Cognitive Consequences of Thalamic, Basal Ganglia, and Deep White Matter Lacunes in Brain Aging and Dementia

Abstract

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␤-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

Cerebral Microinfarcts: A Systematic Review of Neuropathological Studies

“…For the other two cohorts in that paper (i.e., the ACT (Adult Changes in Thought) Study and the HAAS (Honolulu Asia Aging Study)), data were extracted from the original published articles (White et al, 2002;White, 2009;Wang et al, 2009). When more than one paper reported on the same population (Sonnen et al, 2007(Sonnen et al, , 2009a(Sonnen et al, , 2010Wang et al, 2009;Gold et al, 1997Gold et al, , 2002Gold et al, , 2005Gold et al, , 2007Kö vari et al, 2004Kö vari et al, , 2007Santos et al, 2010;Sinka et al, 2010), the paper with the largest population sample and the most detailed information on microinfarcts was included. There were two exceptions.…”

“…Two out of four papers concerning the ACT cohort (Sonnen et al, 2007(Sonnen et al, , 2009a(Sonnen et al, , 2010Wang et al, 2009) were included, because they described different samples from this cohort (Wang et al, 2009;Sonnen et al, 2007). Three out of eight papers concerning a cohort of autopsied patients at the Geriatric and Psychiatric Hospitals of the University of Geneva were included (Kö vari et al, 2004(Kö vari et al, , 2007Gold et al, 2002Gold et al, , 1997Gold et al, , 2005Gold et al, , 2007Santos et al, 2010;Sinka et al, 2010). The paper by Gold et al (2007) described the largest sample.…”

Elevated Levels of Hemoglobin A1c Are Associated With Cerebral White Matter Disease in Patients With Stroke

“…34 Whereas, hyperglycemia has been shown to lead to microinfarctions and white matter lesions indirectly. 36 These processes could be explained by capillary thickening followed by narrowing of vessel lumen and subsequent chronic ischemia as found in the brains of patients with DM and WMD. 1 Endothelial dysfunction in hyperglycemic states may also contribute to small vessel injury.…”

Visualizing Recovery of Cognitive Function in Stroke

“…Cognitive impairment is most often coupled to infarcts localized in the left anterior and PCA territories post-stroke [20]. Stroke may impair cognition by injury to large regions of cerebral cortex, subcortical white matter connection fibers, or specific regions of the thalamus that are implicated in memory and attention [23].…”