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Plasma d-glutamate levels for detecting mild cognitive impairment and Alzheimer's disease: Machine learning approaches
Chang CH, Lin CH, Liu CY, Huang CS, Chen SJ, Lin WC, Yang HT, Lane HY.. Journal of psychopharmacology (Oxford, England), 2021-02-15
Topic: Amyloid, tau and blood-test diagnosis
Background d-glutamate, which is involved in N-methyl-d-aspartate receptor modulation, may be associated with cognitive ageing. Aims This study aimed to use peripheral plasma d-glutamate levels to differentiate patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from healthy individuals and to evaluate its prediction ability using machine learning. Methods Overall, 31 healthy controls, 21 patients with MCI and 133 patients with AD were recruited. Serum d-glutamate levels were measured using high-performance liquid chromatography (HPLC). Cognitive deficit severity was assessed using the Clinical Dementia Rating scale and the Mini-Mental Status Examination (MMSE). We employed four machine learning algorithms (support vector machine, logistic regression, random forest and naïve Bayes) to build an optimal predictive model to distinguish patients with MCI or AD from healthy controls. Results The MCI and AD groups had lower plasma d-glutamate levels (1097.79 ± 283.99 and 785.10 ± 720.06 ng/mL, respectively) compared to healthy controls (1620.08 ± 548.80 ng/mL). The naïve Bayes model and random forest model appeared to be the best models for determining MCI and AD susceptibility, respectively (area under the receiver operating characteristic curve: 0.8207 and 0.7900; sensitivity: 0.8438 and 0.6997; and specificity: 0.8158 and 0.9188, respectively). The total MMSE score was positively correlated with d-glutamate levels ( r = 0.368, p B = 0.003, 95% confidence interval 0.002-0.005, p Conclusions Peripheral plasma d-glutamate levels were associated with cognitive impairment and may therefore be a suitable peripheral biomarker for detecting MCI and AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing MCI and AD in outpatient clinics.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Chang, C. H., Lin, C. H., Liu, C. Y., Huang, C. S., Chen, S. J., Lin, W. C., et al. (2021). Plasma d-glutamate levels for detecting mild cognitive impairment and Alzheimer's disease: Machine learning approaches. Journal of psychopharmacology (Oxford, England). https://doi.org/10.1177/0269881120972331
Vancouver
Chang CH, Lin CH, Liu CY, Huang CS, Chen SJ, Lin WC, et al. Plasma d-glutamate levels for detecting mild cognitive impairment and Alzheimer's disease: Machine learning approaches. Journal of psychopharmacology (Oxford, England). 2021. doi:10.1177/0269881120972331. PMID: 33586518.
BibTeX
@article{chang2021-33586518,
author = {Chang, C. H. and Lin, C. H. and Liu, C. Y. and Huang, C. S. and Chen, S. J. and Lin, W. C. and Yang, H. T. and Lane, H. Y.},
title = {{Plasma d-glutamate levels for detecting mild cognitive impairment and Alzheimer's disease: Machine learning approaches}},
journal = {Journal of psychopharmacology (Oxford, England)},
year = {2021},
doi = {10.1177/0269881120972331},
pmid = {33586518},
url = {https://doi.org/10.1177/0269881120972331}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Background d-glutamate, which is involved in N-methyl-d-aspartate receptor modulation, may be associated with cognitive ageing.
- Methods Overall, 31 healthy controls, 21 patients with MCI and 133 patients with AD were recruited.
- Results The MCI and AD groups had lower plasma d-glutamate levels (1097.79 ± 283.99 and 785.10 ± 720.06 ng/mL, respectively) compared to healthy controls (1620.08 ± 548.80 ng/mL).
- The total MMSE score was positively correlated with d-glutamate levels ( r = 0.368, p < 0.001).
Why it matters
In 31 healthy controls, 21 patients with mild cognitive impairment and 133 patients with Alzheimer's disease, plasma d-glutamate levels were lower in the MCI and AD groups, and machine learning models distinguished them from controls with area under the curve of 0.8207 and 0.7900. This suggests d-glutamate may help identify these conditions, but it does not test any treatment, cure or prevention.
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Study details
- Participants21
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of psychopharmacology (Oxford, England)) |
| Journal's citation record | 2 / 4 | Journal of Psychopharmacology: journal h-index 168 (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 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 21 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 52 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.4 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 5.9× 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 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Hsien‐Yuan Lane: h-index 58 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Chang Gung University: institution h-index 411 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33586518) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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