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Can a Healthy Lifestyle Reduce Genetic Risk for Dementia?

3 months, 2 weeks ago

1649  0
Posted on Feb 12, 2020, 2 p.m.

A combination of genetic and lifestyle factors can play a role in determining an individual’s risk of Alzheimer’s disease and other types of dementia. Although most cases occur in older adults in whom multiple genes influence overall risk, high levels of LDL cholesterol, diabetes, atherosclerosis, and other health factors can further elevate risk. While some risk factors may be difficult to mitigate, others are easily modifiable – for example, weight and lipid management through a combination of lifestyle changes.

A growing body of evidence suggests that individuals who lead a healthy lifestyle – avoid smoking tobacco, engage in regular physical activity, and consume a healthy diet – have a lower risk of developing dementia. Previous research has investigated the impact of lifestyle factors on many other health conditions such as cardiovascular disease, however, the extent to which these variables can influence dementia risk is unknown. A new study published online in JAMA, uses data from a large population-based cohort to investigate whether adherence to a healthy lifestyle can offset existing genetic risk for dementia.

Association of Lifestyle Habits with Dementia Risk

Led by Ilianna Lourida, PhD from the University of Exeter Medical School, a team of researchers conducted a retrospective cohort study of nearly 200,000 European adults aged 60 and above to investigate whether a healthy lifestyle is associated with a reduced risk of dementia – regardless of genetic factors. At baseline, none of the participants had cognitive impairment or dementia. The main outcome was the incidence of all-cause dementia identified through hospital records.

Researchers calculated a polygenic risk score comprised of common genetic variants linked to Alzheimer’s disease and dementia risk, as well as a weighted healthy lifestyle score – which included smoking status, physical activity levels, dietary patterns, and alcohol consumption.

Healthy Lifestyle May Reduce Dementia Incidence

A total of 196,383 participants with a mean age of 64.1 were followed for a median of 8 years, during which there were 1,769 cases of incident all-cause dementia. Overall, over 68% of the cohort had followed a healthy lifestyle, 23.6% followed an intermediate lifestyle, and 8.2% followed an unfavorable lifestyle. Researchers found that 20% of individuals had high polygenic risk scores, 60% had intermediate-risk scores, and 20% had low-risk scores.

Of those with a high genetic risk, 1.23% developed dementia, compared with 0.63% of participants with low genetic risk. Meanwhile, participants with both a high genetic risk and unfavorable lifestyle developed dementia at a rate of 1.78% compared with 0.56% of participants with low genetic risk and a favorable lifestyle. Researchers found no significant interaction between genetic risk and lifestyle factors. Among individuals with high genetic risk, 1.13% of those leading a healthy lifestyle developed dementia, in comparison with the 1.78% with unfavorable lifestyle.

Risk Reduction

Dr. Lourida and her team found that an unfavorable lifestyle coupled with high genetic risk was significantly associated with a higher risk for developing dementia in older adults without pre-existing cognitive impairment. Meanwhile, a healthy lifestyle was associated with a lower dementia risk even among participants with a high genetic risk. While there was no significant interaction between genetic risk and a healthy lifestyle, a favorable lifestyle was associated with reduced dementia risk regardless of genetic factors.

Overall, the authors found an absolute risk reduction for dementia among the high genetic risk group of 0.65% associated with leading a favorable lifestyle.

The study’s authors acknowledged the trial’s limitations. Firstly, the lifestyle score used in calculations was not independently validated to indicate a high-risk lifestyle outside of trial conditions. Furthermore, there was a possibility of unmeasured confounding and reverse causation. In addition, lifestyle factors were self-reported and some cases of dementia might not have been recorded in medical records or death registers. Nonetheless, the study expands on current knowledge of neurodegenerative diseases and their connection to lifestyle choices.

“This risk reduction implies that, if lifestyle is causal, 1 case of dementia would be prevented for each 121 individuals per 10 years with high genetic risk who improved their lifestyle from unfavorable to favorable,” authors wrote. Aside from the many mental and physical health benefits associated with leading a health-conscious lifestyle, doing so may also contribute to lowering dementia risk by reducing oxidative damage, having anti-thrombotic and anti-inflammatory effects as well as increasing cerebral blood flow. Thus, it is important to encourage patients to follow a favorable lifestyle and support lifestyle interventions when necessary, especially in cases of high genetic risk.

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