title: Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study.
abstract: OBJECTIVE
  On cerebral magnetic resonance imaging (MRI), white matter hyperintensities (WMH) and lacunes are generally viewed as evidence of small vessel disease. The clinical significance of small vessel disease in terms of global cognitive function has as yet not been completely clarified. We investigated the independent contribution of WMH and lacunes to general cognitive function in a group of independently living elderly with varying degrees of small vessel disease.
  
  
  METHODS
  Data were drawn from the multicenter, multinational Leukokraurosis and Disability (LADIS) study. There were 633 independently living participants. General cognitive function was assessed using the Mini Mental State Examination (MMSE) and the modified Alzheimer Disease Assessment Scale (ADAS). On MRI, WMH was rated as mild, moderate, or severe. Lacunes were rated as none, few (1 to 3), or many (4 or more).
  
  
  RESULTS
  In the basic analysis, increasing severity of both WMH and lacunes was related to deteriorating score on the MMSE and ADAS. When WMH and lacunes were entered simultaneously, both MRI measures remained significantly associated with MMSE score. Increasing severity of WMH remained associated with ADAS score, whereas the association with lacunes became less prominent. These associations were independent of other risk factors for dementia, like education, depression, vascular risk factors, or stroke.
  
  
  CONCLUSIONS
  We found WMH and lacunes to be independently associated with general cognitive function in a sample of independently living elderly. These results highlight the fact that WMH and lacunes should both be evaluated when assessing small vessel disease in relation to cognitive function.
authors.affiliation: Alzheimer Center, Department of Neurology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. wm.vdflier@vumc.nl
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: Elizabeth C W
authors.initials: EC
authors.lastname: van Straaten
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Ana
authors.initials: A
authors.lastname: Verdelho
authors.forename: Sofia
authors.initials: S
authors.lastname: Madureira
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: Militta
authors.initials: M
authors.lastname: Crisby
authors.forename: Gunhild
authors.initials: G
authors.lastname: Waldemar
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000473:pathology*; D020520:Brain Infarction / Q000175:diagnosis; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology*; D001931:Brain Mapping; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000473:pathology; D002561:Cerebrovascular Disorders / Q000175:diagnosis; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis; D003704:Dementia / Q000175:diagnosis; D015140:Dementia, Vascular / Q000175:diagnosis; D003863:Depression; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000175:diagnosis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D020521:Stroke / Q000175:diagnosis; D011795:Surveys and Questionnaires