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. 2019 Sep;25(9):1364-1369.
doi: 10.1038/s41591-019-0547-7. Epub 2019 Aug 26.

Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population

Silvan Licher  1 , Shahzad Ahmad  2 , Hata Karamujić-Čomić  2 , Trudy Voortman  2 , Maarten J G Leening  2   3   4 , M Arfan Ikram  2 , M Kamran Ikram  5   6
Affiliations

Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population

Silvan Licher et al. Nat Med. 2019 Sep.

Abstract

The exact etiology of dementia is still unclear, but both genetic and lifestyle factors are thought to be key drivers of this complex disease. The recognition of familial patterns of dementia has led to the discovery of genetic factors that have a role in the pathogenesis of dementia, including the apolipoprotein E (APOE) genotype and a large and still-growing number of genetic variants1,2. Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia3. Prevention trials of measures to halt or delay cognitive decline are increasingly recruiting older individuals who are genetically predisposed to dementia. However, it remains unclear whether targeted health and lifestyle interventions can attenuate or even offset increased genetic risk. Here, we leverage long-term data on both genetic and modifiable risk factors from 6,352 individuals aged 55 years and older in the population-based Rotterdam Study. In this study, we demonstrate that, in individuals at low and intermediate genetic risk, favorable modifiable-risk profiles are related to a lower risk of dementia compared to unfavorable profiles. In contrast, these protective associations were not found in those at high genetic risk.

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Conflict of interest statement

Competing Interests Statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Cumulative incidence of dementia during follow-up.
a, according to genetic risk based on APOE genotyping, and b, according to modifiable risk factor profiles. For a and b, shaded areas represent 95% confidence intervals.
See this image and copyright information in PMC

Comment in

References

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