Genetics influence dementia and mortality relationship

The relationship between dementia and mortality
Imagine a world where two identical twins, possessing the same genes and childhood memories, embark on different life paths—one develops dementia, while the other remains cognitively healthy. Identical twins share all their genetic material, while fraternal twins share about half—just like siblings. By comparing the lifespans of twins where only one had dementia, scientists could sift through the clues. If genetics were the key player, survival differences between fraternal twins would be more pronounced than between identical twins. But here’s the twist: what if dementia itself cut life short? Then even identical twins would show differences in survival. This would mean that something beyond genes—perhaps the experience of dementia itself-influenced life length.

To shed more light on the links between dementia and mortality, case-control and co-twin control methodologies were used to examine the genetics and common environmental contributions affecting the association between dementia and mortality.

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Three NEAR population studies: the Swedish Adoption/Twin Study of Aging (SATSA), a Longitudinal Study of Gender Differences in Health Behavior and Health among Elderly (GENDER), and the Origins of Variance in the Oldest-Old: Octogenarian Twins (OCTO-Twin), as well as the Study of Dementia in Swedish Twins (HARMONY) were used to examine this. In detail, 987 twins with dementia and 2938 age- and sex-matched controls without dementia, as well as 90 identical and 288 fraternal twins and their intact co-twins were followed.

Genetics influence dementia and mortality relationship
The study revealed that the median survival duration after a dementia diagnosis was around seven years, and individuals with dementia exhibited a significantly heightened mortality risk when compared to their contemporaries without dementia. Notably, the study also observed that in fraternal twin pairs with discordant dementia diagnoses, the disparity in survival was less pronounced than in the case-control analysis. This trend continued in identical twins, where the elevated mortality risk was further mitigated, suggesting that both genetic and environmental factors shared by twins contribute to the dementia-mortality association.

However, twins without a dementia diagnosis whose co-twin was affected—also faced an increased mortality risk, supporting the hypothesis that genetic factors influence the dementia-mortality association. This implies that even individuals without a dementia diagnosis may have a reduced lifespan due to their genetic makeup.

Collectively, these findings indicate that genetics may confound the association between dementia and mortality. Given the substantial genetic influence on Alzheimer’s disease and other dementias, it is plausible that the same genetic factors linked to dementia also impact longevity. 

Publication
Jang JY, Beam CR, Karlsson IK, Pedersen NL, Gatz M. Dementia and mortality in older adults: A twin study. Alzheimer’s & Dementia. 2024; 20(3):1682–1692. https://doi.org/10.1002/alz.13553.