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      Glucose Metabolism Measured by Positron Emission Tomography is Reduced in Patients with White Matter Presumably Ischemic Lesions

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          Abstract

          Background

          The severity and progression of white matter ischemic lesion (WMIL) are closely linked to vascular dementia. The function of neural tissue is closely linked to glucose consumption as the most important energy-supplying metabolic process. At present, 18fluorine-fluorodeoxy glucose ( 18FDG) positron emission tomography (PET) can provide regional and 3-dimensional quantification of glucose metabolism in the human brain. Although MMSE and MoCA are commonly used screens in cognitive impairment, no research team has yet validated their performance in WMIL. The purpose of our study was to compare MMSE and MoCA in screening for cognitive impairment and to explore the correlations between CMRglu values and executive function.

          Material/Methods

          All the participants underwent comprehensive clinical, MoCA, MMSE, MRI, and PET examinations. Patients in the WMIL group were subdivided into 3 severity subgroups according to the Fazekas scale.

          Results

          The MoCA scores were lower in the WMIL group. Our research indicates that MoCA is a more sensitive screening tool than the commonly used MMSE in detecting cognitive impairment in patients with WMIL. CMRglu values of gray matter were decreased in the WMIL group. Reductions of CMRglu in parietal lobe, frontal lobe, and white matter centrum semiovale were observed to different degrees in the WMIL groups according to the modified Fazekas scale. A significant negative correlation was found between executive function and CMRglu in the frontal lobe.

          Conclusions

          MoCA appears to be a more sensitive screening tool than the commonly used MMSE in detecting cognitive impairment in patients with WMIL. CMRglu can potentially be used as a biomarker for predicting the severity of WMIL.

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          Most cited references23

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          Understanding white matter disease: imaging-pathological correlations in vascular cognitive impairment.

          Most strokes are covert and observed incidentally on brain scans, but their presence increases risk of overt stroke and dementia. Amyloid angiopathy, associated with Alzheimer Disease (AD) causes stroke, and when even small strokes coexist with AD, they lower the threshold for dementia. Diffuse ischemic white matter disease impairs executive functioning, information processing speed, and gait. Neuroimaging techniques, such as tissue segmentation, Diffusion Tensor Imaging, MR Spectroscopy, functional MRI and amyloid PET, probe microstructural integrity, molecular biology, and activation patterns, providing new insights into brain-behavior relationships. MR-pathological studies of periventricular hyperintensity (leukoaraiosis) in aging and dementia reveal arteriolar tortuosity, reduced vessel density, and occlusive venous collagenosis which causes venous insufficiency and vasogenic edema. Activated microglia, oligodendroglial apoptosis, clasmatodendritic astrocytosis, and upregulated hypoxia-markers are seen on immunohistochemistry. Further research is needed to understand and treat this chronic subcortical vascular disease, which is epidemic in our aging population.
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            Location of lacunar infarcts correlates with cognition in a sample of non-disabled subjects with age-related white-matter changes: the LADIS study.

            In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (beta = -0.61; p = 0.043), and worse compound scores for speed and motor control (beta = -0.25; p = 0.006), executive functions (beta = -0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (beta = -0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.
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              Adenosine A2A receptors in secondary progressive multiple sclerosis: a [(11)C]TMSX brain PET study.

              In this study, positron emission tomography (PET) imaging with a radioligand to adenosine A2A receptors (A2AR)-a potent regulator of inflammation-was used to gain insight into the molecular alterations in normal-appearing white matter (NAWM) and gray matter (GM) in secondary progressive multiple sclerosis (SPMS). Normal-appearing white matter and GM, despite seeming normal in conventional magnetic resonance imaging (MRI), are important loci of widespread inflammation, neuronal damage, and source of progressive disability in multiple sclerosis (MS). Dynamic PET imaging using A2AR-specific [(11)C]TMSX and brain MRI with diffusion tensor imaging were performed to eight SPMS patients and seven healthy controls. Distribution volumes (VT) of [(11)C]TMSX were analyzed from 13 regions of interest using Logan plot with arterial plasma input. The SPMS patients had significantly increased [(11)C]TMSX-VT in NAWM compared with controls (mean (s.d.): 0.55 (±0.08) vs. 0.45 (±0.05); P=0.036). Both the increased VT and the decreased fractional anisotropy (FA) in NAWM were associated with higher expanded disability status scale (EDSS) scores (P=0.030 and P=0.012, respectively), whereas the T2-lesion load of SPMS patients did not correlate with EDSS. This study shows, that A2ARs are increased in the brain of SPMS patients, and that [(11)C]TMSX-PET provides a novel approach to learn about central nervous system pathology in SPMS in vivo.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2014
                27 August 2014
                : 20
                : 1525-1530
                Affiliations
                Department of Neurology, Beijing Chaoyang Hospital (Xi District), Capital Medical University, Beijing, China
                Author notes
                Corresponding Author: Wenli Hu, e-mail: deepwater1985@ 123456163.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                892137
                10.12659/MSM.892137
                4156339
                25159539
                d5c91e19-3808-4650-bb06-03be0787f5b9
                © Med Sci Monit, 2014

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 31 July 2014
                : 05 August 2014
                Categories
                Clinical Research

                leukoaraiosis,mild cognitive impairment,positron-emission tomography

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