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The aim of the present study was to predict amyloid-beta positivity using a conventional T1-weighted image, radiomics, and a diffusion-tensor image obtained by magnetic resonance imaging (MRI). We included 186 patients with mild cognitive impairment (MCI) who underwent Florbetaben positron emission tomography (PET), MRI (three-dimensional T1-weighted and diffusion-tensor images), and neuropsychological tests at the Asan Medical Center. We developed a stepwise machine learning algorithm using demographics, T1 MRI features (volume, cortical thickness and radiomics), and diffusion-tensor image to distinguish amyloid-beta positivity on Florbetaben PET. We compared the performance of each algorithm based on the MRI features used. The study population included 72 patients with MCI in the amyloid-beta-negative group and 114 patients with MCI in the amyloid-beta-positive group. The machine learning algorithm using T1 volume performed better than that using only clinical information (mean area under the curve [AUC]: 0.73 vs. 0.69, p < 0.001). The machine learning algorithm using T1 volume showed better performance than that using cortical thickness (mean AUC: 0.73 vs. 0.68, p < 0.001) or texture (mean AUC: 0.73 vs. 0.71, p = 0.002). The performance of the machine learning algorithm using fractional anisotropy in addition to T1 volume was not better than that using T1 volume alone (mean AUC: 0.73 vs. 0.73, p = 0.60). Among MRI features, T1 volume was the best predictor of amyloid PET positivity. Radiomics or diffusion-tensor images did not provide additional benefits. [ABSTRACT FROM AUTHOR]

We determined whether the severity of sleep apnea increases the risk of mortality in patients with multiple system atrophy (MSA) with and without stridor. MethodsThis retrospective study included patients who underwent polysomnography within one year after diagnosis of probable MSA. Stridor, sleep apnea, and arousal from sleep were determined using full-night polysomnography. Disease severity was measured using the Unified MSA Rating Scale (UMSARS). Survival data were collected and analyzed using Cox regression analysis. Sixty-four patients with MSA were included. During a median follow-up of 34.5 months, 49 (76.6 %) patients died. Stridor was present in 56.3 % of patients. Patients with stridor had more severe sleep apnea and shorter sleep time than those without, but the hazard ratio (HR) for death did not differ between patients with and without stridor. Among patients without stridor, apnea-hypopnea index ≥30/h (HR, 6.850; 95 % confidence interval [CI], 1.983–23.664; p = 0.002) and a score of UMSARS I + II (HR, 1.080; 95 % CI, 1.040–1.121; p < 0.001) were independently associated with death. In contrast, among patients with stridor, frequent arousals from sleep (HR, 0.254; 95 % CI, 0.089–0.729; p = 0.011) were a significant factor associated with longer survival, while MSA-cerebellar type tended to be associated with poor survival (HR, 2.195; 95 % CI, 0.941–5.120; p = 0.069). The severity of sleep apnea might be a significant predictor of shorter survival in MSA patients without stridor, whereas frequent arousals from sleep might be a significant predictor for longer survival in MSA patients with stridor. • Nocturnal stridor was present in 56.3 % of patients with multiple system atrophy (MSA). • The risk for mortality did not differ between MSA patients with and without stridor. • Severity of sleep apnea was related to shorter survival in patients without stridor. • Frequent arousals from sleep were associated with longer survival in patients with stridor. [ABSTRACT FROM AUTHOR]

Background: Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline.Objective: We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA.Methods: This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aβ+ CAA) and patients with Alzheimer's disease (Aβ+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition.Results: We analyzed 30 patients with Aβ+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aβ+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aβ+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aβ+ AD group(family-wise error-corrected p < 0.05). The correlation between the number of lobar microbleeds and visuospatial function was indirectly mediated by white matter tract abnormality of right posterior thalamic radiation (PTR) and tapetum, while lobar microbleeds and language function was indirectly mediated by the abnormality of left PTR and sagittal stratum. Cortical thickness did not mediate the association between lobar microbleeds and cognition.Conclusion: This result supports the hypothesis that microbleeds burden leads to white matter tract damage and subsequent cognitive decline in CAA. [ABSTRACT FROM AUTHOR]

Introduction: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia.Methods: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS.Results: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia.Conclusion: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS. [ABSTRACT FROM AUTHOR]

We aimed to investigate the role of the APOE genotype in cognitive and motor trajectories in Parkinson's disease (PD). Using PD registry data, we retrospectively investigated a total of 253 patients with PD who underwent the Mini-Mental State Exam (MMSE) two or more times at least 5 years apart, were aged over 40 years, and free of dementia at the time of enrollment. We performed group-based trajectory modeling to identify patterns of cognitive change using the MMSE. Kaplan–Meier survival analysis was used to investigate the role of the APOE genotype in cognitive and motor progression. Trajectory analysis divided patients into four groups: early fast decline, fast decline, gradual decline, and stable groups with annual MMSE scores decline of − 2.8, − 1.8, − 0.6, and − 0.1 points per year, respectively. The frequency of APOE ε4 was higher in patients in the early fast decline and fast decline groups (50.0%) than those in the stable group (20.1%) (p = 0.007). APOE ε4, in addition to older age at onset, depressive mood, and higher H&Y stage, was associated with the cognitive decline rate, but no APOE genotype was associated with motor progression. APOE genotype could be used to predict the cognitive trajectory in PD. [ABSTRACT FROM AUTHOR]

Background: Little is known about newly developed stroke in patients admitted to the intensive care unit (ICU). Objective: This study aimed to investigate characteristics and outcomes of newly developed stroke in patients admitted to the non-neurological intensive care units (ICU-onset stroke, IOS). Methods: A consecutive series of adult patients who were admitted to the non-neurological ICU were included in this study. We compared neurological profiles, risk factors, and mortality rates between patients with IOS and those without IOS. Results: Of 18,604 patients admitted to the ICU for non-neurological illness, 218 (1.2%) developed stroke (ischemic, n = 182; hemorrhagic, n = 36). The most common neurological presentation was altered mental status (n = 149), followed by hemiparesis (n = 55), and seizures (n = 28). The most common etiology of IOS was cardioembolism (50% [91/182]) for ischemic IOS and coagulopathy (67% [24/36]) for hemorrhagic IOS. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (adjusted odds ratio [AOR] = 1.04, 95% CI = 1.03−1.06, P < 0.001), prothrombin time (AOR = 0.99, 95% CI = 0.98−0.99, P = 0.013), cardiovascular surgery (AOR = 1.84, 95% CI = 1.34−2.50, P < 0.001), mechanical ventilation (AOR = 6.75, 95% CI = 4.87−9.45, P < 0.001), and extracorporeal membrane oxygenation (AOR = 2.77, 95% CI = 1.62−4.55, P < 0.001) were related to the development of IOS. Stroke was associated with increased 3-month mortality after hospital discharge (AOR, 2.20; 95% CI, 1.58–3.05; P < 0.001), after adjustment for APACHE II and comorbidities. Conclusions: Patients who developed IOS had characteristics of initial critical illness and managements performed in the ICU as well as neurological presentations. The occurrence of IOS was related to high morbidity and mortality. [ABSTRACT FROM AUTHOR]

The prevalence of Parkinson's disease (PD) has increased steadily with the increase of the elderly population. PD may influence dietary intake and quality, and the gut microbiome composition. The present study examined differences in dietary intake and quality between PD patients and controls according to sex. In addition, we assessed the gut microbiome composition. This cross-sectional study was conducted at A Medical Center, Seoul, South Korea. PD severity, swallowing function, olfactory function, and constipation status were examined by a skilled nurse. Dietary data were collected through a semi-quantitative food frequency questionnaire. Stool samples were subjected to microbiome analysis. To examine dietary quality, the Dietary Quality Index-International (DQI-I), Healthy Eating Index (HEI), Index of Nutritional Quality (INQ), Dietary Diversity Score (DDS), and Mediterranean Diet Score (MDS) were used. An independent t-test was used to determine differences between patients and controls. A chi-square test was used to examine frequency differences. Dietary intake did not differ between the PD patient and control groups. Regarding dietary quality, the patients consumed more saturated fat compared to controls. Overall, the dietary differences between the groups were minor. The composition of the gut microbiome differed between PD patients and controls. Lactobacillus and Bifidobacterium genus were most abundant in PD patients. Prevotella VZCB and other Faecalibacterium were most abundant in controls. Our results indicated that PD patients may experience gut microbiome change even in the early stage, while nutritional needs can be met when a balanced diet including various food groups are consumed. [ABSTRACT FROM AUTHOR]

Background: This study investigated the protective effect of rapid eye movement (REM) sleep without atonia against obstructive sleep apnea (OSA) in patients with idiopathic REM sleep behavior disorder (RBD).Methods: In this case-control study, patients with idiopathic RBD and OSA (RBD-OSA) were consecutively enrolled and OSA controls without RBD were matched for age, sex, and apnea-hypopnea index (AHI). Clinical and polysomnographic characteristics were compared between RBD-OSA patients and OSA controls. Additionally, differences in AHIs depending on sleep state and posture were analyzed.Results: In total, 109 OSA patients (81 males and 28 females) with idiopathic RBD were included in the study. In OSA controls without RBD, AHI and respiratory distress index (RDI) were significantly higher during REM sleep than during non-rapid eye movement (NREM) sleep (p < 0.01). In RBD-OSA patients, however, AHI and RDI were slightly lower during REM sleep than during NREM sleep (p < 0.05). During REM sleep, AHI and RDI were significantly lower in RBD-OSA patients than in OSA controls (p < 0.001). Differences in apnea severity between RBD-OSA patients and OSA controls increased in supine REM sleep but disappeared or lessened in non-supine REM sleep. The prevalence of REM-related OSA was lower in RBD-OSA patients (9.2%) than in OSA controls (33.0%).Conclusions: REM sleep without atonia has protective effects against OSA in patients with idiopathic RBD. These protective effects are much more potent in supine sleep than in non-supine sleep. [ABSTRACT FROM AUTHOR]

Deep brain stimulation (DBS) of globus pallidus interna (GPi) is an established treatment for advanced Parkinson's disease (PD). However, in contrast to subthalamic nucleus (STN)-DBS, long-term outcomes of GPi-DBS have rarely been studied. We investigated the long-term motor outcomes in PD patients at 5 years after GPi-DBS. We retrospectively analyzed the clinical data for PD patients who underwent GPi-DBS. Longitudinal changes of UPDRS scores from baseline to 5 years after surgery were assessed. Forty PD patients with a mean age of 59.5 ± 7.9 years at DBS surgery (mean duration of PD: 11.4 ± 3.4 years) were included at baseline and 25 patients were included in 5-year evaluation after DBS. Compared to baseline, sub-scores for tremor, levodopa-induced dyskinesia (LID), and motor fluctuation indicated improved states up to 5 years after surgery (p < 0.001). However, UPDRS Part 3 total score and sub-score for postural instability and gait disturbance (PIGD) gradually worsened over time until 5 years after surgery (p > 0.017 after Bonferroni correction). In a logistic regression model, only preoperative levodopa response was associated with the long-term benefits on UPDRS Part 3 total score and PIGD sub-score (OR = 1.20; 95% CI = 1.04–1.39; p = 0.015 and OR = 4.99; 95% CI = 1.39–17.89; p = 0.014, respectively). GPi-DBS provides long-term beneficial effects against tremor, motor fluctuation and LID, but PIGD symptoms gradually worsen. This selective long-term benefit has implications for the optimal application of DBS in PD patients. • We investigated the long-term motor outcomes in PD patients at 5 years after GPi-DBS. • GPi-DBS provides long-term beneficial effects against tremor, motor fluctuation and LID. • However, PIGD symptoms gradually worsen after improvement by GPi-DBS. • Preoperative levodopa response was associated with the long-term benefits on PIGD symptoms. • This selective long-term benefit has implications for the optimal application of DBS in PD patients. [ABSTRACT FROM AUTHOR]

Dementia is one of the most disabling nonmotor symptoms of Parkinson's disease (PD). However, the risk factors contributing to its development remain unclear. To investigate genetic variants associated with dementia in PD, we performed microarray genotyping based on a customized platform utilizing variants identified in previous genetic studies. Microarray genotyping was performed in 313 PD patients with dementia, 321 PD patients without dementia, and 635 healthy controls. The primary analysis was performed using a multiple logistic regression model adjusted for age and sex. SNCA single nucleotide polymorphism (SNP) rs11931074 was determined to be most significantly associated with PD (odds ratio = 0.66, 95% confidence interval = 0.56–0.78, p = 7.75 × 10−7). In the analysis performed for patients with PD only, MUL1 SNP rs3738128 (odds ratio = 2.52, 95% confidence interval = 1.68–3.79, p = 8.75 × 10−6) was found to be most significantly associated with dementia in PD. SNPs in ZHX2 and ERP29 were also associated with dementia in PD. This microarray genomic study identified new loci of MUL1 associated with dementia in PD, suggesting an essential role of mitochondrial dysfunction in the development of dementia in patients with PD. [ABSTRACT FROM AUTHOR]

• A patient with ATP1A3 mutation can present with paroxysmal generalized dystonia without hemiplegic event. • Menstrual cycle could be a precipitating factor of paroxysmal movement disorder in patients with ATP1A3 mutation. • Progesterone, which peaks during the mid-luteal phase might have an inhibitory effect on Na+/K+ ATPase activity. [ABSTRACT FROM AUTHOR]

Accumulation of aggregated amyloid-β (Aβ) in the brain is considered the first pathological event within the pathogenesis of Alzheimer's disease (AD). It is difficult to accurately identify the initial brain regions of Aβ accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aβ deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aβ accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aβ accumulation in the brain of people with AD continuum. [ABSTRACT FROM AUTHOR]

Although dementia is a contraindication for deep brain stimulation (DBS) in patients with Parkinson's disease (PD), the concept is supported by little scientific evidence. Moreover, it is unclear whether PD with mild cognitive impairment (PD-MCI) or domain-specific cognitive impairments affect the outcome of DBS in non-demented PD patients. To investigate the influence of baseline cognitive profiles of PD on the outcome of DBS. Baseline cognitive levels of patients with PD who underwent DBS were classified into PD with dementia (PDD) (n = 15), PD-MCI (n = 210), and normal cognition (PD-NC) (n = 79). The impact of the cognitive level on key DBS outcome measures [mortality, nursing home admission, progression to Hoehn&Yahr (HY) stage 5 and progression to PDD] were analyzed using Cox regression models. We also investigated whether impairment of a specific cognitive domain could predict these outcomes in non-demented patients. Patients with PDD showed a substantially higher risk of nursing home admission and progression to HY stage 5 compared with patients with PD-MCI [hazard ratio (HR) 4.20, P =.002; HR = 5.29, P <.001] and PD-NC (HR 7.50, P <.001; HR = 7.93, P <.001). MCI did not alter the prognosis in patients without dementia, but those with visuospatial impairment showed poorer outcomes for nursing home admission (P =.015), progression to HY stage 5 (P =.027) and PDD (P =.006). Cognitive profiles may stratify the pre-operative risk and predict long-term outcomes of DBS in PD. • We studied the outcome of deep brain stimulation in patients with PD with dementia. • PD with dementia poses greater risk for deep brain stimulation than those without. • Mild cognitive impairment does not impact the outcome of deep brain stimulation. • Visuospatial impairment is predictive of poorer outcome of deep brain stimulation. • Cognitive profiles can stratify the pre-operative risk for deep brain stimulation. [ABSTRACT FROM AUTHOR]

Clinical factors associated with daytime sleepiness and insomnia in persons with epilepsy (PWE) were examined in this cross-sectional study of 126 participants (men, 50.8%). Excessive daytime sleepiness (EDS; score of ≥ 11 on the Epworth Sleepiness Scale (ESS)) was noted in 17.5% of participants (mean score, 6.1 ± 4.2), and moderate-to-severe insomnia (Insomnia Severity Index (ISI) scores of ≥ 15) was noted in 20.6% (mean score, 7.8 ± 6.4). Linear regression analyses revealed that ESS scores were independently associated with obstructive sleep apnea (OSA; snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and gender (STOP-Bang) score of ≥ 3), an antiepileptic drug (AED) load of > 3, depression (Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10), female sex, and nocturnal seizures. Insomnia Severity Indices were independently associated with depression and anxiety (Generalized Anxiety Disorder-7 (GAD-7) score of ≥ 7). Notably, significant sex differences were found. Epworth Sleepiness Scale scores were associated with OSA in men but were associated with depression in women. In addition, anxiety was associated with insomnia in women only. Overall, OSA and depression were the most important significant clinical factors associated with daytime sleepiness and insomnia, respectively. However, there were sex differences for the associations between individual factors and sleep disturbances. • Daytime sleepiness is related to OSA, AED load, and depression in PWE. • Insomnia is associated with depression and anxiety in persons with epilepsy. • Factors associated with daytime sleepiness and insomnia are sex-specific. • Daytime sleepiness is linked with OSA in men and with depression in women. • Anxiety is associated with insomnia in women but not in men. [ABSTRACT FROM AUTHOR]

Background and purpose: As part of network‐specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello–cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid‐negative mild cognitive impairment (MCI). Methods: This study was a retrospective cohort study of patients over the age 50 years with amyloid‐negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36‐month follow‐up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three‐dimensional T1 imaging, and fluorine‐18[F18]‐florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume. Results: During the 36 months of follow‐up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group. Conclusions: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid‐negative amnestic MCI patients. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP). Background: Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied. Methods: In this exploratory, retrospective, case–control study, we included 19 patients with SIH recurrence after EBP and 36 age‐ and sex‐matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment. Results: There were no significant differences in clinical features between the recurrence and no‐recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no‐recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain–pons angle decreased in the recurrence group compared to the no‐recurrence group after EBP, at a mean (standard deviation [SD]) of –12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no‐recurrence group in intracranial cerebrospinal fluid (mean [SD] −11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52). Conclusion: Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH. Plain Language Summary: There is not much research about patients who experience symptom relapse after successful epidural blood patch (EBP) treatment for spontaneous intracranial hypotension (SIH). We used machine learning (an analysis that helps us understand patterns in data) to learn about medical records from 19 patients with SIH whose symptoms came back and 36 patients whose symptoms did not recur after EBP treatment. Our results suggest that changes in the amount of cerebrospinal fluid in the brain and the size of the ventricles can help predict the recurrence of SIH after EBP treatment. [ABSTRACT FROM AUTHOR]

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case–control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0–12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity. [ABSTRACT FROM AUTHOR]

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case–control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0–12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a nomogram based on MRI features for predicting iNPH. Methods: Patients aged ≥ 60 years (clinically diagnosed with iNPH, Parkinson's disease, or Alzheimer's disease or healthy controls) who underwent MRI including three-dimensional T1-weighted volumetric MRI were retrospectively identified from two tertiary referral hospitals (one hospital for derivation set and the other for validation set). Clinical and imaging features for iNPH were assessed. Deep learning–based brain segmentation software was used for 3D volumetry. A prediction model was developed using logistic regression and transformed into a nomogram. The performance of the nomogram was assessed with respect to discrimination and calibration abilities. The nomogram was internally and externally validated. Results: A total of 452 patients (mean age ± SD, 73.2 ± 6.5 years; 200 men) were evaluated as the derivation set. One hundred eleven and 341 patients were categorized into the iNPH and non-iNPH groups, respectively. In multivariable analysis, high-convexity tightness (odds ratio [OR], 35.1; 95% CI: 4.5, 275.5), callosal angle < 90° (OR, 12.5; 95% CI: 3.1, 50.0), and normalized lateral ventricle volume (OR, 4.2; 95% CI: 2.7, 6.7) were associated with iNPH. The nomogram combining these three variables showed an area under the curve of 0.995 (95% CI: 0.991, 0.999) in the study sample, 0.994 (95% CI: 0.990, 0.998) in the internal validation sample, and 0.969 (95% CI: 0.940, 0.997) in the external validation sample. Conclusion: A brain morphometry–based nomogram including high-convexity tightness, callosal angle < 90°, and normalized lateral ventricle volume can help accurately estimate the probability of iNPH. Key Points: • The nomogram with MRI findings (high-convexity tightness, callosal angle, and normalized lateral ventricle volume) helped in predicting the probability of idiopathic normal-pressure hydrocephalus. • The nomogram may facilitate the prediction of idiopathic normal-pressure hydrocephalus and consequently avoid unnecessary invasive procedures such as the cerebrospinal fluid tap test, drainage test, and cerebrospinal fluid shunt surgery. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of a home-based self-management intervention in community-dwelling patients with early Parkinson's diseases (PD). A randomized-controlled design. Thirty-two patients participated (15=intervention, 17=control), and the intervention group received 16 weeks of the intervention. Physical activity and non-motor symptoms improved more in the intervention group than in the control group. Home-based self-management intervention was effective in improving physical activity and non-motor symptoms for them. Home-based intervention – comprising education, telephone counseling, smartphone-based message and information, and smart wearable devices – was feasible for patients with early PD. [ABSTRACT FROM AUTHOR]

We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson's disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [18F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD. [ABSTRACT FROM AUTHOR]

Background: About 40–50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans. Methods: This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [18F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together. Results: During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006). Conclusion: Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. Methods: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). Results: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). Conclusions: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. Key Points: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners. [ABSTRACT FROM AUTHOR]

Brain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown. In this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD. The TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD. We introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction, paving the way for non-invasive neurological diagnoses. [Display omitted] • A transferrin conjugated magnetic nanoparticles (TMNs) method to isolate extracellular vesicles including exosomes. • TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment. • Evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates in Parkinson's diseases. • Identified exosomal miRNA biomarkers may emerge as innovative tools for precise diagnosis in neurological disorders. [ABSTRACT FROM AUTHOR]

Introduction: Deep brain stimulation (DBS) has showed variable therapeutic effect on freezing of gait (FOG) in Parkinson's disease (PD). It is unclear which factors associated with the effect of DBS on FOG in patients with advanced PD. In this study, we investigated the correlation of pre and postoperative factors with the therapeutic effect of globus pallidus interna (GPi) DBS on FOG in PD patients.Methods: We retrospectively analyzed PD patients with FOG (N = 20) who underwent GPi DBS surgery. Postoperatively, video-based analysis for FOG severity was performed at the first DBS programming and patients were categorized into two groups according to DBS effect on FOG (11 FOG responders and 9 FOG non-responders) at medication-off state. We analyzed preoperative clinical characteristics, cognitive function, striatal dopamine transporter availability, postoperative DBS programming parameters, lead locations, and volume of tissue activated in functional subregions of GPi. Bootstrap enhanced Elastic-Net logistic regression was used to select pre and postoperative factors associated with the effect of GPi DBS.Results: Therapeutic effect of GPi DBS on FOG were correlated with the disease duration of PD before DBS surgery, preoperative improvement in FOG severity by levodopa medication, and the distance from active contact of DBS electrode to the prefrontal region of GPi anatomical site.Conclusions: Our study results suggest that the effect of GPi DBS on FOG is correlated with disease duration, levodopa responsiveness on FOG before DBS surgery and DBS electrode location, providing useful information to predict FOG outcome after GPi DBS in PD patients. [ABSTRACT FROM AUTHOR]

Microglial activation is a central player in the pathophysiology of Alzheimer's disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive impairment is not uncommon in patients with multiple system atrophy (MSA). This study investigated the cortical metabolic changes of MSA and the cortical structure associated with cognitive impairment.Methods: The study included probable/definite MSA patients who underwent fluorodeoxyglucose positron emission tomography and cognitive evaluation based on mini-mental status examination (MMSE). Cerebral metabolism of the entire MSA patients (n = 88) was compared with healthy controls (n = 19) by voxel-wise statistical parametric mapping. Eight brain regions of interest (ROIs) were selected accordingly: the dorsolateral prefrontal, medial superior frontal, insular, posterior parietal, precuneus, lateral temporal, medial temporal, and posterior cingulate regions. Using validated population-based norms, MSA patients were divided by MMSE z-scores into MSA with cognitive dysfunction (MSA-D, n = 30) and without cognitive dysfunction (MSA-ND, n = 58). Regional metabolism of the selected ROIs was compared between the MSA-D and MSA-ND groups by logistic regression models. Correlations between the regional metabolism of the selected ROIs and MMSE z-scores were analyzed with a linear regression model.Results: Voxel-wise analysis showed hypometabolism in the frontal, temporal, parietal, and limbic areas in MSA patients than in controls. ROI-based comparisons showed that metabolism in the posterior cingulate (P = 0.006) and medial temporal (P = 0.039) regions was significantly lower in the MSA-D than in the MSA-ND group. The degree of posterior cingulate metabolism correlated significantly with MMSE z-score (P = 0.023).Conclusions: MSA shows fronto-temporo-parietal cortical involvement. Hypometabolism of the limbic regions is associated with cognitive impairment in MSA. [ABSTRACT FROM AUTHOR]

The potential benefit of perampanel for sleep disturbances is unknown. This study determined whether insomnia is less prevalent and less severe in patients with epilepsy (PWE) who take perampanel as an adjuvant. This cross-sectional study was conducted in adults with epilepsy. Insomnia in patients treated or not treated with perampanel was diagnosed according to the criteria of the International Classification of Sleep Disorders, the third edition (ICSD-3) and the Insomnia Severity Index (ISI). Patients were also scored on the Epworth Sleepiness Scale (ESS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7), and the groups were compared by stepwise linear or logistic regression analyses. One hundred and twenty-six PWE were included in the study: 31 patients (24.6%) were taking perampanel. Insomnia was diagnosed in 15.9% and 20.6% of all patients according to the ICSD-3 and an ISI score of ≥ 15, respectively. Agreement between the two diagnostic methods was moderate (Cohen's kappa, 0.470). In a stepwise logistic regression model, insomnia diagnosed by either method was negatively associated with perampanel use (P < 0.05) but positively correlated with depressive symptoms, anxiety, and duration of epilepsy. In a stepwise linear regression model, ISI scores correlated negatively with perampanel use (P = 0.004) but positively with depressive symptoms (P < 0.001) and anxiety (P = 0.001). Insomnia is less prevalent and less severe in PWE treated with perampanel independent of depressive symptoms, which will be helpful for treating PWE and comorbid sleep disturbances. • We determined whether perampanel is associated with reduced insomnia in PWE. • Insomnia was diagnosed in 15.9% and 20.6% of PWE via ICSD-3 and ISI ≥ 15, respectively. • Insomnia was less prevalent and less severe in PWE treated with perampanel. • These findings were independent of depressive symptoms and anxiety. [ABSTRACT FROM AUTHOR]