on May 12, 2005
Published online before print May 12, 2005, doi: 10.1161/01.STR.0000166052.89772.b5
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Submitted on November 30, 2004
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; Fishberg Research Center for Neurobiology and Kastor Neurobiology of Aging Laboratories (P.R.H., C.B.), and the Departments of Geriatrics and Adult Development and Ophthalmology (P.R.H.), Mount Sinai School of Medicine, New York, NY. * To whom correspondence should be addressed. E-mail: gabriel.gold{at}hcuge.ch.
Background and Purpose--Most previous studies addressed the cognitive impact of lacunar infarcts using radiologic correlations that are known to correlate poorly with neuropathological data. Moreover, absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports. To define the relative contribution of silent lacunes to cognitive decline, we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions. Methods--Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included A Results--Thalamic and basal ganglia lacunes were negatively associated with CDR scores; cortical microinfarcts, periventricular and diffuse white matter demyelination also significantly affected cognition. In a multivariate model, cortical microinfarcts and thalamic and basal ganglia lacunes explained 22% of CDR variability; amyloid deposits and microvascular pathology explained 12%, and the assessment of thalamic and basal ganglia lacunes added an extra 17%. Deep white matter lacunes were not related to cognitive status in univariate and multivariate models. Conclusions--In agreement with the recently proposed concept of subcortical ischemic vascular dementia, our autopsy series provides important evidence that gray matter lacunes are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer disease.
Revised on February 15, 2005
Accepted on February 25, 2005
Cognitive Consequences of Thalamic, Basal Ganglia, and Deep White Matter Lacunes in Brain Aging and Dementia
Gabriel Gold MD*;
-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes; statistical analysis included multivariate models controlling for age, amyloid deposits, and microvascular pathology.
Key words: aging • brain injuries • cognition • dementia • lacunar infarction • vascular diseases
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