title: Independent cognitive effects of atrophy and diffuse subcortical and thalamico-cortical cerebrovascular disease in dementia.
abstract: OBJECTIVE
  Brain atrophy, cortical infarction, and subcortical ischemic vasculopathy have all been associated with cognitive dysfunction. The interrelationships between these pathologies and their independent contributions to cognitive function remain unclear. Despite the high frequency of Alzheimer disease (AD) in those with clinically diagnosed vascular dementia, and the frequent findings of vascular disease in those with clinically diagnosed AD, many studies of brain-behavior relationships in dementia consider these populations separately. The present study sought to identify the correlates of independent domains of cognitive impairment in an unselected sample across a large range of severity and overlap of AD and VaD.
  
  
  METHODS
  Two hundred five individuals from the Sunnybrook Dementia Study recruited from a university Memory clinic had detailed neuropsychological testing and MRI quantification using a multi-step postprocessing algorithm. A factor analysis of the cognitive protocol yielded a 3-factor solution, provisionally labeled: (1) short-term memory and language, (2) attention and working memory, and (3) mental flexibility.
  
  
  RESULTS
  A factor analysis of brain measures identified 3 independent factors with measures of (1) brain atrophy, (2) subcortical vascular disease, and (3) strategic infarcts (anterior-medial thalamus and cortical infarcts). After accounting for the effects of age and education, measures of brain atrophy were the strongest correlates of all cognitive domains. Small vessel disease was independently associated with general severity, impaired short-term memory/language, and reduced mental flexibility, but not with poor working memory, presumably through disruption of frontal-subcortical connections. In contrast, strategic infarcts to anterior-medial thalamus and cortical gray matter were associated with poor short-term and working memory, but not with impairments in mental flexibility or global severity measures.
  
  
  CONCLUSIONS
  These data support the hypothesis that the thalamico-cortical network subserves both short-term and working memory. The findings also suggest that each type of pathology (atrophy, small vessel disease, and strategic infarcts) contribute independently to the pattern of cognitive disabilities associated with dementia. Particular attention to cerebrovascular disease in deep white or gray matter structures of the thalamico-cortical system is certainly warranted.
authors.affiliation: Institute of Medical Science, Department of Medicine, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada. rick.swartz@utoronto.ca
authors.forename: Richard H
authors.initials: RH
authors.lastname: Swartz
authors.forename: Donald T
authors.initials: DT
authors.lastname: Stuss
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Gao
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Black
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply*; D002544:Cerebral Infarction / Q000175:diagnosis / Q000523:psychology; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D015140:Dementia, Vascular / Q000175:diagnosis* / Q000523:psychology; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008606:Mental Processes; D008875:Middle Aged; D009483:Neuropsychological Tests; D012720:Severity of Illness Index; D013788:Thalamus / Q000098:blood supply*