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Background: Subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease (AD); however, the rates of cognitive decline are variable according to underlying pathologies and biomarker status. We conducted an observational study and aimed to investigate baseline characteristics and biomarkers related with cognitive declines in SCD. Our study also assessed whether SCD participants showed different cognitive and biomarker trajectories according to baseline amyloid deposition. Methods: This study is a part of a longitudinal cohort study conducted in multi-centers in South Korea between 2018 and 2021. Individuals (≥ 60 years old) with persistent cognitive complaint despite of normal cognitive functions were eligible for the study. All participants underwent neuropsychological tests, florbetaben PET scans, plasma amyloid markers, and brain MRI scans. Annual follow-up evaluations included neuropsychological tests and assessments for clinical progressions. Regional brain volumetry and amyloid burden represented by PET-based standardized uptake value ratio (SUVR) were measured. We compared cognitive and brain atrophic changes over 24 months between amyloid positive-SCD (Aβ + SCD) and amyloid negative-SCD (Aβ-SCD) groups. Baseline factors associated with cognitive outcomes were investigated. Results: A total of 120 participants with SCD were enrolled and 107 completed follow-up evaluations. Aβ + SCD participants (n = 20, 18.5%) were older and more frequently APOE4 carriers compared with Aβ-SCD participants (n = 87). Baseline cognitive scores were not different between the two groups, except the Seoul Verbal Learning Test (SVLT) scores showing lower scores in the Aβ + SCD group. After 24 months, plasma amyloid markers were higher, and regional volumes (entorhinal, hippocampal, and pallidum) were smaller in the Aβ + SCD participants compared with Aβ-SCD participants adjusted by age, sex, and baseline volumes. SVLT delayed recall and controlled oral word association test (COWAT) scores indicated more declines in Aβ + SCD participants. Baseline left entorhinal volumes were related to verbal memory decline, while baseline frontal volumes and global SUVR values were related to frontal functional decline. Conclusion: Aβ + SCD participants showed more cognitive decline and medial temporal atrophic changes during 24 months. Baseline neurodegeneration and amyloid burden were related with future cognitive trajectories in SCD. Trial registration: This study was registered at CRIS (KCT0003397). [ABSTRACT FROM AUTHOR]

The correlations between apolipoprotein epsilon 4 (APOE4) status and regional amyloid, tau, and cortical thickness in cognitively normal elderly are not fully understood. Our cross-sectional study aimed to compare regional amyloid/tau burden, and cortical thickness according to APOE4 carrier status and assess correlations between APOE4 and Alzheimer's disease (AD)-related biomarker burdens. We analyzed 185 cognitively normal participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Participants aged 55–90 with normal cognitive function were divided into amyloid ß-positive (Aß+) APOE4 carriers (group 1, n = 27), Aß+ APOE4 non-carriers (group 2, n = 29), and Aß− normal controls (group 0, n = 129). We compared amyloid depositions, tau depositions, and cortical thickness among the three groups and assessed correlations between APOE4 existence and imaging biomarkers adjusted for age and sex. The participants in group 2 were older than those in the other groups. The regional amyloid/tau standardized uptake value ratios (SUVRs) did not differ between groups 1 and 2, but the amyloid/tau SUVRs in most regions were numerically higher after adjusting for age difference. APOE4 allele had robust correlations with increased amyloid burden in the fronto-temporo-parietal cortical areas after adjustment for age and sex, but it had weaker and mixed correlations with the regional tau burden and did not have significant correlation with cortical thickness. We identified that the presence of APOE4 allele might be more highly associated with amyloid deposition than with other AD-related biomarkers such as tau or cortical thickness in cognitively normal elderly. [ABSTRACT FROM AUTHOR]

Abstract: Flow of two immiscible stratified liquids in a pipe is observed in many industrial applications. Estimating the interfacial boundary between the immiscible liquids inside the pipeline can provide valuable information about volume fraction therefore can aid in monitoring the flow process. Several methods are proposed to represent the shape of an open boundary using linear combination of known functions. In this paper, the open boundary is characterized by discrete front points from the reference horizontal line at the center. The boundary parameterization with front points eliminates the fixed end problem that is caused while using Fourier series or a polynomial like a Bezier curve. Therefore, it can be more suitable to practical conditions and can be used to represent any complex shape with fewer unknowns. The forward problem is solved using boundary element method (BEM) with the integral equations solved analytically. The proposed BEM formulation is computationally efficient due to less number of system equations to solve. The unknown front points locations that describe the boundary surface are estimated using Levenberg–Marquardt method. Numerical and phantom experiments are performed to validate the performance of the proposed computational method. [Copyright &y& Elsevier]

Background: High-dose donepezil is currently prescribed for patients with Alzheimer's disease (AD) who showed poor or waning response to a lower dose at the risk of increasing cholinergic side effects. However, the adverse events (AEs) depending on the method of dose escalation have not been clarified yet. This study aimed to find out whether dose titration before escalating to donepezil 23 mg is preferred. We investigated safety and tolerability of donepezil 23 mg during the first 12 weeks of dose escalation in patients with moderate to severe AD. Methods: This study was a 12-week, multicenter, randomized, open-label prospective trial. We included patients with moderate to severe AD who were treated with a stable dose of donepezil 10 mg/day. Patients were randomized into 3 groups according to the dose escalation method: 15 mg of donepezil for 4 weeks before escalating to 23 mg (group 1), 10 mg and 23 mg on alternate days for 4 weeks prior to escalation (group 2), and direct escalation to 23 mg (group 3). Safety analyses included incidence, severity, timing of AEs, relationship to the study drug, and premature study discontinuation due to AEs between the groups. Results: Among 175 enrolled, 110 patients completed the study. Baseline characteristics were similar among the groups. Using safety population (N = 160), cholinergic gastrointestinal symptoms including anorexia and nausea were the most common AEs and titration groups showed significantly fewer cases of nausea as compared with those in no-titration group. Conclusions: In this study, dose titration before escalating to donepezil 23 mg/day showed better safety in terms of cholinergic AEs. We suggest that dose titration during the first 4 weeks can be recommended for patients with moderate to severe AD. Trial registration: Clinicaltrials.gov, NCT02550665. Retrospectively registered on 15 Sep 2015. [ABSTRACT FROM AUTHOR]

Epilepsy is a common neurological disease. Systemic tumors are associated with an increased risk of epileptic events. Paraneoplastic encephalitis related to gonadal teratoma is frequently accompanied by seizures and life-threatening status epilepticus (SE). However, the risk of epilepsy in gonadal teratoma has not been studied. This study aims to investigate the relationship between epileptic events and gonadal teratoma. This retrospective cohort study used the Korean National Health Insurance (KNHI) database. The study population was divided into two study arms (ovarian teratoma vs. control and testicular teratoma vs. control) with 1:2 age and gender-matched control groups without a history of gonadal teratoma or other malignancy. Participants with other malignancies, neurologic disorders, and metastatic brain lesions were excluded. We observed the occurrence of epileptic events during the observation period (2013–2018) and investigated the risk of epileptic events in each gonadal teratoma group compared to controls. In addition, the influence of malignancy and tumor removal was investigated. The final analysis included 94,203 women with ovarian teratoma, 2314 men with testicular teratoma, and controls. Ovarian teratoma is associated with a higher risk of epilepsy without SE (HR, 1.244; 95% CI 1.112–1.391) and epilepsy with SE (HR, 2.012; 95% CI 1.220–3.318) compared to the control group. The risk of epilepsy without SE was higher in malignant ovarian teratoma (HR, 1.661; 95% CI 1.358–2.033) than in benign (HR, 1.172; 95% CI 1.037–1.324). Testicular teratoma did not show significant relations with epileptic events. The risk of epileptic events showed a tendency to decrease after removing the ovarian teratoma. This study found that ovarian teratoma is associated with a higher risk of epileptic events, especially in malignant tumors, whereas testicular teratoma did not show significant differences in epileptic events compared to the control group. This study adds to the current understanding of the association between gonadal teratoma and epileptic events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A simple fluorescence-based cell-free DNA (CFD) assay has been previously developed that can directly measure nucleic acids without prior DNA extraction and amplification. However, studies on fluorescence-based CFD are lacking. In particular, there is no known information regarding the stability with regard to pre-analytical storage conditions in relation to time and temperature, or on the influence of freeze-thawing. Plasma was directly assayed to measure CFD using PicoGreen™ reagent. Standard linearity and accuracy were confirmed using salmon sperm DNA. Whole blood was left at room temperature (RT) and at 4˚C, and then plasma was separated. The CFD was also measured using thawed plasma after 1 week of freezing. As a correlation with a sperm DNA concentration, CFD demonstrated linearity over a wide range of concentrations, with a 0.998 correlation coefficient. The CFD level showed a change of up to 2.5 µg/ml according to pre-analytical storage time, and the changes were not consistent over time. The CFD values at RT after 1 h were similar to the baseline values, and the relative standard deviation was lowest under this condition. The CFD values between 4˚C and RT were similar over all time periods assessed. After freeze-thawing, the change in CFD value was reduced compared to that before freezing. The present study showed that CFD measurements using plasma processed within 1 h were optimal. Additionally, the effects of substantial changes according to storage conditions were reduced after freeze-thawing, and thus studies using stored samples is viable and relevant. [ABSTRACT FROM AUTHOR]