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Multisystem failure, tipping points, and risk of Alzheimer's disease
Simona Merlini, Edward J Bedrick, Roberta Diaz Brinton, Francesca Vitali. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-05
Topic: Genetics and APOE
Hypertension or diabetes before age 62 exerted greater AD risk than APOEε4 alone. Obesity before age 62 increased AD risk by 54%, with the risk nearly tripling between ages 62-72. Hyperlipidemia and depression were associated with age-independent risk increases of 33% and 69%, respectively. After age 72, APOEε4 became the dominant RF. Duration of AD-risk-factors can have a greater impact than APOEε4. Identification of critical age-related tipping points highlights temporal dynamics of AD progression and role of multisystem failure in AD progression. HIGHLIGHTS: AD risk factors impact AD onset, especially diagnosed between ages 62 and 72. Later diagnoses of hypertension, diabetes, and obesity delayed AD onset. Hyperlipidemia and depression increased AD risk by 33% and 69%, age-independent. APOEε4 carriers regardless of sex exhibited a higher risk increasing with age. Trajectories differed between APOEε4 carriers and non-carriers across sex.
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APA 7th
Merlini, S., Bedrick, E. J., Brinton, R. D., & Vitali, F. (2025). Multisystem failure, tipping points, and risk of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70249
Vancouver
Merlini S, Bedrick EJ, Brinton RD, Vitali F. Multisystem failure, tipping points, and risk of Alzheimer's disease. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70249. PMID: 40346724.
BibTeX
@article{merlini2025-40346724,
author = {Merlini, Simona and Bedrick, Edward J and Brinton, Roberta Diaz and Vitali, Francesca},
title = {{Multisystem failure, tipping points, and risk of Alzheimer's disease}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70249},
pmid = {40346724},
url = {https://doi.org/10.1002/alz.70249}
}
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Key findings
- Hypertension or diabetes before age 62 exerted greater AD risk than APOEε4 alone.
- Obesity before age 62 increased AD risk by 54%, with the risk nearly tripling between ages 62-72.
- Hyperlipidemia and depression were associated with age-independent risk increases of 33% and 69%, respectively.
- After age 72, APOEε4 became the dominant RF.
- Duration of AD-risk-factors can have a greater impact than APOEε4.
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Study details
- Evidence strengthLow
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40346724) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
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