Incidence and risk factors of age-related macular degeneration in patients with Parkinson's disease: a population-based study.

Background and objective: The association between age-related macular degeneration (AMD) and Parkinson' disease (PD) remains unclear. The aim of the present study was to assess the incidence of AMD in patients with PD, elucidate differences by age and sex, and investigate potential risk factors for AMD. Methods: Data were extracted from the Korean National Health Insurance System database, which covers 97% of the Korean population (2002 through 2019). We calculated the incidence of newly diagnosed AMD in patients with PD and used Cox proportional-hazards models to estimate risk factors for AMD, presenting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Results: Of 172,726 patients with PD, 15,800 were newly diagnosed with AMD during the follow-up, including 5,624 men and 10,176 women. The overall incidence of AMD in patients with PD was 13.59 per 1,000 person-years. Stratified by age group and sex, the incidence was higher in women aged 40-69, and conversely higher in men aged 70-89. Risk of AMD was high in older age groups (aHR = 4.36, 95% CI: 3.74-5.09 in the 70 s), female sex (aHR = 1.07, 95% CI: 1.04-1.11), patients with diabetes mellitus (DM) (aHR = 1.14, 95% CI: 1.10-1.18), and patients with hyperlipidemia (aHR = 1.17, 95% CI: 1.13-1.21). Conclusion: Our findings suggest that the AMD incidence is higher in patients with PD than in the general population, with varying patterns of sex differences across age groups. Particularly, old age, female sex, presence of DM, and hyperlipidemia are potential risk factors. Therefore, clinicians should pay greater attention to AMD in patients with PD.

Effect of Dietary Habits on Alzheimer's Disease Progression.

PURPOSE: Research on the relationship between diet and dementia among Koreans are lacking. This study investigated the association between dietary habits and dementia progression over 3 years in patients with Alzheimer's disease dementia (ADD). MATERIALS AND METHODS: This study included 705 patients with mild-to-moderate ADD. Dietary habits were assessed using the Mini Dietary Assessment Index, comprising 10 questions. Outcome measures included the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB), Seoul-Instrumental Activities of Daily Living, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and neuropsychological test battery (NTB) z-scores, which were evaluated annually over 3 years. RESULTS: In Q10 (eat all food evenly without being picky), the 3-year mean differences in CDR-SB (increases in scores represent worsening) compared to the "rarely" group were -1.86 [95% confidence interval (CI)=-3.64 - -0.09, p=0.039] for the "usually" group and -2.23 (95% CI=-4.40 - -0.06, p=0.044) for the "always" group. In Q7 (add salt or soy sauce to food when eating), the 3-year mean differences in CDR-SB compared to the "always" group were -2.47 (95% CI=-4.70 - -0.24, p=0.030) for the "usually" group and -3.16 (95% CI=-5.36 - -0.96, p=0.005) for the "rarely" group. The "rarely" and "usually" groups in Q7 showed significantly less decline in NTB z-score and CGA-NPI compared to the "always" group. CONCLUSION: Eating a balanced diet and reducing salt intake were associated with a slower decline in dementia severity, cognition, and behavioral alterations in patients with ADD.

Utilizing a Paper-Based Platform for Oilfield Applications: Time-Resolved Fluorescence Imaging and Detection of Interwell Chemical Tracers.

Chemical tracers are indispensable tools for enhancing reservoir characterization and optimizing production processes in the oil and gas industry. Particularly, interwell water tracers provide key data for efficient water flood management and the improvement of production rates. However, the analysis of these water tracers within reservoir fluids is challenging, requiring laborious separation and extraction steps that often rely on complex instruments and skilled operators. Real-time analysis is especially problematic in remote areas with limited access to well-equipped laboratories. To address these challenges, we introduce a paper-based platform for the time-resolved fluorescence detection of dipicolinic acid (DPA) tracers complexed with terbium ion (Tb3+). Our innovation is driven by the need to simplify tracer analysis, make it portable, and enhance accessibility for oilfield applications. By leveraging the unique properties of cyclen-based macrocyclic ligands, we have achieved the stable and sensitive immobilization of Tb3+ on quartz microfilter paper, eliminating the need for extensive laboratory-based procedures. We achieve the stable and sensitive immobilization of Tb3+ on quartz microfilter paper by leveraging the unique properties of cyclen-based macrocyclic ligands. This innovation enables the formation of highly fluorescent, oil-blind, and optically detectable DPA-Tb3+ complexes at the paper surface. We visualize and capture these fluorescence signals using an intensified charge-coupled device camera via time gating, effectively suppressing undesirable fluorescence originating from crude oil. The quantification of DPA concentrations is achievable down to 158 ppb (9.45 × 10-7 M), as confirmed through time-resolved fluorescence microplate reader measurements. We also demonstrate the practicality of our technology by detecting DPA tracers in the presence of crude oil contamination, a common challenge encountered in oil production wells.

The Usefulness of 18F-FDG PET to Differentiate Subtypes of Dementia: The Systematic Review and Meta-Analysis.

Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: 18F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

A Multicentre, Randomised, Open-Label, Prospective Study to Estimate the Add-On Effects Of Memantine as Ebixa® Oral Pump (Solution) on Language in Patients with Moderate to Severe Alzheimer's Disease Already Receiving Donepezil (ROMEO-AD).

INTRODUCTION: This multicentre, randomised, open-label, and prospective study aimed to evaluate the effectiveness of memantine (memantine solution) on speech function in patients with moderate to severe Alzheimer's disease (AD) who were already on donepezil therapy. METHODS: Participants were divided into two groups: the drug trial group was administered donepezil + memantine (memantine solution), while the control group was administered only donepezil. Patients in the test group were required to increase the dose of memantine by 5 mg/day per week for the first 4 weeks and were maintained at 20 mg/day until the end of the trial. RESULTS: Of the 188 participants, 24 dropped out, and 164 completed the final research process. As the primary outcome, K-WAB showed an increase in scores in both groups compared to baseline scores; however, the difference was not statistically significant (P = 0.678). After 12 weeks, the donepezil treatment group had higher K-MMSE and lower CDR-SB scores than the donepezil and memantine combination group, indicating better cognitive and functional status. However, this effect was not sustained for 24 weeks. Patients who were assigned to receive only donepezil had Relevant Outcome Scale for AD (ROSA) scores that were higher by an average of 4.6 points compared to the donepezil and memantine combination group. The NPI-Q index improved compared to baseline values in both groups. CONCLUSIONS: Although several clinical studies have reported significant improvements in speech function after the administration of memantine, clinical studies on speech function improvement in patients with Alzheimer's disease are still insignificant. There are no studies on the effect of donepezil and memantine in combination treatment on language function in the moderate and severe stages of AD. Therefore, we investigated the effect of memantine (memantine solution) on speech function in patients with moderate to severe AD who were administered donepezil at a stable dose. Although the efficacy of the combination therapy was not superior to that of donepezil monotherapy alone, memantine was effective in improving behavioural symptoms in patients with moderate or severe AD.

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.

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.

Patterns of dementia treatment in older adults with Parkinson's disease using nationwide medical claims data.

BACKGROUND: Dementia is a common feature in Parkinson's disease (PD); however, data on dementia treatment patterns in patients with PD are scarce. This study aimed to evaluate the incidence of dementia in individuals with PD and to describe the dementia treatment patterns in the Korean elderly population. METHODS: We conducted a retrospective population-based cohort study using data obtained from the Korean National Health Insurance Service-Senior Cohort (NHIS-SC) database. The dataset comprised more than 500,000 health insurance beneficiaries from January 1, 2002 to December 31, 2015. We estimated the incidence of patients newly diagnosed with dementia during this observational period, compared patient demographics, and analyzed the exposure to anticholinergic drugs among PD patients with (PD + D) and without (PD-D) dementia. Furthermore, the duration to dementia diagnosis and patterns of dementia treatment were evaluated. RESULTS: A cohort of 28,537 patients aged 60 years or older who were diagnosed with PD by the NHIS was established. Within this cohort, 8620 patients were eligible study participants according to strict inclusion/exclusion criteria. Of these individuals, 3879 (45.0%) patients were newly diagnosed with dementia; the incidence of dementia in PD was 15.2 per 1000 person-years. The proportion of women was higher in the PD + D (64.6%) than the PD-D group (58.2%) (P < 0.001); furthermore, the use of anticholinergic medication was greater in PD + D (37.6%) than in PD-D (24.0%) patients. The incidence curves for dementia over time were the steepest during the first year and decreased every year thereafter. Approximately 60% of PD patients were diagnosed with dementia during the first 3 years. Regarding the use of anti-dementia drugs, 2539 (65.5%) of 3879 PD + D were prescribed medication. During the observation period, 1799 (70.9%) patients were prescribed only one type of anti-dementia drug. In this monotherapy group, the most commonly prescribed medication was donepezil (1313[73.0%]), followed by rivastigmine (capsule and patch; 246[13.7%]), memantine (187[10.4%]), and galantamine (53[2.9%]). CONCLUSIONS: In Korea, dementia was observed to occur relatively soon after the diagnosis of PD. Anti-dementia medication was prescribed to approximately 66% of PD + D patients, with the majority receiving donepezil as monotherapy.

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 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.

Abnormal tau in amyloid PET negative individuals.

We examined the characteristics of individuals with biomarker evidence of tauopathy but without ß-amyloid (Aß) (A-T+) in relation to individuals with (A+T+) and without (A-T-) evidence of Alzheimer's disease (AD). We included 561 participants with Aß and tau PET from the Alzheimer's Disease Neuroimaging Initiative (ADNI). We compared A-T- (n = 316), A-T+ (n = 63), and A+T+ (n = 182) individuals on demographics, amyloid, tau, hippocampal volumes, and cognition. A-T+ individuals were low on apolipoprotein E ɛ4 prevalence (17%) and had no evidence of subtly elevated brain Aß within the negative range. The severity of tau deposition, hippocampal atrophy, and cognitive dysfunction in the A-T+ group was intermediate between A-T- and A+T+ (all p < 0.001). Tau uptake patterns in A-T+ individuals were heterogeneous, but approximately 29% showed tau deposition in the medial temporal lobe only, consistent with primary age-related tauopathy and an additional 32% showed a pattern consistent with AD. A-T+ individuals also share other features that are characteristic of AD such as cognitive impairment and neurodegeneration, but this group is heterogeneous and likely reflects more than one disorder.

Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. METHODS: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. RESULTS: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). CONCLUSIONS: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.

Cognitive decline according to amyloid uptake in patients with poststroke cognitive impairment.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment (PSCI) is common, but the impact of ß-amyloid (Aß) on PSCI is uncertain. The proposed study will investigate amyloid pathology in participants with PSCI and how differently their cognition progress according to the amyloid pathology. METHODS: This multicenter study was designed to be prospective and observational based on a projected cohort size of 196 participants with either newly developed cognitive impairment, or rapidly aggravated CI, within 3 months after acute cerebral infarction. They will undergo 18F-flutemetamol positron emission tomography at baseline and will be categorized as either amyloid-positive (A+) or amyloid-negative (A-) by visual rating. The primary outcome measures will be based on Korean Mini-Mental State Examination changes (baseline to 12 months) between the A+ and A- groups. The secondary outcome measures will be the dementia-conversion rate and changes in the Korean version of the Montreal Cognitive Assessment (baseline to 12 months) between the A+ and A- groups. CONCLUSIONS: This study will provide a broadened perspective on the impact of Aß on the cause and outcomes of PSCI in clinical practice. Identifying amyloid pathology in patients with PSCI will help select patients who need more focused treatments such as acetylcholinesterase inhibitors. TRIAL REGISTRATION: Clinical Research Information Service identifier: KCT0005086.

Flexible Chemiresistive Cyclohexanone Sensors Based on Single-Walled Carbon Nanotube-Polymer Composites.

We report a chemiresistive cyclohexanone sensor on a flexible substrate based on single-walled carbon nanotubes (SWCNTs) functionalized with thiourea (TU) derivatives. A wrapper polymer containing both 4-vinylpyridine (4VP) groups and azide groups (P(4VP-VBAz)) was employed to obtain a homogeneous SWCNT dispersion via noncovalent functionalization of SWCNTs. The P(4VP-VBAz)-SWCNT composite dispersion was then spray-coated onto an organosilanized flexible poly(ethylene terephthalate) (PET) film to achieve immobilizing quaternization between the pyridyl groups from the polymer and the functional PET substrate, thereby surface anchoring SWCNTs. Subsequent surface functionalization was performed to incorporate a TU selector into the composites, resulting in P(Q4VP-VBTU)-SWCNT, for the detection of cyclohexanone via hydrogen bonding interactions. An increase in conductance was observed as a result of the hydrogen-bonded complex with cyclohexanone resulting in a higher hole density and/or mobility in SWCNTs. As a result, a sensor device fabricated with P(Q4VP-VBTU)-SWCNT composites exhibited chemiresistive responses (ΔG/G0) of 7.9 ± 0.6% in N2 (RH 0.1%) and 4.7 ± 0.4% in air (RH 5%), respectively, upon exposure to 200 ppm cyclohexanone. Selective cyclohexanone detection was achieved with minor responses (ΔG/G0 < 1.4% at 500 ppm) toward interfering volatile organic compounds (VOC). analytes. We demonstrate a robust sensing platform using the polymer-SWCNT composites on a flexible PET substrate for potential application in wearable sensors.

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.

Tarsal tunnel syndrome in patients with fibromyalgia.

OBJECTIVES: This study aims to evaluate the frequency of tarsal tunnel syndrome (TTS) in fibromyalgia (FM) patients. PATIENTS AND METHODS: In this prospective study, we investigated paresthesia of the foot, sensory and motor deficits, atrophy of the abductor hallucis muscle, and the presence of Tinel's sign in 76 female FM patients (mean age 39.3±7.4 years; range, 24 to 52 years) and 60 sex-matched healthy control subjects (mean age 38.6±8.2 years; range, 28 to 49 years) without FM between July 2016 and June 2018. Bilateral electrophysiological studies of the tibial, peroneal, sural, and medial as well as lateral plantar nerves were performed. RESULTS: Paresthesia was observed in 22 FM patient extremities and four control subject extremities (p=0.002). Local tenderness at the tarsal tunnel was observed in 12 FM patient extremities and two control subject extremities (p=0.021). TTS was detected electrophysiologically in 14 FM patient extremities and two control subject extremities (p=0.009). CONCLUSION: Paresthesia of the foot and local tenderness at the tarsal tunnel were significantly more prevalent in FM patients than in healthy control subjects. TTS is statistically more frequent in patients with FM than the normal population. The potential comorbidities of TTS and paresthesia of the foot should be carefully examined in FM patients.

A systematic review and meta-analysis of the clinical effects of Souvenaid in patients with Alzheimer's disease.

BACKGROUND AND OBJECTIVES: We conducted this meta-analysis about the effects of Souvenaid on cognition and functional abilities, with the hypothesis that Souvenaid may have beneficial effects in certain groups and the goal of finding the outcome measures, disease states, and so on, applicable for further clinical trials. METHODS AND STUDY DESIGN: We searched Medline, Embase, Web of Science, CINAHL, and the Cochrane Library. Only double- blind randomized controlled trials were included. Outcome measurements were cognition, clinical global change, functional ability, and adverse events. The duration of treatment was not restricted, but trials performed in patients who did not have Alzheimer's disease (AD) were excluded. RESULTS: This review using meta-analyses of 4 clinical trials showed that Souvenaid had no significant effects on cognition as measured by ADAS-Cog (MD=0.08, 95% CI=-0.71-0.88) and the neuropsychological test battery total scores (MD=0.05, 95% CI=-0,02- 0.12), on global clinical function as measured by CDR-SB (MD=-0.21, 95% CI=-0.47-0.06), or on functional ability as measured by ADCS-ADL (MD=0.36, 95% CI=-0.54-1.25). There were no differences in any adverse events (OR=0.84, 95% CI=0.63-1.12) or in serious adverse events (OR=0.95, 95% CI=0.66-1.36). However, Souvenaid may benefit the domains of cognition that are affected by AD (attention, memory, and executive function), and it may have greater potential for benefits earlier rather than later in the disease. CONCLUSIONS: The results of current clinical trials do not suggest that Souvenaid has any beneficial effects on cognition, functional ability, or global clinical change. Further studies with outcome measures suitable in patients with early stages of AD will be needed.

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.