Associations of Circulating Platelet Endothelial Cell Adhesion Molecule‐1 Levels with Progression of Cerebral Small Vessel Disease, Cognitive Performance and Incident Dementia
Bibliographic record
Abstract
Abstract Background The association between platelet endothelial cell adhesion molecule‐1 (PECAM‐1) with cerebral small vessel disease (CSVD) and cognition in non‐demented subjects remains un‐investigated. Method A longitudinal, prospective cohort of subjects recruited from memory clinics was followed‐up for 5 years. Non‐demented subjects were included and classified as no cognitive impairment (NCI) or mild cognitive impairment (MCI). Annual neuropsychological assessments and 2‐yearly magnetic resonance imaging (MRI) scans were performed. The associations of baseline circulating plasma PECAM‐1 levels with neuroimaging markers of CSVD, cognitive decline (Montreal Cognitive Assessment [MoCA] scores and executive function Z‐scores), and conversion to dementia were evaluated. Result Of 213 subjects (age 70.2±7.7 years, 51.2% male, 122 (57.3%) NCI, and 91 (42.7%) MCI), median PECAM‐1 levels were 0.790 [IQR 0.645‐0.955] ng/ml). Compared with the highest tertile, subjects within the lowest PECAM‐1 tertile had higher age‐related white matter changes scores (first tertile: β 1.50, 95% C.I. 0.23‐2.77, p=0.02) and cerebral microbleeds (first tertile: Adjusted risk ratio [ARR] 2.59, 95% C.I. 1.81‐3.72, p<0.0001). PECAM‐1 levels were not associated with baseline MOCA and executive function. Of the 204 participants with follow‐up data (median 60.0 [IQR 60.0‐60.0] months), 24 (11.8) had incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM‐1 were independently associated with higher risk of incident dementia (first tertile: Adjusted Hazard Ratio [AHR] 4.18, 95% C.I. 1.26‐13.93, p=0.020; second tertile: AHR 3.45, 95% C.I. 1.07‐11.14, p=0.038, Figure 1). The lowest PECAM‐1 tertile was associated with greater 4‐year progression of cerebral microbleeds (Incident Relative Risk [IRR] 2.44, 95% C.I. 1.20‐4.98, p=0.014), and decline in executive function (β ‐0.43, 95% C.I. ‐0.73, ‐0.14, p=0.004), and MoCA (β ‐1.32, 95% C.I. ‐2.30, ‐0.35, p=0.008) scores. Conclusion In non‐demented subjects, lower circulating PECAM‐1 levels are associated with greater CSVD progression, cognitive decline, and incident dementia. PECAM‐1 may be a potential therapeutic target for CSVD and cognitive decline.
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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) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".