Can a Healthy Lifestyle Reduce Your Risk of Dementia Regardless of Your Genes? – Part II

A new, long term cohort study suggests that healthy lifestyle is associated with a lower risk for dementia among people considered at lower and intermediate genetic risk but not for those considered at high genetic risk.

In our August 14, 2019 blog, we discussed the findings from a July 2019 JAMA article describing a large retrospective, cohort study of 196,383 in the UK Biobank which found that a healthy lifestyle is associated with a lower risk for dementia regardless of genetic risk. Research has increasingly provided evidence that there is a link between a healthy lifestyle and a reduced risk for developing dementia, but the UK Biobank research had been one of the first studies to show that even people at high genetic risk might benefit from a healthy lifestyle.

Soon after, on August 26, 2019, the findings of a study of 6,352 participants and an accompanying commentary were published in the journal Nature Medicine. This smaller, but population representative study in Rotterdam examined a similar research question. Like the UK Biobank study, the Rotterdam study found that a healthy lifestyle was associated with lower risk of dementia in people determined to be at low and intermediate genetic risk. Both studies also confirmed the important, increased risk association of the APOE4 allele and high polygenic risk scores with dementia. However, unlike the UK Biobank study, the Rotterdam study did not find a healthy lifestyle to be associated with a lower risk of dementia among people considered to be at highest genetic risk including those with the E (APOE) genotype.

Rotterdam Based Genetic Risk Level and Healthy Lifestyle – Dementia Risk Study
Incidence of dementia within favorable lifestyle group by risk level

Data Source: Nature Medicine

While there were similarities between the observational studies, there were many differences including criteria and methodology. Like the UK biobank study, the Rotterdam study also included the lifestyle risk factors of: smoking status, alcohol consumption, physical activity levels, and adherence to a healthy diet. However, the Rotterdam study also included other factors including: absence of depression and avoidance of social isolation. The Rotterdam study also used other methodology to assess lifestyle and/or health measures including the European cardiovascular disease risk assessment model. The UK Biobank study defined development of dementia disease through linkage to healthcare records, while the more recently published Rotterdam study used research-grade diagnoses for this purpose. The UK Biobank cohort was younger at baseline with a mean age of 65.1 versus the Rotterdam cohort which had a mean age of 69.1. Furthermore, median years of follow up differed: 8.0 years for the UK Biobank study and 14.1 years for the Rotterdam study.

There were several limitations to the Rotterdam based study including that modifiable-risk-factor profiles were measured at baseline and did not take into account potential changes over time. Also, by stratifying participants by both genetic and environmental data, results were based on small samples in each strata. In addition, the study population was a relatively older population in comparison but, like the UK Biobank study, was predominantly of European descent (97%), and this may limit generalizability of the findings to other populations.

Just as we concluded in our previous blog, there is still much to learn about the linkage between lifestyle and brain health over time. It is often the normal course of science to have some conflicting findings as evidence advances. Several clinical trials are currently underway that are assessing questions of lifestyle and genetic risk such as the 7 year FINGER trial follow-up. For now, it is important not to “throw the baby out with the bathwater.” Even if not efficacious among people considered at high risk, such as people with certain APOE variants, there is a growing body of evidence that a healthy lifestyle may lower risk of dementia for most people. Perhaps Dr. Licher, the lead author of the Rotterdam based study, says it best: “The importance of a healthy lifestyle to lower the risk of dementia is increasingly recognized. I think these results should not alter that message.”