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Risk factors for predicting progression from mild cognitive impairment to Alzheimer's disease: a systematic review and meta-analysis of cohort studies
Li JQ, Tan L, Wang HF, Tan MS, Tan L, Xu W, Zhao QF, Wang J et al.. Journal of neurology, neurosurgery, and psychiatry, 2015-05-22
Topic: Amyloid, tau and blood-test diagnosis
Objective We sought to identify the risk factors for predicting the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Methods We searched 6 electronic databases for cohort studies published from January 1966 to March 2015. Eligible studies were required to be relevant to the subject and provide sufficient data for our needs. Results 60 cohort studies with 14,821 participants from 16 countries were included in the meta-analysis. The strongest positive associations between risk factors and the progression from MCI to AD were found for abnormal cerebrospinal fluid (CSF), phosphorylated τ (p-τ) (relative risk (RR)=2.43, 95% CI=1.70 to 3.48), abnormal CSF τ/Aβ1-42 (RR=3.77, 95% CI=2.34 to 6.09), hippocampal atrophy (RR=2.59, 95% CI=1.95 to 3.44), medial temporal lobe atrophy (RR=2.11, 95% CI=1.70 to 2.63) and entorhinal atrophy (RR=2.03, 95% CI=1.57 to 2.62). Further positive associations were found for the presence of apolipoprotein E (APOE)ε4ε4 and at least 1 APOEε4 allele, CSF total-τ (t-τ), white matter hyperintensity volume, depression, diabetes, hypertension, older age, female gender, lower mini-mental state examination (MMSE) score and higher AD assessment scale cognitive subscale (ADAS-cog) score. Negative associations were found for high body mass index (RR=0.85, 95% CI=0.76 to 0.96) and higher auditory verbal learning test delay score (RR=0.86, 95% CI=0.77 to 0.96). Conclusions Patients with MCI with APOEε4, abnormal CSF τ level, hippocampal and medial temporal lobe atrophy, entorhinal atrophy, depression, diabetes, hypertension, older age, female gender, lower MMSE score and higher ADAS-cog score, had a high risk for the progression to AD.
Key findings
- Results 60 cohort studies with 14,821 participants from 16 countries were included in the meta-analysis.
Why it matters
This review of 60 studies found that several factors, including abnormal cerebrospinal fluid proteins, brain shrinkage in certain regions, and the APOEε4 gene, were linked to a higher risk of progressing from mild cognitive impairment to Alzheimer's disease. These markers may help predict who will develop the disease, but the review does not show that any treatment targeting them can prevent it.
Study details
- Study designmeta-analysis
- Participants14,821
- Effect sizeRR=3.77; RR=2.59; RR=2.11
- Evidence strengthHigh
How this study scored 75/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology, neurosurgery, and psychiatry) |
| Journal's citation record | 3 / 4 | Journal of Neurology Neurosurgery & Psychiatry: journal h-index 336 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| 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 | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 4 / 4 | 14,821 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 361 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 30.1 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 2 / 6 | Cited 2.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 3 / 4 | Cited 107 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jin‐Tai Yu: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26001840) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 75 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1136/jnnp-2014-310095
- PubMed: 26001840
- Original source →
- Free full text: Journal of Neurology Neurosurgery & Psychiatry →
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. 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
Li, J. Q., Tan, L., Wang, H. F., Tan, M. S., Xu, W., Zhao, Q. F., et al. (2016). Risk factors for predicting progression from mild cognitive impairment to Alzheimer's disease: a systematic review and meta-analysis of cohort studies. Journal of neurology, neurosurgery, and psychiatry. https://doi.org/10.1136/jnnp-2014-310095
Vancouver
Li JQ, Tan L, Wang HF, Tan MS, Xu W, Zhao QF, et al. Risk factors for predicting progression from mild cognitive impairment to Alzheimer's disease: a systematic review and meta-analysis of cohort studies. Journal of neurology, neurosurgery, and psychiatry. 2016. doi:10.1136/jnnp-2014-310095. PMID: 26001840.
BibTeX
@article{li2016-26001840,
author = {Li, J. Q. and Tan, L. and Wang, H. F. and Tan, M. S. and Xu, W. and Zhao, Q. F. and Wang, J. and others},
title = {{Risk factors for predicting progression from mild cognitive impairment to Alzheimer's disease: a systematic review and meta-analysis of cohort studies}},
journal = {Journal of neurology, neurosurgery, and psychiatry},
year = {2016},
doi = {10.1136/jnnp-2014-310095},
pmid = {26001840},
url = {https://doi.org/10.1136/jnnp-2014-310095}
}
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