Dataset Information

Physical fitness and dementia risk in the very old: a study of the Lothian Birth Cohort 1921.

ABSTRACT:

Background

Previous studies have demonstrated that individual measures of fitness - such as reduced pulmonary function, slow walking speed and weak handgrip - are associated with an increased risk of dementia. Only a minority of participants included in these studies were aged over 80. The aim of this study was therefore to investigate the association between physical fitness and dementia in the oldest old.

Methods

Subjects (n = 488) were enrolled in the Lothian Birth Cohort 1921 and aged 79 at baseline. Dementia cases arising after enrolment were determined using data from death certificates, electronic patient records and clinical reviews. Fitness measures included grip strength, forced expiratory volume in 1 s (FEV₁) and walking speed over 6 m, measured at 79 years. Dementia risk associated with each fitness variable was initially determined by logistic regression analysis, followed by Cox regression analysis, where death was considered as a competing risk. APOE ε4 status, age, sex, height, childhood IQ, smoking, history of cardiovascular or cerebrovascular disease, hypertension and diabetes were included as additional variables. Cumulative incidence graphs were calculated using Aalen-Johansen Estimator.

Results

Although initial results indicated that greater FEV₁ was associated with an increased risk of dementia (OR (odds ratio per unit increase) 1.93, p = 0.03, n = 416), taking into account the competing risk of mortality, none of the fitness measures were found to be associated with dementia; FEV₁ (HR (hazard ratio per unit increase) 1.30, p = 0.37, n = 416), grip strength (HR 0.98, p = 0.35, n = 416), walking speed (HR 0.99, p = 0.90, n = 416). The presence of an APOE ɛ4 allele was however an important predictor for dementia (HR 2.85, p < 0.001, n = 416). Cumulative incidence graphs supported these findings, with an increased risk of dementia for APOE ɛ4 carriers compared with non-carriers. While increased FEV₁ was associated with reduced risk of death, there was no reduction in risk for dementia.

Conclusions

In contrast to previous studies, this study found that lower fitness beyond age 79 was not a risk factor for subsequent dementia. This finding is not explained by those with poorer physical fitness, who would have been more likely to develop dementia, having died before onset of dementia symptoms.

SUBMITTER: Sibbett RA

PROVIDER: S-EPMC6123983 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Previous studies have demonstrated an association between DNA methylation-based measures of accelerated ageing and age-related health outcomes and mortality. As a disease closely associated with advancing age, we hypothesized that DNA methylation-based measures of accelerated ageing might be associated with risk for dementia. This study therefore aimed to examine the association between four recognised measures of age acceleration and subsequent dementia. METHODS:Study subjects (n =?488) were members of the Lothian Birth Cohort 1921. Dementia case ascertainment used data from death certificates, electronic hospital records, and clinical reviews. Venous blood samples were taken at baseline, at age 79?years. DNA methylation and measures of epigenetic age were calculated in accordance with Horvath's epigenetic clock tutorial, using the online calculator (https://dnamage.genetics.ucla.edu/). From these values, four measures of accelerated ageing were calculated: extrinsic epigenetic age acceleration (EEAA), intrinsic epigenetic age acceleration (IEAA), AgeAccelPheno and AgeAccelGrim. Competing risk regression models - with death as a competing risk - were performed to examine the association between each measure of accelerated ageing and incident dementia. APOE ?4 status, sex, age, smoking status, history of cardiovascular disease, cerebrovascular disease, hypertension, and diabetes were included as covariates. RESULTS:None of the multivariate models revealed a positive association between increased epigenetic age acceleration and dementia risk. Across all included models, never-smoking increased risk for dementia (HR 1.69 [1.06, 2.71], p =?0.03), and having no APOE ?4 alleles reduced risk for dementia (HR 0.44 [0.29, 0.67], p <?0.001). CONCLUSIONS:The present study did not demonstrate any consistent association between DNA methylation-based measures of accelerated ageing and dementia in subjects aged over 79?years. Further, larger studies - including separate analyses of dementia subtypes - are required to further investigate the potential association between DNA methylation-based measures of accelerated ageing and dementia.

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