期刊
NEUROBIOLOGY OF AGING
卷 57, 期 -, 页码 8-17出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2017.04.021
关键词
Alzheimer's disease; Diffusion tensor imaging; Neurite orientation dispersion and density; imaging; Apoe; White matter; Phenotype
资金
- Alzheimer's Research UK
- Brain Research Trust
- Wolfson Foundation
- NIHR Queen Square Dementia Biomedical Research Unit
- NIHR UCL/H Biomedical Research Centre
- EPSRC [EP/L022680/1, EP/M006093/1, EP/H046410/1, EP/J020990/1, EP/K005278]
- ESRC/NIHR [ES/L001810/1]
- Alzheimer's Research UK Senior Research Fellowship
- Alzheimer Society [AS-PG-15-025]
- Alzheimer's Research UK [ARUK-PG2014-1946]
- MRC [MR/M023664/1, MR/J01107X/1, CSUB19166]
- UCL Leonard Wolfson Experimental Neurology Centre [PR/ylr/18575]
- Alzheimer's Society [AS-PG-15-025]
- EU-FP7 project VPH-DARE@IT [FP7-ICT-2011-9-601055]
- NIHR Biomedical Research Unit (Dementia) at UCL
- ARUK [ARUK-PG2014-1946, ARUK-Network 2012-6-ICE]
- European Union's Horizon research and innovation programme [666992]
- China Scholarship Council
- National Institute for Health Research University College London Hospitals Biomedical Research Centre [NIHR BRC UCLH/UCL High Impact Initiative-BW.mn.BRC10269]
- EPSRC [EP/L022680/1, EP/H046410/1, EP/G007748/1, EP/M006093/1, EP/M020533/1, EP/N018702/1, EP/J020990/1] Funding Source: UKRI
- MRC [MR/J01107X/1, MR/M009106/1, MR/M023664/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/M006093/1, EP/H046410/1, EP/L022680/1, EP/M020533/1, EP/N018702/1, EP/G007748/1, EP/J020990/1] Funding Source: researchfish
- Medical Research Council [MR/J01107X/1, MR/M023664/1, MR/M009106/1] Funding Source: researchfish
- National Institute for Health Research [CL-2016-18-004, NF-SI-0513-10134] Funding Source: researchfish
Mechanisms underlying phenotypic heterogeneity in young onset Alzheimer disease (YOAD) are poorly understood. We used diffusion tensor imaging and neurite orientation dispersion and density imaging (NODDI) with tract-based spatial statistics to investigate apolipoprotein (APOE) epsilon 4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE e4 positive) and 23 age-matched controls. Correlation between neurite density index (NDI) and neuropsychological performance was assessed in 4 white-matter regions of interest. White-matter disruption was more widespread in epsilon 4+ individuals but more focal (posterior predominant) in the absence of an e4 allele. NODDI metrics indicate fractional anisotropy changes are underpinned by combinations of axonal loss and morphological change. Regional NDI in parieto-occipital white matter correlated with visual object and spatial perception battery performance (right and left, both p = 0.02), and performance (nonverbal) intelligence (WASI matrices, right, p = 0.04). NODDI provides tissue-specific microstructural metrics of white-matter tract damage in YOAD, including NDI which correlates with focal cognitive deficits, and APOE epsilon 4 status is associated with different patterns of white-matter neurodegeneration. (C) 2017 The Authors. Published by Elsevier Inc.
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