Key result
Higher baseline platelet aggregation response to adenosine diphosphate was independently associated with incident dementia (154 cases among 1,847 participants) over a median 20.5-year follow-up.
Why the study?
Vascular function is compromised in Alzheimer disease years before pathology is detected and abnormal platelet activation is observed, but whether platelet function in middle age independently associates with future Alzheimer disease risk was unknown.
Is higher baseline platelet function associated with an increased risk of incident dementia in middle-aged individuals?
Cohort (n=1,847)
Is higher baseline platelet function associated with an increased risk of incident dementia in middle-aged individuals?
Higher baseline platelet aggregation response in middle age is independently associated with an increased risk of incident dementia over a 20-year follow-up.
Midlife platelet hyper-responsiveness was associated with higher dementia risk; extends prior observations but remains hypothesis-generating for risk stratification.
Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine. Conclusions Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.
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A 2022 study conducted a cohort in Dementia (n=1,847). Baseline platelet aggregation response vs. Lower platelet aggregation response was evaluated on Incident dementia. Higher baseline platelet aggregation response to adenosine diphosphate was independently associated with incident dementia (154 cases among 1,847 participants) over a median 20.5-year follow-up.
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