Background: and Purpose: The Cognitive Impairment Screening Test (CIST) was developed for use at the Community Dementia Reassurance Center in South Korea. This study evaluated convergent and discriminant validity of CIST, as well as its clinical utility in identifying cognitive impairment and differentiating amyloid deposition. Methods: We enrolled 252 participants from a hospital memory clinic (47 cognitively unimpaired [CU], 116 amnestic mild cognitive impairment, and 89 dementia). Participants completed CIST, K-MMSE-2, the Seoul Neuropsychological Screening Battery, 2nd edition (SNSB-II), and underwent amyloid positron emission tomography. To evaluate the convergent and discriminant validity of CIST, we conducted correlation analyses with SNSBII. Receiver operating characteristic analyses were used to evaluate the ability to discriminate cognitive impairment and to distinguish amyloid positivity. Areas under the curve (AUCs) for CIST and K-MMSE-2 were compared using DeLong’s test. Results: The total score of CIST correlated significantly with all SNSB-II subtests, and the domain scores of CIST showed stronger associations with corresponding SNSB-II subtests than with unrelated ones. Both CIST and K-MMSE-2 effectively distinguished cognitively impaired individuals from CU, with CIST demonstrating superior discrimination (AUC=0.926 vs.0.887, p=0.042). In the non-demented group, both CIST and K-MMSE-2 showed acceptable discrimination for amyloid positivity (AUC≈0.73), with high specificity but low sensitivity;however, there were no significant differences between the two tests. Conclusions The CIST demonstrated strong validity and discriminatory ability for detecting cognitive impairment. It also showed acceptable discrimination for amyloid positivity in non-demented participants, supporting its utility as a screening tool in both clinical and community settings.

Background: and Purpose: Given the irreversible nature of dementia, this study examined the effects of a 20-week exercise-based dementia prevention program in community-dwelling older adults, focusing on prior exercise experience and program adherence. Methods: In this exploratory, non-randomized trial, 55 older adults (65–79 years) were allocated to an intervention (n=26) or control (n=29) group, and blinding was not feasible.The intervention comprised supervised rhythmic aerobic exercise with cognitive-motor components performed three times per week. Cognition was the primary outcome, and secondary outcomes included physical fitness, blood pressure, and blood biomarkers.Subgroup analyses classified participants by prior exercise experience and intervention exposure: G1 and G2 comprised control subgroups with no intervention exposure, whereas G3 and G4 comprised intervention-exposed subgroups stratified by adherence. Results: No significant group-by-time interactions were observed for cognitive outcomes.Participants with prior exercise experience and low adherence (G2) showed significant improvement on the Korean Mini-Mental State Examination (β=1.66, p=0.024) despite declines in physical fitness, whereas higher adherence in G3–G4 was associated with stable or favorable physical performance, with G4 showing a positive trend in the 30-second sit-tostand test. Systolic blood pressure decreased significantly in G2–G4. Conclusions Although overall cognitive gains were modest and not group specific, prior exercise experience and sustained adherence were associated with favorable changes in physical fitness and vascular outcomes, suggesting that tailored multicomponent exercise programs and long-term engagement may help promote cognitive health in older adults.

Background: and Purpose: Clinicians typically use 2 methods to determine impairment in a specific cognitive domain based on the Seoul Neuropsychological Screening Battery, 2nd Edition: (1) identifying impairment when one or more subtests fall below the normal range (< mean −1.5 standard deviation), and (2) using the cognitive domain score. Because agreement between these methods may differ by the severity of cognitive impairment, this study examined their concordance in the overall sample and across Clinical Dementia Rating (CDR) levels. Methods: A total of 1,086 patients (age 74.27±9.62 years; education 9.07±4.77 years) were included. Concordance between subtest-based and domain score-based classifications was assessed for each cognitive domain using cross-tabulation analyses and Cohen’s kappa statistics. To assess the influence of the severity of cognitive impairment, analyses were conducted across CDR levels. Results: When impairment was defined as having at least one abnormal subtest, concordance rates were 90.8% for Attention, 88.8% for Language, 84.6% for Visuospatial Function, 74.3% for Memory, and 73.6% for Frontal/Executive Function. In the Frontal/ Executive Function domain, requiring 2 or more abnormal subtests increased concordance to 90.9%. CDR subgroup analyses showed that Memory concordance was particularly low in the CDR 0.5 group (65.8%) compared with the CDR 1 (85.5%) and CDR 2 (98.5%) groups. Conclusions Concordance between the 2 classification methods was moderately high for Attention, Language, and Visuospatial Function but substantially lower for Memory and Frontal/Executive Function, especially in individuals with mild cognitive impairment. These findings highlight the need to consider both subtest-level performance and domain scores when determining impairment in memory or frontal/executive function.

Background: and Purpose: To assess the long-term effectiveness, safety, and economic viability of recently approved Alzheimer’s disease (AD) therapies, as well as to evaluate the real-world application of novel diagnostics among AD patients with diverse comorbidities, comprehensive real-world data (RWD) analysis is essential. The Korean JOint RegistrY for ALZheimer’s Treatment and Diagnostics (JOY-ALZ) endeavors to create a registry of RWD derived from clinical practice on new diagnostic methods and therapeutic agents for AD introduced in Korea since 2021. Methods: Participants must fulfill all the following: 1) be at least 19 years old; 2) be actively receiving, scheduled to initiate, or undergoing evaluation for any AD disease-modifying treatment; 3) have completed amyloid positron emission tomography or cerebrospinal fluid AD immunoassay (a positive result is not essential for participation); 4) have a clinical classification of cognitively unimpaired, mild cognitive impairment, or probable AD dementia. Data generated during routine care is segmented into a minimum dataset, extended dataset, and research-only dataset requiring extra consent. Assessments encompass clinical, cognitive, functional, neurobehavioral, neuroimaging, and biomarker evaluations, in addition to systematic monitoring of new AD treatments and their safety.Data are collected and monitored at baseline, at semiannual intervals during the initial 2 years, and then annually up to 2034. To date, 46 medical centers will participate in JOY-ALZ. Conclusions JOY-ALZ is expected to promote understanding of the long-term clinical outcomes, safety, and cost-effectiveness of recently introduced diagnostics and treatments for AD, thereby supporting the progress of precision medicine in AD care and diagnosis.

Alzheimer’s disease (AD), the primary cause of dementia accounting for 60% to 70% of cases globally, results in a gradual decline in cognitive abilities, affecting memory, executive function, and daily activities. Recent research highlights the essential involvement of the microbiota-gut-brain axis in AD pathogenesis, characterized by complex bidirectional signaling that modulates neuroinflammation, neurogenesis, neurotransmission, and immune functions. This manuscript extends the discussion beyond the gut alone by emphasizing the significance of the oral-gut microbiota axis as a dynamic and relatively under-investigated factor in AD progression. Microbial populations in both the oral cavity and gastrointestinal tract produce key neurotransmitters, such as gamma-aminobutyric acid, noradrenaline, and dopamine, as well as neuroactive metabolites like short-chain fatty acids, which together impact brain physiology. Disturbances in gut and oral microbial balance can compromise barrier integrity, promoting systemic inflammation and neuroinflammation, and facilitating amyloid-β plaque formation and tau-related changes typical of AD. This review introduces a novel probiotic, prebiotics, synbiotics, and postbiotics (PPSP) therapeutic model designed to modulate both oral and gut microbiota, aiming to restore homeostasis, regulate neuroimmune interactions, and counteract cognitive impairment.We comprehensively assess emerging clinical and translational findings supporting the effectiveness of microbiota-targeted therapies in the scope of this dual-axis framework, addressing both their potential to alter disease course and recognized limitations.By underscoring the importance of the integrated oral-gut microbiota axis alongside targeted PPSP interventions, this manuscript puts forth a paradigm-shifting conceptual strategy that may redefine approaches to AD management and improve cognitive outcomes.

Background: and Purpose: Amyloid positron emission tomography (PET) is a crucial diagnostic tool for Alzheimer's disease (AD), but its application is constrained by cost and accessibility. This study aimed to create a practical composite index to predict cerebral amyloid positivity in patients with cognitive impairment. Methods: We included patients with mild cognitive impairment or early-stage AD who underwent amyloid PET. Various combinations of clinical and imaging variables were assessed through receiver operating characteristic analysis to identify the optimal model for predicting amyloid positivity. The Amyloid Beta Composite (ABC) index, a risk scoring model, was developed using logistic regression and a weighted scoring system. We evaluated the ABC index's performance based on accuracy, sensitivity, and specificity, and conducted internal validation using a chronological split-sample from the same cohort. Results: We analyzed a total of 223 patients. The best-performing model incorporated five variables: Mini-Mental State Examination (MMSE), secondary memory recall from the modified MMSE, Clinical Dementia Rating-Sum of Boxes, medial temporal lobe atrophy, and apolipoprotein E genotype. This model demonstrated excellent performance in the development group (area under the curve [AUC], 0.88; 95% confidence interval, 0.82–0.94).In the validation group, the ABC index achieved an AUC of 0.74, with an accuracy of 0.70, sensitivity of 0.63, and specificity of 0.78. Conclusions The ABC index, utilizing commonly accessible clinical data, serves as a simple and practical screening tool for predicting cerebral amyloid deposition. It may aid in patient selection for amyloid PET, anti-amyloid therapies, and clinical trials, thereby reducing unnecessary imaging.

Background: and Purpose: Tailored physical exercise interventions have the potential to promote cognitive health in older adults and offer significant advantages for those more vulnerable to decline. The specific relationship between physical fitness and cognition among the elderly has not been clearly established. The purpose of this investigation was to assess the relationship between physical fitness and cognitive function in older Korean adults. Methods: Eighty-four community-dwelling older adults (mean age: 70.7±5.3 years; 81.0% female) completed a standardized physical fitness battery assessing handgrip strength, sit-and-reach, 30-second sit-to-stand, 2-minute stationary march, 3-m sit-walk-and-return, figure-8-walk, and T-wall response time. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Descriptive statistics, partial correlation analyses, and stepwise multiple linear regression were conducted. Results: Slower T-wall response time was significantly correlated with lower RBANS total index, immediate memory, and delayed memory scores. In regression models, slower T-wall response time was independently associated with lower RBANS total index (β=−0.234, p=0.026) and delayed memory scores (β=−0.295, p=0.029). The regression model for immediate memory was not statistically significant overall; therefore, no predictive conclusion was drawn for this domain. Higher education showed a significant positive association with cognitive performance. Conclusions Coordination, as measured by T-wall response time, emerged as the only physical fitness component consistently associated with cognitive performance in older adults. Coordination-related fitness may be an important correlate of cognitive function in older adults and a promising target for future exercise interventions.

Background: and Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer’s disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification.To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI). Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages. Methods: We included 2,428 individuals recruited from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research project. We calculated regional Aβ cutoffs using Gaussian Mixture Modeling. Participants were classified into subgroups based on global, regional, and striatal Aβ positivity across cognitive stages (cognitively unimpaired [CU], mild cognitive impairment, and dementia of the Alzheimer’s type). Results: MRI-based and CT-based global Aβ cutoffs were highly comparable and consistent with previously reported Centiloid values. Regional cutoffs revealed both similarities and differences between MRI- and CT-based methods, reflecting modality-specific segmentation processes. Subgroups such as global(−)regional(+) were more frequent in non-dementia stages, while global(+)striatal(−) was primarily observed in CU individuals. Conclusions Our study established robust regional Aβ cutoffs using a CT-based rdcCL method and demonstrated its clinical utility in classifying amyloid subgroups across cognitive stages. These findings highlight the importance of regional Aβ quantification in understanding amyloid pathology and its implications for biomarker-guided diagnosis and treatment in AD.

Background: and Purpose: The Cognitive Impairment Screening Test in Korea (CIST-K) was designed to detect cognitive decline. Developed independently and widely used in Korea, it is yet to be validated with other screening tests. This study aimed to introduce normative data to the CIST-K and assess its clinical usefulness through correlation analysis with the Korean version of the Mini-Mental State Examination, 2nd edition (K-MMSE-2). Methods: We enrolled 85 participants from a tertiary university hospital in Korea, including patients diagnosed with mild cognitive impairment and Alzheimer’s disease by experienced neurologists. Both the CIST-K and K-MMSE-2 were administered to assess the cognitive function of the participants, with scores from each subtest of the neuropsychological tests compared. Results: Multivariate correlation analysis, which was adjusted for age, sex, and education level, revealed a significant correlation between the two tests in orientation, memory, and attention. However, no significant correlation was found between the two tests in visuospatial and language functions. Conclusions In conclusion, this study demonstrates that some subtests in the CIST-K align with corresponding scores on the K-MMSE-2. However, caution is advised when interpreting visuospatial and language test scores from the CIST-K. Further validity studies are necessary to enhance the sensitivity of each subtest.