Even With High Genetic Risk for Alzheimer's, Lifestyle Factors Matter

Midlife scores on the American Heart Association's Life's Simple 7 -- an assessment of physical activity, diet, obesity, smoking, blood pressure, cholesterol, and blood sugar -- were tied to dementia risk later in life, even in people at high genetic risk for Alzheimer's disease.

Across genetic risk profiles, higher midlife scores on Life's Simple 7, a metric for cardiovascular and brain health, were largely associated with reduced incident dementia, an analysis of data from the Atherosclerosis Risk in Communities (ARIC) cohort showed.

Associations were consistent for European-American study participants, even among people with the highest genetic risk (HR 0.92 per point on the Life's Simple 7 score, 95% CI 0.88-0.96), reported Adrienne Tin, PhD, of the University of Mississippi Medical Center in Jackson, and co-authors.

For African-American participants, associations followed similar patterns but were statistically not significant, with wide confidence intervals and smaller sample sizes limiting reliable inferences, the researchers wrote in Neurology.

"Although it's known that higher Life's Simple 7 scores are associated with better brain health in the general population, it's been uncertain whether this protective association can be observed among those with high genetic risk," Tin told MedPage Today.

"Our study finds that higher Life's Simple 7 scores remain associated with lower risk of dementia across the range of genetic risk," she added. "It's particularly advantageous to maintain a high Life's Simple 7 score early in life since our study finds that higher scores in midlife are associated with lower risk for dementia with 30 years of follow-up data."

The study followed 11,561 people in the ARIC cohort for incident dementia for a median of 26.2 years, including 8,823 people with European ancestry and 2,738 people with African ancestry. Participants had a mean age of 54 at baseline.

Life's Simple 7 scores ranged from 0 to 14, with 14 representing the most healthy lifestyle. Mean baseline scores were 8.3 among European Americans and 6.6 among African Americans.

Genetic risk scores were generated using data from genome-wide association studies of Alzheimer's disease. The highest genetic risk group had at least one copy of the Alzheimer's risk variant APOE4, which was found in 27.9% of European Americans and 40.4% of African Americans in the study.

Over the course of the study, 1,603 European Americans and 631 African Americans developed dementia. Higher Life's Simple 7 scores were associated with lower risk of dementia in both groups.

For European Americans, intermediate scores (7 or 8) and high scores (9-14) on Life's Simple 7 were associated with a 30% and 43% lower dementia risk, respectively, compared with lower scores (P<0.001). Higher Life's Simple 7 scores were also linked to patterns of declining dementia risk among African Americans, though sample sizes were small and findings were not statistically significant.

"The wide confidence intervals of the estimates among African-American participants limit their interpretation and underscore the need for studies of larger sample size among African-American individuals," Tin and co-authors noted.

The study had several limitations, the researchers pointed out. Genetic risk scores were generated based on genome-wide association studies of Alzheimer's disease, but the analysis used all-cause dementia as its outcome. In addition, Life's Simple 7 scores were captured once, at baseline, and the researchers could not assess the effects of the longitudinal changes on incident dementia.

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