title: Cognitive reserve moderates long-term cognitive and functional outcome in cerebral small vessel disease.
abstract: BACKGROUND
  Cerebral small vessel disease (SVD) is characterised by progressive white matter hyperintensities (WMH), cognitive decline and loss of functional independence. The correspondence between neuroimaging findings and the severity of clinical symptoms has been modest, however, and thus the outcome may be affected by various host factors. We investigated the predictive value of educational and occupational attainments as proxy measures of cognitive reserve on long-term cognitive and functional outcome in patients with different degrees of WMH.
  
  
  METHODS
  In the Leukoaraiosis and Disability (LADIS) study, 615 older individuals with WMH were evaluated with brain MRI and detailed clinical and neuropsychological assessments at 3-year follow-up. A prolonged follow-up of functional and cognitive status was administered with a structured telephone interview after up to 7 years.
  
  
  RESULTS
  Higher levels of educational and occupational attainment were strongly related to baseline cognitive scores and predicted a slower rate of decline at 3-year follow-up in measures of processing speed, executive functions and memory independently of WMH volume and other confounders. The deleterious effect of WMH on processing speed and memory was moderated by education and occupation. Education mitigated the relation of WMH volume on 7-year cognitive status. Moreover, higher education and occupational attainments were related to favourable outcome at 7-year follow-up as defined by sustained functional independence and lower mortality.
  
  
  CONCLUSIONS
  The results support the presumption that cognitive reserve plays a significant role as a buffer against the clinical manifestations of SVD and may in part explain high individual variability in outcome.
authors.affiliation: Department of Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Jokinen
authors.affiliation: Department of Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Melkas
authors.affiliation: Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Madureira
authors.affiliation: Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Verdelho
authors.affiliation: Serviço de Neurologia, Centro de Estudos Egas Moniz, Hospital de Santa Maria, Lisbon, Portugal.
authors.forename: José M
authors.initials: JM
authors.lastname: Ferro
authors.affiliation: Department of Neurology and MRI Institute, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: Department of Neurology and MRI Institute, Medical University of Graz, Graz, Austria.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Department of Radiology and Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Department of Radiology and Neurology, VU University Medical Center, Amsterdam, The Netherlands.|UCL Institutes of Neurology & Healthcare Engineering, London, UK.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Division of Neuroimaging Sciences, Centre for Clinical Brain Sciences and Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.affiliation: Institute of Neuroscience, Italian National Research Council, Florence, Italy.|Department NEUROFARBA, University of Florence, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.affiliation: Department NEUROFARBA, University of Florence, Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
authors.affiliation: Department of Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Erkinjuntti
mesh_terms: D000124:Achievement; D000203:Activities of Daily Living / Q000145:classification; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D001921:Brain / Q000473:pathology; D059345:Cerebral Small Vessel Diseases / Q000175:diagnosis*; D003072:Cognition Disorders / Q000175:diagnosis*; D058245:Cognitive Reserve; D015331:Cohort Studies; D004185:Disability Evaluation; D004522:Educational Status; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D049292:Leukoaraiosis / Q000175:diagnosis*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011379:Prognosis