Association of Lifestyle and Genetic Risk With Incidence of Dementia

Abstract

OBJECTIVE To investigate whether a healthy lifestyle is associated with lower risk of dementia regardless of genetic risk. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study that included adults of European ancestry aged at least 60 years without cognitive impairment or dementia at baseline. Participants joined the UK Biobank study from 2006 to 2010 and were followed up until 2016 or 2017. EXPOSURES A polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption, categorized into favorable, intermediate, and unfavorable lifestyles. MAIN OUTCOMES AND MEASURES Incident all-cause dementia, ascertained through hospital inpatient and death records. RESULTS A total of 196 383 individuals (mean [SD] age, 64.1 [2.9] years; 52.7% were women) were followed up for 1 545 433 person-years (median [interquartile range] follow-up, 8.0 [7.4-8.6] years). Overall, 68.1% of participants followed a favorable lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Twenty percent had high polygenic risk scores, 60% had intermediate risk scores, and 20% had low risk scores. Of the participants with high genetic risk, 1.23% (95% CI, 1.13%-1.35%) developed dementia compared with 0.63% (95% CI, 0.56%-0.71%) of the participants with low genetic risk (adjusted hazard ratio, 1.91 [95% CI, 1.64-2.23]). Of the participants with a high genetic risk and unfavorable lifestyle, 1.78% (95% CI, 1.38%-2.28%) developed dementia compared with 0.56% (95% CI, 0.48%-0.66%) of participants with low genetic risk and favorable lifestyle (hazard ratio, 2.83 [95% CI, 2.09-3.83]). There was no significant interaction between genetic risk and lifestyle factors (P = .99). Among participants with high genetic risk, 1.13% (95% CI, 1.01%-1.26%) of those with a favorable lifestyle developed dementia compared with 1.78% (95% CI, 1.38%-2.28%) with an unfavorable lifestyle (hazard ratio, 0.68 [95% CI, 0.51-0.90]). CONCLUSIONS AND RELEVANCE Among older adults without cognitive impairment or dementia, both an unfavorable lifestyle and high genetic risk were significantly associated with higher dementia risk. A favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk.

Experiences of dementia and attitude towards prevention: a qualitative study among older adults participating in a prevention trial

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Addition of Genetics to Quantitative MRI Facilitates Earlier Prediction of Dementia: A Non-invasive Alternative to Amyloid Measures

“…Nonetheless, early risk identification is desirable, as it provides greater opportunity for intervention and risk mitigation 7 , potentially enabling individuals and families to better prepare for, postpone the effects of and reduce the severity of the disease's impacts. In particular, modifiable lifestyle factors have a significant influence on an individual's risk 6 , including key factors such as management of type II diabetes, managing hearing loss, and reducing alcohol use [38][39][40] .…”

“…However, it has been established that amyloid deposits begin to accumulate years before symptoms begin to appear 2,3 . Furthermore, lifestyle is key in influencing an individual's risk 6 , and early risk identification provides greater opportunity for intervention and risk mitigation 7 . To accomplish the early identification of at-risk individuals, prediction must rely on evidence prior to the onset of symptoms.…”

Self-reported health behaviors and longitudinal cognitive performance: Results from the Wisconsin Registry for Alzheimer’s Prevention

“…A recent large retrospective cohort study developed a weighted healthy lifestyle score, including no smoking, regular physical activity, healthy diet, and moderate alcohol consumption, which they categorized in to favoarable, intermediate and unfavorable lifestyles. Using this approach, the authors found that a favorable lifestyle was associated with lower dementia risk, including in those participants with higher genetic risk for dementia 30 .…”