Duk L. Na

Brief Screening for Mild Cognitive Impairment in Elderly Outpatient Clinic : Validation of the Korean Version of the Montreal Cognitive Assessment

The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening tool with high sensitivity for screening patients with mild cognitive impairment (MCI). The authors examined the validity and reliability of the Korean version of the MoCA (MoCA-K) in elderly outpatients. The MoCA-K, a Korean version of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and neuropsychological batteries were administered to 196 elderly persons (mild Alzheimers disease [AD] = 44, MCI = 37, normal controls [NC] = 115). MoCA-K scores were highly correlated with those of MMSE and CDR. Using a cutoff score of 22/23, the MoCA-K had an excellent sensitivity of 89% and a good specificity of 84% for screening MCI. Internal consistency and test−retest reliability were good. The results obtained show that the MoCA-K is brief, reliable, and suitable for use as a screening tool to screen MCI patients in elderly outpatient clinic settings.

Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients

The Seoul Neuropsychological Screening Battery (SNSB) is one of the standardized neuropsychological test batteries widely used in Korea. However, it may be a bit too lengthy for patients with decreased attention span; and it does not provide the score of global cognitive function (GCF), which is useful for monitoring patients longitudinally. We sought to validate a dementia version of SNSB (SNSB-D) that was shorter than the original SNSB and contained only scorable tests with a GCF score of 300. We administered SNSB-D to patients with mild cognitive impairment (MCI) (n=43) and Alzheimers disease (AD) (n=93), and normal controls (NC) (n=77). MCI and AD groups had GCF scores significantly different from NC group, and GCF scores were able to distinguish patients with Clinical Dementia Rating of 0.5 and 1. Test-retest reliability was high, with a correlation coefficient of 0.918 for AD, 0.999 for MCI, and 0.960 for NC. The GCF score significantly correlated with the Mini-Mental State Examination (MMSE). Through ROC-curve analysis, GCF scores were found to yield more accurate diagnoses than the MMSE. The SNSB-D is a valid, reliable tool for assessing the overall cognitive function, and can be used to monitor cognitive changes in patients with dementia.

Systematic review of health behavioral risks and cognitive health in older adults

BACKGROUND An increasing body of evidence suggests that health behaviors may protect against cognitive impairment and dementia. The purpose of this study was to summarize the current evidence on health behavioral factors predicting cognitive health through a systematic review of the published literature. METHODS PubMed, Embase, and PsycINFO databases were searched for studies on community representative samples aged 65 and older, with prospective cohort design and multivariate analysis. The outcome--cognitive health--was defined as a continuum of cognitive function ranging from cognitive decline to impairment and dementia, and health behaviors included physical activity, smoking, alcohol drinking, body mass index, and diet and nutrition. RESULTS Of 12,105 abstracts identified, 690 relevant full-texts were reviewed. The final yield amounted to 115 articles of which 37 studies were chosen that met the highest standards of quality. Leisure time physical activity, even of moderate level, showed protective effects against dementia, whereas smoking elevated the risk of Alzheimers disease. Moderate alcohol consumption tended to be protective against cognitive decline and dementia, but nondrinkers and frequent drinkers exhibited a higher risk for dementia and cognitive impairment. Midlife obesity had an adverse effect on cognitive function in later life. Analysis showed vegetable and fish consumption to be of benefit, whereas, persons consuming a diet high in saturated fat had an increased dementia risk. CONCLUSION The review demonstrates accumulating evidence supporting health behavioral effects in reducing the risk of cognitive decline and dementia. Results indicate potential benefits of healthy lifestyles in protecting cognitive health in later life.

Cortical thickness in single- versus multiple-domain amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. However, there have been no studies that specifically investigate the structural differences that support this classification. In an attempt to compare regional cortical thickness in two subtypes of aMCI, we aimed to map the distribution of cortical thinning using a surface based cortical analysis of magnetic resonance imaging. The cortical thickness across the entire brain was measured in 9 patients with S-aMCI, 22 patients with M-aMCI, and 61 normal healthy subjects. Differences in the patterns of cortical thinning between S-aMCI and M-aMCI were assessed using ANCOVA on a vertex-by-vertex basis, and statistical maps of differences in cortical thickness between the groups were constructed using a surface model. Relative to controls, S-aMCI patients showed cortical thinning in the left medial temporal lobe, and M-aMCI patients showed cortical thinning in the left medial temporal lobe, precuneus, and anterior and inferior basal temporal, insular, and temporal association cortices. When the two MCI groups were directly compared, M-aMCI patients showed cortical thinning in left precuneus. Our studies suggest that M-aMCI is a transitional state between S-aMCI and Alzheimers disease, and that the cortical thinning is evidence that the precuneus is responsible for the multiple cognitive impairments in M-aMCI.

Functional magnetic resonance imaging during pantomiming tool-use gestures.

Abstract. The purpose of this study was to identify the functional fields activated in relation to gestural movements. Using functional magnetic resonance imaging (fMRI), we mapped brain activity in ten right-handed, normal volunteers during activation and control tasks. The activation condition consisted of pantomiming tool-use gestures with either the left hand or right hand, whereas the control condition comprised repetitive, oppositional movements between thumb and index finger. Activated cortical regions were highly lateralized to the left hemisphere during pantomiming of tool use regardless of hand used. Praxis with either hand commonly activated the superior parietal lobule, supplementary motor area, premotor area of the left hemisphere, and cerebellar vermis. However, minimal activation occurred in the inferior parietal lobule, which has been known to be a critical area for praxis generation. Compared with left-hand praxis, right-hand praxis exhibited additional activation in the left putamen and posterior part of the left inferior temporal region. Our findings concur with neuropsychological observations that the left hemisphere in right-handers mediates programming and executing skilled movements and that, within the left hemisphere, praxis is predominantly subserved by the parietal lobe, supplementary motor area, and premotor area. However, unlike previous lesion studies, the results of our fMRI study suggested that the superior parietal lobule more likely than the inferior parietal lobule play an important role in gesture production.

Clinical Significance of Microbleeds in Subcortical Vascular Dementia

Background and Purpose— Despite many studies investigating the association between the ischemic changes and cognitive impairment in subcortical vascular dementia (SVaD), few studies correlated cognitive impairment with microbleeds (MBs) frequently seen in SVaD. Methods— Participants consisted of 86 patients with SVaD who fulfilled the criteria proposed by Erkinjuntti et al. Results— MBs occurred in 73 of 86 (84.9%) patients with SVaD. MBs were most commonly distributed in the cortex, and the cortical MBs were most pronounced in the temporoparietal area. A multiple regression showed that the number of cerebral MB was an independent predictor of cognitive impairment in multiple domains and the severity of dementia even after controlling confounding factors such as age, education, ischemic severity, and number of lacunes. Conclusion— These results indicate that cerebral MB is one of the important factors that cause cognitive impairments in SVaD.

Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B

Background: Subcortical vascular dementia (SVaD) is considered the most common type of vascular dementia and often follows a slowly progressive course, simulating Alzheimer disease (AD). Whether the progressive cognitive decline is associated with pure SVaD or concomitant AD remains unknown. The purpose of this study was to determine what proportion of patients with SVaD lack abnormal amyloid imaging, and to examine differences in the clinical or MRI features between subjects with SVaD with cortical amyloid deposition and those without. Methods: We measured brain amyloid deposition using 11C-Pittsburgh compound B (PiB) PET in 45 patients (men: women = 19:26; mean age 74.2 ± 7.6 years) with SVaD. They all met DSM-IV criteria for vascular dementia and had severe white matter high signal intensities without territorial infarction or macrohemorrhage on MRI. Results: Thirty-one (68.9%) of 45 patients with SVaD were negative for cortical PiB binding. There was significant difference between 11C-PiB-positive and 11C-PiB-negative groups in terms of age (79.5 vs 71.9 years), Mini-Mental State Examination score (18.6 vs 22.6), the number of lacunes (3.9 vs 9.0), and the visual rating scale of hippocampal atrophy (3.1 vs 2.3). The neuropsychological assessments revealed that patients with 11C-PiB-negative SVaD performed better on the delayed recall of both the verbal and visual memory test than did those with 11C-PiB-positive scan. Conclusion: SVaD without abnormal amyloid imaging was more common than expected. Patients with SVaD with and without abnormal amyloid imaging differed in clinical and MRI features, although there was considerable overlap.

Dissociation of sensory-attentional from motor-intentional neglect

OBJECTIVES Spatial neglect may result from disruption of sensory-attentional systems that spatially allocate perceptual resources and the motor-intentional systems that direct exploration and action. Previous studies have suggested that the line bisection task is more sensitive to sensory-attentional disorders and the cancellation task to motor-intentional disorders. A new technique was developed that allows the dissociation of sensory-attentional and motor-intentional deficits in both tasks and thereby allows comparison of these tasks. METHODS Ten patients with right hemispheric injury and hemispatial neglect performed line bisection and cancellation tasks while viewing stimuli on closed circuit TV. Direct view of the exploring hand and the target was precluded; the TV monitor guided performance. The direct condition made the direction of hand movement on the table (workspace) congruent with that on the monitor. Inverting the camera produced the indirect condition wherein the lateral movement in the workspace occurred in the opposite direction on the monitor. RESULTS On the cancellation task, five patients marked targets in the right workspace in the direct condition but the left workspace in the indirect condition, indicating sensory-attentional neglect. However, four other patients cancelled targets only in the right workspace in both conditions, failing to explore the left workspace, suggesting motor-intentional neglect. A patient who performed ambiguously may have elements of both types of neglect. Only two out of five patients designated as sensory-attentional in cancellation tasks showed sensory neglect on line bisection. The other three patients, as well as patients defined as motor-intentional by cancellation performance, exhibited motor-intentional neglect on line bisection. CONCLUSION The designation of sensory-attentional versus motor-intentional neglect therefore, in part, depends on task specific demands.

Soluble intracellular adhesion molecule-1 secreted by human umbilical cord blood-derived mesenchymal stem cell reduces amyloid-β plaques

Presently, co-culture of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) with BV2 microglia under amyloid-β42 (Aβ42) exposure induced a reduction of Aβ42 in the medium as well as an overexpression of the Aβ-degrading enzyme neprilysin (NEP) in microglia. Cytokine array examinations of co-cultured media revealed elevated release of soluble intracellular adhesion molecule-1 (sICAM-1) from hUCB-MSCs. Administration of human recombinant ICAM-1 in BV2 cells and wild-type mice brains induced NEP expression in time- and dose-dependent manners. In co-culturing with BV2 cells under Aβ42 exposure, knockdown of ICAM-1 expression on hUCB-MSCs by small interfering RNA (siRNA) abolished the induction of NEP in BV2 cells as well as reduction of added Aβ42 in the co-cultured media. By contrast, siRNA-mediated inhibition of the sICAM-1 receptor, lymphocyte function-associated antigen-1 (LFA-1), on BV2 cells reduced NEP expression by ICAM-1 exposure. When hUCB-MSCs were transplanted into the hippocampus of a 10-month-old transgenic mouse model of Alzheimers disease for 10, 20, or 40 days, NEP expression was increased in the mice brains. Moreover, Aβ42 plaques in the hippocampus and other regions were decreased by active migration of hUCB-MSCs toward Aβ deposits. These data suggest that hUCB-MSC-derived sICAM-1 decreases Aβ plaques by inducing NEP expression in microglia through the sICAM-1/LFA-1 signaling pathway.

Motor perseverative behavior on a line cancellation task

Objectives: To study the behavioral and neuroanatomic characteristics of perseverative behavior encountered on a target cancellation task in patients with neglect. Methods: Motor perseverative behavior during line cancellation task was evaluated retrospectively in 60 patients with left hemispatial neglect from right hemispheric stroke. Results: More than 30% of the patients (21 of 60) showed perseveration, manifested as either repetitive cancellation of the same target (18/21) or cancelling extra lines created by the patients themselves (3/21). Neglect severity correlated positively with the frequency of perseverative errors. Perseveration was most prominent in the rightmost portion of the array. Anterior lesions or massive lesions involving anterior and posterior regions were more likely to be associated with motor perseveration than were lesions restricted to posterior areas. Conclusions: Although the mechanism of motor perseveration remains to be elucidated, our findings suggest that the combination of aberrant approach behaviors associated with frontal lobe injury and an attentional or intentional bias toward the rightsided targets might explain the behavior.