期刊
NEUROBIOLOGY OF AGING
卷 53, 期 -, 页码 67-75出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.01.014
关键词
White matter hyperintensities; APOE; Alzheimer's disease; Longitudinal
资金
- Wolfson Foundation
- UCL Faculty of Engineering
- EPSRC [EP/H046410/1, EP/J020990/1, EP/K005278]
- MRC [MR/J01107X/1]
- EU-FP7 project VPH-DARE@IT [FP7-ICT-2011-9-601055]
- NIHR Biomedical Research Unit (Dementia) at UCL
- National Institute for Health Research University College London Hospitals Biomedical Research Centre (NIHR BRC UCLH/UCL High Impact Initiative) [BW.mn.BRC10269]
- EPSRC
- NIA
- Alzheimer's Research UK
- Brain Research Trust
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc
- Eisai Inc
- Elan Pharmaceuticals, Inc
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research and Development, LLC
- Johnson and Johnson Pharmaceutical Research and Development LLC
- Lumosity
- Lundbeck
- Merck and Co, Inc
- Meso Scale Diagnostics, LLC
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- EPSRC [EP/J020990/1, EP/H046410/1] Funding Source: UKRI
- MRC [MR/J01107X/1, MR/M009106/1] Funding Source: UKRI
- Alzheimers Research UK [ARUK-SRF2016A-2, ARUK-SRF2013-5] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/H046410/1, EP/J020990/1] Funding Source: researchfish
- Medical Research Council [MR/M009106/1, MR/J01107X/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10134] Funding Source: researchfish
To assess the relationship between carriage of APOE epsilon 4 allele and evolution of white matter hyperintensities (WMHs) volume, we longitudinally studied 339 subjects from the Alzheimer's Disease Neuroimaging Initiative cohort with diagnoses ranging from normal controls to probable Alzheimer's disease (AD). A purpose-built longitudinal automatic method was used to segment WMH using constraints derived from an atlas-based model selection applied to a time-averaged image. Linear mixed models were used to evaluate the differences in rate of change across diagnosis and genetic groups. After adjustment for covariates (age, sex, and total intracranial volume), homozygous APOE epsilon 4 epsilon 4 subjects had a significantly higher rate of WMH accumulation (22.5% per year 95% CI [14.4, 31.2] for a standardized population having typical values of covariates) compared with the heterozygous (epsilon 4 epsilon 3) subjects (10.0% per year [6.7, 13.4]) and homozygous e3e3 (6.6% per year [4.1, 9.3]) subjects. Rates of accumulation increased with diagnostic severity; controls accumulated 5.8% per year 95% CI: [2.2, 9.6] for the standardized population, early mild cognitive impairment 6.6% per year [3.9, 9.4], late mild cognitive impairment 12.5% per year [8.2, 17.0] and AD subjects 14.7% per year [6.0, 24.0]. Following adjustment for APOE status, these differences became nonstatistically significant suggesting that APOE epsilon 4 genotype is the major driver of accumulation of WMH volume rather than diagnosis of AD. (C) 2017 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license
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