and adjusted analyses. However, a 22% increased mortality risk was observed for aPoe 4 carriers. The aPoe 2 allele did not show a significant protective effect on mortality among the oldest old, but it may have a protective effect on cognitive decline. There were no significant differences in mean cognitive score and its components among aPoe subgroups 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. Blood samples were taken from consenting participants and DNA was extracted using the QIAamp DNA Mini kit. The cognitive function was measured using a cognitive composite score based on specific tasks. Logistic regression analysis was used to analyze dichotomized cognitive function and its components by aPoe haplotypes at each study wave. The study found no significant protective effect of the aPoe 2 allele on mortality compared with the aPoe 3 allele, but it suggested an increased protection against cognitive decline over time for persons with the aPoe 2 allele.cohort with a similar follow-up, we found an increased effect for aPoe 4 allele carriers with age, suggesting that other factors may have influenced the observed discrepancy. Additionally, the limited number of men alive in the present study may make chance an important factor in the findings.

The study found no significant protective effect of the aPoe 2 allele on mortality compared to the aPoe 3 allele. However, carriers of the aPoe 2 allele were increasingly protected against cognitive decline over time, with a maximum protection of 39% at the third study wave. Carriers of the aPoe 4 allele had a 22% increased risk of dying compared to those with the aPoe 33 diplotype. Cognitive score did not significantly modify the mortality risk of the various aPoe genotypes.

The study's strengths include its long follow-up period, high participation rate, and measurement of cognitive function over time. However, information on causes of death was not available, and survival selection may have weakened the association between aPoe and mortality. The results are relevant for the oldest old but not for younger persons. Future studies should investigate this topic among younger persons.July 13, 2014.

In this cohort study, we did not observe any attenuation of the association between aPoe and mortality with age (3). On the contrary, our findings suggest that the association may even be stronger at younger ages than those studied here. Cognitive function is an intermediate factor in the causal chain between aPoe genotype and mortality. However, our analysis showed that stratification by cognitive function and examining the separate effect of aPoe genotype within strata yielded similar results. For the individual aPoe genotypes investigated in this study, we found no significant differences in mortality risk for individuals with low or high cognitive scores. In conclusion, we did not find an overall protective effect of the aPoe 2 allele on mortality among the oldest old. Instead, we found a 22% increased mortality risk for carriers of the aPoe 4 allele. The aPoe 2 allele had a protective effect on cognitive decline among the oldest old.

Figure 1 shows cumulative mortality rates over age for different aPoe genotypes, stratified by cognitive score. Figure 2 depicts the relative risk of dying compared to the aPoe 33 diplotype, stratified by aPoe genotype. The vertical lines on bars represent 95% confidence intervals. Figure 3 shows odds ratios for low cognitive score and its components over study waves when compared to the aPoe 33 diplotype.

This work was supported by the INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N 19-1.5-08/16052 (by EU funds from the European Regional Development Fund).