Prognostic Value of A/T/N Biomarkers: Comparing Plasma and Imaging Modalities in Alzheimer Disease.

Background: Alzheimer disease (AD) is characterized by amyloid-β plaques (A), tau tangles (T), and neurodegeneration (N), collectively defining the ATN framework. While imaging biomarkers are well-established, the prognostic value of plasma biomarkers in predicting cognitive decline remains underexplored. This study compares plasma and imaging A/T/N biomarkers in predicting cognitive decline and evaluate the impact of combining biomarkers across modalities.

Potential utility of plasma pTau217 for assessing amyloid and tau biomarker profiles.

Purpose: Plasma phosphorylated tau 217 (pTau217) is a promising biomarker for Alzheimer's disease, reflecting both amyloid β (Aβ) and tau positron emission tomography (PET) results. While its diagnostic role is actively being investigated, this study aims to expand its application to staging disease progression and predicting cognitive decline.

Methods: A total of 2,919 participants, primarily diagnosed as Alzheimer's clinical syndrome, were recruited.

Diverse Clinical Phenotypes of Neuronal Intranuclear Inclusion Disease in South Korea.

Background And Purpose: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by a wide range of clinical manifestations. GGC-repeat expansion in was recently identified as the genetic cause of NIID. Here we report clinical, radiological, pathological, and genetic findings in NIID patients.

Validation of criteria for frontotemporal dementia with right anterior temporal lobe predominance.

Introduction: Frontotemporal dementia (FTD) with right anterior temporal lobe (rATL) predominance lacks universally agreed-upon diagnostic criteria. This study validated the Amsterdam diagnostic tree (ADT) for right temporal variant FTD (rtvFTD) and the diagnostic criteria for semantic behavioral variant FTD (sbvFTD), examining clinical, behavioral, and imaging differences.

Methods: The study included 138 patients with behavioral variant FTD and 87 with semantic variant primary progressive aphasia who had 3D T1-weighted magnetic resonance imaging scans.

Generation of an induced pluripotent stem cell line (PNUYHi003-A) from peripheral blood mononuclear cells of a patient with neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disordercharacterized by eosinophilic hyaline intranuclear inclusions in the nervous system. NIID is associated with GGC repeat expansions in the 5' untranslatedregion of the NOTCH2NLC gene. The induced pluripotent stem cells (iPSC), generated from peripheral blood mononuclear cells of a 75-year-old male patient with NIID, exhibited stem cell marker expression, normal karyotype, absence of viral factors, successful differentiation into the three germ layers, and were analyzed for GGC repeat expansion.

Semantic variant primary progressive aphasia with ANXA11 p.D40G.

Introduction: Pathogenic variants of annexin A11 (ANXA11) have been identified in patients with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). We explored ANXA11 pathogenic variants in a Korean FTD cohort to investigate the prevalence and the role of ANXA11 variation in FTD.

Methods: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea.

Profile for Brain Disease Research Infrastructure for Data Gathering and Exploration (BRIDGE) Platform.

Brain diseases complexity have necessitated advanced research platforms for better understanding, treatment, and prevention strategies. However, existing brain disease registries face limitations such as incomplete variable sets, lack of standardization, insufficient linkage to external databases, absence of integrated platforms for comprehensive data collection, and lack of continuity. To address these challenges, the Korea National Institute of Health initiated the Brain disease Research Infrastructure for Data Gathering and Exploration (BRIDGE), a national prospective platform designed to overcome the shortcomings of current registries.

Temporal Dynamics and Biological Variability of Alzheimer Biomarkers.

Importance: Understanding the characteristics of discordance between plasma biomarkers and positron emission tomography (PET) results in Alzheimer disease (AD) is crucial for accurate interpretation of the findings.

Objective: To compare (1) medical comorbidities affecting plasma biomarker concentrations, (2) imaging and clinical features, and (3) cognitive changes between plasma biomarker and PET discordant and concordant cases.

Design, Setting, And Participants: This multicenter cohort study, conducted between 2016 and 2023, included individuals with unimpaired cognition, mild cognitive impairment, or Alzheimer-type dementia, who had both amyloid β (Aβ) PET imaging and plasma biomarkers.

Differential roles of Alzheimer's disease plasma biomarkers in stepwise biomarker-guided diagnostics.

Introduction: This study aimed to investigate the differential roles of various plasma biomarkers in a stepwise diagnostic strategy for Alzheimer's disease (AD).

Methods: A total of 2984 participants, including 666 cognitively unimpaired (CU), 2032 with Alzheimer's clinical syndrome (ACS), and 286 non-ACS individuals, were recruited. Plasma amyloid beta (Aβ) 42/40, four phosphorylated tau (p-tau) epitopes, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were measured using immunoassays.

Development of the Diagnostic Matrix of the Seoul Cognitive Status Test, Compared to Traditional Paper-and-Pencil Neuropsychological Tests.

Background And Purpose: We aimed to develop the diagnostic matrix of the Seoul Cognitive Status Test (SCST) and compare its performance with traditional paper-and-pencil neuropsychological tests, including the Seoul Neuropsychological Screening Battery-II (SNSB-II) and the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K).

Methods: We recruited 197 participants from the head-to-head SCST-SNSB cohort, and 204 participants from the head-to-head SCST-CERAD cohort. They underwent either SNSB-II or CERAD-K, in addition to SCST.

A Two-Year Observational Study to Evaluate Conversion Rates from High- and Low-Risk Patients with Amnestic Mild Cognitive Impairment to Probable Alzheimer's Disease in a Real-World Setting.

Background: Predicting conversion to probable Alzheimer&s disease (AD) from amnestic mild cognitive impairment (aMCI) is difficult but important. A nomogram was developed previously for determining the risk of 3-year probable AD conversion in aMCI.

Objective: To compare the probable AD conversion rates with cognitive and neurodegenerative changes for 2 years from high- and low risk aMCI groups classified using the nomogram.

Executive Summary of 2023 International Conference of the Korean Dementia Association (IC-KDA 2023): A Report From the Academic Committee of the Korean Dementia Association.

The Korean Dementia Association (KDA) has been organizing biennial international academic conferences since 2019, with the International Conference of the KDA (IC-KDA) 2023 held in Busan under the theme 'Beyond Boundaries: Advancing Global Dementia Solutions.' The conference comprised 6 scientific sessions, 3 plenary lectures, and 4 luncheon symposiums, drawing 804 participants from 35 countries. Notably, a Korea-Taiwan Joint Symposium addressed insights into Alzheimer's disease (AD).

Simple modeling of familial Alzheimer's disease using human pluripotent stem cell-derived cerebral organoid technology.

Background: Cerebral organoids (COs) are the most advanced in vitro models that resemble the human brain. The use of COs as a model for Alzheimer's disease (AD), as well as other brain diseases, has recently gained attention. This study aimed to develop a human AD CO model using normal human pluripotent stem cells (hPSCs) that recapitulates the pathological phenotypes of AD and to determine the usefulness of this model for drug screening.

Comparison of Enlarged Perivascular Spaces in Early-Onset and Late-Onset Alzheimer Disease-related Cognitive Impairment: A Single Clinic-based Study in South Korea.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI).

Case report: Neuronal intranuclear inclusion disease initially mimicking reversible cerebral vasoconstriction syndrome: serial neuroimaging findings during an 11-year follow-up.

Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disorder known for its diverse clinical manifestations. Although episodic neurogenic events can be associated with NIID, no reported cases have demonstrated concurrent clinical features or MRI findings resembling reversible cerebral vasoconstriction syndrome (RCVS). Here, we present the inaugural case of an adult-onset NIID patient who initially displayed symptoms reminiscent of RCVS.

A distinctive subgingival microbiome in patients with periodontitis and Alzheimer's disease compared with cognitively unimpaired periodontitis patients.

Aim: Periodontitis is caused by dysbiosis of oral microbes and is associated with increased cognitive decline in Alzheimer's disease (AD), and recently, a potential functional link was proposed between oral microbes and AD. We compared the oral microbiomes of patients with or without AD to evaluate the association between oral microbes and AD in periodontitis.

Materials And Methods: Periodontitis patients with AD (n = 15) and cognitively unimpaired periodontitis patients (CU) (n = 14) were recruited for this study.

Pearls & Oy-sters: Familial Verbal Auditory Agnosia Due to Repeat Expansion.

Chromosome 9 open reading frame 72 () gene pathogenic variants have been typically associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), but recent studies suggest their involvement in other disorders. This report describes a family with an autosomal dominant pattern of inheritance of progressive verbal auditory agnosia due to GGGGCC repeat expansion in C9orf72. A 60-year-old right-handed male truck driver presented with slowly progressive poor speech perception for 8 years, which became most troublesome when receiving verbal orders over the phone.

Case report: Cerebrotendinous xanthomatosis with a novel mutation in the gene mimicking behavioral variant frontotemporal dementia.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by a mutation in the gene. Due to the disruption of bile acid synthesis leading to cholesterol and cholestanol accumulation, CTX manifests as premature cataracts, chronic diarrhea, and intellectual disability in childhood and adolescence. This report presents a case of CTX with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD) in middle age.

Comparison of Retinal Structural and Neurovascular Changes between Patients with and without Amyloid Pathology.

To evaluate whether an impaired anterior visual pathway (retinal structures with microvasculature) is associated with underlying beta-amyloid (Aβ) pathologies in patients with Alzheimer's disease dementia (ADD) and mild cognitive impairment (MCI), we compared retinal structural and vascular factors in each subgroup with positive or negative amyloid biomarkers. Twenty-seven patients with dementia, thirty-five with MCI, and nine with cognitively unimpaired (CU) controls were consecutively recruited. All participants were divided into positive Aβ (A+) or negative Aβ (A-) pathology based on amyloid positron emission tomography or cerebrospinal fluid Aβ.

Genetic Screening in Korean Patients with Frontotemporal Dementia Syndrome.

Background: Frontotemporal dementia (FTD) syndrome is a genetically heterogeneous group of diseases. Pathogenic variants in the chromosome 9 open reading frame 72 (), microtubule-associated protein tau (), and progranulin () genes are mainly associated with genetic FTD in Caucasian populations.

Objective: To understand the genetic background of Korean patients with FTD syndrome.

Semantic variant primary progressive aphasia with a pathogenic variant p.Asp40Gly in the ANXA11 gene.

We report a patient with right-predominant semantic variant primary progressive aphsia linked with p.Asp40Gly variant of ANXA11, which is the first description of frontotemporal dementia without clinical and electrophysiological evidences of amyotrophic lateral sclerosis associated with a known pathogenic variant of ANXA11.