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Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction
Karim HT, Aizenstein HJ, Mizuno A, Ly M, Andreescu C, Wu M, Hong CH, Roh HW et al.. Molecular psychiatry, 2022-08-16
Topic: Risk, prevention and care in population studies
We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33-2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44-3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43-4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Karim, H. T., Aizenstein, H. J., Mizuno, A., Ly, M., Andreescu, C., Wu, M., et al. (2022). Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction. Molecular psychiatry. https://doi.org/10.1038/s41380-022-01728-y
Vancouver
Karim HT, Aizenstein HJ, Mizuno A, Ly M, Andreescu C, Wu M, et al. Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction. Molecular psychiatry. 2022. doi:10.1038/s41380-022-01728-y. PMID: 35974140.
BibTeX
@article{karim2022-35974140,
author = {Karim, H. T. and Aizenstein, H. J. and Mizuno, A. and Ly, M. and Andreescu, C. and Wu, M. and Hong, C. H. and Roh, H. W. and others},
title = {{Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction}},
journal = {Molecular psychiatry},
year = {2022},
doi = {10.1038/s41380-022-01728-y},
pmid = {35974140},
url = {https://doi.org/10.1038/s41380-022-01728-y}
}
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Key findings
- We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia.
- Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia].
- In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status.
Why it matters
This study found that a machine-learning brain age model could estimate brain age and that greater brain age was associated with more amyloid and worse cognitive function, and predicted future cognitive worsening. It is a prediction and monitoring tool, not a treatment, cure, or prevention.
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Study details
- Participants757
- Effect sizeor = 5.68
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | 3 / 4 | Molecular Psychiatry: journal h-index 318 (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 | 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 | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 757 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 3 / 7 | Cited 34 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.7 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 3 / 6 | Cited 4.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 29 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sang Joon Son: h-index 26 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35974140) |
| Free to read | 2 / 2 | Free to read |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41380-022-01728-y
- PubMed: 35974140
- Original source →
- Free full text: Molecular Psychiatry →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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