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Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population
Licher S, Ahmad S, Karamujić-Čomić H, Voortman T, Leening MJG, Ikram MA, Ikram MK.. Nature medicine, 2019-08-26
Topic: Risk, prevention and care in population studies
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 variants 1,2 . Beyond genetic architecture, several modifiable risk factors have been implicated in the development of dementia 3 . 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.
Key findings
- 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.
Why it matters
In 6,352 adults aged 55 and older from the population-based Rotterdam Study, people at low or intermediate genetic risk who had a favorable profile of modifiable risk factors had a lower risk of dementia than those with an unfavorable profile. Among people at high genetic risk, the study did not find this association. Because this is an observational study, it shows a link rather than an effect of changing lifestyle, and failing to find a link in the high-risk group does not show that no link exists.
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Study details
- Participants6,352
- Evidence strengthLow
How this study scored 63/100
Published in a top-tier journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 6,352 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 235 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.1 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 16.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 29 other studies in this library |
| Still being cited | 3 / 4 | Cited 104 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author M. Kamran Ikram: h-index 86 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31451782) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Licher, S., Ahmad, S., Karamujić-Čomić, H., Voortman, T., Leening, M. J. G., Ikram, M. A., et al. (2019). Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population. Nature medicine. https://doi.org/10.1038/s41591-019-0547-7
Vancouver
Licher S, Ahmad S, Karamujić-Čomić H, Voortman T, Leening MJG, Ikram MA, et al. Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population. Nature medicine. 2019. doi:10.1038/s41591-019-0547-7. PMID: 31451782.
BibTeX
@article{licher2019-31451782,
author = {Licher, S. and Ahmad, S. and Karamujić-Čomić, H. and Voortman, T. and Leening, M. J. G. and Ikram, M. A. and Ikram, M. K.},
title = {{Genetic predisposition, modifiable-risk-factor profile and long-term dementia risk in the general population}},
journal = {Nature medicine},
year = {2019},
doi = {10.1038/s41591-019-0547-7},
pmid = {31451782},
url = {https://doi.org/10.1038/s41591-019-0547-7}
}
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