Journal
JOURNAL OF THE AMERICAN HEART ASSOCIATION
Volume 11, Issue 9, Pages -Publisher
WILEY
DOI: 10.1161/JAHA.121.023918
Keywords
aggregation; Alzheimer's disease; dementia; Framingham; LTA; platelet function; risk prediction
Categories
Funding
- intergovernmental Personnel Act (IPA)
- Veterans Affairs (VA) Cooperative Studies Program
- National Heart, Lung, and Blood Institute (NHLBI) intramural funds
- NIH/National Institute on Aging (NIA) [R01AG054076]
- NIH [UH2 NS100605, RF1AG063507, 75N92019D00031, AG054076, K23AG068534, R25HL105444, P30AG059303, P30AG066512, L30-AG064670, AASMF BS-231-20, K25HL151912]
- NIH/NHLBI [2018-AARG-591645, RF1AG059421-01]
- Alzheimer's Association [75N92019D00031]
- NIH/NIA [R01AG059725, R01AG062531-01A1]
- NIH AARG-D 2020
- VA Cooperative Studies Program
- American Heart Association
- Itamar Medical Ltd
- NIH (a) [5R01NS094610-05, 1R25AG067931-01, 5P30DK040561-24, P30AG066512-01, 2P01AG036694-11, R01DA054990-01]
- NSF [2034022]
- Boston University [75N92019D00031]
- NIH Dementia RO1 grant [AG054076]
- [R01NS017950]
- [K23AG057760]
- [P30 AG066512]
- [P01 AG060882]
- [R01AG056531]
- [R01AG056031]
- Direct For Biological Sciences
- Division Of Environmental Biology [2034022] Funding Source: National Science Foundation
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Platelet function in middle age is independently associated with future risk of Alzheimer's disease (AD). Individuals with a higher platelet response have a higher risk of dementia during a 20-year follow-up, highlighting the importance of platelet function in AD risk.
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 mu mol/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 mu mol/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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