A new study from the UK addressed whether a person’s genetic risk of dementia modifies the extent to which healthy lifestyle factors are associated with a reduced risk of dementia. The study included a very large, population-based sample of more than 500,000 White adults age 60 and over from the UK. Participants were categorized into low, intermediate, or high genetic risk of dementia based on a polygenic risk score (i.e., a weighted estimate of genetic risk for dementia from a number of single nucleotide repeats or SNPS). They were also categorized into favorable (3-4 healthy lifestyle factors), intermediate (2 healthy lifestyle factors), and unfavorable (0-1 healthy lifestyle factors) lifestyle categories based on four factors – healthy diet, physical activity, alcohol consumption and smoking. Lifestyle factors were assessed at baseline and incident all-cause dementia was assessed from hospital records and death records an average of 8 years later. Results showed that for those with an intermediate genetic risk of dementia, an intermediate or favorable lifestyle was associated with a decreased risk of dementia compared to an unfavorable lifestyle. Among those at the highest genetic risk of dementia, a favorable lifestyle was associated with a lower risk of dementia compared with an intermediate or unfavorable lifestyle. In other words, findings suggested it may be possible to lower the risk of dementia through lifestyle modification but that the greater the genetic risk of dementia, the healthier the lifestyle must be.
Menopause practitioners have an important role to play in counseling patients on how lifestyle factors at midlife can affect their later health, including their risk for dementia. Women are right to fear dementia, as two-thirds of patients with Alzheimer’s disease are female  and every clinical trial of a pharmacological agent to prevent or treat Alzheimer’s disease has failed. The benefits of multicomponent lifestyle interventions on cognition and perhaps dementia risk are supported by numerous observational studies as well as a growing number of randomized clinical trials . These lifestyle interventions are multi-faceted and focus on increasing adherence to the Mediterranean Diet, physical activity, cognitive engagement, and social engagement, as well as smoking cessation and moderate use of alcohol. Some but not all of those interventions were evaluated in the JAMA study. The number of healthy behaviors is key, as prior studies  and the current JAMA article show an additive role of lifestyle factors. How much physical activity is necessary to minimize cognitive difficulties? Favorable physical activity was defined on either the basis of duration (i.e., > 150 minutes of moderate activity or 75 minutes of vigorous activity per week) or frequency (i.e., moderate physical activity at least 5 days a week or vigorous activity once a week). Moderate consumption of alcohol was defined as 0 to 14 g/d for women, or about one glass of wine per day. Although this study included a white-only population of European ancestry, prior work demonstrates that lifestyle modification works also for diverse populations  though the moderating effect of genetic risk of dementia in that population is yet to be determined.
Pauline M. Maki
Professor of Psychiatry, Psychology and Obstetrics & Gynecology, University of Illinois at Chicago
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