-ε4 allele[s]-associated adverse events reported from placebo arm in clinical trials for Alzheimer's disease: implications for anti-amyloid beta therapy.

-ε4 allele[s] is a risk factor for Alzheimer's disease (AD) and Amyloid-Related Imaging Abnormalities (ARIA) in anti-amyloid beta therapy, and is also associated with cerebrovascular risk factors such as hyperlipidemia or atherosclerosis. During AD clinical trials, -ε4 carriers may experience neuropsychiatric adverse events (AEs) related to these risks, complicating the differentiation of ARIA from cerebrovascular events based on symptoms. This study aimed to examine the hypothetical impact of considering the -ε4 allele's risk for non-ARIA AEs during AD clinical trials.

Clinical Application of 18 F-THK5351 PET to Image Ongoing Astrogliosis in MSA-P and MSA-C.

18 F-labeled THK5351 PET can visualize ongoing astrogliosis by estimating monoamine oxidase B levels and can be used as an adjunct for diagnosing neurodegenerative disorders. Little has been reported on multiple system atrophy (MSA) in the differential diagnosis of parkinsonian syndromes. Here, we present 18 F-THK5351 images in typical cases of MSA-P (parkinsonian type) and MSA-C (cerebellar type), showing intense 18 F-THK5351 uptake in the lateral-posterior part of the putamen (MSA-P) and in the pons and middle cerebellar peduncles (MSA-C).

Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly.

Background: Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD.

Methods: We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study.

Simplifying Alzheimer's Disease Monitoring: A Novel Machine-Learning Approach to Estimate the Clinical Dementia Rating Sum of Box Changes Using the Mini-Mental State Examination and Functional Activities Questionnaire.

Background: Primary outcome measure in the clinical trials of disease modifying therapy (DMT) drugs for Alzheimer's disease (AD) has often been evaluated by Clinical Dementia Rating sum of boxes (CDRSB). However, CDR testing requires specialized training and 30-50 minutes to complete, not being suitable for daily clinical practice.

Objective: Herein, we proposed a machine-learning method to estimate CDRSB changes using simpler cognitive/functional batteries (Mini-Mental State Examination [MMSE] and Functional Activities Questionnaire [FAQ]), to replace CDR testing.

Advertisement by medical facilities as an opportunity route of APOE genetic testing in Japan: a website analysis.

The APOE-ε4 allele(s) is a strong risk factor for Alzheimer's disease (AD). A significant point of access for this allele testing is through services provided by medical facilities in Japan, which advertise out-of-insurance APOE testing on their websites. There is a concern that website advertisements for APOE testing may influence the ability for individuals to adequately self-determine whether to undergo APOE testing.

Detailed Assessment of 18F-THK5351 Distribution Pattern in the Midbrain: Comparison With Progressive Supranuclear Palsy and Corticobasal Syndrome.

Background: 18F-THK5351 PET is used to image ongoing astrogliosis by estimating monoamine oxidase B levels. 18F-THK5351 preferentially accumulates around the substantia nigra (SN) and periaqueductal gray (PG) in the midbrain under healthy conditions and exhibits a "trimodal pattern." In progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), the midbrain 18F-THK5351 uptake can be increased by astrogliosis, collapsing the "trimodal pattern.

A first-in-human study of the anti-inflammatory profibrinolytic TMS-007, an SMTP family triprenyl phenol.

Aims: TMS-007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen-fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti-inflammatory action, mediated by soluble epoxide hydrolase inhibition, may contribute to its efficacy. Evidence suggests that TMS-007 can effectively treat experimental thrombotic and embolic strokes with a wide time window, while reducing haemorrhagic transformation.

Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid.

Background: The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.

Methods: We stratified 177 individuals who participated in the Japanese Alzheimer's Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers.

Efficacy and Cost-effectiveness of Promotion Methods to Recruit Participants to an Online Screening Registry for Alzheimer Disease Prevention Trials: Observational Study.

Background: Web-based screening may be suitable for identifying individuals with presymptomatic latent diseases for recruitment to clinical studies, as such people do not often visit hospitals in the presymptomatic stage. The promotion of such online screening studies is critical to their success, although it remains uncertain how the effectiveness of such promotion can differ, depending on the different promotion methods, domains of interest, or countries of implementation.

Objective: The Japanese Trial-Ready Cohort (J-TRC) web study is our ongoing online screening registry to identify individuals with presymptomatic Alzheimer disease (AD), aimed at facilitating the clinical trials for AD prevention.

Predicting amyloid risk by machine learning algorithms based on the A4 screen data: Application to the Japanese Trial-Ready Cohort study.

Background: Selecting cognitively normal elderly individuals with higher risk of brain amyloid deposition is critical to the success of prevention trials for Alzheimer's disease (AD).

Methods: Based on the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease study data, we built machine-learning models and applied them to our ongoing Japanese Trial-Ready Cohort (J-TRC) webstudy participants registered within the first 9 months ( = 3081) of launch to predict standard uptake value ratio (SUVr) of amyloid positron emission tomography.

Results: Age, family history, online Cognitive Function Instrument and CogState scores were important predictors.

Effect of apolipoprotein E ε4 allele on the progression of cognitive decline in the early stage of Alzheimer's disease.

Introduction: Possession of the apolipoprotein E ( ) ε4 allele advances amyloid β (Aβ) deposition and symptomatic onset of Alzheimer's disease (AD), whereas its effect on the rate of cognitive decline remained controversial. We examined the effects of ε4 allele on cognition in biomarker-confirmed late mild cognitive impairment (LMCI) and mild AD subjects in the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and North American ADNI (NA-ADNI).

Methods: The "early AD" (ie, combined LMCI and mild AD) cohort of 649 subjects from J-ADNI and NA-ADNI were selected based on positivity of Aβ confirmed by amyloid positron emission tomography (PET) or cerebrospinal fluid testing.

Identification of prognostic factors to predict cognitive decline of patients with early Alzheimer's disease in the Japanese Alzheimer's Disease Neuroimaging Initiative study.

Introduction: The objective of this study was to determine the factors including neuropsychological test performances and cerebrospinal fluid (CSF) biomarkers which can predict disease progression of early Alzheimer's disease (AD) in a Japanese population.

Methods: The group classification on early AD population in both Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and North American ADNI (NA-ADNI) was performed using the inclusion criteria including brain amyloid positivity on positron emission tomography or CSF. Participants with early AD from each cohort were stratified into two groups based on a cutoff 1.

Visualizing modules of coordinated structural brain atrophy during the course of conversion to Alzheimer's disease by applying methodology from gene co-expression analysis.

Objective: We aimed to identify modularized structural atrophy of brain regions with a high degree of connectivity and its longitudinal changes associated with the progression of Alzheimer's disease (AD) using weighted gene co-expression network analysis (WGCNA), which is an unsupervised hierarchical clustering method originally used in genetic analysis.

Methods: We included participants with late mild cognitive impairment (MCI) at baseline from the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) study. We imputed normalized and Z-transformed structural volume or cortical thickness data of 164 parcellated brain regions/structures based on the calculations of the FreeSurfer software.

Effects of sex, educational background, and chronic kidney disease grading on longitudinal cognitive and functional decline in patients in the Japanese Alzheimer's Disease Neuroimaging Initiative study.

Introduction: The objective of this study was to determine whether sex or education level affects the longitudinal rate of cognitive decline in Japanese patients in the Alzheimer's disease Neuroimaging Initiative study with defined mild cognitive impairment (MCI).

Methods: We accessed the entire Japanese Alzheimer's Disease Neuroimaging Initiative data set of 537 individuals, among whom 234 had MCI and 149 had Alzheimer's disease. We classified participants into three categories of educational history: (1) low, 0 to 9 years; (2) moderate, 10 to 15 years; and (3) high ≥16 years.