@article{68a493e9abc543cdb7f9d4dc9dadc9d8,
title = "Cerebrovascular risk factors and preclinical memory decline in healthy APOE ε4 homozygotes",
abstract = "Objective: To characterize the effects of cerebrovascular (CV) risk factors on preclinical memory decline in cognitively normal individuals at 3 levels of genetic risk for Alzheimer disease (AD) based on APOE genotype. Methods: We performed longitudinal neuropsychological testing on an APOE ε4 enriched cohort, ages 21-97. The long-term memory (LTM) score of the Auditory Verbal Learning Test (AVLT) was the primary outcome measure. Any of 4 CV risk factors (CVany), including hypercholesterolemia (CHOL), prior cigarette use (CIG), diabetes mellitus (DM), and hypertension (HTN), was treated as a dichotomized variable. We estimated the longitudinal effect of age using statistical models that simultaneously modeled the cross-sectional and longitudinal effects of age on AVLT LTM by APOE genotype, CVany, and the interaction between the two. Results: A total of 74 APOE ε4 homozygotes (HMZ), 239 ε4 heterozygotes (HTZ), and 494 ε4 noncarriers were included. APOE ε4 carrier status showed a significant quadratic effect with age-related LTM decline in all models as previously reported. CVany was associated with further longitudinal AVLT LTM decline in APOE ε4 carriers (p = 0.02), but had no effect in noncarriers. When ε4 HTZ and HMZ were considered separately, there was a striking effect in HMZ (p < 0.001) but not in HTZ. In exploratory analyses, significant deleterious effects were found for CIG (p = 0.001), DM (p = 0.03), and HTN (p = 0.05) in APOE ε4 carriers only that remained significant only for CIG after correction for multiple comparisons. Conclusion: CV risk factors influence age-related memory decline in APOE ε4 HMZ.",
author = "Caselli, {R. J.} and Dueck, {A. C.} and Locke, {D. E.C.} and Sabbagh, {M. N.} and Ahern, {G. L.} and Rapcsak, {S. Z.} and Baxter, {L. C.} and R. Yaari and Woodruff, {B. K.} and C. Hoffman-Snyder and R. Rademakers and S. Findley and Reiman, {E. M.}",
note = "Funding Information: Dr. Caselli serves as Medical Editor for Clinical Neurology News and receives research support from the NIH/NIA and The Arizona Alzheimer's Research Consortium. Dr. Dueck and Dr. Locke report no disclosures. Dr. Sabbagh serves on scientific advisory boards for AmeriSciences and Allon Therapeutics, Inc.; serves on the editorial boards of Clinical Neurology News, the Journal of Alzheimer's Disease, and BMC Neurology; receives publishing royalties for The Alzheimer's Answer (Wiley, 2008); serves as a consultant for Elan Corporation, GlaxoSmithKline, Pfizer Inc., Eisai Inc., and AmeriSciences; receives research support from Elan Corporation, Wyeth, Medivation, Inc., Avid Radiopharmaceuticals, Inc., Baxter International Inc., Eli Lilly and Company, GE Healthcare, Bayer Schering Pharma, Eisai Inc., and the NIH/NIA; and receives royalties from AmeriSciences for the commercial product Cognivite. Dr. Ahern reports no disclosures. Dr. Rapcsak receives research support from the NIH (NIA, NIDCD). Dr. Baxter and Dr. Yaari report no disclosures. Dr. Woodruff receives research support from the NIH/NIA. C. Hoffman-Snyder reports no disclosures. Dr. Rademakers holds patents re: Methods and materials for detecting and treating dementia and receives research support from the NIH, the Pacific Alzheimer Research Foundation (Canada), the Association for Frontotemporal Dementia, the Amyotrophic Lateral Sclerosis Association, and CurePSP. S. Findley reports no disclosures. Dr. Reiman serves on scientific advisory boards for Accera, Inc., Bayer Schering Pharma, Elan Corporation, Eli Lilly and Company, AstraZeneca, GlaxoSmithKline, Siemens, Takeda Pharmaceutical Company Limited, and Eisai Inc.; serves as Deputy Editor for the Journal of Clinical Psychiatry; holds a patent re: Methods for tracking the progression of Alzheimer's disease identifying treatment using transgenic mice; serves as a consultant for Amnestix/Sygnis; receives research support from Kronos Life Sciences, GlaxoSmithKline, AstraZeneca, Avid Radiopharmaceuticals, Inc., the NIH (NIA, NIMH), and the state of Arizona; and serves as Executive Director of the Banner Alzheimer's Institute and Director of the Arizona Alzheimer's Consortium, 501C3 organizations which have emphasized the use of brain imaging and other biomarker measurements in the evaluation of putative pre-symptomatic treatments for Alzheimer's disease. Funding Information: Study funding: Supported by the National Institute on Aging (P30-AG19610 and R01-AG031581) , the National Institute of Mental Health (R01-MH057899) , the Alzheimer's Association (IIRG-98-078) , the Arizona Alzheimer's Consortium, the State of Arizona, and with resources from Southern Arizona VA Health Care System. ",
year = "2011",
month = mar,
day = "22",
doi = "10.1212/WNL.0b013e318211c3ae",
language = "English (US)",
volume = "76",
pages = "1078--1084",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "12",
}