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Prevalence and risk of progression of preclinical Alzheimer's disease stages: a systematic review and meta-analysis
Parnetti L, Chipi E, Salvadori N, D'Andrea K, Eusebi P.. Alzheimer's research & therapy, 2019-01-15
Topic: Amyloid, tau and blood-test diagnosis
Background Alzheimer's disease (AD) pathology begins several years before the clinical onset. The long preclinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer's Association (NIA-AA) criteria, followed by mild cognitive impairment (MCI), a featured clinical entity defined as "due to AD", or "prodromal AD", when pathophysiological biomarkers (i.e., cerebrospinal fluid or positron emission tomography with amyloid tracer) are positive. In the clinical setting, there is a clear need to detect the earliest symptoms not yet fulfilling MCI criteria, in order to proceed to biomarker assessment for diagnostic definition, thus offering treatment with disease-modifying drugs to patients as early as possible. According to the available evidence, we thus estimated the prevalence and risk of progression at each preclinical AD stage, with special interest in Stage 3. Methods Cross-sectional and longitudinal studies published from April 2008 to May 2018 were obtained through MEDLINE-PubMed, screened, and systematically reviewed by four independent reviewers. Data from included studies were meta-analyzed using random-effects models. Heterogeneity was assessed by I 2 statistics. Results Estimated overall prevalence of preclinical AD was 22% (95% CI = 18-26%). Rate of biomarker positivity overlapped in cognitively normal individuals and people with subjective cognitive decline. The risk of progression increases across preclinical AD stages, with individuals classified as NIA-AA Stage 3 showing the highest risk (73%, 95% CI = 40-92%) compared to those in Stage 2 (38%, 95% CI = 21-59%) and Stage 1 (20%, 95% CI = 10-34%). Conclusion Available data consistently show that risk of progression increases across the preclinical AD stages, where Stage 3 shows a risk of progression comparable to MCI due to AD. Accordingly, an effort should be made to also operationalize the diagnostic work-up in subjects with subtle cognitive deficits not yet fulfilling MCI criteria. The possibility to define, in the clinical routine, a patient as "pre-MCI due to AD" could offer these subjects the opportunity to use disease-modifying drugs at best.
Key findings
- Results Estimated overall prevalence of preclinical AD was 22% (95% CI = 18-26%).
- The risk of progression increases across preclinical AD stages, with individuals classified as NIA-AA Stage 3 showing the highest risk (73%, 95% CI = 40-92%) compared to those in Stage 2 (38%, 95% CI = 21-59%) and Stage 1 (20%, 95% CI = 10-34%).
Why it matters
This systematic review and meta-analysis estimated overall prevalence of preclinical Alzheimer's disease at 22%, with the risk of progression increasing across preclinical stages and reaching 73% in Stage 3. The findings concern estimating prevalence and progression risk, not treating or preventing the disease.
Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 60/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies (from PubMed type “Meta-Analysis”) |
| 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 | 2 / 5 | 2019 — within 10 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 | A review of other studies — randomisation is not credited here |
| Times cited | 5 / 7 | Cited 190 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 21.1 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 3 / 6 | Cited 3.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 93 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Paolo Eusebi: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Perugia: institution h-index 747 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30646955) |
| Free to read | 2 / 2 | Free to read |
| Total | 60 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13195-018-0459-7
- PubMed: 30646955
- Original source →
- Free full text: Alzheimer s Research & Therapy →
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. Check the citation against the original before you use it.
APA 7th
Parnetti, L., Chipi, E., Salvadori, N., D'Andrea, K., & Eusebi, P. (2019). Prevalence and risk of progression of preclinical Alzheimer's disease stages: a systematic review and meta-analysis. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-018-0459-7
Vancouver
Parnetti L, Chipi E, Salvadori N, D'Andrea K, Eusebi P. Prevalence and risk of progression of preclinical Alzheimer's disease stages: a systematic review and meta-analysis. Alzheimer's research & therapy. 2019. doi:10.1186/s13195-018-0459-7. PMID: 30646955.
BibTeX
@article{parnetti2019-30646955,
author = {Parnetti, L. and Chipi, E. and Salvadori, N. and D'Andrea, K. and Eusebi, P.},
title = {{Prevalence and risk of progression of preclinical Alzheimer's disease stages: a systematic review and meta-analysis}},
journal = {Alzheimer's research \& therapy},
year = {2019},
doi = {10.1186/s13195-018-0459-7},
pmid = {30646955},
url = {https://doi.org/10.1186/s13195-018-0459-7}
}
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