Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia.
OBJECTIVE
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 Abeta-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.


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.
Gold
Gabriel
G
Department of Geriatrics, HUG Belle-Idée, University of Geneva School of Medicine, Geneva, Switzerland. gabriel.gold@hcuge.ch
Kövari
Enikö
E
Herrmann
François R
FR
Canuto
Alessandra
A
Hof
Patrick R
PR
Michel
Jean-Pierre
JP
Bouras
Constantin
C
Giannakopoulos
Panteleimon
P
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D016229:Amyloid beta-Peptides / Q000737:chemistry; D001344:Autopsy; D001479:Basal Ganglia / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D020520:Brain Infarction / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D003071:Cognition; D003072:Cognition Disorders / Q000209:etiology*; D015161:Dementia, Multi-Infarct / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation; D015999:Multivariate Analysis; D016874:Neurofibrillary Tangles / Q000473:pathology; D013788:Thalamus / Q000473:pathology*
D016229:Amyloid beta-Peptides