A prospective population-based cohort study in the Netherlands suggests that in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are associated with a lower risk of dementia compared to unfavorable profiles. However, these protective associations were not found in those at high genetic risk. The study included 6,352 individuals aged 55 years and older, 56.2% women. During a median follow-up of 14.1 years, 915 individuals were diagnosed with dementia, of whom 739 were diagnosed with Alzheimer’s disease. Genetic risk was defined by APOE genotype and a weighted polygenic-risk score based on 27 genetic variants (excluding APOE). The favorable modifiable-risk profiles include non-smoking, regular physical activity, a healthy diet, as well as absence of depression, diabetes and social isolation. Those with an unfavorable profile (≤2 out of 6 factors) had a 32% higher risk of dementia than participants with a favorable one (≥5 out of 6 factors). In those at low or intermediate APOE risk, the risk of dementia in participants with an unfavorable profile was higher than that for those with a favorable one (HR 2.51 and 1.39, respectively); However, there was no differences in dementia risk between individuals with unfavorable or intermediate profiles compared with those who had a favorable profile (HR 1.00 and 1.05, respectively) in those at high APOE risk. The patterns across polygenic-risk strata were attenuated yet largely comparable to those of the APOE-risk groups. The findings for individuals at high genetic risk of dementia are not consistent with some previous studies and may imply that these individuals need to be targeted earlier in the disease process to influence their risk. Source: https://www.nature.com/
