title: Longitudinal changes in microstructural white matter metrics in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter.
  
  
  
  Longitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points.
  
  
  
  1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum.
  
  
  
  The current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.
authors.affiliation: Department of Psychology, University of Victoria, PO Box 1700 STN CSC, Victoria, BC V8W 2Y2, Canada.
authors.forename: Chantel D
authors.initials: CD
authors.lastname: Mayo
authors.affiliation: Department of Radiology and the Hotchkiss Brain Institute, University of Calgary, HSC 2905, 3330 Hospital Dr NW, Calgary, AB T2N 1N4, Canada.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Mazerolle
authors.affiliation: Department of Clinical Health Psychology, University of Manitoba, 350-771 Bannatyne Avenue, Winnipeg, MB R3E 3N4, Canada.
authors.forename: Lesley
authors.initials: L
authors.lastname: Ritchie
authors.affiliation: Psychology, Nova Scotia Health Authority, Queen Elizabeth II Health Centre, 4066, 4th Floor, Abbie J. Lane Memorial Building, 5909 Veterans' Memorial Lane, Halifax, NS B3H 2E2, Canada; Department of Psychiatry, Dalhousie University, 4066, Abbie J. Lane Memorial Building, 5909 Veterans' Memorial Lane, Halifax, NS B3H 2E2, Canada; Department of Psychology & Neuroscience, Dalhousie University, 4066, Abbie J. Lane Memorial Building, 5909 Veterans' Memorial Lane, Halifax, NS B3H 2E2, Canada; Department of Medicine, Dalhousie University, 4066, Abbie J. Lane Memorial Building, 5909 Veterans' Memorial Lane, Halifax, NS B3H 2E2, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Fisk
authors.affiliation: Department of Psychology, University of Victoria, PO Box 1700 STN CSC, Victoria, BC V8W 2Y2, Canada.
authors.forename: Jodie R
authors.initials: JR
authors.lastname: Gawryluk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D015415:Biomarkers; D016208:Databases, Factual; D056324:Diffusion Tensor Imaging / Q000379:methods*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D066127:White Matter / Q000000981:diagnostic imaging*
chemical_list: D015415:Biomarkers
keywords: AD, Alzheimer's disease; ADNI, Alzheimer's Disease Neuroimaging Initiative; Aging; Alzheimer's disease; DTI, diffusion tensor imaging; Diffusion tensor imaging; FA, fractional anisotropy; FSL, Functional MRI of the Brain Software Library; HC, healthy controls; MCI, mild cognitive impairment; MD, mean diffusivity; MMSE, Mini Mental Status Exam; MRI, magnetic resonance imaging; Magnetic resonance imaging; ROI, region of interest; TBSS, Tract-Based Spatial Statistics; WMS, Wechsler Memory Scale; White matter