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Frequency of Biologically Defined Alzheimer Disease in Relation to Age, Sex, APOE ε4, and Cognitive Impairment
Therriault J, Pascoal TA, Benedet AL, Tissot C, Savard M, Chamoun M, Lussier F, Kang MS et al.. Neurology, 2020-12-21
Topic: Amyloid, tau and blood-test diagnosis
Objective To assess the frequency of biologically defined Alzheimer disease (AD) in relation to age, sex, APOE ε4, and clinical diagnosis in a prospective cohort study evaluated with amyloid-PET and tau-PET. Methods We assessed cognitively unimpaired (CU) elderly (n = 166), patients with amnestic mild cognitive impairment (n = 77), and patients with probable AD dementia (n = 62) who underwent evaluation by dementia specialists and neuropsychologists in addition to amyloid-PET with [ 18 F]AZD4694 and tau-PET with [ 18 F]MK6240. Individuals were grouped according to their AD biomarker profile. Positive predictive value for biologically defined AD was assessed in relation to clinical diagnosis. Frequency of AD biomarker profiles was assessed using logistic regressions with odds ratios (ORs) and 95% confidence intervals (CIs). Results The clinical diagnosis of probable AD dementia demonstrated good agreement with biologically defined AD (positive predictive value 85.2%). A total of 7.88% of CU were positive for both amyloid-PET and tau-PET. Frequency of biologically defined AD increased with age (OR 1.14; p APOE ε4 allele carriers (single ε4: OR 3.82; p p Conclusion Whereas we observed strong, but not complete, agreement between clinically defined probable AD dementia and biomarker positivity for both β-amyloid and tau, we also observed that biologically defined AD was not rare in CU elderly. Abnormal tau-PET was almost exclusively observed in individuals with abnormal amyloid-PET. Our results highlight that even in tertiary care memory clinics, detailed evaluation by dementia specialists systematically underestimates the frequency of biologically defined AD and related entities. Classification of evidence This study provides Class I evidence that biologically defined AD (abnormal amyloid PET and tau PET) was observed in 85.2% of people with clinically defined AD and 7.88% of CU elderly.
Key findings
- Results The clinical diagnosis of probable AD dementia demonstrated good agreement with biologically defined AD (positive predictive value 85.2%).
- Frequency of biologically defined AD increased with age (OR 1.14; p < 0.0001) and frequency of APOE ε4 allele carriers (single ε4: OR 3.82; p < 0.0001; double ε4: OR 17.55, p < 0.0001).
- Our results highlight that even in tertiary care memory clinics, detailed evaluation by dementia specialists systematically underestimates the frequency of biologically defined AD and related entities.
Why it matters
In this cohort, clinical diagnosis of probable Alzheimer dementia agreed well with biologically defined Alzheimer disease, and biologically defined disease was more frequent with older age and APOE ε4. This is about how often biomarker-defined disease occurs and does not test any treatment, cure, or prevention.
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Study details
- Study designcohort study
- Participants166
- Effect size85.2%; 7.88%; OR 1.14
- Evidence strengthModerate
How this study scored 68/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| 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 | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 166 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 | 4 / 7 | Cited 89 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.7 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 6.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 15 other studies in this library |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Pedro Rosa‐Neto: h-index 89 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Montreal Neurological Institute and Hospital: institution h-index 593 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33443136) |
| Free to read | 2 / 2 | Free to read |
| Total | 68 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000011416
- PubMed: 33443136
- 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).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Therriault, J., Pascoal, T. A., Benedet, A. L., Tissot, C., Savard, M., Chamoun, M., et al. (2021). Frequency of Biologically Defined Alzheimer Disease in Relation to Age, Sex, APOE ε4, and Cognitive Impairment. Neurology. https://doi.org/10.1212/wnl.0000000000011416
Vancouver
Therriault J, Pascoal TA, Benedet AL, Tissot C, Savard M, Chamoun M, et al. Frequency of Biologically Defined Alzheimer Disease in Relation to Age, Sex, APOE ε4, and Cognitive Impairment. Neurology. 2021. doi:10.1212/wnl.0000000000011416. PMID: 33443136.
BibTeX
@article{therriault2021-33443136,
author = {Therriault, J. and Pascoal, T. A. and Benedet, A. L. and Tissot, C. and Savard, M. and Chamoun, M. and Lussier, F. and Kang, M. S. and others},
title = {{Frequency of Biologically Defined Alzheimer Disease in Relation to Age, Sex, APOE ε4, and Cognitive Impairment}},
journal = {Neurology},
year = {2021},
doi = {10.1212/wnl.0000000000011416},
pmid = {33443136},
url = {https://doi.org/10.1212/wnl.0000000000011416}
}
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