Evaluating the relationship between vascular endothelial growth factor (VEGF) and cognitive improvements following exercised‐primed transcranial direct current stimulation (tDCS) in mild cognitive impairment (MCI) and Alzheimer’s disease (AD)
Bibliographic record
Abstract
Abstract Background VEGF has been associated with memory decline in neurodegenerative diseases. As an angiogenesis biomarker, VEGF should be analyzed to better understand the variable treatment response from tDCS, a non‐invasive brain stimulation, and the priming effect of exercise on tDCS for memory improvements in MCI and AD. Using blinded data from an ongoing clinical trial (EXPRESS), we aimed to evaluate the ability of serum VEGF to predict improvements for recall memory in MCI and mild AD patients. Method Participants were enrolled in a five‐week, randomized, blinded tDCS clinical trial to receive either exercise and sham tDCS, exercise and tDCS, or exercise‐education only and tDCS intervention. Exercise groups included a three‐week ramp‐up period. Participants were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) criteria for major or mild neurocognitive disorder due to AD or mixed AD/vascular disease (etiology). VEGF serum concentrations were measured from blood samples at screening. Recall memory was assessed using the Word Recall Task from the Alzheimer's Disease Assessment Scale‐Cog (ADAS‐Cog) at screening, baseline and endpoint (2 weeks from baseline). Analysis of variance (ANOVA) evaluated recall memory and VEGF concentrations at screening between the two etiology groups. Multiple linear regression analysis determined the association between VEGF concentrations (pg/mL) and recall memory score improvements over treatment period (Δrecall). Result In 17 participants (58.8% male, 70.6% MCI, mean(±SD) age 72.8±7.2, years of education 17.1±2.0, VEGF 332.4±157.5, Δrecall 0.5±0.9), six participants (35.3%) were diagnosed as AD etiology only and eleven participants (64.7%) were mixed vascular/AD etiology with no differences in recall memory [F(1,15)=0.019,p=0.893] or VEGF concentrations [F(1,15)=1.488,p=0.241] between these two groups at screening. The regression analysis found that VEGF and etiology predicted Δrecall [F(2,14)=7.103,p=0.007,R2=0.504]. Controlling for etiology, VEGF concentrations were associated with Δrecall [B(SE)=‐0.003(0.001),p=0.039]; Δrecall decreased 0.003 for each pg/mL of VEGF. Conclusion In this pilot sample, lower serum VEGF concentrations at screening predicted greater recall memory improvements when controlling for etiology. After un‐blinding, longitudinal analysis and a larger sample size will allow further examination of VEGF’s predictive and monitoring capacity as a biomarker for recall memory and other cognitive responses to exercise‐primed tDCS.
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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 | 0.001 |
| 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) | 0.001 | 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".