: In the oldest old, several known predictors of mortality, such as sociodemographic factors, smoking, and obesity, have lost their importance, but a high disability level, poor physical and cognitive performance, and self-rated health (women only), predict mortality, which shows that mortality in the oldest old is not a stochastic process.
The Danish 1905 cohort survey is the largest and the only nationwide survey of a whole birth-cohort of nonagenarians. A total of 2,262 fairly nonselected nonagenarians participated. The level of both self-reported disability and functional limitations measured by physical performance tests among nonagenarians was high. Despite their lower mortality, women were more disabled than men and did not perform as well as men in the physical performance tests. Nevertheless, the majority of the participants considered their health to be good and were satisfied with their lives.
Despite the known difficulties of conducting surveys among the extremely old, it was possible to conduct a nationwide survey, including collection of DNA, among more than 2,000 fairly nonselected nonagenarians using lay interviewers.
Cognitive impairment has been associated with increased mortality. Most studies, however, have only included small numbers, if at all, of the very old. In a large nationwide survey of all Danes born in 1905 and still alive in 1998, where the baseline examination was conducted, we examined the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24–30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18–23 points, and severe impairment was defined as a score of 0–17 points. Cox regression analysis was applied to adjust for a number of known and suspected factors known or suspected of being associated with cognition and mortality (e.g. sociodemographic factors, sex, smoking, alcohol consumption, depressive symptoms, and physical abilities), and yielded hazard ratios (95% confidence interval) of 1.24 (1.00–1.55) for mildly impaired and 1.73 (1.37–2.20) for severely impaired Danes compared to individuals with no impairment. Cognitive impairment predicts mortality among the very old, even after controlling for most known predictors of mortality.
We developed a method to estimate genotype-specific average relative mortality risk, R, from genotype distributions in cross-sectional studies of people belonging to different age-groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data from a study of 40-year-old Danish men. Twenty-one percent of the centenarians were epsilon 2-carriers (genotypes epsilon 2 epsilon 2 and epsilon 3 epsilon 2) and 15% were epsilon 4-carriers (genotypes epsilon 4 epsilon 4 and epsilon 4 epsilon 3) compared to 13 and 29%, respectively, of the young men. The R-values were 0.95 (95% CI 0.88 to 1.02) for epsilon 2-carriers and 1.13 (95% CI 1.05 to 1.22) for epsilon 4-carriers, using epsilon 3 epsilon 3- and epsilon 4 epsilon 2 genotypes as reference. Corresponding values for epsilon 4-carriers were obtained by using published data from a French and a Finnish study of centenarians, whereas the values for epsilon 2-carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a "frailty gene." On the other hand, if odds ratios are used to summarize data from studies of this kind, they are more impressive and may propagate the misconception that apoE is a "longevity gene".
Parental life span is positively associated with the children's physical and cognitive functioning and avoidance of some of the common chronic diseases. However, the effects are small and are seen among offspring who are elderly, but not among the middle-aged or the oldest old.
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