Individuals with a high genetic risk for coronary artery disease (CAD) also have an increased risk of developing dementia, according to a large UK population study published April 4 in Circulation. The risk was reduced, however, in those who maintained optimal cardiovascular health in the years before diagnosis, particularly in those at risk of developing vascular dementia.

Arisa Sittichokkananon, et al., looked at a UK Biobank cohort of 365,782 participants free from dementia for at least five years after baseline assessment to determine whether an elevated genetic risk for CAD was associated with long-term risks of developing Alzheimer's disease (AD) or all-cause or vascular dementia. They used a genome-wide polygenic risk score (PRS) to assess genetic risk for CAD and a modified American Heart Association Life's Essential 8 Lifestyle Risk Score (LRS) to evaluate lifestyle risk.

Results showed that 8,870 individuals developed all-cause dementia during a median follow-up of 14 years; 4,021 individuals developed AD and 1,994 developed vascular dementia. Participants with dementia were older at baseline (by about 5 years) vs. those without dementia. More participants with AD were women (53%) compared with those with vascular dementia (42% women).

The findings also demonstrated that both genetic (PRS) and lifestyle (LRS) risk scores for CAD were associated with a slightly elevated risk of all-cause dementia (subhazard ratio [sHR] per SD increase, 1.10 (p<0.001) for PRS and 1.04 (p=0.006) for LRS). The risk was mostly due to underlying vascular dementia diagnoses (sHR, 1.16 (p<0.001) for PRS and 1.15 (p<0.001 for LRS), with AD only demonstrating a moderate association with PRS (sHR, 1.09; p<0.001).

Notably, LRS was shown to have an additive effect to PRS, whereby participants in the highest tertiles for both genetic and lifestyle risk for CAD were approximately 70% more likely to develop vascular dementia during follow-up vs. those in the lowest tertiles for both (sHR, 1.71; p<0.001). Those with a low LRS at baseline had a significantly lower risk, however, regardless of underlying genetic risk (40-50% reduction for low vs. high LRS tertile regardless of PRS tertile; p<0.001 for all).

Regarding the finding that healthy lifestyle behaviors may attenuate the risk of developing dementia in this cohort, the study authors write that "mid- to late-life prevention strategies aimed at reducing the population burden of cardiovascular disease may also protect against progression to vascular dementia in older age."