title: White matter hyperintensities and cognition: testing the reserve hypothesis.
abstract: OBJECTIVE
  White matter hyperintensities (WMH), visualized on T2-weighted MRI, are thought to reflect small-vessel vascular disease. Much like other markers of brain disease, the association between WMH and cognition is imperfect. The concept of reserve may account for this imperfect relationship. The purpose of this study was to test the reserve hypothesis in the association between WMH severity and cognition. We hypothesized that individuals with higher amounts of reserve would be able to tolerate greater amounts of pathology than those with lower reserve.
  
  
  METHODS
  Neurologically healthy older adults (n=717) from a community-based study received structural MRI, neuropsychological assessment, and evaluation of reserve. WMH volume was quantified algorithmically. We derived latent constructs representing four neuropsychological domains, a measure of cognitive reserve, and a measure of brain reserve. Measures of cognitive and brain reserve consisted of psychosocial (e.g., education) and anthropometric (e.g., craniometry) variables, respectively.
  
  
  RESULTS
  Increased WMH volume was associated with poorer cognition and higher cognitive and brain reserve were associated with better cognition. Controlling for speed/executive function or for language function, those with higher estimates of cognitive reserve had significantly greater degrees of WMH volume, particularly among women. Controlling for cognitive functioning across all domains, individuals with higher estimates of brain reserve had significantly greater WMH volume.
  
  
  CONCLUSIONS
  For any given level of cognitive function, those with higher reserve had more pathology in the form of WMH, suggesting that they are better able to cope with pathology than those with lower reserve. Both brain reserve and cognitive reserve appear to mitigate the impact of pathology on cognition.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. amb2139@columbia.edu
authors.forename: Adam M
authors.initials: AM
authors.lastname: Brickman
authors.forename: Karen L
authors.initials: KL
authors.lastname: Siedlecki
authors.forename: Jordan
authors.initials: J
authors.lastname: Muraskin
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Manly
authors.forename: José A
authors.initials: JA
authors.lastname: Luchsinger
authors.forename: Lok-Kin
authors.initials: LK
authors.lastname: Yeung
authors.forename: Truman R
authors.initials: TR
authors.lastname: Brown
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Stern
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D058245:Cognitive Reserve / Q000502:physiology*; D015331:Cohort Studies; D015140:Dementia, Vascular / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies