White matter lesions impair frontal lobe function regardless of their location

Abstract

Objective-To analyze the effect of white matter lesions in different brain regions on regional cortical glucose metabolism, regional cortical atrophy, and cognitive function in a sample with a broad range of cerebrovascular disease and cognitive function.Methods-Subjects (n = 78) were recruited for a study of subcortical ischemic vascular disease (SIVD) and Alzheimer disease (AD) contributions to dementia. A new method was developed to define volumes of interest from high-resolution three-dimensional T1-weighted MR images. Volumetric measures of MRI segmented white matter signal hyperintensities (WMH) in five different brain regions were related to regional PET glucose metabolism (rCMRglc) in cerebral cortex, MRI measures of regional cortical atrophy, and neuropsychological assessment of executive and memory function.Results-WMH was significantly higher in the prefrontal region compared to the other brain regions. In all subjects, higher frontal and parietal WMH were associated with reduced frontal rCMRglc, whereas occipitotemporal WMH was only marginally associated with frontal rCMRglc. These associations were stronger and more widely distributed in nondemented subjects where reduced frontal rCMRglc was correlated with WMH for all regions measured. In contrast, there was no relationship between WMH in any brain region and rCMRglc in either parietal or occipitotemporal regions. WMHs in all brain regions were associated with low executive scores in nondemented subjects.Conclusions-The frontal lobes are most severely affected by SIVD. WMHs are more abundant in the frontal region. Regardless of where in the brain these WMHs are located, they are associated with frontal hypometabolism and executive dysfunction.Vascular factors are increasingly recognized as important contributors to cognitive decline and dementia. Subcortical ischemic vascular disease (SIVD) accounts for 36 to 67% of all vascular

White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age

“…We and others have previously reported cross‐sectional associations of WMH with cognition, most notably perceptual speed and executive functions, and WMH are generally thought to have a relatively domain‐specific effect on cognition 11, 12, 21. In this study, we again observed that the impact of WMH on the initial level of cognition was domain specific, affecting perceptual speed only.…”

“…The degree to which WMH contribute to progressive cognitive decline among older persons initially free of cognitive impairment also is poorly understood. Cross‐sectional studies have shown that WMH are associated with subtle cognitive decrements, particularly in perceptual speed and executive functions,10, 11, 12 but little data are available on the relation of WMH with cognitive decline among persons initially free of cognitive impairment 7, 13, 14, 15, 16. A better understanding of the degree to which WMH increase the risk of MCI and contribute to progressive decline in multiple cognitive systems is needed to facilitate strategies to promote cognitive health in old age.…”

A Voxel-Based Analysis of FDG-PET in Traumatic Brain Injury: Regional Metabolism and Relationship between the Thalamus and Cortical Areas

“…It has been suggested that the strong convergence of white matter fibers in the frontal lobes may explain why lesions in any region of the brain tend to show a proportionally robust effect in this broad associative cortical area. [33] The precuneus seems to be involved in modulating consciousness via corticosubcortical connections that include the thalamus. [26,34] The proper activation of the precuneus has been considered to be critical in the recovery of low-level states of consciousness and has been considered to be a key player in the default mode network.…”

“…In this sense, the loss of connectivity between the precuneus and the frontal or temporal areas has been associated with autism and cognitive impairment with a high risk of developing Alzheimer`s disease, respectively. [33] It is now assumed that brain functions, from the basic mechanism that regulates consciousness to the most complex cognitive processes, are not located in specific brain areas of isolated functioning but occur via intricate neural connections underlying the dynamic interactions between brain regions.…”

Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey

“…Bowley et al (2010) and many others (Feldman and Peters 1998;Peters and Sethares 2002;Sandell and Peters 2003) have reported an age-related accumulation of myelin defects and axon loss in forebrain white matter pathways of the rhesus monkey (e.g., the corpus callosum and cingulum bundle, anterior commissure). Additionally, others have shown age-related loss of white matter volume in MRI (Guttmann et al 1998;Wisco et al 2008), increases in white matter hyperintensities in MRI (Tullberg et al 2004;Wakefield et al 2010) and increased myelin damage inferred by loss of fractional anisotropy from diffusion tensor imaging (DTI; Makris et al 2007). As myelin defects accumulate with age, it is likely that microglia would be activated and participate in the clearance of damaged white matter and axons.…”