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Dementia Incidence Reduced in People With High-Risk Genetics

LOS ANGELES — A healthy lifestyle reduced dementia incidence in people with high-risk genetics, an analysis of nearly 200,000 older adults in the UK Biobank showed.

The incidence of dementia was 32% lower in people with a high genetic risk for dementia and a healthy lifestyle than in people with similar genetic risk and an unhealthy lifestyle, reported Elzbieta Kuzma, PhD, of the University of Exeter Medical School in England, at the Alzheimer’s Association International Conference (AAIC). The study was published simultaneously in JAMA.

This is the first analysis to investigate the relationship between multiple genetic risk factors for dementia and a combination of lifestyle factors in a very large sample, Kuzma noted.

“Genetic risk and lifestyle factors were independently associated with risk of dementia, indicating that healthy lifestyle was associated with a reduced risk of dementia regardless of genetic risk,” she told MedPage Today. “Our findings are exciting as they show that although we can’t change our genes, we can live a healthy lifestyle to try to reduce our risk of dementia.”

These results “really challenge the genetic fatalism that you often hear in popular discussions about Alzheimer’s,” noted John Haaga, PhD, Director of Behavioral and Social Research at the NIH National Institute on Aging (NIA), which helped fund the research.

“People understand there’s an inherited element to the risk and tend to get very fatalistic, that they were dealt this hand by their genetic inheritance,” Haaga told MedPage Today. “What’s interesting about this data is at the highest level of genetic risk, lifestyle choices still seemed to make a big difference.”

In this analysis, researchers analyzed UK Biobank data from 193,383 older adults of European descent ages ≥60, excluding people with prevalent cognitive impairment or dementia at baseline. Participants joined the study from 2006 to 2010 and were followed until 2016 or 2017. Their average age was 64 and 53% were women.

To assess genetic risk, the researchers constructed a polygenic risk score based on previously published statistics from genome-wide association studies, weighting each genetic risk factor by the strength of its association with Alzheimer’s disease. In total, 20% of participants had high polygenic risk scores, 60% intermediate, and 20% low.

To evaluate lifestyle factors, the researchers created a healthy lifestyle score based on four behaviors that participants self-reported at baseline: no current smoking, regular physical activity, healthy diet, and moderate alcohol consumption. Lifestyle index scores ranged from 0 to 4; three or four healthy lifestyle factors was a favorable score, two intermediate, and zero or one unfavorable. Overall, 61.8% of participants followed a favorable lifestyle, 23.6% intermediate, and 8.2% unfavorable.

Over a median of 8 years, 1,769 cases of incident all-cause dementia emerged. People with high genetic risk and an unfavorable lifestyle were nearly three times more likely to develop dementia than people with low genetic risk and a favorable lifestyle (HR 2.83, 95% CI 2.09-3.83, P<0.001).

Among people with a high genetic risk score, 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%) of those with an unfavorable lifestyle (HR 0.68, 95% CI 0.51-0.90; P=0.008).

Genetic factors did not significantly modify the relationship between a healthy lifestyle and dementia risk.

This research has several limitations, Haaga pointed out. The population in the study was “overwhelmingly people with European ancestry: that’s a problem with all our genetic studies that really has to be fixed,” he said. “What little we do know — where we have the ability to study it — is that the influences of genetic factors vary among populations.”

The analysis also was based on people who volunteered to participate in the UK Biobank. “Well-educated people tend to be overrepresented in studies like this,” Haaga said. Unmeasured confounding and reverse causation also may have influenced results.

The study was conducted using the UK Biobank resource application. Researchers disclosed support from the James Tudor Foundation, the Mary Kinross Charitable Trust, the Halpin Trust, the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for the SouthWest Peninsula and the National Health and Medical Research Council in Australia, the National Institute on Aging/NIH, and the Alan Turing Institute.

Kuzma disclosed relevant relationships with the James Tudor Foundation, the Mary Kinross Charitable Trust, and the Halpin Trust.


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