Cost-benefit of dementia insurance for cognitively-unimpaired ε4 homozygotes: A simulation study.

Background: Dementia insurance, a private insurance product covering the first diagnosis of dementia of the insured, may be beneficial for asymptomatic individuals who recognize their own high genetic risk for Alzheimer's disease.

Objective: We aimed to examine the cost-benefit of dementia insurance in cognitively unimpaired individuals, stratified by ε4 genotype.

Methods: A simulation study using 18 years of longitudinal data from National Alzheimer's Coordinating Center study to simulate the income and expenses of dementia insurance from the insured's perspective.

Age-related trends in amyloid positivity in Parkinson's disease without dementia.

Amyloid-beta (Aβ) plays a pivotal role in cognitive decline in Parkinson's disease (PD). The prevalence of amyloid positivity, evaluated using the cerebrospinal fluid (CSF) of patients with PD without dementia in their sixties, is lower than that in individuals with normal cognition without PD diagnosis in the same age range. However, it is unclear whether this is also the case in patients with PD without dementia in their eighties.

Modernizing diagnosis of Alzheimer's disease: A review of global trends and Asia-specific perspectives.

The landscape of Alzheimer's disease (AD) and related dementias (ADRD) diagnosis is evolving rapidly, driven by advances in disease understanding, biomarker tools, and disease-modifying therapies. Modern diagnostic approaches emphasize biological precision, early detection, and dynamic frameworks that adapt to treatment-induced changes in disease biology. These frameworks enable opportunities for personalized interventions-encompassing pharmacological and non-pharmacological strategies-and for enhanced clinical trial design.

How many sites are enough? a novel, site-based power analysis method for real-world registry studies of anti-amyloid monoclonal antibodies.

Background: Real-world registries ALZ-NET (US) and AD-DMT (Japan) support safety surveillance of anti-amyloid antibodies. Conventional power calculations-dividing required patients by mean per-site caseload-can underestimate the number of centers needed because of patient counts variability.

Objectives: To develop and evaluate a simulation-based method for site-level sample size planning that incorporates inter-site variability.

Effect of corrections for renal function on plasma phosphorylated tau performance for Alzheimer's disease.

BackgroundBlood-based biomarkers (BBMs), including plasma phosphorylated tau (pTau), have been considered as a promising, less-invasive tool for detecting Alzheimer's disease (AD) pathology in real-world applications. Plasma pTau levels are known to be elevated in individuals with chronic kidney disease, which may require caution when corrected for renal function since it alters testing performance-decreased sensitivity and increased specificity.ObjectiveWe aimed to quantify how correcting for renal function affects BBM test performance.

Audio review as a measure of quality assurance and control of cognitive assessments in Alzheimer's disease studies: An experience from Japanese Trial-Ready Cohort Study.

Background: Clinical trials targeting preclinical Alzheimer's disease (AD) require accurate cognitive assessments to detect subtle changes over time. Audio review of assessment sessions has been proposed as a quality assurance (QA) and control (QC) measure, yet evidence regarding its effectiveness remains limited.

Objective: We aim to investigate how audio review contributes to the QA/QC process.

Therapeutic time window of disease-modifying therapy for early Alzheimer's disease.

Introduction: Recently approved disease-modifying therapies (DMT) for early Alzheimer's disease (AD), including lecanemab and donanemab, require patients to meet specific eligibility criteria for treatment. These criteria define a limited "therapeutic time window," after which patients become ineligible as the disease advances. Understanding factors influencing this window may help clinicians optimize patient management and reduce lost treatment opportunities.

Impact of istradefylline on motor and non-motor symptoms in patients with Parkinson's disease: Subanalysis of the ISTRA ADJUST PD.

Introduction: Parkinson's disease (PD) presents with diverse motor and non-motor symptoms, some of which do not fully respond to dopamine replacement therapy. To clarify the effects of the adenosine A receptor antagonist istradefylline (IST) on PD symptoms, we conducted a subanalysis of the 37-week ISTRA ADJUST PD randomized controlled trial.

Methods: Patients with PD experiencing wearing-off with levodopa at 300-400 mg/day were randomized 1:1 to receive IST or no IST (control).

Blood-based biomarker prescreening with different testing combinations and cutoffs: A simulation study examining efficacy and cost-effectiveness in Alzheimer's disease prevention studies.

Introduction: Blood-based biomarkers (BBBMs), including plasma amyloid beta (Aβ) or phosphorylated tau (p-tau), combined with apolipoprotein E () testing, are anticipated to serve as prescreening tools before amyloid positron emission tomography (PET) for recruiting participants for Alzheimer's disease (AD) prevention studies. The predictive efficacy and cost-effectiveness of prescreening may vary with different testing combinations, sequences, and cutoff levels.

Methods: We conducted a simulation study utilizing data from our ongoing Japanese Trial-Ready Cohort (J-TRC) onsite study ( = 202) recruited online.

Sentiment analysis of social media responses to the approval of lecanemab for the treatment of Alzheimer's disease in Japan.

Lecanemab, an anti-amyloid therapy for early Alzheimer's disease, received approval by the FDA and Japan in 2023. Public response on social media was scrutinized, aiming to obtain insights into communication and treatment development. For 478 posts from X and Facebook, their sentiments on efficacy, safety, societal significance, and overall lecanemab impression were assessed by GPT-4 and the authors.

Cognitive function instrument-based anosognosia to predict amyloid status.

Anosognosia, a lack of self-awareness regarding cognitive dysfunction, often accompanies the progression of Alzheimer's disease (AD) pathology. This study explored the relationship between AD pathology and anosognosia measured by discrepancies in Cognitive Function Instrument (CFI) scores, as rated by participants and their study partners (SP). Using mixed-effects models on non-demented participant data, the results revealed that lower self-reported CFI score compared to SP ratings was significantly associated with positive amyloid PET results (odds ratio 1.

-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.