title: Microstructural white matter changes in cognitively normal individuals at risk of amnestic MCI.
abstract: OBJECTIVE
  Since Alzheimer disease (AD) is a slowly progressive disorder and its pathologic features are likely to be present for many years before symptoms become manifest, we investigated whether microstructural white matter changes similar to those identified in patients with AD can be detected in cognitively normal individuals without dementia destined to develop amnestic mild cognitive impairment (aMCI).
  
  
  METHODS
  We studied 193 cognitively normal individuals, of whom 173 remained cognitively stable (CN-stable) and 20 were diagnosed with aMCI (CN-aMCI converter) 2 years later. Structural MRI and diffusion tensor imaging were acquired at baseline to assess gray matter atrophy and microstructural white matter changes, respectively.
  
  
  RESULTS
  At baseline, compared with CN-stable, CN-aMCI converters had substantial reductions in white matter integrity in the precuneus, parahippocampal cingulum, parahippocampal gyrus white matter, and fornix. Other diffuse white matter changes were observed in the frontal, parietal, and subcortical regions, whereas gray matter structures were relatively intact. The fractional anisotropy (FA) values of the precuneus were found to be a predictor of conversion from cognitively normal to aMCI. In addition, the FA values of the left parahippocampal gyrus white matter were predictive of subsequent episodic memory decline.
  
  
  CONCLUSIONS
  Microstructural white matter changes are present in cognitively normal individuals in the pre-aMCI stage, and may serve as a potential imaging marker of early AD-related brain changes.
authors: Brain and Ageing Research Program, School of Psychiatry, University of New South Wales, Randwick, Australia.
authors: Lin
authors: L
authors: Zhuang
authors: Perminder S
authors: PS
authors: Sachdev
authors: Julian N
authors: JN
authors: Trollor
authors: Nicole A
authors: NA
authors: Kochan
authors: Simone
authors: S
authors: Reppermund
authors: Henry
authors: H
authors: Brodaty
authors: Wei
authors: W
authors: Wen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000647:Amnesia / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D016880:Anisotropy; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D056324:Diffusion Tensor Imaging / Q000379:methods; D042241:Early Diagnosis; D005260:Female; D015577:Geriatric Assessment / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology* / Q000648:ultrastructure*; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D059906:Neuroimaging / Q000379:methods*; D011237:Predictive Value of Tests