eligible participants with a mean age of 56.9 years, 58.4%, 38.2%, and 3.4% were non-frail, pre-frail, and frail, respectively. Over a 10-year follow-up, 1,688 (0.76%), 1,949 (1.34%), and 378 (2.90%) dementia cases were identified among non-frail, pre-frail, and frail adults. The odds ratios for low education, physical inactivity, central obesity, hearing impairment, high NO2 exposure, and traumatic brain injury increased, but those for smoking, depression, hypertension, and diabetes decreased. Population intervention effects for single risk factors (excluding smoking and excessive alcohol use) increased with severer frailty status. For interventions achieving 100% coverage, the population intervention effect was 0.002, 0.007, and 0.022 in the non-frail, pre-frail, and frail populations, respectively. Even with intervention coverage of only 25% and 50%, the population intervention effect remained highest among the frail population.ConclusionWe found that frailty modifies the associations between established risk factors and dementia among middle-aged and older adults. Dementia intervention effectiveness appears to be greatest among frail adults. Therefore, routine frailty evaluation should be adopted to identify those who will gain the most from personalized dementia prevention strategies.