title: Associative learning and regional white matter deficits in mild cognitive impairment.
abstract: BACKGROUND
  While diagnostic criteria for Alzheimer's disease (AD) include neuroimaging biomarkers, there remains no definitive biomarker of mild cognitive impairment (MCI). MCI is a risk factor for AD that may be amenable to early intervention. Early decline in white matter (WM) integrity identified by diffusion tensor imaging (DTI) is a predictor of future progression of neurodegeneration.
  
  
  OBJECTIVE
  Identify regionally specific WM differences between individuals with MCI and those with age-associated memory impairment (AAMI) and relationships with specific memory decrements.
  
  
  METHODS
  DTI and neuropsychological data were acquired from 38 participants (23 MCI and 15 AAMI). A region of interest approach was used to evaluate regional differences between groups and correlative relationships with performance on memory tasks.
  
  
  RESULTS
  Fornix WM had higher mean (MD), radial (DR), and axial (DA) diffusivity in MCI participants relative to AAMI. Temporal stem (TS) WM had higher MD and DR in MCI than in AAMI. In MCI, TS MD and DR varied, while fornix MD and DR was uniformly high, and in AAMI, TS MD and DR were uniformly low and fornix MD and DR varied. In MCI, TS MD and DA were inversely associated with associative learning but not list learning.
  
  
  CONCLUSIONS
  In addition to supporting prior evidence implicating the fornix in early AD pathology, these data implicate a profile of neurodegeneration associated with early MCI. Further, they suggest that associative learning tasks are more sensitive to early neurodegeneration and may be useful in identifying individuals at risk for AD.
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Boespflug
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: James
authors.initials: J
authors.lastname: Eliassen
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Academic Health Center, Cincinnati, OH, USA Department of Environmental Health (Division of Epidemiology & Biostatistics), University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Welge
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Krikorian
mesh_terms: D000368:Aged; D001245:Association Learning; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000473:pathology* / Q000523:psychology; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007858:Learning; D008297:Male; D008569:Memory Disorders / Q000473:pathology* / Q000523:psychology; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*
keywords: Alzheimer's disease; biomarker; diffusion tensor imaging; fornix; mild cognitive impairment; paired-associate learning