會議議程

Executive Summary：
Dr. Wei-Min Ho is a neurologist specializing in dementia and neurodegenerative disorders. He received his MD from China Medical University in Taiwan and completed his PhD in Translational Medicine through the joint program of National Taiwan University and Academia Sinica.

Dr. Ho currently serves as an Attending Physician in the Division of Dementia, Department of Neurology at Chang Gung Memorial Hospital, Linkou, where he has been actively involved in the clinical care and research of cognitive disorders. He also holds an Assistant Professor appointment in the Department of Neurology at Chang Gung Memorial Hospital and is an Instructor at the School of Medicine, National Tsing Hua University.

His research focuses on Alzheimer’s disease and related neurodegenerative disorders, particularly young-onset cognitive impairment affecting memory and language. His work integrates clinical neurology, genetics, and bioinformatics, with interests spanning neurodegeneration, brain tumors, medical informatics, and post-transcriptomic regulation including non-coding RNA. He is also exploring novel anti-senescence therapeutic strategies.

Dr. Ho has authored multiple peer-reviewed publications on neurogenetics, dementia, and neuro-oncology, including studies on genetic polymorphisms associated with Alzheimer’s disease and transcriptomic evolution in glioblastoma. His work reflects a translational approach that connects molecular mechanisms with clinical neurological disease.

In addition to his clinical and academic roles, Dr. Ho is actively involved in several professional organizations, including the Taiwan Neurological Society and the Taiwan Dementia Society, and has participated in the Taiwan AI Academy Smart Healthcare Program.

Together, his work bridges clinical neurology, genomics, and translational research to advance the understanding and treatment of neurodegenerative diseases.

Lecture Abstract：
Frontotemporal dementia (FTD) represents a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the frontal and temporal lobes, leading to profound disturbances in behavior, personality, and language. It is the third most common cause of dementia overall and a leading cause of early-onset dementia, typically presenting between 45 and 64 years of age. Diagnostic delays are common because early behavioral or psychiatric symptoms are frequently misinterpreted as primary psychiatric disorders.
Clinically, FTD encompasses several syndromes defined by the predominant domain of impairment. Behavioral variant FTD (bvFTD) is the most prevalent presentation and is characterized by early behavioral disinhibition, apathy, loss of empathy, compulsive behaviors, and executive dysfunction with relatively preserved memory. Language-dominant forms fall under the spectrum of primary progressive aphasia (PPA), including the semantic variant (svPPA), non-fluent/agrammatic variant (nfvPPA), and logopenic variant (lvPPA). A right temporal variant has also been recognized, often presenting with prosopagnosia and socio-emotional disturbances.
At the molecular level, FTD is primarily associated with frontotemporal lobar degeneration (FTLD), characterized by abnormal protein aggregation involving tau (FTLD-Tau), TDP-43 (FTLD-TDP), or FUS (FTLD-FUS). Genetic contributions are substantial, with autosomal dominant inheritance observed in a significant subset of cases. Mutations or repeat expansions in three major genes—C9orf72, GRN, and MAPT—account for the majority of familial FTD and provide key insights into disease mechanisms.
Recent advances in biomarker development, including neurofilament light chain, plasma progranulin levels, and neuroimaging patterns, have improved diagnostic accuracy and disease monitoring. Although current treatment strategies remain largely symptomatic—emphasizing behavioral management, caregiver support, and selective pharmacotherapy—rapid progress in gene-targeted therapies, antisense oligonucleotides, and protein-directed treatments is reshaping the therapeutic landscape.
Together, emerging molecular insights, biomarker innovations, and precision therapeutic strategies are transforming the conceptual and clinical framework of FTD, offering new opportunities for earlier diagnosis and disease-modifying interventions.

Executive Summary：
Dr. Cathy S.J. Fann is a Research Fellow at the Institute of Biomedical Sciences, Academia Sinica, specializing in biostatistics, statistical genetics, and precision medicine. She received her Ph.D. in Biostatistics from the University of Iowa, followed by research and faculty positions at Columbia University’s New York State Psychiatric Institute and Albert Einstein College of Medicine before returning to Taiwan.
Since joining Academia Sinica in 1999, Dr. Fann has led and collaborated on major genetic and epidemiologic studies, with joint appointments at National Yang Ming University that helped train a new generation of biostatisticians and genomic scientists. Her research focuses on genome-wide association studies, polygenic risk scores, trans-ethnic and population-specific risk prediction, and integration of large biobank resources, particularly in Han Chinese and Asian populations.
She has authored more than 150 publications, including recent papers in Nature, Nature Communications, European Respiratory Journal, Bioinformatics, and other leading journals, covering topics such as population-specific PRS, the Taiwan Precision Medicine Initiative, pharmacogenomics, asthma genetics, vertigo, and novel methods like the PNL deep-learning PRS framework.
Dr. Fann also holds multiple patents related to genetic risk prediction and biomarkers, underscoring her impact at the interface of methodology, genomics, and clinical translation.

Lecture Abstract：
Background
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder shaped by interactions among genetic, environmental, vascular, and neurobiological factors. However, the genetic architecture of AD and related brain changes remains underexplored in East Asian populations.
Methods
We integrated genome-wide association studies (GWAS), polygenic risk scores (PRS), environmental exposures, vascular burden, and MRI-derived imaging endophenotypes across three Taiwanese cohorts: clinically diagnosed AD, AD-by-proxy cases, and population-based controls. GWAS and meta-analysis were conducted in >12,000 AD cases and ~120,000 controls. PRS were constructed using clumping-and-thresholding and evaluated jointly with vascular burden and long-term PM₂.₅ exposure. A subset with structural MRI (n=271) underwent brain-wide GWAS of hippocampal volume and cortical thickness, including stratified analyses by ALDH2 rs671.
Results
Meta-GWAS confirmed the APOE/TOMM40/NECTIN2 region as the primary AD risk locus in Taiwanese, with conditional analyses revealing multiple independent signals. PRS significantly stratified AD risk; individuals in the highest quartile had a 2.12-fold higher risk versus the lowest quartile. Vascular burden and PM₂.₅ exposure further amplified genetic risk, with the greatest vulnerability observed in participants with both high PRS and high vascular/metabolic load or high pollution exposure.
MRI GWAS identified APOE as the major determinant of hippocampal volume loss, achieving genome-wide significance, and highlighted suggestive loci at DLG2 and ABCB1 for hippocampal volume and LINC00511 for parahippocampal cortical thickness. Stratified analyses by ALDH2 rs671 showed attenuated but directionally consistent APOE effects, suggesting potential modulation by aldehyde metabolism pathways despite limited power.
Conclusions
This multi-dimensional analysis delineates how inherited susceptibility, vascular burden, air pollution, and neurodegeneration converge to shape AD risk in East Asians, providing a framework for precision prevention in genetically susceptible, environmentally exposed populations.

Executive Summary：
Dr Yi-Chun Kuan, MD, is a neurologist and Professor of Neurology at Taipei Medical University, Director of the Neurodegeneration Department at the Taipei Neuroscience Institute, and a PhD student in Biomedical Engineering at National Taiwan University. Her research integrates cognitive neurology, sleep medicine, and human movement science to investigate early mechanisms of cognitive impairment. She leads government-funded studies on sleep-disordered breathing, slow-wave sleep physiology, motion-capture biomechanics, and neuromodulation in mild cognitive impairment and early Alzheimer’s disease. Her work focuses on identifying early biomarkers, characterising cognitive–motor interactions, and developing translational approaches for dementia detection and intervention.

Lecture Abstract：
The treatment paradigm of Alzheimer’s disease (AD) is undergoing a fundamental transition from symptomatic management to molecularly targeted disease-modifying therapy. Anti-amyloid monoclonal antibodies have provided the first consistent clinical evidence that modifying disease biology can slow cognitive and functional decline in patients with early-stage AD, supported by robust biomarker confirmation of amyloid clearance.

This presentation provides an update on the mechanisms and key clinical trial results of currently available molecular therapies, with particular focus on patient selection, efficacy interpretation, and safety considerations such as amyloid-related imaging abnormalities (ARIA). Practical aspects of treatment implementation, including risk stratification, MRI monitoring, and clinical decision-making in routine neurology practice, will be discussed.

Beyond amyloid, emerging molecular strategies targeting tau pathology, neuroinflammation, and downstream neurodegeneration are briefly discussed to illustrate the evolving therapeutic landscape. By integrating pathophysiological insight with clinical evidence, molecular therapy can be more appropriately contextualised within contemporary dementia care.