Coated-platelet levels and progression from mild cognitive impairment to Alzheimer disease

Coated-platelets are a subset of platelets produced by dual-agonist activation with collagen and thrombin. These platelets retain full-length amyloid precursor protein on their surface, are elevated in patients with amnestic as compared to nonamnestic mild cognitive impairment (MCI), and correlate with disease progression in Alzheimer disease (AD). Prompted by these findings, we investigated the association between coated-platelet production in amnestic MCI and rate of progression to AD. Coated-platelet levels were assayed in 74 patients with amnestic MCI who were subsequently followed longitudinally for up to 36 months in an outpatient dementia clinic. Levels are reported as percent of cells converted into coated-platelets. Subjects were categorized into tertiles of coated-platelet levels. The distributions of time to progression to AD were estimated for each tertile using cumulative incidence curves and compared statistically using a log-rank test. Cox proportional hazards regression was used to adjust for potential confounders. The 24-month cumulative incidence of progression to AD was different among tertiles: 4% for the first tertile (lowest coated-platelet levels), 13% for the second tertile, and 37% for the third tertile (overall log-rank test, p = 0.02). The hazard rate of progression to AD for patients in the highest coated-platelet tertile was 5.1 times that for patients in the lowest tertile (p = 0.04), whereas the hazard rate for the middle tertile was similar to that for the lowest tertile (hazard rate ratio = 1.5, p = 0.7). Elevated coated-platelet levels in patients with amnestic MCI are associated with increased risk for progression to AD.