Frailty and the risk of dementia: is the association explained by shared environmental and genetic factors?

Abstract

Background Frailty 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. Methods The 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. Results A 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. Conclusions A 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.

Liver Enzymes in a Cohort of Community-Dwelling Older Persons: Focus on Sex Contribution

“…Frailty has been reported to predict incident dementia [ 58 ]; therefore, the lowest FI values found in our demented persons were expected. Moreover, the men in our cohort were frailer than the women.…”

Multi-Concept Frailty Predicts the Late-Life Occurrence of Cognitive Decline or Dementia: An Updated Systematic Review and Meta-Analysis of Longitudinal Studies

“…After scanning the titles and abstracts, 79 articles were considered as potentially eligible. After reviewing the bibliography and full-texts, 30 studies met the eligibility criteria, and 20 studies reporting risk estimates were included in the meta-analysis ( Buchman et al, 2007 ; Avila-Funes et al, 2009 , 2012 ; Boyle et al, 2010 ; Gray et al, 2013 ; Solfrizzi et al, 2013 , 2017a , 2017b , 2019 ; Montero-Odasso et al, 2016 ; Feng et al, 2017 ; Rogers et al, 2017 ; Trebbastoni et al, 2017 ; Chen et al, 2018 ; Shimada et al, 2018a , b ; Li et al, 2020 ; Sugimoto et al, 2020 ; Bai et al, 2021 ; Ward et al, 2021 ) cognitive domains ( Boyle et al, 2010 ; Bunce et al, 2019 ; Magnuson et al, 2019 ; Thibeau et al, 2019 ; Gale et al, 2020 ; Paolillo et al, 2020 ; Chen et al, 2021 ; Williams et al, 2021 ), two literature investigated the association between social frailty and cognition ( Tsutsumimoto et al, 2019 ; Huang et al, 2021 ), and one literature investigated the correlation between cognition and frailty status transitions ( Liu et al, 2021 ). The detailed characteristics of studies included in the systematic review and meta-analysis are summarized in Table 1 (for more details see Supplementary Table 1 ).…”

“…Seven (35%) studies investigated the relationship between cognitive frailty and ACD ( Avila-Funes et al, 2009 ; Montero-Odasso et al, 2016 ; Solfrizzi et al, 2017a , b ; Shimada et al, 2018a , b ; Sugimoto et al, 2020 ) (35%), AD ( Solfrizzi et al, 2017b ) (5%), or cognitive decline ( Montero-Odasso et al, 2016 ) (5%). Six (30%) studies reported the connection between biopsychosocial frailty and ACD ( Rogers et al, 2017 ; Solfrizzi et al, 2019 ; Li et al, 2020 ; Bai et al, 2021 ; Ward et al, 2021 ) (25%) or AD ( Trebbastoni et al, 2017 ; Solfrizzi et al, 2019 ) (10%).…”

Pneumonia and subsequent risk of dementia: Evidence from the Japan Gerontological evaluation study

“…A prospective study from UK Biobank found an increased risk of dementia among participants with pre‐frailty [HR (95% CI): 1.21 (1.04–1.42)] and frailty [HR (95% CI): 1.98 (1.47–2.67)] 4 . Similarly, the Screening Across the Lifespan Twin Study (SALT) showed that a 10% increase in the Rockwood frailty index was associated with a higher risk of dementia, independent of familial factors such as genetic predisposition [HR (95% CI): 1.17 (1.07–1.18) 33 . Frailty is associated with a poor immune system causing a failure to sufficiently respond to acute inflammation 34,35 .…”

“…Similarly, the Screening Across the Lifespan Twin Study (SALT) showed that a 10% increase in the Rockwood frailty index was associated with a higher risk of dementia, independent of familial factors such as genetic predisposition [HR (95% CI): 1.17 (1.07-1.18). 33 Frailty is associated with a poor immune system causing a failure to sufficiently respond to acute inflammation. 34,35 Frailty could increase susceptibility and mortality from pneumonia.…”