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Background: Brain and cortical atrophy play crucial roles in supporting the clinical diagnosis of Alzheimer's disease (AD). This study hypothesized that the ratios of brain or cortical volume to subcortical gray matter structure volumes are potential imaging markers for cognitive alterations in AD dementia and amnestic mild cognitive impairment (aMCI)., Methods: Seventy-seven subjects diagnosed with AD dementia or aMCI underwent baseline neuropsychological testing, 2-year follow-up cognitive assessments, and high-resolution T1-weighted MRI scans. Total brain/cortical volume and subcortical gray matter structure volumes were automatically segmented and measured. Univariate and multiple linear regression analyses were conducted to determine the associations between volumetric ratios and interval changes in cognitive scores., Results: The ratio of cortical volume to caudate volume showed the most significant association with changes in MoCA (B = 0.132, SE = 0.042, p = 0.002), MMSE (B = 0.140, SE = 0.040, p = 0.001), and CDR-SOB (B = -0.013, SE = 0.005, p = 0.007) scores over the 2-year follow-up period. These associations remained significant after adjusting for various covariates. Similar associations were observed for the ratios of cortical volume to putamen and globus pallidum volumes., Conclusions: The cortex-to-caudate volume ratio is significantly associated with cognitive decline in AD dementia and aMCI. This ratio may serve as a useful biomarker for monitoring disease progression and predicting cognitive outcomes. Our findings highlight the importance of considering the relative atrophy of cortical and subcortical structures in understanding AD pathology., Competing Interests: Declaration of competing interest The authors report no disclosures relevant to the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson's disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog)., Methods: We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test-retest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. Spearman's rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity., Results: The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively)., Conclusion: Our., Results: demonstrate that the K-SCOPA-Cog has good reliability and validity.

Background: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients., Objectives: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients., Methods: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change., Results: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied., Conclusions: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off., (© 2024 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Transcranial direct current stimulation (tDCS) can potentially enhance brain function and cognition in healthy individuals as well as in patients with cognitive impairment. However, neural correlates of repeated tDCS remain relatively unexplored in a healthy population., Purpose: To assess the effects of repeated tDCS on regional cerebral blood flow (rCBF) in healthy volunteers in a pilot investigation., Material and Methods: Five healthy adults received bifrontal tDCS to the dorsolateral prefrontal cortex (F3-F4 montage, 1 mA intensity, 30 minutes/session, five sessions/week) over four weeks. All participants underwent brain single-photon emission computed tomography (SPECT) scans at baseline and one week after the last tDCS session. Changes in rCBF were examined using Statistical Parametric Mapping., Results: Resting rCBF was significantly improved in the right superior frontal gyrus at the follow-up ( P  < 0.001). Adverse events were not reported and the stimulation was well-tolerated., Conclusion: Repeated tDCS may be effective for enhancing brain function in healthy participants. Larger sham-controlled studies should be performed to confirm our preliminary findings.

There has been an increasing demand for robotic coil positioning during repetitive transcranial magnetic stimulation (rTMS) treatment. Accurate coil positioning is crucial because rTMS generally targets specific brain regions for both research and clinical application with other reasons such as safety, consistency and reliability and individual variablity. Some previous studies have employed industrial robots or co-robots and showed they can more precisely stimulate the target cortical regions than traditional manual methods. In this study, we not only developed a custom-TMS robot for better TMS coil placement but also analyzed the therapeutic effects on depression. Treatment effects were evaluated by measuring regional cerebral blood flow (rCBF) using single-photon emission computed tomography and depression severity before and after rTMS for the two positioning methods. The rTMS preparation time with our robotic coil placement was reduced by 53% compared with that of the manual method. The position and orientation errors were also significantly reduced from 11.17 mm and 4.06° to 0.94 mm and 0.11°, respectively, confirming the superiority of robotic positioning. The results from clinical and neuroimaging assessments indicated comparable improvements in depression severity and rCBF in the left dorsolateral prefrontal cortex between the robotic and manual rTMS groups. A questionnaire was used to determine the patients' feelings about the robotic system, including the safety and preparation time. A high safety score indicated good acceptability of robotic rTMS at the clinical site., (© 2023. Springer Nature Limited.)

Introduction: This study is to explore the long-term functional outcome of antihypertensive medication-naïve, untreated hypertension (HTN) patients with acute ischemic stroke compared to those with no prior HTN and those with treated HTN., Patients and Methods: We analyzed a prospectively collected stroke registry of all patients with acute ischemic stroke consecutively admitted to Incheon St. Mary's Hospital. Patients who received reperfusion therapy were excluded. Long-term functional outcomes were assessed at a 3-month follow-up visit using the modified Rankin Scale., Results: A total of 1044 patients was enrolled. Compared to patients with no or treated HTN, those with untreated HTN had higher odds for more favorable outcomes (adjusted odds ratio (OR): 1.7 [95% CI: 1.0-2.7, p = 0.050*] and 1.7 [95% CI: 1.0-2.8, p = 0.047*], respectively) when the stroke was large vessel atherosclerosis (LAA)/cardioembolic (CE) with large vessel occlusion/stenosis. However, no such association was observed when there was no large vessel occlusion or stenosis, in total patients, or if the index stroke was related to SVO. In untreated HTN patients with LAA/CE and large vessel occlusion/stenosis compared to patients in the lowest mean arterial pressure quartile (< 96.7 mmHg), patients in the second and third highest quartiles had higher odds of favorable outcomes., Conclusions: Patients with untreated HTN had significantly more favorable outcomes at 3 months after ischemic stroke compared to those with no or treated HTN when the stroke was LAA/CE with large vessel occlusion/stenosis. Untreated HTN patients also showed an association between higher MAP and favorable outcomes., (© 2023. Fondazione Società Italiana di Neurologia.)

Introduction: Studies regarding multiple chronic lacunes (MCLs) and clinical outcome according to stroke etiology are scarce. We sought to evaluate the association between MCL and short-term/long-term clinical outcomes according to stroke etiology., Patients and Methods: We analyzed a prospectively collected stroke registry of acute ischemic stroke patients over 4 years. The enrolled patients were classified as having large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic (CE) stroke, and other etiology. The early neurological deterioration (END) and favorable outcome at 3 months were assessed., Results: A total of 1070 patients were enrolled. Patients with MCL had significantly more END compared to those without MCL both in total population (adjusted odds ratio (OR), 1.7; 95% confidence interval [CI], 1.1-2.5; p = 0.013*) and in the LAA group (adjusted OR, 2.3; 95% CI, 1.3-4.2, p < 0.006). Patients with MCL had a significantly lower OR for favorable outcome at 3 months compared to those without MCL both in total population (adjusted OR, 0.7; 95% CI, 0.5-1.0, p = 0.035) and in the LAA group (adjusted OR, 0.6; 95% CI, 0.3-1.0, p = 0.043). However, MCL was not associated with END or long-term functional outcome in patients with SVO, CE, or other etiology., Conclusions: The presence of MCL was an independent predictive factor for END as well as long-term poor functional outcome in acute ischemic stroke patients. These associations were only observed in patients with LAA, not in those with SVO, CE, or other etiology., (© 2022. Fondazione Società Italiana di Neurologia.)

Purpose: We evaluated the associations between serum complement levels and tuberculous meningitis (TBM), bacterial meningitis (BM), and viral meningitis (VM), as well as the association between serum complement levels and mortality in TBM., Methods: Background information and blood/cerebrospinal fluid analysis results were collected from 2009 to 2019. Patients who had serum complement level data collected at admission and who were diagnosed with TBM (n = 97), BM (n = 31), or VM (n = 557) were enrolled., Results: Initial serum complement levels were significantly lower in the TBM group than the VM group in both the total population and the propensity score-matched population. In the TBM and VM groups, compared to patients with initial highest-quartile C4 level, patients in the lowest quartile (C4 < 24.3 mg/dL) had significantly greater odds of TBM diagnosis (odds ratio, 2.2; 95% confidence interval, 1.0-4.5; p = 0.038). In the TBM group, patients with the lowest-quartile C3 level (<96.9 mg/dL) experienced a significantly higher 90-day mortality rate compared to other TBM patients (hazard ratio, 19.0; 95% confidence interval, 2.1-167.4.5; p = 0.008)., Conclusion: Both serum C3 and C4 levels were significantly lower in the TBM group than in the VM group. TBM patients with lower serum C3 level had a significantly higher mortality rate than those with higher C3 level., Competing Interests: Conflicts of Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2023 Korean Encephalitis and Neuroinflammation Society.)

Introduction: Cervical dystonia is considered as a network disorder affecting various brain regions in recent days. Presumably, deep brain stimulation (DBS) of the internal segment of globus pallidus (GPi) may exert therapeutic effects for cervical dystonia through modulation of the aberrant brain networks. In the present study, we investigated postoperative regional cerebral blood flow (rCBF) changes after GPi DBS using single-photon emission computed tomography (SPECT) to identify significant activity changes in several relevant brain areas of cervical dystonia patients., Methods: A total of 9 patients with idiopathic cervical dystonia were recruited, and SPECT scans were conducted at baseline and 3 months after the bilateral GPi DBS. Voxel-wise changes of rCBF were analyzed using Statistical Parametric Mapping. Symptom severity of dystonia was measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at the baseline, and 1 week, and 3 months after GPi DBS., Results: At the 3-month follow-up after DBS, rCBF was increased in the left pons and right postcentral gyrus and decreased in the left middle frontal gyrus, left cerebellum, right putamen and pallidum, and left thalamus (p < 0.001). Severity of cervical dystonia assessed by TWSTRS was significantly decreased at 1-week and 3-month follow-up (p = 0.004)., Conclusions: Clinical improvement of cervical dystonia after GPi DBS may be accompanied by rCBF changes in several brain areas of the cortico-basal ganglia-cerebellar network which are important for sensorimotor integration., (© 2022. The Author(s).)

Objective: Acute ischemic stroke in the territory of anterior cerebral artery (ACA) is uncommon. Therefore, large population studies evaluating ACA infarction are scarce. We sought to evaluate epidemiological and etiological characteristics of ACA infarction compared to other territorial infarctions., Methods: We analyzed a prospectively collected stroke registry of all acute ischemic stroke patients for 19 years at two tertiary hospitals. We included patients with acute ischemic stroke caused by large vessel stenosis or occlusion including ACA, middle cerebral artery (MCA), posterior cerebral artery (PCA), and vertebrobasilar artery (VBA)., Results: A total of 4171 patients were enrolled. Patients with ACA infarction (N = 288) were significantly older with more females than those with MCA, PCA, or VBA infarction. There were more patients with history of prior ischemic stroke in the ACA infarction group than in other groups. The etiology of the ACA infarction was similar to those of the MCA, PCA and also the total population (66.7-71.8% of LAA and 17.9-20.9% of CE). When patients had prior ischemic stroke history, ACA infarction was more likely to be caused by LAA than MCA or PCA infarction (OR = 6.2, 95% CI 2.0-19.2, p = 0.002 and OR = 4.0, 95% CI 1.1-14.6, p = 0.038, respectively)., Conclusions: Patients with ACA infarction had significantly more prior ischemic stroke than those with MCA, PCA, or VBA infarction. The etiology of ACA infarction in patients with prior ischemic stroke showed significantly more LAA than that of MCA or PCA infarction., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Although various neuropsychiatric symptoms are frequently accompanied with Alzheimer's disease (AD) and pose a substantial burden to both patients and caregivers, their neurobiological underpinnings remain unclear. This study investigated associations between regional cerebral blood flow (rCBF) and neuropsychiatric symptom domains in early AD. A total of 59 patients with early AD underwent brain technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) scans. Neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory and clustered into the affective, apathy, hyperactivity, and psychotic domains. A voxel-wise multiple regression analysis was performed with four domain scores as independent variables and age, sex, and Mini-Mental State Examination scores as covariates. The affective domain score was negatively correlated with rCBF in the prefrontal cortex, thalamus, and caudate. The apathy domain score showed inverse correlations with rCBF in the prefrontal and pre/postcentral gyri and midbrain. Patients with higher hyperactivity domain scores had increased rCBF in the prefrontal and temporal lobes. The psychotic symptom domain was positively correlated with rCBF in the cuneus and negatively associated with rCBF in the prefrontal, cingulate, and occipital regions and putamen. The score of each neuropsychiatric symptom domain showed the differential correlates of brain perfusion, while altered rCBF in the prefrontal cortex was found in all domains. Although preliminary, our results may suggest common and distinct patterns of rCBF underlying neuropsychiatric symptoms in early AD. Further studies with larger samples and control participants are warranted to confirm these findings.

Preclinical studies have suggested that low-intensity transcranial focused ultrasound (tFUS) may have therapeutic potential for Alzheimer's disease (AD) by opening the blood-brain barrier (BBB), reducing amyloid pathology, and improving cognition. This study investigated the effects of tFUS on BBB opening, regional cerebral metabolic rate of glucose (rCMRglu), and cognitive function in AD patients. Eight patients with AD received image-guided tFUS to the right hippocampus immediately after intravenous injection of microbubble ultrasound contrast agents. Patients completed magnetic resonance imaging (MRI), 18 F-fluoro-2-deoxyglucose positron emission tomography (PET), and cognitive assessments before and after the sonication. No evidence of transient BBB opening was found on T1 dynamic contrast-enhanced MRI. However, immediate recall ( p = 0.03) and recognition memory ( p = 0.02) were significantly improved on the verbal learning test. PET image analysis demonstrated increased rCMRglu in the right hippocampus ( p = 0.001). In addition, increases of hippocampal rCMRglu were correlated with improvement in recognition memory (Spearman's ρ = 0.77, p = 0.02). No adverse event was observed. Our results suggest that tFUS to the hippocampus of AD patients may improve rCMRglu of the target area and memory in the short term, even without BBB opening. Further larger sham-controlled trials with loger follow-up are warranted to evaluate the efficacy and safety of tFUS in patients with AD.

Objectives: Transcranial Doppler ultrasound (TCD) is noninvasive and highly sensitive and specific for the diagnosis of patent foramen ovale (PFO). We evaluated the diagnostic implications of the TCD with a saline agitation test as a routine work-up for ischemic stroke patients., Methods: A TCD bubble study was performed in all consecutive ischemic stroke patients as a routine work-up. We evaluated the prevalence of microembolic signals (MES) for each stroke etiology and the optimal number of MES for predicting the PFO-attributable stroke., Results: Subjects (N = 499) with acute ischemic stroke were enrolled. A significant fraction of patients had MES during both normal respiration (5.7-44.4%) and the Valsalva maneuver (19.5-55.6%) across all stroke etiology categories. The optimal MES threshold for the diagnosis of PFO-attributable stroke confirmed by transesophageal echocardiography was 46 MES during the Valsalva maneuver (96% sensitivity and 95% specificity). Applying ≥46 MES during the Valsalva maneuver as a threshold effectively increased the ability to differentially diagnose PFO-attributable stroke from other etiologies. The number of MES during the Valsalva maneuver was negatively correlated with increasing age (r = -.108; P = .016)., Conclusions: A significant fraction of patients had right to left shunt across all Trial of ORG 10172 in Acute Stroke Treatment etiologies. A threshold number of MES facilitated the differential diagnosis of PFO-attributable stroke from other etiologies, and the optimal threshold was 46 MES during the Valsalva maneuver., (© 2021 American Institute of Ultrasound in Medicine.)

Objective: Clinical and radiological findings on neurosyphilis are fairly non-specific and there is a paucity of functional neuroimaging studies on neurosyphilis other than case reports and case series. The purpose of this study was to investigate brain perfusion abnormalities in patients with neurosyphilis. Methods: Four HIV-negative neurosyphilis patients and 4 healthy controls underwent clinical evaluation, brain technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT) imaging, and neuropsychological assessments which included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating-Sum of Boxes (CDR-SOB), and Global Deterioration Scale (GDS). Voxel-wise differences in regional cerebral blood flow were compared between the two groups. Results: Neuropsychological test results indicated cognitive impairment in all patients. SPECT analysis revealed multifocal hypoperfusion predominantly in the frontal, insular, and posterior cingulate regions in neurosyphilis patients compared with healthy controls (family-wise error corrected p < 0.05). Conclusions: Together with previous findings, our results suggest that the hypoperfusion in the frontal, insular, and posterior cingulate regions may reflect cognitive impairments observed in neurosyphilis patients. Further studies with larger samples are needed to confirm our findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Im, Jeong, Kim, Jang, Song and Chung.)

Purpose: Increasing attention has been paid to low-intensity transcranial focused ultrasound (tFUS) for its potential therapeutic effects in Alzheimer's disease (AD). While preclinical studies have shown promising therapeutic effects of low-intensity tFUS in AD models, its efficacy and safety remain unclear in humans. In this pilot study, we investigated the effects of low-intensity tFUS on blood-brain barrier opening, the regional cerebral metabolic rate of glucose (rCMRglu), and cognition in patients with AD., Methods: After receiving institutional review board approval, four patients with AD received tFUS to the hippocampus immediately after an intravenous injection of a microbubble ultrasound contrast agent. Sonication was delivered at low-intensity, at a pressure level below the threshold for blood-brain barrier opening. Patients underwent brain magnetic resonance imaging, 18F-fluoro-2-deoxyglucose positron emission tomography, and neuropsychological assessments before and after the tFUS procedure. A whole-brain voxel-wise paired t test was conducted to compare rCMRglu before and after tFUS., Results: The sonication, as anticipated, did not show evidence of active blood-brain barrier opening on T1 dynamic contrast-enhanced magnetic resonance imaging. rCMRglu in the superior frontal gyrus (P<0.001), middle cingulate gyrus (P<0.001), and fusiform gyrus increased after tFUS (P=0.001). Patients demonstrated mild improvement in measures of memory, executive, and global cognitive function following tFUS. No adverse events were reported., Conclusion: These results suggest that hippocampal sonication with low-intensity tFUS may have beneficial effects on cerebral glucose metabolism and cognitive function in patients with AD. Further larger studies are needed to confirm the therapeutic efficacy of tFUS in AD.

Background: The current lack of effective treatments for Alzheimer's disease (AD) and the rapidly increasing burden of the disease highlight the urgent need to find new treatments. Despite accumulating evidence of the beneficial effects of rasagiline in neurodegenerative diseases such as Parkinson's disease, the effects of rasagiline on the brains of patients with AD have not been elucidated., Purpose: To examine the effects of rasagiline on regional cerebral flow (rCBF) in patients with AD using single photon emission computed tomography (SPECT)., Material and Methods: Among 22 patients with AD, 11 patients received adjunctive rasagiline at 1 mg/day in conjunction with acetylcholinesterase inhibitors (AChEI); 11 patients were only treated with AChEI for about 1.6 years. All patients underwent brain technetium-99m hexamethylpropylene amine oxime SPECT scans and clinical assessments at baseline and follow-up visits. Annual percent changes in rCBF were compared between the groups in a voxel-wise manner., Results: SPECT analysis revealed that the rasagiline-treated group showed more increased rCBF in the cingulate gyrus, inferior frontal gyrus, putamen, and thalamus compared to the comparison group ( P  < 0.005)., Conclusion: We demonstrated that adjunctive rasagiline treatment may have beneficial effects on brain perfusion in patients with AD, suggesting potential neuroprotective effects.

We evaluated the association between hyponatremia and tuberculous meningitis (TBM) with the aim of providing additional information for differential diagnosis from other types of infectious meningitis, especially viral meningitis (VM). Cross-sectional and longitudinal data involving 5026 participants older than 18 years were analyzed in the total population and a propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, bacterial meningitis (BM), and VM patients were compared. Participants in the TBM group were enrolled when they were diagnosed as possible, probable, or definite TBM according to the Marais' criteria. The initial serum sodium level was significantly lower in TBM patients than in BM and VM patients (136.9 ± 5.9 vs. 138.3 ± 4.7 mmol/L, p < 0.001 for TBM vs. BM, and 139.0 ± 3.1, p < 0.001 for TBM vs. VM), and it decreased significantly more steeply to lower levels in both the TBM and BM patients compared with VM patients. The lowest serum sodium level was in the order of TBM < BM < VM patients, and the change was statistically significant in all subgroups (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p < 0.001). Participants with lower serum sodium level were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium level than the initial sodium level [OR 4.6 (95% CI 2.4-8.8, p < 0.001)]. These findings indicate that baseline and longitudinal evaluation of serum sodium level can provide information for differential diagnosis of TBM from BM or VM.

Background and Aims: Some online gamers may encounter difficulties in controlling their gaming behavior. Previous studies have demonstrated beneficial effects of transcranial direct current stimulation (tDCS) on various kinds of addiction. This study investigated the effects of tDCS on addictive behavior and regional cerebral metabolic rate of glucose (rCMRglu) in problematic online gamers., Methods: Problematic online gamers were randomized and received 12 sessions of either active (n = 13) or sham tDCS (n = 13) to the dorsolateral prefrontal cortex over 4 weeks (anode F3/cathode F4, 2 mA for 30 min, 3 sessions per week). Participants underwent brain 18F-fluoro-2-deoxyglucose positron emission tomography scans and completed questionnaires including the Internet Addiction Test (IAT), Brief Self-Control Scale (BSCS), and Behavioral Inhibition System/Behavioral Activation System scales (BIS/BAS) at the baseline and 4-week follow-up., Results: Significant decreases in time spent on gaming (P = 0.005), BIS (P = 0.03), BAS-fun seeking (P = 0.04), and BAS-reward responsiveness (P = 0.01), and increases in BSCS (P = 0.03) were found in the active tDCS group, while decreases in IAT were shown in both groups (P < 0.001). Group-by-time interaction effects were not significant for these measures. Increases in BSCS scores were correlated with decreases in IAT scores in the active group (β = -0.85, P < 0.001). rCMRglu in the left putamen, pallidum, and insula was increased in the active group compared to the sham group (P for interaction < 0.001)., Discussion and Conclusions: tDCS may be beneficial for problematic online gaming potentially through changes in self-control, motivation, and striatal/insular metabolism. Further larger studies with longer follow-up period are warranted to confirm our findings.

The Ritchey-Common test is a widely used method for testing flat mirrors with a larger reference spherical mirror. However, with the increase in the size of the flat mirror, the fabrication of the spherical mirror becomes more time consuming and expensive. In this study, we developed a novel technique to test a large flat mirror with a smaller reference sphere using a dual subaperture stitching (DSS) method. One part of the DSS technique is a modified Ritchey-Common test, which uses a reference sphere smaller than the flat mirror. The other part involves scanning along the centerline of the flat mirror. The former can be used to determine the surface form error (SFE), except for rotationally symmetric components, such as power and spherical aberrations, which can be measured by the latter. To perform the stitching process using a smaller reference sphere, the flat mirror was repeatedly rotated by a fixed angular step. One of the advantages of the rotation of the flat mirror is that it can be used to identify the errors resulting from the reference sphere, which do not vary during the rotation of the flat mirror. We verified the DSS method using a 152 mm diameter optical flat mirror and determined the root-mean-square (rms) measurement error to be only 0.2 nm, which was comparable to the error of the full-aperture interferometric measurement. In addition, we tested a 1.2 m diameter flat mirror with a reference sphere with an aperture of 0.8 m and measured its SFE to be 11.9±0.5 n m rms.

Dizziness is a common symptom among the general population, especially in the elderly. Previous studies have reported that dizziness may be associated with various cognitive functions including memory impairment. However, few studies have investigated the neural correlates of dizziness in patients with cognitive impairment. The aim of this study was to examine regional cerebral blood flow (rCBF) in mild cognitive impairment (MCI) patients with or without dizziness using single photon emission computed tomography (SPECT). A total of 50 patients with MCI were recruited. All participants underwent technetium-99m ethyl cysteinate dimer brain SPECT and a neuropsychological battery and completed the Dizziness Handicap Inventory (DHI). Participants were divided into a dizziness group (DHI ≥ 1, n = 18) and a non-dizziness group (DHI = 0, n = 32). Voxel wise differences in rCBF between the groups were estimated. SPECT analysis revealed decreased rCBF in the left superior temporal gyrus, left lateral orbital gyrus, and right middle frontal gyrus in the dizziness group compared with the non-dizziness group ( p < 0.005). No significant clusters of increased rCBF were observed in the dizziness group compared with the non-dizziness group. Results of the neuropsychological tests showed a significant difference in Controlled Oral Word Association Test performance between MCI patients with and without dizziness. In conclusion, MCI patients with dizziness showed multifocal frontal and left temporal hypoperfusion compared with patients without dizziness. Our results suggest that hypoperfusion in the frontal and temporal cortices might be reflecting the negative impact of dizziness in MCI patients.

The neuropathology of Parkinson's disease dementia (PDD) is heterogenous, and the impacts of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency and impacts of co-existence with Alzheimer's disease in patients with PDD by using 18F-florbetaben PET imaging. A total of 23 patients with PDD participated in the study. All participants underwent 18F-florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F-florbetaben PET groups. Four patients (17.4%) showed significant amyloid burden. Patients with amyloid-beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid-beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups. The amyloid PET scan of a patient with PDD can effectively reflect a co-existing Alzheimer's disease pathology. Amyloid PET scans might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.

Background and Purpose: Elevated high-sensitivity C-reactive protein (hs-CRP) has been suggested as a risk factor for ischemic stroke. However, the predictive value of hs-CRP for long-term outcomes is poorly defined. Therefore, we conducted this study to evaluate whether change in hs-CRP level plays a role in the prognostic value of long-term functional disability., Methods: We studied 263 patients with acute ischemic stroke and 104 healthy controls (67.5±11.26 and 68.17±11.21 y, respectively). hs-CRP was measured on admission and on the seventh day of hospitalization. The patients were classified into 2 groups on the basis of difference in hs-CRP level from admission to the seventh day of hospitalization (group 1, hs-CRP on admission>the seventh hospital day; group 2, hs-CRP on admission

Background: Early consciousness recovery after cardiac arrest (CA) is one of the most explicit and self-evident prognostic factors for clinical outcomes. We aimed to evaluate the prognostic value of electroencephalography (EEG) phenotypes according to the American Clinical Neurophysiology Society's Critical Care EEG classification for predicting early recovery after CA., Methods: Consecutive patients admitted to the ICU after CA were enrolled. We analyzed Glasgow Coma Scale (GCS) score within 10 days after CA and evaluated mortality within 28 days according to EEG pattern subtype., Results: Among the total of 71 patients, 9 had periodic discharges (PDs) EEG pattern, 4 had rhythmic delta activity (RDA), 8 had spike-and-wave (SW), 22 had low voltage, 5 had burst suppression, and 23 had other EEG patterns. Initial GCS scores, GCS scores 3 days after CA (or 3 days after targeted temperature management [TTM]), and 10 days after CA (or 10 days after TTM) were significantly different among EEG subtypes (p < 0.001, respectively) (Table 2). GCS scores were significantly higher in RDA and the other EEG group compared to the PDs, SW, low voltage, and burst suppression groups (p < 0.001). Significant group × time interactions were observed for the follow-up period between EEG phenotypes (p < 0.001) demonstrating the most increase in the other EEG pattern group., Conclusions: Consciousness states were significantly worse in the PDs, SW, burst suppression, and low-voltage groups compared to the RDA and the other EEG pattern within 10 days after CA. The degree of consciousness recovery differed significantly by EEG pattern subtype within 10 days.

Background and Purpose: Impulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS)., Methods: The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test-retest reliability of the K-QUIP-RS was assessed over an interval of 10-14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed., Results: This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test-retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose., Conclusions: The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Neurological Association.)

Background and Purpose: Over the course of treatment for Parkinson's disease (PD), the clinical effects of dopaminergic medication diminish and side effects emerge. Therefore, searching for new therapeutic alternatives or complementary treatments is required. Transcranial direct current stimulation (tDCS) could potentially complement the current therapeutic armamentarium, but only a few studies have investigated the therapeutic effects of tDCS in PD. The present pilot study aimed to investigate the effects of repeated tDCS treatment on motor symptoms and regional cerebral blood flow (rCBF) in patients with PD using single photon emission computed tomography (SPECT)., Methods: Four patients with PD received tDCS to the dorsolateral prefrontal cortex two times per week (anode F3/cathode F4, 2 mA for 30 minutes) over a period of 12 months. Patients underwent brain SPECT scans and clinical motor evaluation at baseline and 12-month follow-up. For SPECT data, voxel-wise changes in rCBF were analyzed., Results: There was no significant change of the motor severity scale, but the follow-up SPECT showed significant hyperperfusion in the left superior frontal gyrus medial segment and left superior parietal lobule compared to baseline (P < .001)., Conclusions: This study shows that tDCS application may improve rCBF in the frontal and parietal lobes in patients with PD, suggesting beneficial effects of tDCS on brain function. Our results are preliminary and further large-scale studies are needed to confirm our findings., (© 2019 by the American Society of Neuroimaging.)

Background and Purpose: This study aimed to determine the clinimetric properties of the Korean version of Parkinson's Disease Sleep Scale-2 (K-PDSS-2) and whether distinct subtypes of sleep disturbance can be empirically identified in patients with Parkinson's disease (PD) using the cross-culturally validated K-PDSS-2., Methods: The internal consistency, test-retest reliability, scale precision, and convergent validity of K-PDSS-2 were assessed in a nationwide, multicenter study of 122 patients with PD. Latent class analysis (LCA) was used to derive subgroups of patients who experienced similar patterns of sleep-related problems and nocturnal disabilities., Results: The total K-PDSS-2 score was 11.67±9.87 (mean±standard deviation) at baseline and 12.61±11.17 at the retest. Cronbach's α coefficients of the total K-PDSS-2 scores at baseline and follow-up were 0.851 and 0.880, respectively. The intraclass correlation coefficients over the 2-week study period ranged from 0.672 to 0.848. The total K-PDSS-2 score was strongly correlated with health-related quality of life measures and other corresponding nonmotor scales. LCA revealed three distinct subtypes of sleep disturbance in the study patients: "less-troubled sleepers," "PD-related nocturnal difficulties," and "disturbed sleepers.", Conclusions: K-PDSS-2 showed good clinimetric attributes in accordance with previous studies that employed the original version of the PDSS-2, therefore confirming the cross-cultural usefulness of the scale. This study has further documented the first application of an LCA approach for identifying subtypes of sleep disturbance in patients with PD., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 Korean Neurological Association.)

Parkinson's disease (PD) has a variable spectrum of cognitive impairment. However, there are no clear evident-based management guidelines for PD with dementia (PDD). Alternative treatments for PDD are therefore required. We conducted this longitudinal study to evaluate the efficacy of nicergoline in treating PDD by analyzing changes in regional cerebral blood flow (rCBF) and neuropsychological tests before and after nicergoline administration. A total of nine PDD patients who received nicergoline therapy (PDD + N) and 14 PD patients who did not receive nicergoline therapy (PDD - N) underwent single photon emission computed tomography (SPECT) and clinical assessments at baseline and 12-month follow-up visits. The PDD + N received nicergoline at 30 mg twice per day. Changes in rCBF were compared between the groups, and correlation analysis was performed to determine possible relationship between rCBF and clinical characteristics. There were no significant differences in rCBF between the two groups at baseline. Although changes in cognitive test scores and the motor severity scale were not significantly different between baseline and the 12-month follow-up within groups, rCBF was lower in both the temporal and inferior frontal restricted areas in the PDD - N group than the PDD + N at the 12-month follow-up visit. In conclusions, nicergoline appears to delay the speed of deterioration of cognitive function in patients with PDD based on our observation of decreased rCBF in the temporal regions and inferior frontal regions of PDD - N patients compared to PDD + N patients after 12-month of nicergoline therapy. Therefore, we cautiously suggest that nicergoline administration in PDD patients may slow progression of cognitive impairment in affected brain regions., (Copyright © 2019. Published by Elsevier Ltd.)

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that applies a weak electric current to the scalp to modulate neuronal membrane potentials. Compared to other brain stimulation methods, tDCS is relatively safe, simple, and inexpensive to administer. Since excessive online gaming can negatively affect mental health and daily functioning, developing treatment options for gamers is necessary. Although tDCS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated promising results for various addictions, it has not been tested in gamers. This paper describes a protocol and a feasibility study for applying repeated tDCS over the DLPFC and neuroimaging to examine the underlying neural correlates in gamers. At baseline, individuals who play online games report average weekly hours spent on games, complete questionnaires on addiction symptoms and self-control, and undergo brain 18 F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). The tDCS protocol consists of 12 sessions over the DLPFC for 4 weeks (anode F3/cathode F4, 2 mA for 30 min per session). Then, a follow-up is conducted using the same protocol as the baseline. Individuals who do not play online games receive only baseline FDG-PET scans without tDCS. Changes of clinical characteristics and asymmetry of regional cerebral metabolic rate of glucose (rCMRglu) in the DLPFC are examined in gamers. In addition, asymmetry of rCMRglu is compared between gamers and non-gamers at baseline. In our experiment, 15 gamers received tDCS sessions and completed baseline and follow-up scans. Ten non-gamers underwent FDG-PET scans at the baseline. The tDCS reduced addiction symptoms, time spent on games, and increased self-control. Moreover, abnormal asymmetry of rCMRglu in the DLPFC at baseline was alleviated after tDCS. The current protocol may be useful for assessing treatment efficacy of tDCS and its underlying brain changes in gamers. Further randomized sham-controlled studies are warranted. Moreover, the protocol can be applied to other neurological and psychiatric disorders.

Background and Purpose: Despite accumulating evidence for the clinical efficacy and neuroprotective properties of rasagiline in Parkinson's disease (PD), effects of rasagiline on brain perfusion in PD patients have not been elucidated. The present study aimed to investigate the effects of rasagiline on regional cerebral blood flow (rCBF) in patients with PD using single-photon emission computed tomography (SPECT)., Methods: A total of 44 PD patients were recruited and treated with dopamine agonist, either alone or in combination with levodopa. Twenty-two of these patients (referred to as the rasagiline group) additionally received rasagiline (1 mg/day). All patients underwent brain SPECT scans and clinical assessments at baseline and follow-up visits. The mean follow-up period was 2.2 years. Changes in rCBF were compared between the rasagiline group and the comparison group in a voxel-wise manner., Results: Annual change in Unified Parkinson's Disease Rating Scale motor score was lower in the rasagiline group compared to the comparison group (P = .01). A significant group-by-time interaction effect on rCBF was found in the right precuneus (P = .001), where rCBF was decreased in the comparison group and remained stable in the rasagiline group., Conclusions: Our results show that adjunctive rasagiline treatment had beneficial effects on perfusion in the precuneus of PD patients, suggesting potential neuroprotective effects., (© 2019 by the American Society of Neuroimaging.)

Background: Although single or multiple sessions of transcranial direct current stimulation (tDCS) on the prefrontal cortex over a few weeks improved cognition in patients with Alzheimer's disease (AD), effects of repeated tDCS over longer period and underlying neural correlates remain to be elucidated., Objective: This study investigated changes in cognitive performances and regional cerebral metabolic rate for glucose (rCMRglc) after administration of prefrontal tDCS over 6 months in early AD patients., Methods: Patients with early AD were randomized to receive either active (n = 11) or sham tDCS (n = 7) over the dorsolateral prefrontal cortex (DLPFC) at home every day for 6 months (anode F3/cathode F4, 2 mA for 30 min). All patients underwent neuropsychological tests and brain 18 F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scans at baseline and 6-month follow-up. Changes in cognitive performances and rCMRglc were compared between the two groups., Results: Compared to sham tDCS, active tDCS improved global cognition measured with Mini-Mental State Examination (p for interaction = 0.02) and language function assessed by Boston Naming Test (p for interaction = 0.04), but not delayed recall performance. In addition, active tDCS prevented decreases in executive function at a marginal level (p for interaction < 0.10). rCMRglc in the left middle/inferior temporal gyrus was preserved in the active group, but decreased in the sham group (p for interaction < 0.001)., Conclusions: Daily tDCS over the DLPFC for 6 months may improve or stabilize cognition and rCMRglc in AD patients, suggesting the therapeutic potential of repeated at-home tDCS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Amnestic mild cognitive impairment (aMCI) is highly likely to progress to dementia of the Alzheimer type (DAT). One of the most frequently reported symptoms in aMCI and DAT patients is memory impairment. This study compared the levels of beliefs about memory efficacy and control, cognitive activity, and depression among healthy older adults (OA), patients with aMCI, and patients with DAT., Methods: This study included 21 OA (11 males, 10 females), 16 aMCI patients (6 males, 10 females), and 18 DAT patients (10 males, 8 females). The memory efficacy questionnaire, memory control questionnaire, cognitive activity questionnaire, depression questionnaire, and Seoul Verbal Learning Test were administered to all subjects., Results: DAT patients showed significantly lower scores on the recognition test than did the OA and aMCI patients, and no difference in these scores was observed between the OA and aMCI patients. Regarding the memory efficacy, memory control, and cognitive activity questionnaires, DAT and aMCI patients showed significantly lower scores than did OA. However, there were no differences in these scores between aMCI and DAT patients., Conclusion: The results of this study suggest that aMCI patients experienced impairment in memory beliefs and memory control in the same way as DAT patients did. These results suggest that the early application of cognitive rehabilitation therapy for patients with aMCI may be effective in preventing or alleviating memory deterioration., Competing Interests: The researchers claim no conflicts of interest., (Copyright © 2019 by The Korean Geriatric Society.)

Persistent postural-perceptual dizziness (PPPD) is a recently defined syndrome with chronic dizziness interrupting daily life. Although the high levels of anxiety and functional changes in postural control strategy and multi-sensory information processing and integration may be underlying the pathophysiology, its neural mechanisms are poorly understood. The aim of this study was to examine the regional cerebral blood flow (rCBF) in patients with PPPD using single photon emission computed tomography (SPECT). A total of 25 patients with PPPD and 25 healthy controls participated in the study. All participants underwent brain SPECT and the patients completed the Dizziness Handicap Inventory. SPECT images were compared between the groups, and the correlation of rCBF and disease severity/duration was assessed in patients. Compared with controls, PPPD patients showed a significantly decreased rCBF in the insula and frontal lobe, mainly in the left posterior insula, bilateral superior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, and left medial orbital gyrus. Additionally, PPPD patients showed a significant rCBF increase in the bilateral cerebellum compared with controls. The results of our study suggest that the altered rCBF in the insular, frontal, and cerebellar cortices might be reflecting the process of maladaptation and the compensatory responses for the changes in PPPD.

Aim: Excessive use of online games can have negative influences on mental health and daily functioning. Although the effects of transcranial direct current stimulation (tDCS) have been investigated for the treatment of addiction, it has not been evaluated for excessive online game use. This study aimed to investigate the feasibility and tolerability of tDCS over the dorsolateral prefrontal cortex (DLPFC) in online gamers., Methods: A total of 15 online gamers received 12 active tDCS sessions over the DLPFC (anodal left/cathodal right, 2 mA for 30 min, 3 times per week for 4 weeks). Before and after tDCS sessions, all participants underwent 18 F-fluoro-2-deoxyglucose positron emission tomography scans and completed the Internet Addiction Test (IAT), Brief Self Control Scale (BSCS), and Beck Depression Inventory-II (BDI-II)., Results: After tDCS sessions, weekly hours spent on games (p = .02) and scores of IAT (p < .001) and BDI-II (p = .01) were decreased, whereas BSCS score was increased (p = .01). Increases in self-control were associated with decreases in both addiction severity (p = .002) and time spent on games (p = .02). Moreover, abnormal right-greater-than-left asymmetry of regional cerebral glucose metabolism in the DLPFC was partially alleviated (p = .04)., Conclusions: Our preliminary results suggest that tDCS may be useful for reducing online game use by improving interhemispheric balance of glucose metabolism in the DLPFC and enhancing self-control. Larger sham-controlled studies with longer follow-up period are warranted to validate the efficacy of tDCS in gamers.

Hemorrhagic transformation (HT) is one of the most feared complications of acute recanalization therapies. The aim of this study was to evaluate whether blood-brain barrier permeability (BBBP) imaging can predict HT in the setting of acute recanalization therapy and to determine the sensitivity and specificity of BBBP for the prediction of HT according to the type of reperfusion therapy. We assessed a total of 46 patients who received recanalization therapy (intravenous (IV) recombinant tissue plasminogen activator (tPA), mechanical thrombectomy with a stent retriever or both) for acute ischemic stroke within the internal carotid artery or middle cerebral artery. BBBP above the threshold was significantly associated with HT after adjustment for confounding factors in all patients (OR 45.4, 95% CI 2.9~711.2, p = 0.007), patients who received IV tPA (OR 20.1, 95% CI 1.2-336.7, p = 0.037), and patients who received endovascular therapy (OR 47.2, 95% CI 1.9-1252.5, p = 0.022). The sensitivity and specificity of the initial BBBP measurement as a predictor of HT in the overall 46 patients were 80 and 71%, respectively. These values were 75 and 64% in only IV tPA group, 100 and 80% in only endovascular group, 77 and 67% in IV tPA with or without endovascular therapy group, and 86 and 76% in endovascular therapy with or without bridging IV tPA therapy group. Increased pretreatment BBBP values were significantly associated with HT after acute recanalization therapy. This correlation with HT was stronger in patients receiving endovascular mechanical thrombectomy than in patients receiving IV rtPA.

The purpose of this study was to evaluate postoperative changes in the neuropsychological function of cervical dystonia patients who had undergone deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and to investigate how DBS affects neuropsychological function by altering the neural networks of the brain. In 12 cervical dystonia patients, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was used to measure the preoperative and postoperative status of cervical dystonia, and the Seoul Neuropsychological Screening Battery was used to gather neuropsychological data. The data were analyzed using a Wilcoxon signed-rank test. The average improvement in the TWSTRS score at the time of the postoperative neuropsychological battery was 56.1 ± 26.8%. In the neuropsychological battery, inhibitory control, as evaluated by the Stroop test, was significantly decreased after GPi DBS. The average pre-/postoperative Stroop test word and color reading correct response score were 107.9/99.2 (P = 0.043) and 85.3/75.8 (P = 0.032), respectively. The observed neuropsychological consequence of GPi DBS in this study, i.e., decreased inhibitory control, implies that electrical stimulation of the GPi may alter brain networks via the centromedian-parafascicular nuclear complex, suppressing the inhibitory control function of the prefrontal cortex., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Purpose: Apathy is one of the most common neuropsychiatric symptoms in patients with Alzheimer's disease (AD). It may have adverse impacts on the progression of AD. However, its neurobiological underpinnings remain unclear. The objective of this study was to investigate differences in regional cerebral blood flow (rCBF) between AD patients with apathy and those without apathy., Methods: Sixty-six apathetic AD patients and 66 AD patients without apathy completed Neuropsychiatric Inventory (NPI) and underwent technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) scans. Voxel-wise differences in rCBF between the 2 groups were examined. Association between rCBF and levels of apathy in the apathetic group was also assessed., Results: AD patients with apathy showed lower rCBF in the bilateral orbitofrontal cortex, left putamen, left nucleus accumbens, left thalamus, and bilateral insula than those without (all p <0.005). Mean perfusion across all significant clusters showed a negative linear correlation with NPI apathy score in AD patients with apathy (β=-0.25; p =0.04)., Conclusions: Hypoperfusion in the prefrontal, striatal, and insular areas may be neural correlates of apathy in AD patients., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD., Methods: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10-14 days., Results: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ., Conclusion: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2018 The Korean Academy of Medical Sciences.)

Background and Purpose: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT)., Methods: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale., Results: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus., Conclusions: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background and Purpose: Although sleep disturbances are common and considered a major burden for patients with Alzheimer's disease (AD), the fundamental mechanisms underlying the development and maintenance of sleep disturbance in AD patients have yet to be elucidated. The aim of this study was to examine the correlation between regional cerebral blood flow (rCBF) and sleep disturbance in AD patients using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT)., Methods: A total of 140 AD patients were included in this cross-sectional study. Seventy patients were assigned to the AD with sleep loss (SL) group and the rest were assigned to the AD without SL group. SL was measured using the sleep subscale of the Neuropsychiatric Inventory. A whole-brain voxel-wise analysis of brain SPECT data was conducted to compare the rCBF between the two groups., Results: The two groups did not differ in demographic characteristics, severity of dementia, general cognitive function, and neuropsychiatric symptoms, with the exception of sleep disturbances. The SPECT imaging analysis displayed decreased perfusion in the bilateral inferior frontal gyrus, bilateral temporal pole, and right precentral gyrus in the AD patients with SL group compared with the AD patients without SL group. It also revealed increased perfusion in the right precuneus, right occipital pole, and left middle occipital gyrus in the AD with SL group compared with the AD without SL group., Conclusions: The AD patients who experienced sleep disturbance had notably decreased perfusion in the frontal and temporal lobes and increased rCBF in the parietal and occipital regions. The findings of this study suggest that functional alterations in these brain areas may be the underlying neural correlates of sleep disturbance in AD patients., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background: Although D-dimer levels are significantly associated with cardioembolic infarction, the significance of D-dimer levels in relation to the severity and functional outcomes of other stroke subtypes, such as lacunar and large artery atherosclerosis infarction, remains unclear. The purpose of this study was to evaluate whether elevated initial D-dimer levels are significantly and cross-sectionally associated with poor functional outcomes at each time point during a 9-month follow-up period. We also investigated the significance of D-dimer levels in longitudinal temporal changes of functional outcomes in these patients., Methods: We recruited 146 patients with lacunar infarction and 161 patients with large artery atherosclerosis infarction who were consecutively admitted to our hospital after acute stroke. Serum D-dimer levels were evaluated initially and the modified Rankin scale were measured initially and at 1-, 3-, 6-, and 9-month follow-up visits., Results: Patients with higher D-dimer levels had significantly worse initial functional outcomes, and these worse outcomes were maintained throughout the 9-month follow-up period compared with the low D-dimer group. However, regardless of stroke subtype, D-dimer levels did not influence long-term changes in functional outcomes over the 9-month follow-up period., Conclusion: This study suggests that elevated D-dimer levels can be used as a surrogate marker for poor functional outcomes only during the acute stage. Further evaluation of serum D-dimer levels could provide a helpful predictive marker for stroke prognosis.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. Cerebrovascular diseases such as cerebral ischemic lesion (CIL) also commonly occur in elderly adults. However, previous studies on the relationship between PD and cerebrovascular disease have not found consistent results. Therefore, we conducted this study to evaluate whether or not PD is related to an increased prevalence of ischemic cerebrovascular lesions., Methods: This study recruited 241 patients with PD and 112 healthy controls (HCs). All subjects underwent brain magnetic resonance imaging and general neuropsychological tests. The motor severity of PD was evaluated according to the Hoehn and Yahr stage (HY stage), and the severity of CIL in all subjects was classified according to Fazekas grade. The PD patients were classified into two subgroups according to HY stage (Group 1 - HY 1, 2; Group 2 - HY 3 to 5)., Results: Among all PD patients, 76% had small vessel disease, while 44% of all HCs had small vessel disease (p<0.001). Regarding the difference between the two subgroups according to motor severity, group 2 showed significantly higher Fazekas scale score and more severe CIL, indicating a higher prevalence of small vessel disease compared to group 1., Conclusion: This study demonstrates that PD patients have a significantly higher prevalence of CIL compared to HCs. Therefore, although the present study is not a large-scale study, we cautiously suggest that PD can play an important role as a risk factor in the occurrence of ischemic cerebrovascular disease., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background and Purpose: Although acetyl-L-carnitine (ALC) treatment may have beneficial effects on Alzheimer's disease (AD), its underlying neural correlates remain unclear. The purpose of this study was to investigate cerebral perfusion changes after ALC treatment in AD patients using technetium- 99 m hexamethylpropylene amine oxime single photon emission computed tomography (SPECT)., Methods: A total of 18 patients with early AD were prospectively recruited and treated with ALC at 1.5 g/day for 1.4±0.3 years. At baseline and follow-up, brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI) were used to assess participants. After ALC administration, changes in brain perfusion, severity of dementia, cognitive performance, and neuropsychiatric disturbances were examined., Results: After ALC administration, changes in scores of MMSE, CDR, GDS, and NPI were not statistically significant ( p >0.05). Voxel-wise whole-brain image analysis revealed that perfusion was significantly ( p <0.001) increased in the right precuneus whereas perfusion was reduced in the left inferior temporal gyrus ( p <0.001), the right middle frontal gyrus ( p <0.001), and the right insular cortex ( p =0.001) at follow-up., Conclusions: Although previous studies have suggested that AD patients generally demonstrate progressive deterioration in brain perfusion and clinical symptoms, this study reveals that the perfusion of the precuneus is increased in AD patients after ALC administration and their cognitive and neuropsychiatric symptoms are not aggravated. Further studies are warranted to determine the potential association between perfusion increase in the precuneus and clinical symptoms after ALC treatment in AD patients., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Background and Purpose: Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinson's disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non-motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake., Methods: Among 160 de-novo cases of PD, 44 had normal MIBG uptake. Twelve candidate non-motor features were evaluated using questionnaires and laboratory tests., Results: Patients with decreased MIBG uptake had more constipation, RBD, cognitive impairment, hyposmia and orthostatic hypotension than did those with normal MIBG uptake. On linear regression analysis, orthostatic hypotension, olfactory function and probable RBD were significantly associated with MIBG uptake in PD. The principal component analysis showed that the group with normal MIBG was not associated with non-motor impairments., Conclusions: These results suggest that patients with PD with normal MIBG scans have a relatively low disease burden compared with those with abnormal MIBG. Fewer synuclein pathologies in the myocardia and sympathetic ganglia in PD with preserved MIBG uptake might be associated with lower threshold patterns of Braak synuclein pathology for non-motor manifestations compared with PD with decreased MIBG., (© 2016 EAN.)