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Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials
Brenowitz WD, Yaffe K.. Nature reviews. Neurology, 2022-10-31
Topic: Amyloid, tau and blood-test diagnosis
Recent high-profile failures of Alzheimer disease treatments at the clinical trial stage have led to renewed efforts to identify and test novel interventions for Alzheimer disease and related dementias (ADRD). In this Perspective, we highlight the importance of including well-designed observational studies as part of these efforts. Observational research is an important cornerstone for gathering evidence on risk factors and causes of ADRD; this evidence can then be combined with data from preclinical studies and randomized controlled trials to inform the development of effective interventions. Observational study designs can be particularly beneficial for hypothesis generation, posing questions that are unethical or impractical for a trial setting, studying life-course associations, research in populations typically not included in trials, and public health surveillance. Here, we discuss each of these situations in the specific context of ADRD research. We also highlight novel approaches to enhance causal inference and provide a timely discussion on how observational epidemiological studies help provide a bridge between preclinical studies and successful interventions for ADRD.
Key findings
- In this Perspective, we highlight the importance of including well-designed observational studies as part of these efforts.
- Observational research is an important cornerstone for gathering evidence on risk factors and causes of ADRD; this evidence can then be combined with data from preclinical studies and randomized controlled trials to inform the development of effective interventions.
- Observational study designs can be particularly beneficial for hypothesis generation, posing questions that are unethical or impractical for a trial setting, studying life-course associations, research in populations typically not included in trials, and public health surveillance.
- Here, we discuss each of these situations in the specific context of ADRD research.
- We also highlight novel approaches to enhance causal inference and provide a timely discussion on how observational epidemiological studies help provide a bridge between preclinical studies and successful interventions for ADRD.
Why it matters
This perspective argues that well-designed observational studies are an important complement to preclinical studies and randomized controlled trials in Alzheimer's disease research. It does not report new treatment results, but discusses how observational research can help generate hypotheses and bridge the gap to successful interventions.
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Study details
- Evidence strengthHigh
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Neurology) |
| Journal's citation record | 3 / 4 | Nature Reviews Neurology: journal h-index 269 (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 | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 14 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 1 / 6 | Cited 0.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Kristine S. Yaffe: h-index 155 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36316487) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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. Check the citation against the original before you use it.
APA 7th
Brenowitz, W. D., & Yaffe, K. (2022). Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials. Nature reviews. Neurology. https://doi.org/10.1038/s41582-022-00733-7
Vancouver
Brenowitz WD, Yaffe K. Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials. Nature reviews. Neurology. 2022. doi:10.1038/s41582-022-00733-7. PMID: 36316487.
BibTeX
@article{brenowitz2022-36316487,
author = {Brenowitz, W. D. and Yaffe, K.},
title = {{Observational studies in Alzheimer disease: bridging preclinical studies and clinical trials}},
journal = {Nature reviews. Neurology},
year = {2022},
doi = {10.1038/s41582-022-00733-7},
pmid = {36316487},
url = {https://doi.org/10.1038/s41582-022-00733-7}
}
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