title: Correlations between MRI white matter lesion location and executive function and episodic memory.
abstract: OBJECTIVE
  MRI white matter hyperintensity (WMH) volume is associated with cognitive impairment. We hypothesized that specific loci of WMH would correlate with cognition even after accounting for total WMH volume.
  
  
  METHODS
  Subjects were identified from a prospective community-based study: 40 had normal cognition, 94 had mild impairment (defined here as a Clinical Dementia Rating [CDR] score of 0.5 without dementia), and 11 had mild Alzheimer's dementia. Factor analysis of a 22-item neuropsychological battery yielded 4 factors (episodic memory, executive function, spatial skills, and general knowledge). MRI WMH segmentation and analysis was performed using FreeSurfer software.
  
  
  RESULTS
  Higher WMH volume was independently associated with lower executive function and episodic memory factor scores. Voxel-based general linear models showed loci where WMH was strongly inversely associated with specific cognitive factor scores (p < 0.001), controlling for age, education, sex, APOE genotype, and total WMH volume. For episodic memory, clusters were observed in bilateral temporal-occipital and right parietal periventricular white matter, and the left anterior limb of the internal capsule. For executive function, clusters were observed in bilateral inferior frontal white matter, bilateral temporal-occipital and right parietal periventricular white matter, and the anterior limb of the internal capsule bilaterally.
  
  
  CONCLUSIONS
  Specific WMH loci are closely associated with executive function and episodic memory, independent of total WMH volume. The anatomic locations suggest that WMH may cause cognitive impairment by affecting connections between cortex and subcortical structures, including the thalamus and striatum, or connections between the occipital lobe and frontal or parietal lobes.
authors.affiliation: Department of Clinical Neurosciences, Foothills Medical Centre, Calgary, Alberta, Canada. eesmith@ucalgary.ca
authors.forename: E E
authors.initials: EE
authors.lastname: Smith
authors.forename: D H
authors.initials: DH
authors.lastname: Salat
authors.forename: J
authors.initials: J
authors.lastname: Jeng
authors.forename: C R
authors.initials: CR
authors.lastname: McCreary
authors.forename: B
authors.initials: B
authors.lastname: Fischl
authors.forename: J D
authors.initials: JD
authors.lastname: Schmahmann
authors.forename: B C
authors.initials: BC
authors.lastname: Dickerson
authors.forename: A
authors.initials: A
authors.lastname: Viswanathan
authors.forename: M S
authors.initials: MS
authors.lastname: Albert
authors.forename: D
authors.initials: D
authors.lastname: Blacker
authors.forename: S M
authors.initials: SM
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D003072:Cognition Disorders / Q000473:pathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008569:Memory Disorders / Q000473:pathology*; D011939:Mental Recall / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D012111:Residence Characteristics; D013223:Statistics as Topic