title: Brain atrophy accelerates cognitive decline in cerebral small vessel disease: the LADIS study.
abstract: OBJECTIVE
  To examine the independent contributions and combined interactions of medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white matter lesion (WML) volume in longitudinal cognitive performance.
  
  
  METHODS
  A total of 477 subjects with age-related WML were evaluated with brain MRI and annual neuropsychological examinations in 3-year follow-up. Baseline MRI determinants of cognitive decline were analyzed with linear mixed models controlling for multiple confounders.
  
  
  RESULTS
  MTA and subcortical atrophy predicted significantly steeper rate of decline in global cognitive measures as well as compound scores for psychomotor speed, executive functions, and memory after adjusting for age, gender, education, lacunes/infarcts, and WML volume. Cortical atrophy independently predicted decline in psychomotor speed. WML volume remained significantly associated with cognitive decline even after controlling for the atrophy scores. Moreover, significant synergistic interactions were found between WML and atrophy measures in overall cognitive performance across time and the rate of cognitive decline. Synergistic effects were also observed between baseline lacunar infarcts and all atrophy measures on change in psychomotor speed. The main results remained robust after exclusion of subjects with clinical stroke or incident dementia, and after additional adjustments for progression of WML and lacunes.
  
  
  CONCLUSIONS
  Brain atrophy and WML are independently related to longitudinal cognitive decline in small vessel disease. MTA, subcortical, and cortical atrophy seem to potentiate the effect of WML and lacunes on cognitive decline.
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. hanna.jokinen@helsinki.fi
authors.forename: H
authors.initials: H
authors.lastname: Jokinen
authors.forename: J
authors.initials: J
authors.lastname: Lipsanen
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: F
authors.initials: F
authors.lastname: Fazekas
authors.forename: A A
authors.initials: AA
authors.lastname: Gouw
authors.forename: W M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: S
authors.initials: S
authors.lastname: Madureira
authors.forename: A
authors.initials: A
authors.lastname: Verdelho
authors.forename: J M
authors.initials: JM
authors.lastname: Ferro
authors.forename: A
authors.initials: A
authors.lastname: Wallin
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; D001284:Atrophy / Q000150:complications; D001921:Brain / Q000473:pathology*; D059345:Cerebral Small Vessel Diseases / Q000150:complications* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000209:etiology / Q000473:pathology*; D003430:Cross-Sectional Studies; D015140:Dementia, Vascular / Q000209:etiology / Q000473:pathology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D013702:Temporal Lobe / Q000473:pathology