Impaired glymphatic clearance measured from DTI‐ALPS in neurodegenerative and cerebrovascular disease
Bibliographic record
Abstract
BACKGROUND: Impaired glymphatic clearance has been associated with neurodegenerative diseases causing dementia. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index has been proposed as a non-invasive measure to assess glymphatic function. This preliminary analysis aimed to examine correlations with DTI-ALPS and changes in brain atrophy in the Ontario Neurodegenerative Disease Research Initiative (ONDRI) cohort. METHODS: The ONDRI study participants (n = 125; age = 54.9+/-7.5 years; 76% male) in this analysis included clinically diagnosed patients with Alzheimer's disease/mild cognitive impairment (ADMCI; n = 44), cerebrovascular disease (CVD; n = 68), and frontotemporal dementia (FTD; n = 13). DTI images were preprocessed with the FSL Diffusion Toolbox, and the ALPS indices (mean, left and right) were calculated using diffusion data from the projection and association fiber regions. Lower DTI-ALPS indices having been linked to reduced glymphatic function. Fractional perivascular space (PVS) and white matter hyperintensity (WMH) volumes were extracted from MRI. Whole brain atrophy was assessed using the brain parenchymal fraction (BPF), including one-year change in BPF. ANOVA, Pearson correlation, and linear regression models were used to analyze the data. Demographics (age, sex, education, handedness) and vascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking, waist-to-hip ratio) were also collected. RESULTS: Mean DTI-ALPS was highest in ADMCI and lowest in CVD (ADMCI=1.49; FTD=1.44, CVD=1.37; contrasts: ADMCI vs. CVD, p <0.05, others n.s.). At baseline, partial correlations controlling for demographics, clinical diagnosis, and vascular risk factors showed mean DTI-ALPS was significantly correlated with baseline BPF (r=.204, p = 0.028) and baseline WMH (r=-0.287, p = 0.002), but not with baseline PVS. Baseline right DTI-ALPS was significantly associated with delta BPF (β=0.209, p = 0.019), independent of demographics, clinical diagnosis, vascular risk factors, and baseline WMH. CONCLUSION: As a possible measure of glymphatic clearance functioning along the perivascular space, our preliminary results showed that baseline DTI-ALPS measures were associated with one-year change in whole brain atrophy in patients with neurodegenerative and cerebrovascular disease. This finding was independent of demographics, clinical diagnosis, and vascular risk factors. Future planned analysis of the ONDRI cohort will examine DTI-ALPS associations with cognitive decline in the presence of white matter changes and elevated plasma glial fibrillary acidic protein as an inflammation marker.
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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 | 0.001 | 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".