Dementia and neurocognitive disorders最新文献

Background and purpose: The Telephone-Montreal Cognitive Assessment (T-MoCA) is a remote cognitive screening tool increasingly used in clinical and research contexts. However, its applicability in Korean populations remains underexplored.

Methods: This study examined the equivalence between the T-MoCA and the face-to-face Korean MoCA-22 (K-MoCA-22) in a community-based sample of 113 cognitively normal adults aged 21-91 years. The sample was stratified into 2 age groups (<60 and ≥60 years) for subgroup analyses. All participants completed both the T-MoCA and K-MoCA-22 in a counterbalanced order, with a one-month interval between assessments.

Results: Both T-MoCA and K-MoCA-22 scores were significantly associated with age and education, but not with sex in either age group. However, none of these variables significantly influenced the score differences between the 2 tests. Lin's concordance correlation coefficient indicated strong agreement between the 2 tests in the overall sample and in participants aged ≥60, with minimal systematic bias. Equivalence testing using the two one-sided tests procedure supported statistical equivalence in the total sample and the <60 group, but not in the ≥60 group. Subtest-level differences were observed in the ≥60 group, with higher repetition scores on the K-MoCA-22 and higher delayed recall scores on the T-MoCA, possibly reflecting absence of visual cues, reduced supervision, and lower anxiety during remote testing.

Conclusions: These findings support the T-MoCA as an equivalent and reliable alternative to the K-MoCA-22 for remote cognitive screening in Korean adults. Nonetheless, age-related and modality-specific factors should be considered when interpreting scores, particularly in older individuals.

Social cognition, including theory of mind, empathy, social perception, and behavior, is crucial for interpersonal relationships and social functioning. Impairments in social cognition have also been recognized in neurodegenerative disorders including frontotemporal dementia, Alzheimer's disease, and Parkinson's disease. This review defines social cognition components, summarizes assessment tools, and evaluates their clinical applicability in these disorders. Despite research, the incorporation of social cognition assessments into clinical practice remains limited. Developing standardized, validated tools and integrating them with current, conventional neuropsychological assessments is crucial for improving the diagnosis, prognosis, and management of neurodegenerative disorders. Emerging interventions targeting specific social cognitive domains or their neural systems hold promise in enhancing the social functioning and quality of life of affected individuals.

Blood and cerebrospinal fluid (CSF) biomarkers are essential tools for the rapid diagnosis and monitoring of neurodegenerative diseases like Alzheimer's disease (AD). However, even minor variations in sample collection and storage procedures can significantly impact biomarker measurements, emphasizing the importance of standardized operating procedures. This review discusses the main pre-analytical factors that influence biomarker stability, outlines the best practices for blood and CSF collection and storage, and extensively analyzes recent research findings to ensure optimal reproducibility in biomarker studies. It also discusses the future directions and recommendations for enhancing biomarker research methodologies, including advancements in automated processing and quality control measures.

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.

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.

Alzheimer's disease (AD), a neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and tau tangles, shows cognitive decline. Recent genetic studies have identified over 30 variants that are resilient to AD pathology, offering new therapeutic opportunities. This review explores key protective mutations of APOE3 Christchurch, RELN-COLBOS, FN1, APP A673T, BDNF Val66Met, SORL1, CR1, TREM2, PICALM, and INPP5 D genes. These affect critical pathways, including lipid metabolism, synaptic function, tau regulation, and immune response. Potential treatments are discussed, including gene therapy and neuroprotective strategies, emphasizing a shift toward precision medicine focused on genetic resilience. By reviewing case studies and relevant literatures, the work explores the mechanisms by which these variants mitigate amyloid accumulation, tau pathology, neurodegeneration, and neuroinflammation, the key contributors to AD progression. Understanding these protective pathways offers critical insights into potential therapeutic applications, such as gene therapy, immune-modulating treatments, and personalized medicine approaches tailored to the individual's genetic profile. The findings highlight the potential to leverage genetic protection mechanisms to develop precision interventions for AD, offering new hope to prevent or delay disease onset and progression. These discoveries could transform future treatment strategies, shifting the focus from risk management to exploiting genetic resilience to combat AD.

Background and purpose: Plasma biomarkers, including phosphorylated tau (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), are promising tools for detecting Alzheimer's disease (AD) pathology. However, cross-laboratory reproducibility remains a challenge, even when using identical analytical platforms such as single-molecule array (Simoa). This study aimed to compare plasma biomarker measurements (ptau217, GFAP, and NfL) between 2 laboratories, the University of Gothenburg (UGOT) and DNAlink, and evaluate their associations with amyloid positron emission tomography (PET) imaging.

Methods: Plasma biomarkers were measured using Simoa platforms at both laboratories: the UGOT and DNAlink Incorporation. Diagnostic performance for predicting amyloid PET positivity, cross-laboratory agreement, and the impact of normalization techniques were assessed. Bland-Altman plots and correlation analyses were employed to evaluate agreement and variability.

Results: Plasma ptau217 concentrations exhibited strong correlations with amyloid PET global centiloid values, with comparable diagnostic performance between laboratories (area under the curve=0.94 for UGOT and 0.95 for DNAlink). Cross-laboratory agreement for ptau217 was excellent (r=0.96), improving further after natural log transformation. GFAP and NfL also demonstrated moderate to strong correlations (r=0.86 for GFAP and r=0.99 for NfL), with normalization reducing variability.

Conclusions: Plasma biomarker measurements were consistent across laboratories using identical Simoa platforms, with strong diagnostic performance and improved agreement after normalization. These findings support the scalability of plasma biomarkers for multi-center studies and underscore their potential for standardized applications in AD research and clinical practice.

Background and purpose: Brain atrophy, characterized by sulcal widening and ventricular enlargement, is a hallmark of neurodegenerative diseases such as Alzheimer's disease. Visual assessments are subjective and variable, while automated methods struggle with subtle intensity differences and standardization, highlighting limitations in both approaches. This study aimed to develop and evaluate a novel method focusing on cerebrospinal fluid (CSF) regions by assessing segmentation accuracy, detecting stage-specific atrophy patterns, and testing generalizability to unstandardized datasets.

Methods: We utilized T1-weighted magnetic resonance imaging data from 3,315 participants from Samsung Medical Center and 1,439 participants from other hospitals. Segmentation accuracy was evaluated using the Dice similarity coefficient (DSC), and W-scores were calculated for each region of interest (ROI) to assess stage-specific atrophy patterns.

Results: The segmentation demonstrated high accuracy, with average DSC values exceeding 0.9 for ventricular and hippocampal regions and above 0.8 for cortical regions. Significant differences in W-scores were observed across cognitive stages (cognitively unimpaired, mild cognitive impairment, dementia of Alzheimer's type) for all ROIs (all, p<0.05). Similar trends were observed in the images from other hospitals, confirming the algorithm's generalizability to datasets without prior standardization.

Conclusions: This study demonstrates the robustness and clinical applicability of a novel CSF-focused segmentation method for assessing brain atrophy. The method provides a scalable and objective framework for evaluating structural changes across cognitive stages and holds potential for broader application in neurodegenerative disease research and clinical practice.

Background and purpose: Mild cognitive impairment (MCI) is a transitional stage to dementia, Alzheimer's disease being a major cause. Although amyloid beta-positive (Aβ+) MCI has been well-characterized, Aβ-negative (Aβ-) MCI has not. This study compared the comprehensive clinical and behavioral characteristics of Aβ+ and Aβ- MCI in a large multi-center cohort to better understand the heterogeneity of MCI, and to identify contributing factors to cognitive impairment.

Methods: A total of 686 MCI participants were included. Aβ positivity was determined using Aβ positron emission tomography imaging with a direct conversion Centiloid cutoff value of 25.5. Standardized assessment and questionnaires were used to collect a wide range of clinical information, including vascular risk factors, cognition, daily living function, neuropsychiatric symptoms, and lifestyle behavior. Groups were compared using independent t-tests and χ² tests.

Results: Aβ+ participants (n=406) were older, predominantly female, and more likely to be ApoE4 carriers. In contrast, Aβ- participants (n=280) showed higher vascular risk factors, including diabetes, elevated body mass index, and higher C-reactive protein levels. Aβ+ participants exhibited worse global cognition and functional decline, with a higher prevalence of delusions and appetite disturbances. Meanwhile, Aβ- participants reported greater social engagement, but poorer sleep quality.

Conclusions: This study highlights the distinct clinical and lifestyle profiles of Aβ+ and Aβ- MCI, illuminating the heterogeneity of MCI and its underlying factors in the Korean population.

Background and purpose: Empathy comprises cognitive and emotional components. However, the impairments in empathy among individuals with mild cognitive impairment (MCI) and dementia of the Alzheimer's type (DAT) are not well understood, particularly in the context of depression, which may exacerbate these deficits. This study aimed to evaluate the effects of neurodegeneration and depression on empathetic abilities.

Methods: The study included 31 healthy elderly (HE) individuals, 30 patients with amnestic multi-domain MCI (amMCI), and 30 patients with DAT. Empathy was assessed using the Korean-Multifaceted Empathy Test (K-MET), and the Interpersonal Response Index (IRI). Participants were classified as depressed or non-depressed using the Geriatric Depression Scale. A two-way MANOVA was conducted to examine differences in empathy based on group and depressive status.

Results: A significant interaction between group and depressive status was found for both cognitive and emotional empathy on the K-MET, but not on the IRI. In the depressed group, cognitive empathy scores were lower in the order of HE, amMCI, and DAT. Similarly, in the non-depressed group, the HE group performed better than both amMCI and DAT, with no significant difference between the latter two. Regarding emotional empathy, the depressed HE group scored higher than both amMCI and DAT, with no significant difference between these groups. In the non-depressed group, emotional empathy declined in the order of HE, amMCI, and DAT.

Conclusions: These findings indicate that both neurodegeneration and depression significantly impair empathetic abilities, with declines in cognitive and emotional empathy evident at the MCI stage, regardless of depressive status.