Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR).

ABSTRACT

BACKGROUND/AIMS: Our aims were two-fold firstly, to investigate the association and interaction between apolipoprotein E (ApoE), lifestyle risk factors and dementia-related mortality and, secondly, to examine if using dementia-related mortality yielded comparable risk estimates for the ApoE genotypes as reported in studies using a clinical dementia diagnosis as the end point. METHODS: We used a nested case-control study with 561 cases drawn from dementia deaths in the Cohort of Norway (CONOR) and 584 alive controls. RESULTS: ApoE ε4 carriers were at increased risk of dementia-related mortality compared to noncarriers [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.93-3.13], and ε4 homozygotes were at particularly high risk (OR 7.86, 95% CI 3.80-13.8), while the ε2 type was associated with a lower risk. The highest risk of dementia-related mortality was found among ε4 carriers with more lifestyle risk factors (ε4 carriers who were smokers, hypertensive, physically inactive and diabetics) versus ε4 noncarriers without lifestyle risk factors (OR 15.4, 95% CI 4.37-52.4). The increased risk was additive, not multiplicative. CONCLUSIONS: Ensuring a healthy lifestyle is important to be able to prevent dementia in populations at large, but especially for ε4 carriers. Using dementia mortality gives comparable results for the ApoE-dementia association as studies using clinical dementia diagnoses.