title: Incident lacunes influence cognitive decline: the LADIS study.
abstract: BACKGROUND
  In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML.
  
  
  METHODS
  Within the Leukoaraiosis and Disability Study (LADIS), 387 subjects were evaluated with repeated MRI and neuropsychological assessment at baseline and after 3 years. Predictors of change in global cognitive function and specific cognitive domains over time were analyzed with multivariate linear regression.
  
  
  RESULTS
  After controlling for demographic factors, baseline cognitive performance, baseline lacunar and WML lesion load, and WML progression, the number of new lacunes was related to subtle decrease in compound scores for executive functions (p = 0.021) and speed and motor control (p = 0.045), but not for memory or global cognitive function. Irrespective of lacunes, WML progression was associated with decrease in executive functions score (p = 0.016).
  
  
  CONCLUSIONS
  Incident lacunes on MRI parallel a steeper rate of decline in executive functions and psychomotor speed. Accordingly, in addition to WML, lacunes determine longitudinal cognitive impairment in small vessel disease. Although the individual contribution of lacunes on cognition was modest, they cannot be considered benign findings, but indicate a risk of progressive cognitive impairment.
authors.affiliation: Memory Research Unit, Department of Neurology, University of Helsinki, Helsinki, Finland. hanna.jokinen@helsinki.fi
authors.forename: H
authors.initials: H
authors.lastname: Jokinen
authors.forename: A A
authors.initials: AA
authors.lastname: Gouw
authors.forename: S
authors.initials: S
authors.lastname: Madureira
authors.forename: R
authors.initials: R
authors.lastname: Ylikoski
authors.forename: E C W
authors.initials: EC
authors.lastname: van Straaten
authors.forename: W M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: P
authors.initials: P
authors.lastname: Scheltens
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Verdelho
authors.forename: J M
authors.initials: JM
authors.lastname: Ferro
authors.forename: L
authors.initials: L
authors.lastname: Pantoni
authors.forename: D
authors.initials: D
authors.lastname: Inzitari
authors.forename: T
authors.initials: T
authors.lastname: Erkinjuntti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D020520:Brain Infarction / Q000150:complications* / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D049292:Leukoaraiosis / Q000473:pathology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests