Blood and CSF Homocysteine Levels in Alzheimer’s Disease: A Meta-Analysis and Meta-Regression of Case–Control Studies
Bibliographic record
Abstract
Ling Zhang1 *, Xinhua Xie2 *, Yangyan Sun1 *, Futao Zhou1 1School of Basic Medicine, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Futao Zhou, School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi Province, 341000, People’s Republic of China, Email zhft522@163.comObjective: Hyperhomocysteinemia (HHcy), as an important risk factor for Alzheimer’s disease (AD), would aggravate cognitive dysfunction. This study aimed to investigate whether and to what degree the homocysteine (Hcy) levels in blood and cerebrospinal fluid (CSF) were elevated in AD patients compared with healthy controls and to explore the factors related to the elevated Hcy levels in AD patients.Methods: PubMed and Embase databases were searched to identify eligible studies, and study quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Ratio of mean (RoM) Hcy concentrations was used as a measure of fold-change between AD patients and healthy control subjects.Results: We identified 35 eligible studies, consisting a total of 2172 patients with AD and 2289 healthy controls. The pooled results showed that patients with AD had a significantly higher blood level of Hcy (RoM, 1.32; 95% CI, 1.25– 1.40; p< 0.001) than controls did, with large heterogeneity across studies (I2=81.4%, p< 0.001). Hcy level in CSF did not differ significantly between patients with AD than controls (RoM, 1.12; 95% CI, 0.90– 1.39, p=0.293; I2=69.4%, p=0.02). A random effects meta-regression analysis revealed that there was an inverse correlation between the blood levels of Hcy and folate (p=0.006). There was no link found between the blood levels of vitamin B12, or the Mini-Mental Status Examination scores reflecting the degree of cognitive impairment, and blood levels of Hcy.Conclusion: Regardless of dementia severity, there is an approximate one-third increase in blood Hcy in AD patients, which is robustly associated with a decreased level of blood folate in AD, but not with that of blood vitamin B12 nor the degree of dementia. Future investigation on the cause-and-effect link between Hcy and folate is warranted to clarify this issue.Keywords: homocysteine, Alzheimer’s disease, meta-regression
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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 | 0.013 | 0.021 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.015 | 0.050 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".