Year: 2017
Type: article
Study design: Observational Study
Abstract: 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) ε4 modulation of white-matter damage in 37 patients with YOAD (22, 59% APOE ε4 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 ε4+ individuals but more focal (posterior predominant) in the absence of an ε4 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 APOEε4 status is associated with different patterns of white-matter neurodegeneration.
Source: Neurobiology of Aging
Authors: Catherine F. Slattery, Jiaying Zhang, Ross W. Paterson, Alexander J.M. Foulkes, Amelia Carton, Kirsty Macpherson, Laura Mancini, David L. Thomas, Marc Modat, Nicolas Toussaint, David M. Cash, John S. Thornton, Susie M.D. Henley, Sebastian J. Crutch, Daniel C. Alexander, Sebastien Ourselin, Nick C. Fox, Hui Zhang, Jonathan M. Schott
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,670
Funders: Alzheimer's Society, Alzheimer Society, National Institute for Health and Care Research, Brain Research Trust, University College London, European Commission, Wolfson Foundation, China Scholarship Council, University College London Hospitals NHS Foundation Trust, Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, FP7 Information and Communication Technologies
Awards: G1072871761, G112140839, G1170993257, G1234573687, Anatomy-Driven Brain Connectivity Mapping, G150562299, G1775974636, G1852290088, G1936895964, G2145614116, NIHR Senior Investigator Award, G2325242462, G2342732959, VPH Dementia Research Enabled by IT, G2810537366, A biophysical simulation framework for magnetic resonance microstructure imaging, G3057370048, G3126617770, Direct Measurements of Microstructure from MRI, Medical image computing for next-generation healthcare technology, Computational PLatform for Assessment of Cognition In Dementia (C-PLACID), G3461104596, Intelligent Imaging: Motion, Form and Function Across Scale, The UK GENetic Frontotemporal dementia Initiative (UK GENFI), G4065409414, Computational models of neurodegenerative disease progression, G422312149, Data-driven models for Progression Of Neurological Disease, G4358921014, G4421367155, G4510347995, G4714631627, G4811888002, Seeing what they see: compensating for cortical visual dysfunction in Alzheimer's disease, G5017848241, G5814724622, G5820456930, G6496510108, G6753471870, G6800468499, G6964704191, G7248478464, G748345579, G7486377412, G7628549173, G7697514025, G8057189669, G8390508323, G8650869886, EPICure@19 - the extremely preterm young adult, G942021869
OpenAlex ID: W2610402968