Published Online
on January 5, 2004

A more recent version of this article appeared on February 1, 2004

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Submitted on October 6, 2003
Accepted on October 13, 2003

Cortical Microinfarcts and Demyelination Significantly Affect Cognition in Brain Aging

Enikö Kövari MD^*; Gabriel Gold MD; François R. Herrmann MD, MPH; Alessandra Canuto MD; Patrick R. Hof MD; Jean-Pierre Michel MD; Constantin Bouras MD; and Panteleimon Giannakopoulos MD

From the Departments of Psychiatry (A.C., E.K., C.B., P.G.) and Geriatrics (G.G., F.R.H., J.-P.M.), HUG Belle-Idée, University of Geneva School of Medicine, Geneva, Switzerland; Service of Old Age Psychiatry (P.G.), University of Lausanne School of Medicine, Lausanne; and Fishberg Research Center for Neurobiology and Kastor Neurobiology of Aging Laboratories (P.R.H., C.B.) and Departments of Geriatrics and Adult Development and of Ophthalmology (P.R.H.), Mount Sinai School of Medicine, New York, NY.

^* To whom correspondence should be addressed. E-mail: eniko.kovari{at}hcuge.ch.

Background and Purpose--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 A-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 A-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.

Key words: aging • brain ischemia • cognition • dementia, vascular • microvascular injury

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