Abstract
BackgroundFrailty has been identified as a risk factor for cognitive impairment and dementia. However, it is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. We analyzed the association between frailty and the risk of dementia in a large twin cohort and examined the role of familial factors in the association.MethodsThe Rockwood frailty index (FI) based on 44 health deficits was used to assess frailty. The population-level association between FI and the risk of all-cause dementia was analyzed in 41,550 participants of the Screening Across the Lifespan Twin (SALT) study (full sample, aged 41–97 years at baseline), using Cox and competing risk models. A subsample of 10,487 SALT participants aged 65 and older who received a cognitive assessment (cognitive sample) was used in a sensitivity analysis to assess the effect of baseline cognitive level on the FI-dementia association. To analyze the influence of familial effects on the FI-dementia association, a within-pair analysis was performed. The within-pair model was also used to assess whether the risk conferred by frailty varies by age at FI assessment.ResultsA total of 3183 individuals were diagnosed with dementia during the 19-year follow-up. A 10% increase in FI was associated with an increased risk of dementia (hazard ratio [HR] 1.17 (95% confidence interval [CI] 1.07, 1.18)) in the full sample adjusted for age, sex, education, and tobacco use. A significant association was likewise found in the cognitive sample, with an HR of 1.13 (95% CI 1.09, 1.20), adjusted for age, sex, and cognitive level at baseline. The associations were not attenuated when adjusted for APOE ɛ4 carrier status or considering the competing risk of death. After adjusting for familial effects, we found no evidence for statistically significant attenuation of the effect. The risk conferred by higher FI on dementia was constant after age 50 until very old age.ConclusionsA higher level of frailty predicts the risk of dementia and the association appears independent of familial factors. Targeting frailty might thus contribute to preventing or delaying dementia.
Highlights
Frailty has been identified as a risk factor for cognitive impairment and dementia
The genetics of frailty are less well understood, twin studies have estimated that the heritability of the frailty index (FI) ranges from 30 to 52% [12, 13], and a genome-wide association study has indicated that variants in brain pathways underlie the risk of frailty [14]
To assess whether the risk carried by increased FI varies over age at FI measurement and whether the association is independent of familial effects throughout the age range, from adulthood into old age, we modeled the association between FI and dementia including a statistical interaction between FI and age and modeled this interaction as a natural cubic spline function
Summary
Frailty has been identified as a risk factor for cognitive impairment and dementia. It is not known whether familial factors, such as genetics and shared environmental factors, underlie this association. Hypertension, hearing impairment, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, traumatic brain injury, and air pollution were recently identified in the 2020 report of the Lancet Commission [3] as 12 common risk factors for incident dementia. Twin studies have shown that Alzheimer’s disease, the most common form of dementia, is highly heritable [10], with the apolipoprotein E (APOE) ɛ4 allele being the strongest genetic risk factor [11]. The genetics of frailty are less well understood, twin studies have estimated that the heritability of the FI ranges from 30 to 52% [12, 13], and a genome-wide association study has indicated that variants in brain pathways underlie the risk of frailty [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
