@article{a1ad492f0fb94be69aac66c41850f7a4,
title = "Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study",
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.",
keywords = "aggregation, Alzheimer{\textquoteright}s disease, dementia, Framingham, LTA, platelet function, risk prediction",
author = "Jaime Ramos-Cejudo and Johnson, {Andrew D.} and Alexa Beiser and Sudha Seshadri and Joel Salinas and Berger, {Jeffrey S.} and Fillmore, {Nathanael R.} and Nhan Do and Chunlei Zheng and Zanetta Kovbasyuk and Ardekani, {Babak A.} and Pomara Nunzio and Bubu, {Omonigho M.} and Ankit Parekh and Antonio Convit and Betensky, {Rebecca A.} and Wisniewski, {Thomas M.} and Osorio, {Ricardo S.}",
note = "Funding Information: Aging (NIA) R01AG054076, NIH UH2 NS100605, NIH RF1AG063507, NIH/ NHLBI 2018-AARG-591645, Alzheimer{\textquoteright}s Association 75N92019D00031, NIH/NHLBI RF1AG059421-01, NIH/NIA R01AG059725, NIH/NIA R01AG062531-01A1, and NIH AARG-D 2020; S.S. is supported by NIH 75N92019D00031 and AG054076; J.S. is supported by K23AG057760; J.S.B. is supported by NCT02106429, NCT01897103; N.R.F. is supported by VA Cooperative Studies Program, NIH, and American Heart Association; O.M.B. is supported by NIH K23AG068534, R25HL105444, P30AG059303, P30AG066512, L30-AG064670, and AASMF BS-231-20; A.P. is supported by NIH K25HL151912 and Itamar Medical Ltd; R.A.B. is supported by NIH 5R01NS094610-05, 1R25AG067931-01, 5P30DK040561-24, P30AG066512-01, 2P01AG036694-11, R01DA054990-01, and NSF 2034022; T.M.W. is supported by P30 AG066512, and P01 AG060882; R.S.O. is supported by R01AG056531, R01AG056031, and P30 AG066512. The FHS is funded by Boston University contract 75N92019D00031 and the NIH Dementia RO1 grant AG054076. Funding Information: J.R.C. is supported by an intergovernmental Personnel Act (IPA) agreement with the Veterans Affairs (VA) Cooperative Studies Program. A.D.J. is supported by National Heart, Lung, and Blood Institute (NHLBI) intramural funds. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI; the National Institutes of Health (NIH); or the US Department of Health and Human Services; A.B. is supported by R01NS017950, NIH/National Institute on Funding Information: We thank the participants of the FHS.Sources of Funding J.R.C. is supported by an intergovernmental Personnel Act (IPA) agreement with the Veterans Affairs (VA) Cooperative Studies Program. A.D.J. is supported by National Heart, Lung, and Blood Institute (NHLBI) intramural funds. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI; the National Institutes of Health (NIH); or the US Department of Health and Human Services; A.B. is supported by R01NS017950, NIH/National Institute onAging (NIA) R01AG054076, NIH UH2 NS100605, NIH RF1AG063507, NIH/ NHLBI 2018-AARG-591645, Alzheimer{\textquoteright}s Association 75N92019D00031, NIH/NHLBI RF1AG059421-01, NIH/NIA R01AG059725, NIH/NIA R01AG062531-01A1, and NIH AARG-D 2020; S.S. is supported by NIH 75N92019D00031 and AG054076; J.S. is supported by K23AG057760; J.S.B. is supported by NCT02106429, NCT01897103; N.R.F. is supported by VA Cooperative Studies Program, NIH, and American Heart Association; O.M.B. is supported by NIH K23AG068534, R25HL105444, P30AG059303, P30AG066512, L30-AG064670, and AASMF BS-231-20; A.P. is supported by NIH K25HL151912 and Itamar Medical Ltd; R.A.B. is supported by NIH 5R01NS094610-05, 1R25AG067931-01, 5P30DK040561-24, P30AG066512-01, 2P01AG036694-11, R01DA054990-01, and NSF 2034022; T.M.W. is supported by P30 AG066512, and P01 AG060882; R.S.O. is supported by R01AG056531, R01AG056031, and P30 AG066512. The FHS is funded by Boston University contract 75N92019D00031 and the NIH Dementia RO1 grant AG054076. Publisher Copyright: {\textcopyright} 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.",
year = "2022",
month = may,
day = "3",
doi = "10.1161/JAHA.121.023918",
language = "English (US)",
volume = "11",
journal = "Journal of the American Heart Association",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "9",
}