DOI: 10.1161/jaha.124.035133 ISSN: 2047-9980

Associations of Circulating Platelet Endothelial Cell Adhesion Molecule‐1 Levels With Progression of Cerebral Small‐Vessel Disease, Cognitive Decline, and Incident Dementia

Ming Ann Sim, Eugene S. J. Tan, Siew Pang Chan, Yuan Cai, Yuek Ling Chai, Joyce Ruifen Chong, Eddie Jun Yi Chong, Caroline Robert, Narayanaswamy Venketasubramanian, Boon Yeow Tan, Mitchell K. P. Lai, Saima Hilal, Christopher L. H. Chen
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Background

The association between platelet endothelial cell adhesion molecule‐1 (PECAM‐1) with cerebral small‐vessel disease and cognition in dementia‐free subjects remains uninvestigated.

Methods and Results

A prospective cohort of dementia‐free subjects was recruited from memory clinics and followed up for 5 years. Annual neurocognitive assessments and twice‐yearly brain magnetic resonance imaging scans were performed. Associations of baseline plasma PECAM‐1 levels with cerebral small‐vessel disease, cognitive decline (Montreal Cognitive Assessment scores and executive function Z scores), and incident dementia were evaluated. Of 213 subjects (aged 70.2±7.7 years, 51.2% men), median PECAM‐1 levels were 0.790 (interquartile range, 0.645–0.955 ng/mL). Compared with the highest tertile, subjects within the lowest PECAM‐1 tertile had greater cross‐sectional white matter hyperintensity volume (β=4.84 [95% CI, 0.67–9.01]; P =0.023), age‐related white matter change scores (β=1.39 [95% CI, 0.12–2.67]; P =0.033), and cerebral microbleeds (Adjusted risk ratio, 2.59 [95% CI, 1.19–5.62]; P =0.016). Of the 204 participants with follow‐up data (median, 60.0 [interquartile range, 60.0–60.0] months), 24 (11.8%) developed incident dementia. Compared with the highest tertile, subjects within the lower tertiles of PECAM‐1 had a higher risk of incident dementia (first tertile: adjusted hazard ratio [AHR], 4.52 [95% CI, 1.35–15.13]; P =0.024; second tertile: AHR, 3.28 [95% CI, 1.02–10.60]; P =0.047). The lowest PECAM‐1 tertile was associated with greater progression of white matter hyperintensity volume (β=4.15 [95% CI, 0.06–8.24]; P =0.047), cerebral microbleeds (incident relative risk [IRR], 2.21 [95% CI, 1.05–4.65]; P =0.036), and decline in executive function (β=−0.45 [95% CI, −0.76 to −0.14]; P =0.004), and Montreal Cognitive Assessment (β=−1.32 [95% CI, −2.30 to −0.35]; P =0.008) scores.

Conclusions

In dementia‐free subjects, lower circulating PECAM‐1 levels are associated with greater cerebral small‐vessel disease progression and cognitive decline, thus warranting future study as a potential therapeutic target.

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