Topic: Amyloid, tau and blood-test diagnosis
Objective To identify factors influencing age at symptom onset and disease course in autosomal dominant Alzheimer disease (ADAD), and develop evidence-based criteria for predicting symptom onset in ADAD. Methods We have collected individual-level data on ages at symptom onset and death from 387 ADAD pedigrees, compiled from 137 peer-reviewed publications, the Dominantly Inherited Alzheimer Network (DIAN) database, and 2 large kindreds of Colombian (PSEN1 E280A) and Volga German (PSEN2 N141I) ancestry. Our combined dataset includes 3,275 individuals, of whom 1,307 were affected by ADAD with known age at symptom onset. We assessed the relative contributions of several factors in influencing age at onset, including parental age at onset, age at onset by mutation type and family, and APOE genotype and sex. We additionally performed survival analysis using data on symptom onset collected from 183 ADAD mutation carriers followed longitudinally in the DIAN Study. Results We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex. Conclusions Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ryman, D. C., Acosta-Baena, N., Aisen, P. S., Bird, T., Danek, A., Fox, N. C., et al. (2014). Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. https://doi.org/10.1212/wnl.0000000000000596
Vancouver
Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, et al. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014. doi:10.1212/wnl.0000000000000596. PMID: 24928124.
BibTeX
@article{ryman2014-24928124,
author = {Ryman, D. C. and Acosta-Baena, N. and Aisen, P. S. and Bird, T. and Danek, A. and Fox, N. C. and Goate, A. and Frommelt, P. and others},
title = {{Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis}},
journal = {Neurology},
year = {2014},
doi = {10.1212/wnl.0000000000000596},
pmid = {24928124},
url = {https://doi.org/10.1212/wnl.0000000000000596}
}
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Key findings
- Results We report summary statistics on age at onset and disease course for 174 ADAD mutations, and discover strong and highly significant (p < 10(-16), r2 > 0.38) correlations between individual age at symptom onset and predicted values based on parental age at onset and mean ages at onset by mutation type and family, which persist after controlling for APOE genotype and sex.
- Conclusions Significant proportions of the observed variance in age at symptom onset in ADAD can be explained by family history and mutation type, providing empirical support for use of these data to estimate onset in clinical research.
Why it matters
This study pooled family records from 387 families carrying inherited Alzheimer's mutations (174 different mutations). In the 1,307 affected people whose age at symptom onset was known, that age tracked closely with their parent's onset age and with the typical onset age for their mutation and family, even after accounting for APOE type and sex. The authors conclude this supports using family history and mutation type to estimate expected onset in clinical research. It applies only to this rare inherited form of Alzheimer's, does not give individuals an exact onset date, and does not test any treatment.
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Study details
- Participants3,275
- Evidence strengthLow
How this study scored 75/100
Published in a leading specialty journal, and it is a meta-analysis pooling many studies. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 72 of the 96 points we could judge it on, which is 75 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies (from PubMed type “Meta-Analysis”) |
| 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 | 1 / 5 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 3 / 4 | 3,275 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 504 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 36.0 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 17.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 55 other studies in this library |
| Still being cited | 3 / 4 | Cited 123 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24928124) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 72 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 72 of the 96 points we could judge it on is 75 out of 100. |
| Total | 75 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000000596
- PubMed: 24928124
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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