title: Regional white matter pathology in mild cognitive impairment: differential influence of lesion type on neuropsychological functioning.
abstract: OBJECTIVE
  Associations between regional white matter lesion pathology and neuropsychological performance across the aging spectrum are not well understood and, to date, research has been largely contradictory and inconclusive. The current study set out to clarify some of the inconsistencies in the literature by relating volumetric analyses of white matter lesions (deep white matter lesions and periventricular lesions) to neuropsychological performance in a large clinical sample of older adults diagnosed with mild cognitive impairment.
  
  
  METHODS
  Seventy older adults with mild cognitive impairment were administered a comprehensive neuropsychological battery. White matter lesions identified on T2-weighted FLAIR images were quantified using a semi-automated volumetric approach (pixel thresholding).
  
  
  RESULTS
  Results showed that, in contrast to performance on memory and naming tasks, total white matter lesions strongly predicted executive impairments, slowed processing speed, and visuospatial/construction difficulties. In addition, separate regression analyses demonstrated that results were primarily accounted for by deep white matter lesions (but not periventricular lesions), most likely due to frontal-subcortical circuitry disruption. Moreover, deep white matter lesions, but not periventricular lesions, significantly predicted overall poorer neuropsychological functioning after controlling for age, education, and level of depression.
  
  
  CONCLUSIONS
  Taken together, findings demonstrate a differential influence of lesion type on cognitive impairment in mild cognitive impairment and implicate deep white matter lesions as being most detrimental in terms of neuropsychological functioning. Clinical, theoretical, and methodological implications of these results are discussed.
authors.affiliation: Department of Psychiatry, University of California, San Diego, San Diego, CA 92161, USA. ldelano@ucsd.edu
authors.forename: Lisa
authors.initials: L
authors.lastname: Delano-Wood
authors.forename: Norm
authors.initials: N
authors.lastname: Abeles
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Sacco
authors.forename: Christina E
authors.initials: CE
authors.lastname: Wierenga
authors.forename: Nikki R
authors.initials: NR
authors.lastname: Horne
authors.forename: Andrea
authors.initials: A
authors.lastname: Bozoki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000503:physiopathology / Q000523:psychology*; D005260:Female; D006801:Humans; D049292:Leukoaraiosis / Q000175:diagnosis* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D012720:Severity of Illness Index