Results

Downloaded from http://biomedgerontology.oxfordjournals.org/ at Bibliotheque de l'Universite Laval on July 13, 2014

At baseline, 19% and 22% of the participants were carrying the aPoe ε2 allele and aPoe ε4 allele, respectively (Table 1). There was a similar distribution on the different aPoe subgroups by sex (Table 1). No significant differences in mean cognitive score and its components among aPoe subgroups were present at baseline or over study waves. When dichotomized into high or low cognitive score, the distribution on each aPoe subgroup followed that of the general distribution on each genotype (Table 1).

Dna analysis

Blood samples were taken from persons who were able to give informed consent. DNA was extracted using QIAamp DNA Mini kit (Qiagen, Hilden, Germany), and predesigned TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA) were used to genotype the two polymor- phisms, rs429358 and rs7412, allowing for grouping into the aPoe genotypes.

The overall cumulative mortality rates of aPoe ε2 allele carriers were similar to the cumulative mortality rates for persons with the aPoe ε33 diplotype (Figure 1A). aPoe ε4 allele carriers had the highest cumulative mortality rates. When stratifying by sex, men had the highest cumulative mortality rates (Figure 1B). For men, the cumulative mor- tality rates of aPoe ε2 allele carriers and the aPoe ε33 diplotype were similar, whereas aPoe ε4 allele carriers had higher cumulative mortality rates until the age of around 100 years. For women, there was a slightly lower mortal- ity for aPoe ε2 allele carriers compared with the aPoe ε33 diplotype, and aPoe ε4 allele carriers had the high- est cumulative mortality rates. When stratified by high or low cognitive score, aPoe ε4 allele carriers had the highest cumulative mortality rates, and the aPoe ε2 allele carriers and the aPoe ε33 diplotype had approximately the same cumulative mortality rates (Figure 1C).

interview content

The participants were invited to a home-based 2-hour multidimensional interview, covering a wide range of ques- tions and tests (22). The cognitive function was measured using a cognitive composite score (23,24). The specific tasks included a fluency task, which involved the number of animals an individual could name in a 1-minute inter- val, forward and backward digit span, and immediate and delayed recall of a 12-item list. A cognitive composite score was found by summing the five components. A higher cog- nitive composite score indicates a better cognitive function (23,24). Cognitive score was further dichotomized into “high” cognitive score (cognitive score above 0) and “low” cognitive score (cognitive score at 0 or less). Analyses of dichotomized cognitive function and its components by aPoe haplotypes at each study wave were done using logistic regression analysis and odds ratios, and 95% confi- dence intervals were calculated.

The relative risk of dying for the aPoe ε2 allele carriers was not significantly different from that of the aPoe ε33 diplotype. This was true for both the unadjusted estimate (RR: 0.94, 95% CI: 0.82–1.08) and when adjusting for sex and age (RR: 0.96, 95% CI: 0.83–1.10) although there were tendencies that aPoe ε2 allele carriers had a lower risk of dying. Carriers of the aPoe ε4 allele had an unadjusted (RR: 1.20, 95% CI: 1.05–1.36) and an adjusted (RR: 1.22, 95% CI: 1.07–1.39) significantly higher risk of dying when compared with the aPoe ε33 diplotype. When stratified by cognitive score, no significant protective effect on mortal- ity was found for the aPoe ε2 allele carriers when com- pared with the participants with the aPoe ε33 diplotype (Figure 2). Carriers of the aPoe ε4 allele had a signifi- cantly higher risk of dying when compared with the aPoe ε33 diplotype for both groups of cognitive score (Figure 2). When further stratified by sex, no major changes in risk pat- tern were found (Figure 2).

Statistical analysis

Information on date of death in the study populations up to the January 1, 2011 was retrieved from the Central Population Registry, which holds information about the total Danish population since 1968 (25) and was linked to the data using a unique identification number given to all Danish citizens. Therefore, a complete and accurate follow-up was done for all participants. In the initial descriptive analysis, we calculated age-specific, cumulated mortality rates and stratified by sex and cognitive score. Mortality rates were analyzed as a function of covariates using multiplicative Poisson regression models (26), and mortality rate ratios and 95% confidence intervals were thereby estimated. Cognitive function could be considered intermediate factors between

Table 1. Characteristics of the Different aPoe Subgroups