Integrative analysis of AT classification, plasma biomarkers, and cognitive trajectories across diverse dementia syndromes
This study aimed to examine amyloid-β (Aβ) and tau (AT) biological stages, plasma biomarkers, and cognitive trajectories according to AT stages in Alzheimer's disease-related cognitive impairment (ADCI), subcortical vascular cognitive impairment (SVCI), and frontotemporal dementia (FTD). A total of 275 participants (42 cognitively unimpaired [CU], 132 ADCI, 73 SVCI, and 28 FTD) underwent Aβ and tau positron emission tomography for assessment of AT stages. Participants with cognitive impairment (ADCI, SVCI, and FTD) were classified according to clinical stages of mild cognitive impairment or dementia. Plasma biomarkers were analysed, and cognitive trajectories were assessed using mixed-effects models over 6.1 years. SVCI and FTD showed more advanced clinical stages than ADCI at equivalent AT stages. SVCI participants had higher plasma glial fibrillary acidic protein (P = 0.012) and neurofilament light chain (P = 0.025) than CU participants in the A - T- stage. In the A - T- stage, SVCI (β = -0.738, P = 0.002) and FTD (β = -4.016, P < 0.001) showed faster cognitive decline than CU, but not ADCI. In the A + T - stage, ADCI (β = -0.634, P = 0.005) and SVCI (β = -0.690, P = 0.006) showed faster decline than CU. In the A + T + stage, only ADCI exhibited significantly faster decline than CU (β = -1.856, P = 0.008). Distinct plasma biomarker profiles and cognitive trajectories characterise ADCI, SVCI, and FTD across AT classification, highlighting the heterogeneity in pathophysiological mechanisms across dementia types.
Authors
- Jun Pyo Kim
- Min Young Chun (ORCID: https://orcid.org/0000-0003-3731-6132)
- Nicholas James Ashton (ORCID: https://orcid.org/0000-0002-3579-8804)
- Seung Hwan Moon (ORCID: https://orcid.org/0000-0003-4302-1920)
- Yuna Gu (ORCID: https://orcid.org/0009-0007-3200-3977)
- Duk Lyul Na (ORCID: https://orcid.org/0000-0002-0098-7592)
- Kaj Blennow (ORCID: https://orcid.org/0000-0002-1890-4193)
- Fernando González‐Ortiz (ORCID: https://orcid.org/0000-0001-7897-9456)
- Su Yeon Park
- Jeong Ho Ha (ORCID: https://orcid.org/0000-0003-1245-1207)
- Soyeon Yoon
- Hongki Ham (ORCID: https://orcid.org/0009-0002-0806-6453)
- Jae Yong Choi (ORCID: https://orcid.org/0000-0003-1901-8238)
- Hyemin Jang (ORCID: https://orcid.org/0000-0003-3152-1274)
- Byung Hyun Byun (ORCID: https://orcid.org/0000-0002-1146-1916)
- Jihwan Yun (ORCID: https://orcid.org/0000-0002-2436-4947)
- Hee Jin Kim (ORCID: https://orcid.org/0000-0003-1554-2657)
- Hanna Cho (ORCID: https://orcid.org/0000-0001-5936-1546)
- Heejin Yoo (ORCID: https://orcid.org/0000-0003-4341-6906)
- Soo Hyun Cho (ORCID: https://orcid.org/0000-0002-4262-1468)
- Daeun Shin (ORCID: https://orcid.org/0000-0003-4834-1026)
- Henrik Zetterberg
Institutions
- University of Science and Technology of China (CN)
- University of Wisconsin–Madison (US)
- King's College London (GB)
- Yonsei University (KR)
- Hong Kong University of Science and Technology (HK)
- Severance Hospital (KR)
- Stavanger University Hospital (NO)
- Sahlgrenska University Hospital (SE)
- Asan Medical Center (KR)
- Samsung Medical Center (KR)
- Centre for Mental Health (GB)
- Kyung Hee University (KR)
- Sorbonne Université (FR)
- University of Ulsan (KR)
- Korea Institute of Radiological and Medical Sciences (KR)
- Institut de Myologie (FR)
- Pitié-Salpêtrière Hospital (FR)
- Dr Youth Clinic (KR)
- UK Dementia Research Institute (GB)
- Gangnam Severance Hospital (KR)
- National Hospital for Neurology and Neurosurgery (GB)
- Institut du Cerveau (FR)
- Yonsei University Health System (KR)
- University College London (GB)
- Sungkyunkwan University (KR)
- University of Gothenburg (SE)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-12-11
- DOI
- https://doi.org/10.1038/s41598-025-30117-y
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Eli Lilly and Company
- Familjen Erling-Perssons Stiftelse
- Cure Alzheimer's Fund
- Stiftelsen för Gamla Tjänarinnor
- EU Joint Programme – Neurodegenerative Disease Research
- National Institute for Health and Care Research
- University College London
- European Commission
- National Research Foundation
- Korea Health Industry Development Institute
- Hjärnfonden
- Vetenskapsrådet
- Ministry of Science and ICT, South Korea
- UK Dementia Research Institute
- Samsung
- Avid Radiopharmaceuticals
- HORIZON EUROPE Framework Programme
- Korea National Institute of Health
- Institute for Information and Communications Technology Promotion