@article{6fcb58893b8143ddb4bf38e43cfc901f,
title = "Vascular risk factors are associated with longitudinal changes in cerebrospinal fluid tau markers and cognition in preclinical Alzheimer's disease",
abstract = "Introduction: Vascular factors increase the risk of Alzheimer's disease (AD). We investigated the associations between such factors, longitudinal AD cerebrospinal fluid biomarkers, and cognition.Methods: 433 cognitively normal participants were classified into four biomarker groups using their baseline amyloid (A+/-) and tau status (T+/-). 184 participants had undergone serial cerebrospinal fluid collection. Frequencies of risk factors and the Framingham Risk Score (FRS) were compared, and we tested the influence of risk factors on change in biomarker concentrations and cognition.Results: The absence of obesity, presence of hypertension, and a high FRS were associated with an increase in tau levels, particularly in A +T + individuals. Risk factors were not associated with amyloid. Depression was associated with higher cognitive scores, whereas high FRS was associated with lower scores and a faster decline.Discussion: Our results demonstrate that vascular risk factors may enhance neurodegeneration but not amyloid accumulation in preclinical AD. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.",
keywords = "Alzheimer's disease, Dementia, Cerebrospinal fluid, Biomarkers, Amyloid-beta, Tau, Neurodegeneration, Vascular risk factors, Hypertension, Obesity, Hypercholesterolemia, Depression, Cardiovascular disorders, Framingham Risk Score, BLOOD-PRESSURE, DEMENTIA, NEURODEGENERATION, BIOMARKERS, NEUROPATHOLOGY, PATHOLOGY, LOAD, CARE",
author = "Isabelle Bos and Vos, {Stephanie J. B.} and Schindler, {Suzanne E.} and Jason Hassenstab and Chengjie Xiong and Elizabeth Grant and Frans Verhey and Morris, {John C.} and Visser, {Pieter Jelle} and Fagan, {Anne M.}",
note = "Funding Information: S.E.S. has a family member with stock in Eli Lilly, which is developing drugs for Alzheimer's disease. J.J.H. is on the advisory board and consults for both Biogen and Lundbeck A/S. J.C.M. has or is currently participating in clinical trials of antidementia drugs sponsored by Janssen Immunotherapy, Eli Lilly and Company, and Pfizer. He has served as a consultant for or has received speaking honoraria from Eisai, Esteve, Janssen Alzheimer Immunotherapy Program/Elan, GlaxoSmithKline, Novartis, and Pfizer. He receives research support from Eli Lilly/Avid Radiopharmaceuticals. A.M.F. has received research funding from Biogen, Fujirebio, and Roche Diagnostics. She is a member of the scientific advisory boards for Roche, Genentech, and AbbVie and also consults for Araclon/Grifols and DiamiR. All other authors report no conflict of interest.The authors are especially grateful to the research volunteers at the Knight ADRC and their families for their participation. Authors' contributions: I.B. S.J.B.V. P.J.V. and A.M.F contributed to study conception and design. All authors contributed to acquisition, analysis, or interpretation of the data. I.B. S.J.B.V. P.J.V. and A.M.F contributed to drafting of the manuscript. Critical revision of the manuscript for important intellectual content was performed by all authors. Statistical analyses were carried out by I.B. J.H. and C.X. All authors obtained funding. Administrative, technical, or material support was provided by all authors. Study supervision was done by A.M.F. Funding: This work was funded by National Institute on Aging grants P50 AG05681 (J.C.M.), P01 AG03991 (J.C.M.), and P01 AG026276 (J.C.M.) and Alzheimer Nederland fellowship WE.15-2016.08 (I.B.). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: Funding: This work was funded by National Institute on Aging grants P50 AG05681 (J.C.M.), P01 AG03991 (J.C.M.), and P01 AG026276 (J.C.M.) and Alzheimer Nederland fellowship WE.15-2016.08 (I.B.). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Funding Information: S.E.S. has a family member with stock in Eli Lilly, which is developing drugs for Alzheimer's disease. J.J.H. is on the advisory board and consults for both Biogen and Lundbeck A/S. J.C.M. has or is currently participating in clinical trials of antidementia drugs sponsored by Janssen Immunotherapy , Eli Lilly and Company , and Pfizer . He has served as a consultant for or has received speaking honoraria from Eisai, Esteve, Janssen Alzheimer Immunotherapy Program/Elan, GlaxoSmithKline, Novartis, and Pfizer. He receives research support from Eli Lilly /Avid Radiopharmaceuticals. A.M.F. has received research funding from Biogen , Fujirebio , and Roche Diagnostics . She is a member of the scientific advisory boards for Roche, Genentech, and AbbVie and also consults for Araclon/Grifols and DiamiR. All other authors report no conflict of interest. Publisher Copyright: {\textcopyright} 2019 the Alzheimer's Association",
year = "2019",
month = sep,
doi = "10.1016/j.jalz.2019.04.015",
language = "English",
volume = "15",
pages = "1149--1159",
journal = "Alzheimer's & Dementia",
issn = "1552-5260",
publisher = "Elsevier Science",
number = "9",
}