Altered central and peripheral glutathione in Alzheimer disease and mild cognitive impairment: A meta‐analysis
Bibliographic record
Abstract
Abstract Background Increasing evidence implicates oxidative stress (OS) in Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS‐mediated neurodegeneration, though post‐mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of brain and peripheral GSH may shed light on GSH changes, with implications for its role as a biomarker and therapeutic target. Aim: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta‐analysis. Method Studies published before June 2020 containing measurements of in vivo brain or peripheral GSH in MCI or AD with a HC group were identified using Medline, PsychInfo, and Embase. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher‐Garwood Point Resolved Spectroscopy (MEGA‐PRESS versus non) in AD and MCI, and peripheral GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias respectively. Results For brain GSH, 4 AD (AD=175, HC=272) and 4 MCI (MCI=254, HC=260) studies were included. For peripheral GSH, 26 AD (AD D =981, HC l =993) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH did not differ in AD or MC compared to HC; however, the subgroup of studies using MEGA‐PRESS reported lower brain GSH in AD (SMD [95%CI] = ‐1.47 [‐1.91, ‐1.02], p=0.02) and MCI (‐1.08 [‐1.53,‐0.64], p=0.01). Peripheral GSH was lower in AD (‐0.94 [‐1.37, ‐0.51], p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (‐0.66 [‐1.11, ‐0.21], p=0.02). Significant heterogeneity was observed in all analyses and supported the use of random effect models. Egger’s test indicated risk of publication bias in MCI brain GSH literature. Conclusion In vivo measures of GSH in AD and MCI had significant heterogeneity. Peripheral analyses suggested intracellular GSH decreases may be prominent in early disease stages with both intra‐ and extracellular decreases in later stages. Brain GSH may be decreased in AD and MCI but heterogeneity and potential bias indicate the need for measurement standardization and replication.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".