But among people at high genetic risk for dementia, these potentially modifiable factors – not smoking, not having depression or diabetes, getting regular physical activity, avoiding social isolation, and following a healthy diet – may not have protective associations, according to research published in Nature Medicine.
Recent analyses have indicated that eliminating known modifiable risk factors for dementia at a population level could prevent one-third of dementia cases, but prevention trials “have yielded inconsistent results so far,” wrote first author Silvan Licher, MD, of the department of epidemiology at Erasmus University Medical Center Rotterdam (the Netherlands) and his colleagues.
“Prior studies have mostly focused on the risk of dementia associated with an individual protective factor, yet the combination of multiple factors may yield more beneficial effects than the individual parts,” they wrote. “Combining data about a number of factors is also important because it takes into account the multifactorial nature of late-life dementia. We used data from the Rotterdam Study to determine to what extent a favorable profile based on modifiable risk factors is associated with a lower risk of dementia among individuals at low, intermediate, or high genetic risk.”
Grouped by APOE genotype
Patients who were apolipoprotein E epsilon-4 allele (APOE4) carriers (i.e., APOE2 and 4, APOE3 and 4, or two APOE4) were classified as having high genetic risk (n = 1,747). Other APOE genotypes were considered intermediate risk (n = 3,718 with two APOE3 alleles) or low risk (n = 887 with either two APOE2 alleles or APOE2 and 3).
The researchers measured six potentially modifiable lifestyle or health factors that “have been implicated in a lower risk of dementia.” Modifiable risk scores ranged from 0 to 6. Participants were classified as having an unfavorable profile (0-2 protective factors), an intermediate profile (3-4 protective factors), or a favorable profile (5-6 factors).
The researchers calculated the relative risk of developing dementia using a Cox proportional hazards model and the absolutely risk using competing risk models.
In all, 56.2% of the participants were women, the average age was about 69 years, and patient characteristics were similar across the categories of APOE risk. APOE4 carriers received dementia diagnoses at a younger age, more often had a parental history of dementia, and had higher total cholesterol levels, compared with noncarriers. In all, 915 people received a dementia diagnosis, of whom 739 received a diagnosis of Alzheimer’s disease. The other 2,644 participants died free from dementia. The median follow-up was 14.1 years.
“Dementia risk was significantly higher among participants at high or intermediate APOE risk, compared with those at low APOE risk,” the researchers said. In addition, the risk of dementia increased in participants who had fewer protective factors. Those with 0-2 protective factors had a 29% higher risk of dementia, compared with participants with 5 or 6 protective factors, after adjusting for age, sex, level of education, parental history of dementia, history of stroke, systolic blood pressure, and total and high-density lipoprotein cholesterol.