Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study

Jaime Ramos-Cejudo, Andrew D. Johnson, Alexa Beiser, Sudha Seshadri, Joel Salinas, Jeffrey S. Berger, Nathanael R. Fillmore, Nhan Do, Chunlei Zheng, Zanetta Kovbasyuk, Babak A. Ardekani, Pomara Nunzio, Omonigho M. Bubu, Ankit Parekh, Antonio Convit, Rebecca A. Betensky, Thomas M. Wisniewski, Ricardo S. Osorio

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere023918
JournalJournal of the American Heart Association
Volume11
Issue number9
DOIs
StatePublished - May 3 2022

Keywords

  • Alzheimer’s disease
  • Framingham
  • LTA
  • aggregation
  • dementia
  • platelet function
  • risk prediction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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