Epidemiological studies on frailty and its associations with mortality, dementia, and polypharmacy

Abstract

Frailty describes the status of decreased physiological reserves and increased vulnerability to adverse outcomes. As the aging population increases, frailty has become an important public health concern. However, longitudinal studies disclosing the associations of frailty with adverse outcomes over the life course are limited. In the thesis, we aimed at investigating the associations of frailty with mortality, dementia, and polypharmacy using three Swedish longitudinal studies of aging and comparing the characteristics of frailty between young and old adults using Swedish and UK data. Frailty was measured using the frailty index (FI).

In Study Ⅰ, we assessed how frailty trajectories look by age at death and compared the predictive values of the level of frailty and the changes of frailty on mortality. We found that individuals who died before the age of 70 years had a steadily increasing trajectory, whereas in those individuals who died at older ages, frailty only increased after 75 years. The level of FI was a stronger predictor of mortality than the rate of change in FI in a longitudinal setting.

In Study Ⅱ, we examined the association between baseline FI and the risk of subsequent dementia using a multivariate Cox model. Familial effects on frailty-dementia association were analyzed using a within-pair analysis. The age-varying effects of FI on dementia were also assessed. We found that the FI was associated with an increased risk of dementia independent of the Apolipoprotein E (APOE) ɛ4 carrier status. After adjusting for familial factors, no attenuation was found in dizygotic (DZ) and monozygotic (MZ) twins, indicating that shared environmental and genetic factors had no influence on the frailty-dementia association. The effect of the FI on dementia was constant after age 50.

In Study Ⅲ, we investigated the differences in the prevalence, characteristics, and risk factors of early-life (aged <65) and late-life (aged ≥65) frailty using data from Sweden and UK. Comparison of the characteristics of early-life and late-life frailty was performed by collating the FI items (deficits) into domains and comparing the domain scores. We found that frailty is prevalent also in younger age groups, with pooled prevalence rates of 10.3% and 14.4% in individuals aged ≤ 55 and 55-65 years, respectively. Younger frail adults had higher scores in immunological, mental wellbeing, and pain-related domains, whereas older frail adults had higher scores in cardiometabolic, cancer, musculoskeletal, and sensory-related domains. Higher age, female sex, smoking, lower alcohol consumption, lower education, obesity, overweight, low income, and maternal smoking were similarly associated with the risk of early-life and late-life frailty.

In Study Ⅳ, we focused on visualizing FI trajectories by polypharmacy and assessing the longitudinal associations between frailty and polypharmacy using a linear mixed model. We found that the long-term polypharmacy group had a higher FI trajectory than the transient and non-polypharmacy group. Polypharmacy was significantly associated with a higher risk of frailty, and the risk of being frail conferred by polypharmacy increased with age.

In conclusion, frailty is a strong and independent predictor of adverse outcomes. Monitoring frailty and frailty progression is of great importance in middle-aged and older adults. Also, appropriate prescribing should be considered for middle-aged and old adults to prevent later frailty.