Search

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]

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]

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]

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]

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]

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]

Background: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition.Object: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI.Methods: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans.Results: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole.Conclusion: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population. [ABSTRACT FROM AUTHOR]

Amyloid (Aβ) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aβ and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([ 18 F]-florbetaben) and tau PET scans ([ 18 F]PI-2620), revealing crossed accumulation of Aβ and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aβ and tau pathogenic pathways in AD. [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]

Background: Cognitive impairment is very common in Parkinson's disease (PD) and constitutes the most debilitating complication of this disease. However, to date, few studies have investigated a genome-wide association in the development of cognitive impairment of PD. We aimed to identify the genetic loci associated with cognitive impairment in patients with sporadic PD by ethnicity-specific genotyping. Materials and methods: We recruited 1,070 patients with PD and performed a genome-wide association study using the Korean Chip, a microarray chip containing 827,400 single-nucleotide polymorphisms (SNPs) optimized for the Korean population. Multiple logistic regression models adjusting for age, sex, years of education, and disease duration were used to compare between patients with and without cognitive impairment, which was defined using the Mini-Mental Status Examination (MMSE) score (MMSE score ≥ 26 vs. < 26) or the Montreal Cognitive Assessment (MoCA) score (MoCA score ≥24 vs. < 24). Results: RYR2 SNP rs10495397 was most significantly associated with cognitive impairment based on the MMSE scores (OR = 3.21; 95% CI = 1.96–5.25, P = 3.36 × 10−6) and CASC17 showed the strongest association with cognitive impairment based on the MoCA scores. However, none of the SNPs were statistically significant after Bonferroni correction. Conclusion: RYR2 may play a role in cognitive impairment in PD by the pathogenic mechanism of neuroinflammation. However, more studies are needed to replicate and validate the results of our functional study. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by a clinical symptomatology involving both motor and non-motor symptoms. Motor complications associated with long-term dopaminergic treatment include motor fluctuations and levodopa-induced dyskinesia (LID), which may have a major impact on the quality of life. The clinical features and onset time of motor complications in the disease course are heterogeneous, and the etiology remains unknown. Objective: We aimed to identify genomic variants associated with the development of motor fluctuations and LID at 5 years after the onset of PD. Methods: Genomic data were obtained using Affymetrix Axiom KORV1.1 array, including an imputation genome-wide association study (GWAS) grid and other GWAS loci; functional variants of the non-synonymous exome; pharmacogenetic variants; variants in genes involved in absorption, distribution, metabolism, and excretion of drugs; and expression quantitative trait loci in 741 patients with PD. Results: FAM129B single-nucleotide polymorphism (SNP) rs10760490 was nominally associated with the occurrence of motor fluctuations at 5 years after the onset of PD [odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8–4.8, P = 6.5 × 10−6]. GALNT14 SNP rs144125291 was significantly associated with the occurrence of LID (OR = 5.5, 95% CI = 2.9–10.3, P = 7.88 × 10−9) and was still significant after Bonferroni correction. Several other genetic variants were associated with the occurrence of motor fluctuations or LID, but the associations were not significant after Bonferroni correction. Conclusion: This study identified new loci associated with the occurrence of motor fluctuations and LID at 5 years after the onset of PD. However, further studies are needed to confirm our findings. [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]

Background: Amyloid positron emission tomography (PET) imaging is appropriate for patients with atypical presentation, unusually rapid course and very early onset of dementia. Standardized uptake value ratios (SUVr) are used for relative quantification of 18F‐florbetaben (18F‐FBB) PET scans and cerebellar cortex can be used as reference region for quantification. Previous study showed that 18F‐FBB PET demonstrated a diffuse cortical uptake and in particular an intense uptake in the basal ganglia in familial Alzheimer’s disease with presenilin‐1(PS‐1) mutation. Method: This report describes the case of a young woman with early‐onset familial Alzheimer’s disease(EOfAD), who has atypical pattern of uptake on amyloid PET. Result: A 37‐year‐old woman with a college level educational background was brought in by her family for further evaluation of cognitive impairment, personality and behavioral changes. At age 30 years of age, the patient presented memory impairment and she had difficulty serving guests in bakery. Patient had positive family history of early onset dementia; her father, grand mother, and two sisters of grand mother. (Fig. 1 Pedigree showing autosomal dominant inheritance trait of early‐onset dementia. (nn/nn) Age at onset/age at death). She had an initial Mini‐Mental State Examination score of 22/30 (time disorientation, dyscalculia, poor delayed recall). Neuropsychological assessment showed global cerebral dysfunction and revealed dementia with psychiatric symptoms. Brain magnetic resonance imaging showed no significant abnormality. On genetic testing, homozygotes for the apolipoprotein E ε3 allele and a PS‐1 mutation (c.616G>A , p.G602S) was identified. 18F‐FBB PET revealed diffusely increased amyloid deposition including not only bilateral frontal, parietal, posterior cingulate gyrus/precuneus, anterior striatum but also bilateral cerebellar cortex. (Fig. 2 18F‐florbetaben PET, at age 37) Conclusion: This will be the first case report of EOfAD with increased bilateral cerebellar cortical uptake on 18F‐ FBB PET, we present the case to increase awareness of this unusual entity. [ABSTRACT FROM AUTHOR]

Background: Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. A previous study shows that conversion to dementia from amyloid‐negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition. We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid‐negative amnestic MCI. Method: This study was a retrospective cohort study of patients over the age 50 with amyloid‐negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36 months follow‐up period. All subjects underwent detailed neuropsychologic tests, three tesla brain magnetic resonance imaging (MRI) scans including 3‐dimensional T1 imaging, and fluorine‐18[F18]‐florbetaben amyloid PET scans. Result: During the 36 months of follow‐up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole. In terms of cerebellar gray matter (GM) volumetric analysis, reduced Crus I/II volume adjusted with total intracranial volume (TIV) and age was observed in the converter group. The converter group had also more severe impairments in all visual memory tasks. Conclusion: Our study showed that the reduced gray matter volume related to visual memory processing in the cerebrum and Significant cerebellar GM atrophy involving the bilateral Crus I/II may predict the clinical progression in this amyloid‐negative MCI population. [ABSTRACT FROM AUTHOR]

Background: Pathophysiology of cognitive decline in CAA is multifactorial, because microbleeds, white matter hyperintensities, and combined concomitant parenchymal Alzheimer’s disease (AD) pathology have been suggested to cause cognitive impairment. The mechanism by which microbleeds affect cognitive impairment is still under investigation. We aimed to investigate the mechanism of how microbleeds contribute to cognitive impairment, in association with white matter tract abnormalities or cortical thickness in CAA with significant amyloid deposition. Method: We retrospectively investigated 30 patients with probable CAA according to Boston criteria and 30 patients with Alzheimer’s disease (AD), all of whom showed severe amyloid deposition on amyloid PET (Aβ+). Age, sex, and clinical deteriorating scale were matched. Using MRI, cortical thickness and white matter tract abnormalities as fractional anisotropy (FA) were obtained. We compared cortical thickness, FA, and cognitive scores of five domains between Aβ+ CAA and Aβ+ AD. Using path analysis, we investigated the correlation between number of regional microbleeds, cortical thickness, FA, and cognitive impairments. Result: Both CAA and AD group showed similar cortical amyloid deposition in AD related regions such as precuneus, and posterior cingulate cortex suggesting that CAA in this study might have AD pathology. Patients with Aβ+ CAA presented with significantly lower FA in clusters of posterior area than patients with Aβ+ AD (FWE‐corrected p value <0.05) Importantly, total number of microbleeds were associated with decreased FA in tapetum of corpus callosum (r=‐0.429, p<0.001), which were consequently associated with visuospatial function (r=0.466, p<0.001). Cortical thickness was not significantly different between CAA and AD, and it did not mediate the association between regional microbleeds and cognition. Conclusion: This study suggests that lobar microbleeds may impact cognitive decline through the mediation of white matter tract abnormalities in CAA. [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]