title: Cortical microinfarcts and demyelination significantly affect cognition in brain aging.
abstract: OBJECTIVE
  Microvascular lesions are common in brain aging, but their clinical impact is debated. Methodological problems such as the masking effect of concomitant pathologies may explain discrepancies among previous studies. To evaluate the cognitive consequences of such lesions, we prospectively investigated elderly individuals with various degrees of cognitive impairment but without significant neurofibrillary tangle pathology or macrovascular lesions.
  
  
  METHODS
  This was a clinicopathological study of 45 elderly individuals. Cognitive status was assessed prospectively with the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Abeta-protein deposition staging and bilateral semiquantitative assessment of cortical microinfarcts, focal cortical and white matter glioses, and diffuse white matter and periventricular demyelination.
  
  
  RESULTS
  In a univariate logistic regression model, cortical microinfarcts explained 36.1% of the variability in CDR; periventricular demyelination, 10.6%; and diffuse white matter demyelination, 4.6%. After controlling for age and Abeta-protein deposition, cortical microinfarcts were the best predictor of cognitive status (19.9% of CDR variability), whereas periventricular and diffuse white matter demyelination accounted for 9.7% and 5.4% of CDR variability, respectively. Altogether, these 3 types of microvascular lesions explained 27.9% of the clinical variability. Focal cortical and white matter glioses were not related to clinical outcome.
  
  
  CONCLUSIONS
  Our data imply that cortical microinfarcts and both periventricular and deep white matter demyelination contribute significantly to the progression of cognitive deficits in brain aging. In contrast, the neuropathological evaluation of focal cortical and white matter gliosis has no clinical validity.
authors.affiliation: Department of Psychiatry, HUG Belle-Idée, University of Geneva School of Medicine, Geneva, Switzerland. eniko.kovari@hcuge.ch
authors.forename: Enikö
authors.initials: E
authors.lastname: Kövari
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gold
authors.forename: François R
authors.initials: FR
authors.lastname: Herrmann
authors.forename: Alessandra
authors.initials: A
authors.lastname: Canuto
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Michel
authors.forename: Constantin
authors.initials: C
authors.lastname: Bouras
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Giannakopoulos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D002544:Cerebral Infarction / Q000150:complications / Q000473:pathology*; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology*; D003711:Demyelinating Diseases / Q000150:complications / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index