An Amino Acid and Carnitine Metabolite Profile for the Early Detection and Differential Diagnosis of Alzheimer's Disease
Bibliographic record
Abstract
As the most common type of dementia, Alzheimer's disease (AD) often presents challenges in terms of early identification. In particular, there is a notable lack of reliable and accessible biomarkers. To measure the levels of amino acids and carnitine metabolites in the peripheral blood of AD patients to identify cognitive impairment-associated metabolites, two cohorts were recruited in this cross-sectional study from September 2018 to October 2023. Serum amino acid and carnitine levels were measured using liquid chromatography-mass spectrometry. The test cohort (normal cognition (NC), n = 70; amnesic mild cognitive impairment (aMCI), n = 41; dementia, n = 92) was used to analyze differences in serum amino acid and carnitine levels and to create a metabolite profile. The diagnostic performance of the metabolite profile was first assessed within the test cohort through receiver operating characteristic (ROC) curve analysis and machine learning approaches. Subsequent cognitive impairment subgroup analysis further confirmed its diagnostic efficacy. Finally, the validation cohort (NC, n = 10; aMCI, n = 10; dementia; n = 10; FDPV (FTD, DLB, PDD and VaD), n = 30) was used to determine the diagnostic and differential diagnostic capabilities of the metabolite profile. In the test cohort, serum levels of a total of 36 amino acids and carnitine metabolites were dysregulated. A profile of seven key metabolites successfully identified patients with NC, aMCI, and dementia. Cognitive subgroup (based on the Montreal Cognitive Assessment) analysis revealed that the profile was suitable for screening for mild, moderate, and severe cognitive impairment. The validation cohort further demonstrated the successful application of the metabolic profile for the discrimination of NC, aMCI, and dementia, as well as for the differential diagnosis of dementia and FDPV. In conclusion, extensive alterations in amino acid and carnitine metabolism levels were found in the peripheral blood of dementia patients, and a profile of seven amino acids and carnitine could be used as potential indicators for aMCI and dementia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".