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Vascular cogitive impairment: new insights into diagnosis and prevention
Abstracts / Brain and Cognition 63 (2007) 191–196
age, both grey and white matter decrease in proportion to the total intracranial capacity gradually and relentlessly usurped by the spinal fluid. In addition to aging, white matter and the deep brain nuclei (basal ganglia and thalamus) are also prime targets for small vessel cerebrovascular disease, manifest as hyperintense lesions in the deep gray and white matter and periventricular regions on T2- weighted or on Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging. These subcortical hyperintensities (SH) are present in up to 96% of elderly subjects, increasing with age and vascular risk factors. The pathological substrates include multiple etiologies including loss of ependyma with gliosis, glial swelling (Clasmatodendrosis), demyelination, dilated perivascular spaces, spongiosis, arteriolar hyalinosis, amyloid angiopathy and cyst formation. SH have often been regarded as clinically silent, but they are associated with cognitive impairment if it is sensitively assessed, particularly slowing of information processing and the so-called dysexecutive syndrome. Even small focal lesions (i.e., covert infarcts which are hypointense on T1 and hyperintense on T2) are bad actors, associated with increased risk of stroke and dementia Whether location of SH is important is not so clear, however. Some studies claim localization effects including the work of our group, which has suggested that SH in the anteromedial thalamus correlate with episodic and working memory and that SH involving cholinergic tracts are associated with executive dysfunction. But others report associations with frontal dysfunction irrespective of SH location. Whether SH contribute independently to cognitive deficits over and above global atrophy also remains somewhat controversial. Recently, researchers have begun to address this issue by quantifying both atrophy and SH burden simultaneously. While these studies agree that atrophy explains most of the variance for cognitive decline, SH lesion load likely also contributes. In a sample of 205 cognitively impaired elderly with varying amounts of white matter lesion burden, our group found that atrophy and hyperintensity volume both independently correlated with global cognitive and functional status as well as language and memory in older but not younger individuals. In other words, with modern segmentation techniques, lesion burden can be meaningfully quantified, localization may be important, and selective lesion-cognitive correlations can be discerned. Another important advance in understanding the contribution of white matter changes to clinic-cognitive status is diffusion tensor imaging, which by using echo planar imaging, allows quantification of the molecular motion of water, including magnitude (diffusivity, D) and directionality (fractional anisotropy, FA). Connectivity algorithms permit tractography of white matter fibre bundles, open exciting new prospects for studying brain connectivity in vivo. This has particular relevance for understanding neurobehavioral effects of stroke, and small vessel disease as well
193
as aging. The tantalizing possibilities for studying brain connectivity using DTI will be discussed. doi:10.1016/j.bandc.2006.08.010
Vascular cogitive impairment: new insights into diagnosis and prevention Philip B. Gorelick John S. Garvin Professor and Head Director, Center for Stroke and Research, Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago, Chicago, IL, USA Vascular cognitive impairment (VCI) represents a spectrum of cognitive dysfunction associated with stroke ranging from slight to severe (dementia) (Gorelick, 2003). VCI is a more inclusive construct than vascular dementia (VaD) and may be divided into 3 categories which include VCI, no dementia (vascular CIND); VaD; and mixed VCI with other dementing illness which is most often Alzheimer disease (AD) (Nyehnuis et al., 2004). The role of cerebrovascular disease in cognitive impairment is undergoing renewed study and clarification. Interest in VCI has peaked as it may be a preventable form of cognitive impairment (Gorelick, 2005). AD patients have been studied largely in ambulatory memory or related outpatient clinics, whereas VCI patients have remained largely hidden from view as the focus has been on neurological and functional deficits with cognitive deficits receiving less emphasis in general. Yet, estimates of the frequency of significant cognitive impairment associated with stroke have been as high as about 33% suggesting that we consider shifting our focus to VCI detection, prevention and treatment. We have carried out a series of MRI-based studies to elucidate possible epidemiological risk factors for vascular CIND. Our goal has been to identify factors which predict who will or not develop cognitive impairment after stroke. Our imaging focus has been on utilization of diffusion tensor imaging (DTI) to assess integrity of white matter, voxel-based morphometry (VBM) to assess tissue density, brain volume of key regions of interest (e.g., hippocampus), white matter volume and white matter lesion location, stroke volume, and side and location of cerebral infarction. We discuss results of studies addressing the possible role of DTI and VBM as predictors of vascular CIND, longitudinal change in white matter integrity, and other associated imaging studies of related vascular factors. Our results suggest possible insights which may be used to begin to develop strategies for prevention of VCI and VaD. (Funding Source: NIH/NIA RO1 AG17934, PI: P. B. Gorelick 2000–2003 and D. Nyenhuis 2004–2005.) doi:10.1016/j.bandc.2006.08.011
age, both grey and white matter decrease in proportion to the total intracranial capacity gradually and relentlessly usurped by the spinal fluid. In addition to aging, white matter and the deep brain nuclei (basal ganglia and thalamus) are also prime targets for small vessel cerebrovascular disease, manifest as hyperintense lesions in the deep gray and white matter and periventricular regions on T2- weighted or on Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging. These subcortical hyperintensities (SH) are present in up to 96% of elderly subjects, increasing with age and vascular risk factors. The pathological substrates include multiple etiologies including loss of ependyma with gliosis, glial swelling (Clasmatodendrosis), demyelination, dilated perivascular spaces, spongiosis, arteriolar hyalinosis, amyloid angiopathy and cyst formation. SH have often been regarded as clinically silent, but they are associated with cognitive impairment if it is sensitively assessed, particularly slowing of information processing and the so-called dysexecutive syndrome. Even small focal lesions (i.e., covert infarcts which are hypointense on T1 and hyperintense on T2) are bad actors, associated with increased risk of stroke and dementia Whether location of SH is important is not so clear, however. Some studies claim localization effects including the work of our group, which has suggested that SH in the anteromedial thalamus correlate with episodic and working memory and that SH involving cholinergic tracts are associated with executive dysfunction. But others report associations with frontal dysfunction irrespective of SH location. Whether SH contribute independently to cognitive deficits over and above global atrophy also remains somewhat controversial. Recently, researchers have begun to address this issue by quantifying both atrophy and SH burden simultaneously. While these studies agree that atrophy explains most of the variance for cognitive decline, SH lesion load likely also contributes. In a sample of 205 cognitively impaired elderly with varying amounts of white matter lesion burden, our group found that atrophy and hyperintensity volume both independently correlated with global cognitive and functional status as well as language and memory in older but not younger individuals. In other words, with modern segmentation techniques, lesion burden can be meaningfully quantified, localization may be important, and selective lesion-cognitive correlations can be discerned. Another important advance in understanding the contribution of white matter changes to clinic-cognitive status is diffusion tensor imaging, which by using echo planar imaging, allows quantification of the molecular motion of water, including magnitude (diffusivity, D) and directionality (fractional anisotropy, FA). Connectivity algorithms permit tractography of white matter fibre bundles, open exciting new prospects for studying brain connectivity in vivo. This has particular relevance for understanding neurobehavioral effects of stroke, and small vessel disease as well
193
as aging. The tantalizing possibilities for studying brain connectivity using DTI will be discussed. doi:10.1016/j.bandc.2006.08.010
Vascular cogitive impairment: new insights into diagnosis and prevention Philip B. Gorelick John S. Garvin Professor and Head Director, Center for Stroke and Research, Department of Neurology and Rehabilitation, University of Illinois College of Medicine at Chicago, Chicago, IL, USA Vascular cognitive impairment (VCI) represents a spectrum of cognitive dysfunction associated with stroke ranging from slight to severe (dementia) (Gorelick, 2003). VCI is a more inclusive construct than vascular dementia (VaD) and may be divided into 3 categories which include VCI, no dementia (vascular CIND); VaD; and mixed VCI with other dementing illness which is most often Alzheimer disease (AD) (Nyehnuis et al., 2004). The role of cerebrovascular disease in cognitive impairment is undergoing renewed study and clarification. Interest in VCI has peaked as it may be a preventable form of cognitive impairment (Gorelick, 2005). AD patients have been studied largely in ambulatory memory or related outpatient clinics, whereas VCI patients have remained largely hidden from view as the focus has been on neurological and functional deficits with cognitive deficits receiving less emphasis in general. Yet, estimates of the frequency of significant cognitive impairment associated with stroke have been as high as about 33% suggesting that we consider shifting our focus to VCI detection, prevention and treatment. We have carried out a series of MRI-based studies to elucidate possible epidemiological risk factors for vascular CIND. Our goal has been to identify factors which predict who will or not develop cognitive impairment after stroke. Our imaging focus has been on utilization of diffusion tensor imaging (DTI) to assess integrity of white matter, voxel-based morphometry (VBM) to assess tissue density, brain volume of key regions of interest (e.g., hippocampus), white matter volume and white matter lesion location, stroke volume, and side and location of cerebral infarction. We discuss results of studies addressing the possible role of DTI and VBM as predictors of vascular CIND, longitudinal change in white matter integrity, and other associated imaging studies of related vascular factors. Our results suggest possible insights which may be used to begin to develop strategies for prevention of VCI and VaD. (Funding Source: NIH/NIA RO1 AG17934, PI: P. B. Gorelick 2000–2003 and D. Nyenhuis 2004–2005.) doi:10.1016/j.bandc.2006.08.011