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Genetic risk for Alzheimer's disease and dementia appeared to be partly offset by high levels of cardiorespiratory fitness, U.K. Biobank data suggested.

Overall, high cardiorespiratory fitness was associated with better global and domain-specific cognitive functions and lower risk of dementia in both middle-age and older adults, reported Weili Xu, PhD, of the Karolinska Institute in Stockholm, and co-authors.

The incidence rate ratio (IRR) of all-cause dementia was 0.60 (95% CI 0.48-0.76) for high versus low cardiorespiratory fitness. Dementia onset was delayed by 1.48 years (95% CI 0.58- 2.39) in the high fitness group.

Among people with moderate or high genetic dementia risk scores, high cardiorespiratory fitness attenuated dementia risk by 35% (IRR 0.65, 95% CI 0.52-0.83) compared with low fitness, Xu and colleagues said in the .

"Cardiorespiratory fitness may be used as a predictor of cognitive health," the researchers stated. "Enhancing cardiorespiratory fitness could be a strategy for the prevention of dementia, even among people with a high genetic predisposition for Alzheimer's disease."

No study to date has explored the combined effect of cardiorespiratory fitness and genetic risk on dementia, Xu and colleagues pointed out. "Open questions remain regarding whether and to what extent favorable cardiorespiratory fitness may reduce dementia risk, even in those with a high genetic predisposition for dementia," they noted.

In this analysis, the researchers followed 61,214 dementia-free participants ages 39-70 for a median of 11.72 years. Mean baseline age was 56 and 52% of participants were female.

A 6-minute submaximal exercise test on a stationary bike was completed at study enrollment (from 2006 through 2010) to estimate cardiorespiratory fitness. Fitness scores were divided into low, moderate, and high tertiles, standardized by age and sex.

Global and domain-specific cognitive function was evaluated at baseline. Dementia was identified over the follow-up period using medical history and medical records. Genetic predisposition for dementia was estimated using polygenic risk scores for Alzheimer's disease derived from genome-wide association studies.

During the follow-up period which spanned to 12 years, 553 people (0.9%) received a diagnosis of dementia. High cardiorespiratory fitness was associated with a lower risk of dementia and a delay in the onset of dementia across middle and older ages.

In multi-adjusted linear regression models, higher cardiorespiratory fitness was associated with better global cognitive function, prospective memory, verbal/numeric memory, and processing speed in all participants. The association between cardiorespiratory fitness and cognitive function was consistent in different age and genetic risk groups.

"Future research on the relationship between cardiorespiratory fitness and brain health, especially in older adults, is warranted, and the mechanisms by which cardiorespiratory fitness modifies the relationship between genetic risk and dementia deserve further investigation," Xu and colleagues observed.

"As the measurement of cardiorespiratory fitness in clinical settings becomes both important and feasible, cardiorespiratory fitness may be used as a routine health monitoring tool or an indicator of health conditions," they added.

The study was observational and cannot determine causality. Also, U.K. Biobank participants often are healthier than the general population, the researchers acknowledged.

U.K. Biobank participants with certain health conditions -- such as chest pain at rest, high weight, high blood pressure, or a pacemaker -- were excluded from the exercise test, which may have influenced outcomes. The submaximal exercise test used in this study is considered less accurate than maximal exercise testing which requires participants to exercise to exhaustion, Xu and co-authors said.

In addition, incident dementia cases were determined through register information, which might have led to an underestimation. Most participants did not have repeated cardiorespiratory fitness measurements, and relationships between changes in cardiorespiratory fitness and dementia risk could not be determined.

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