title: Diffusion-weighted imaging and cognition in the leukoariosis and disability in the elderly study.
abstract: OBJECTIVE
  The mechanisms by which leukoariosis impacts on clinical and cognitive functions are not yet fully understood. We hypothesized that ultrastructural abnormalities of the normal-appearing brain tissue (NABT) assessed by diffusion-weighted imaging played a major and independent role.
  
  
  METHODS
  In addition to a comprehensive clinical, neuropsychologic, and imaging work-up, diffusion-weighted imaging was performed in 340 participants of the multicenter leukoariosis and disability study examining the impact of white matter hyperintensities (WMH) on 65- to 85-year old individuals without previous disability. WMH severity was rated according to the Fazekas score. Multivariate regression analysis served to assess correlations of histogram metrics of the apparent diffusion coefficient (ADC) of whole-brain tissue, NABT, and of the mean ADC of WMH with cognitive functions.
  
  
  RESULTS
  Increasing WMH scores were associated with a higher frequency of hypertension, a greater WMH volume, more brain atrophy, worse overall cognitive performance, and changes in ADC. We found strong associations between the peak height of the ADC histogram of whole-brain tissue and NABT with memory performance, executive dysfunction, and speed, which remained after adjustment for WMH lesion volume and brain atrophy and were consistent among centers. No such association was seen with the mean ADC of WMH.
  
  
  CONCLUSIONS
  Ultrastructural abnormalities of NABT increase with WMH severity and have a strong and independent effect on cognitive functions, whereas diffusion-weighted imaging metrics within WMH have no direct impact. This should be considered when defining outcome measures for trials that attempt to ameliorate the consequences of WMH progression.
authors.affiliation: Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036 Graz, Austria. reinhold.schmidt@medunigraz.at
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
authors.forename: José
authors.initials: J
authors.lastname: Ferro
authors.forename: Sofia
authors.initials: S
authors.lastname: Madureira
authors.forename: Ana
authors.initials: A
authors.lastname: Verdelho
authors.forename: Katja
authors.initials: K
authors.lastname: Petrovic
authors.forename: Alida
authors.initials: A
authors.lastname: Gouw
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.forename: Timo
authors.initials: T
authors.lastname: Erkinjuntti
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.forename: Lars O
authors.initials: LO
authors.lastname: Wahlund
authors.forename: Gunhild
authors.initials: G
authors.lastname: Waldemar
authors.forename: Egill
authors.initials: E
authors.lastname: Rostrup
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D006233:Persons with Disabilities / Q000523:psychology; D005260:Female; D006801:Humans; D049292:Leukoaraiosis / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology; D008297:Male