The association between migraine and Parkinson's disease: a nationwide cohort study.

OBJECTIVES: Clinical studies have suggested an association between migraine and the occurrence of Parkinson's disease (PD). However, it is unknown whether migraine affects PD risk. We aimed to investigate the incidence of PD in patients with migraine and to determine the risk factors affecting the association between migraine and PD incidence. METHODS: Using the Korean National Health Insurance System database (2002-2019), we enrolled all Koreans aged ≥40 years who participated in the national health screening program in 2009. International Classification of Diseases (10th revision) diagnostic codes and Rare Incurable Diseases System diagnostic codes were used to define patients with migraine (within 12 months of enrollment) and newly diagnosed PD. RESULTS: We included 214,193 patients with migraine and 5,879,711 individuals without migraine. During 9.1 years of follow-up (55,435,626 person-years), 1,973 (0.92%) and 30,664 (0.52%) individuals with and without migraine, respectively, were newly diagnosed with PD. Following covariate adjustment, patients with migraine showed a 1.35-fold higher PD risk than individuals without migraine. The incidence of PD was not significantly different between patients with migraine with aura and those without aura. In males with migraine, underlying dyslipidemia increased the risk of PD (p=0.012). In contrast, among females with migraine, younger age (<65 years) increased the risk of PD (p=0.038). CONCLUSIONS: Patients with migraine were more likely to develop PD than individuals without migraine. Preventive management of underlying comorbidities and chronic migraine may affect the incidence of PD in these patients. Future prospective randomized clinical trials are warranted to clarify this association.

Predicting cognitive stage transition using p-tau181, Centiloid, and other measures.

BACKGROUND: A combination of plasma phospho-tau (p-tau), amyloid beta (Aß)-positron emission tomography (PET), brain magnetic resonance imaging, cognitive function tests, and other biomarkers might predict future cognitive decline. This study aimed to investigate the efficacy of combining these biomarkers in predicting future cognitive stage transitions within 3 years. METHODS: Among the participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE-V) study, 49 mild cognitive impairment (MCI) and 113 cognitively unimpaired (CU) participants with Aß-PET and brain imaging data were analyzed. RESULTS: Older age, increased plasma p-tau181, Aß-PET positivity, and decreased semantic fluency were independently associated with cognitive stage transitions. Combining age, p-tau181, the Centiloid scale, semantic fluency, and hippocampal volume produced high predictive value in predicting future cognitive stage transition (area under the curve = 0.879). CONCLUSIONS: Plasma p-tau181 and Centiloid scale alone or in combination with other biomarkers, might predict future cognitive stage transition in non-dementia patients. HIGHLIGHTS: -Plasma p-tau181 and Centiloid scale might predict future cognitive stage transition. -Combining them or adding other biomarkers increased the predictive value. -Factors that independently associated with cognitive stage transition were demonstrated.

Correlations with REM sleep behavior disorder severity in isolated rapid eye movement sleep behavior disorders patients.

OBJECTIVES: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis. METHODS: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography. RESULTS: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls (p < 0.001). There was no difference in upper extremity function between patients and controls (right, p = 0.220; left, p = 0.209), but gait was slower in iRBD patients (walking time, p < 0.001; number of steps, p < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients (p = 0.006, p = 0.003, respectively). Patients with were also more depressed (p = 0.002), had decreased olfactory function (p < 0.001), reported more frequent sleep/fatigue episodes (p < 0.001), worse attention/memory capacity (p < 0.001), gastrointestinal problems (p = 0.009), urinary problems (p = 0.007), and pain (p = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances (p = 0.004), but no difference in daytime sleepiness (p = 0.663). Disease severity was correlated with pain (r = 0.686, p = 0.002) and visuospatial function (r= -0.507, p = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities (p > 0.09). CONCLUSIONS: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Subjective Cognitive Complaints in Cognitively Normal Patients With Parkinson's Disease: A Systematic Review.

Subjective cognitive complaints (SCCs) refer to self-perceived cognitive decline and are related to objective cognitive decline. SCCs in cognitively normal individuals are considered a preclinical sign of subsequent cognitive impairment due to Alzheimer's disease, and SCCs in cognitively normal patients with Parkinson's disease (PD) are also gaining attention. The aim of this review was to provide an overview of the current research on SCCs in cognitively normal patients with PD. A systematic search found a lack of consistency in the methodologies used to define and measure SCCs. Although the association between SCCs and objective cognitive performance in cognitively normal patients with PD is controversial, SCCs appear to be predictive of subsequent cognitive decline. These findings support the clinical value of SCCs in cognitively normal status in PD; however, further convincing evidence from biomarker studies is needed to provide a pathophysiological basis for these findings. Additionally, a consensus on the definition and assessment of SCCs is needed for further investigations.

Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes.

Importance: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. Objective: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. Design, Setting, and Participants: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Main Outcomes and Measures: Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid ß deposition (Aß). Results: A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P < .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aß deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. Conclusions and Relevance: In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.

Fabrication of Wearable Transistor with All-Graphene Electrodes via Hot Pressing.

Textile electronics are ideal for novel electronic devices owing to their flexibility, light weight, and wearability. In this work, wearable organic field-effect transistors (OFETs) with all-graphene electrodes, fabricated using hot pressing, are described. First, highly conductive and flexible electrodes consisting of a cotton textile substrate and electrochemically exfoliated graphene (EEG) were prepared via hot pressing. The EEG/textile electrodes exhibited a low sheet resistance of 1.3 Ω sq-1 and high flexibility; these were used as gate electrodes in the wearable OFETs. In addition, spray-coated EEG was also used as the source/drain (S/D) electrodes of the wearable OFETs, which recorded a sheet resistance of 14.8 Ω sq-1 after hot pressing. The wearable OFETs exhibited stable electrical performance, a field-effect mobility of 13.8 cm2 V-1 s-1, and an on-off current ratio of ~103 during 1000 cycles of bending. Consequently, the fabrication method for wearable transistors developed using textiles and hot-pressed graphene electrodes has potential applications in next-generation wearable devices.

Functionalization of Tailored Porous Carbon Monolith for Decontamination of Radioactive Substances.

As the control over radioactive species becomes critical for the contemporary human life, the development of functional materials for decontamination of radioactive substances has also become important. In this work, a three-dimensional (3D) porous carbon monolith functionalized with Prussian blue particles was prepared through removal of colloidal silica particles from exfoliated graphene/silica composite precursors. The colloidal silica particles with a narrow size distribution were used to act a role of hard template and provide a sufficient surface area that could accommodate potentially hazardous radioactive substances by adsorption. The unique surface and pore structure of the functionalized porous carbon monolith was examined using electron microscopy and energy-dispersive X-ray analysis (EDS). The effective incorporation of PB nanoparticles was confirmed using diverse instrumentations such as X-ray diffraction (XRD), Fourier-transform infrared (FT-IR), and X-ray photoelectron spectroscopy (XPS). A nitrogen adsorption/desorption study showed that surface area and pore volume increased significantly compared with the starting precursor. Adsorption tests were performed with 133Cs ions to examine adsorption isotherms using both Langmuir and Freundlich isotherms. In addition, adsorption kinetics were also investigated and parameters were calculated. The functionalized porous carbon monolith showed a relatively higher adsorption capacity than that of pristine porous carbon monolith and the bulk PB to most radioactive ions such as 133Cs, 85Rb, 138Ba, 88Sr, 140Ce, and 205Tl. This material can be used for decontamination in expanded application fields.

Association between sleep parameters and longitudinal shortening of telomere length.

BACKGROUND: The relationship between sleep parameters and longitudinal shortening of telomere length is unclear. This study aimed to investigate the relationship between sleep parameters and the shortening of leukocyte telomere length (LTL) over a year. METHODS: Among the participants in the validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, participants who measured both baseline and follow-up (two years later) of LTL were analyzed. They were dichotomized according to the degree of LTL attrition over two years. Clinical characteristics were compared between the faster and slower LTL shortening groups (cut-off points: -0.710 kbp, n = 119 each). Multivariable logistic regression analyses were performed to determine independent relationships between faster shortening of LTL length and sleep parameters. RESULTS: A total of 238 participants, aged 55-88 years, were included. Participants with faster LTL shortening had a shorter duration of sleep (P = 0.013) and longer sleep latency (P = 0.007). Among the components of the PSQI, subjective measures of sleep quality, sleep latency, sleep duration, and sleep efficiency were significantly worse in participants with faster LTL shortening. Multivariate logistic regression analysis showed that sleep duration (per hour, OR = 0.831, 95% CI = 0.698-0.989), sleep latency (per minute, OR = 1.013, 95% CI = 1.002-1.024), global PSQI score (OR = 1.134, 95% CI = 1.040-1.236), shortest sleep duration (OR = 5.173, 95% CI = 1.563-17.126), and lowest sleep efficiency (OR = 7.351, 95% CI = 1.943-27.946) were independently associated with faster LTL shortening. CONCLUSIONS: Poor sleep quality, specifically short sleep duration, long sleep latency, and low sleep efficiency were associated with faster longitudinal shortening of LTL.

Association of Hippocampal Subfield Volumes with Amyloid-Beta Deposition in Alzheimer's Disease.

We investigated the relationship between hippocampal subfield volumes and cortical amyloid-beta (Aß) deposition in Alzheimer's disease (AD). Fifty participants (11 cognitively unimpaired [CU], 10 with mild cognitive impairment [MCI], and 29 with AD) who underwent 18F-florbetaben positron emission tomography, magnetic resonance imaging, and neuropsychological tests were enrolled. The hippocampal subfield volumes were obtained using an automated brain volumetry system with the Winterburn atlas and were compared among the diagnostic groups, and the correlations with the Aß deposition and AD risk factors were determined. Patients with MCI and AD showed decreased volume in the stratum radiatum/lacunosum/moleculare (SRLM) of the cornu ammonis (CA)1 and CA4-dentate gyrus (DG) compared with the CU. Decreased SRLM and CA4-DG volumes were associated with an increased Aß deposition in the global cortex (R = −0.459, p = 0.001; R = −0.393, p = 0.005, respectively). The SRLM and CA4-DG volumes aided in the distinction of AD from CU (areas under the receiver operating characteristic [AUROC] curve = 0.994 and 0.981, respectively, p < 0.001), and Aß+ from Aß− individuals (AUROC curve = 0.949 and 0.958, respectively, p < 0.001). Hippocampal subfield volumes demonstrated potential as imaging biomarkers in the diagnosis and detection of AD and Aß deposition, respectively.

Reliability and Validity of the Subjective Cognitive Complaints Questionnaire for Parkinson's Disease (SCCQ-PD).

BACKGROUND AND PURPOSE: Subjective cognitive complaints (SCCs) are gaining attention as a self-perceived symptom for cognitive impairment in patients with Parkinson's disease (PD), but there are few suitable tools for assessing SCCs in PD. This study aimed to develop and validate a questionnaire for assessing SCCs in PD, called the Subjective Cognitive Complaints Questionnaire for Parkinson's Disease (SCCQ-PD). METHODS: The SCCQ-PD consists of 12 yes/no questions on subjective cognitive function, and the questionnaire was completed by patients with PD (score-P) and their caregivers (score-C). The cognitive function of patients was examined using comprehensive neuropsychological tests. RESULTS: This study included 73 patients (38 cognitively normal, 25 with mild cognitive impairment [MCI], and 10 demented) and their caregivers. Score-P and score-C had excellent reliability (Kuder-Richardson formula 20 coefficients of 0.893 and 0.931, respectively), and the scores exhibited a strong intercorrelation. Both score-P and score-C were negatively correlated with cognitive performance, and both were excellent in discriminating demented patients from those with normal cognition or MCI (areas under the receiver operating characteristic curve of 0.83 and 0.88, respectively). CONCLUSIONS: The SCCQ-PD is a reliable tool for assessing SCCs in patients with PD. SCCs measured using the SCCQ-PD are correlated with objective cognitive decline and useful for discriminating demented patients from nondemented patients.

Association Between Body Mass Index and Cognitive Function in Mild Cognitive Impairment Regardless of APOE ε4 Status.

BACKGROUND AND PURPOSE: In this study we aimed to find the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, we investigated the effects of the apolipoprotein E (APOE) genotype in the relationship between the BMI and cognition in MCI. METHODS: We enrolled a cohort of 3,038 subjects with MCI aged 65-90 from the Clinical Research Center for Dementia of South Korea and a dementia cohort of the Ewha Womans University Mokdong Hospital. MCI patients were classified into three subgroups according to the Asian standard of BMI. We compared cognitive performances between groups by one-way analysis of variance. To investigate the effects of the APOE genotype, we used multivariate linear regression models after adjusting for possible confounders. RESULTS: Even though normal BMI groups were younger, had more females, and had less comorbidities, the higher BMI groups had better cognitive functions. Among subjects with APOE ε4 carriers, there was a positive relationship between the BMI and the memory task alone. CONCLUSIONS: Our findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE ε4 genotype in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype-specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.

Serum neurofilament light chain level as a predictor of cognitive stage transition.

BACKGROUND: Neurofilament light chain (NFL) level has been suggested as a blood-based biomarker for neurodegeneration in dementia. However, the association between baseline NFL levels and cognitive stage transition or cortical thickness is unclear. This study aimed to investigate whether baseline NFL levels are associated with cognitive stage transition or cortical thickness in mild cognitive impairment (MCI) and cognitively unimpaired (CU) participants. METHODS: This study analyzed data on participants from the independent validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE-V) study. Among the participants of KBASE-V study, 53 MCI and 146 CU participants who were followed up for ≥ 2 years and had data on the serum NFL levels were eligible for inclusion in this study. Participants were classified into three groups according to baseline serum NFL levels of low, middle, or high. RESULTS: The Kaplan-Meier analysis showed association between the serum NFL tertiles and risk of cognitive stage transition in MCI (P = 0.002) and CU (P = 0.028) participants, analyzed separately. The same is true upon analysis of MCI and CU participants together (P < 0.001). In MCI participants, the highest serum NFL tertile and amyloid-beta positivity were independent predictors for cognitive stage transition after adjusting for covariates. For CU participants, only amyloid-beta positivity was identified to be an independent predictor. CONCLUSION: The study shows that higher serum NFL tertile levels correlate with increased risk of cognitive stage transition in both MCI and CU participants. Serum NFL levels were negatively correlated with the mean cortical thickness of the whole-brain and specific brain regions.

Factors associated with motor severity in vascular parkinsonism with normal dopamine transporter imaging.

INTRODUCTION: To delineate the determinants of motor severity in vascular parkinsonism (VaP), we investigated the impact of regional white matter intensity (WMH) burden and co-morbidities on the motor score in the patients with VaP and normal dopamine transporter (DAT) imaging. METHODS: In this multicenter, retrospective study, we reviewed the records of 63 patients diagnosed with VaP and normal DAT imaging on 18F-FP-CIT PET. Signal hyperintensities in deep white matter (DWMH), periventricular (PVH), basal ganglia (BG) regions, and infratentorial foci (ITF) were rated according to Scheltens scale, a semi-quantitative visual rating system. Motor severity was assessed with Unified Parkinson's Disease Rating Scale (UPDRS) motor score. Regional hyperintensity scores, patients' demographics, and co-morbidities such as type 2 diabetes, hypertension, dyslipidemia, and previous stroke history were used as starting variables, and stepwise regression analysis was performed to select independent predictors of motor severity. RESULTS: PVH (R = 0.33, p = 0.008) and DWMH score (R = 0.31, p = 0.015) correlated with the motor severity, while BG and ITF scores did not. Diabetic patients had significantly higher motor scores compared with non-diabetics (34.7 (13.0) vs. 27.5 (12.4), p = 0.008). Other factors such as sex, BMI, hypertension, dyslipidemia, and previous history of stroke did not impact motor severity. In multivariate analysis, PVH scores and diabetes significantly correlated with motor severity. CONCLUSION: PVH burden and diabetes were independent factors associated with motor severity in VaP with normal DAT imaging. Our results suggest that diabetes, along with white matter hyperintensities, may have a significant role in the development of motor symptoms in VaP.

Comparison of Surface Modification Methods for Improving the Compatibility of Recycled Plastic Film-Based Aggregates.

The surface modification of recycled plastic film-based aggregates was investigated to improve the compatibility between the aggregates and a cement paste. Surface modification was performed using ultraviolet-ozone treatment (UV-O3), a silane coupling agent, O2 atmospheric pressure plasma, and acrylic binder coating methods. The surface properties of the modified aggregates were analyzed using a contact angle measuring instrument. The results revealed that for all surface modification methods, the contact angle decreased with an increase in the treatment time. According to the comparative evaluation results of the changes in the surface characteristics of the aggregates through various surface modification methods, the contact angle reduction rates were 58.9%, 51.4%, 25.5%, and 24.5% for the O2 atmospheric pressure plasma, the acrylic binder coating, the silane coupling agent, and the UV-O3 method, respectively. After 48 h, the contact angle had increased by 110.9%, 29.9%, 16.4%, and 5.9% for the O2 atmospheric pressure plasma, UV-O3, the silane coupling agent, and the acrylic binder coating, respectively. Namely, the surface modification using the acrylic binder coating method was found to be the most effective method in terms of the wettability increase effect and the long-term storage stability.

Development of the Functionalized Nanocomposite Materials for Adsorption/Decontamination of Radioactive Pollutants.

A polymer-based nanofiber membrane with a high specific surface area, high porosity and abundant adsorption sites is demonstrated for selective trapping of radionuclides. The Prussian blue (PB)/poly(methyl methacrylate) (PMMA) nanofiber composites were successfully prepared through a one-step, single-nozzle electrospinning method. Various analytical techniques were used to examine the physical and chemical properties of PB nanoparticles and electrospun nanofibers. It is possible to enhance binding affinity and selectivity to radionuclide targets by incorporation of the PB nanoparticles into the polymer matrix. It is noteworthy that the maximum 133Cs adsorption capacity of hte PB/PMMA nanofiber filter is approximately 28 times higher than that of bulk PB, and the removal efficiency is measured to be 95% at 1 ppm of 133Cs. In addition, adsorption kinetics shows that the PB/PMMA nanofiber has a homogenous surface for adsorption, and all sites on the surface have equal adsorption energies in terms of ion-exchange between cyano groups of the introduced PB nanoparticles and radionuclides.

Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population.

BACKGROUND: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid ß (Aß) positivity using a large sample of Korean population. METHODS: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aß positivity (measured by amyloid positron emission tomography). Aß prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. RESULTS: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aß positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aß positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10-8). Prediction performance for Aß positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. CONCLUSION: The novel genetic variants associated with FGL2 decreased risk of Aß positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.

Hyposmia may predict development of freezing of gait in Parkinson's disease.

To explore the effect of olfactory dysfunction on treatment of motor manifestations in Parkinson's disease (PD). The current longitudinal retrospective cohort study consecutively recruited 108 de novo PD patients. Of whom 29 were normosmia and 79 were hyposmia, respectively, which was determined by the Korean Version of Sniffin' Sticks Test II at the time of diagnosis. All the participants underwent serial clinical examinations including Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination, and Montreal Cognitive Assessment. The normosmic group demonstrated a significantly greater reduction of the UPDRS III score (30.3 ± 5.9 to 21.9 ± 5.1) than that of the hyposmic group (34.5 ± 9.3 to 28.5 ± 8.1) from baseline to 1-year later (p, 0.003; Bonferroni correction for p < 0.0045). Of subdomains in UPDRS III, the axial domain revealed a remarkable decrease in the normosmic group. Further, the hyposmic group exhibited a higher development rate of freezing of gait (FOG) compared to the normosmic group (29/79 (36.7%) vs 2/29 (6.9%); p, 0.002) during 33.9 ± 7.7 months of the mean follow-up period. A Cox proportional hazards model demonstrated the hyposmia to be a significant risk factor for the future development of FOG (HR, 4.23; 95% CI 1.180-17.801; p, 0.05). Our data demonstrated the olfactory dysfunction to be a significant risk factor for the development of the FOG in PD. Hyposmic PD patients should be paid more careful attention to the occurrence of FOG in the clinical practice.

A Review of Polymer Composites Based on Carbon Fillers for Thermal Management Applications: Design, Preparation, and Properties.

With the development of microelectronic devices having miniaturized and integrated electronic components, an efficient thermal management system with lightweight materials, which have outstanding thermal conductivity and processability, is becoming increasingly important. Recently, the use of polymer-based thermal management systems has attracted much interest due to the intrinsic excellent properties of the polymer, such as the high flexibility, low cost, electrical insulation, and excellent processability. However, most polymers possess low thermal conductivity, which limits the thermal management applications of them. To address the low thermal conduction of the polymer materials, many kinds of thermally conductive fillers have been studied, and the carbon-based polymer composite is regarded as one of the most promising materials for the thermal management of the electric and electronic devices. In addition, the next generation electronic devices require composite materials with various additional functions such as flexibility, low density, electrical insulation, and oriented heat conduction, as well as ultrahigh thermal conductivity. In this review, we introduce the latest papers on thermally conductive polymer composites based on carbon fillers with sophisticated structures to meet the above requirements. The topic of this review paper consists of the following four contents. First, we introduce the design of a continuous three-dimensional network structure of carbon fillers to reduce the thermal resistance between the filler-matrix interface and individual filler particles. Second, we discuss various methods of suppressing the electrical conductivity of carbon fillers in order to manufacture the polymer composites that meet both the electrical insulation and thermal conductivity. Third, we describe a strategy for the vertical alignment of carbon fillers to improve the through-plane thermal conductivity of the polymer composite. Finally, we briefly mention the durability of the thermal conductivity performance of the carbon-based composites. This review presents key technologies for a thermal management system of next-generation electronic devices.

Cognitive trajectories of patients with focal ß-amyloid deposition.

BACKGROUND: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition. METHODS: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group. RESULTS: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex. CONCLUSIONS: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.