Frequency and longitudinal clinical outcomes of Alzheimer's AT(N) biomarker profiles: A longitudinal study

Jin-Tai Yu; Jie-Qiong Li; John Suckling; Lei Feng; An Pan; Yan-Jiang Wang; Bo Song; Shan-Liang Zhu; De-Hu Li; Hui-Fu Wang; Chen-Chen Tan; Qiang Dong; Lan Tan; Vincent Mok; Paul S Aisen; Michael M Weiner; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.jalz.2019.05.006

Frequency and longitudinal clinical outcomes of Alzheimer's AT(N) biomarker profiles: A longitudinal study

Alzheimers Dement. 2019 Sep;15(9):1208-1217. doi: 10.1016/j.jalz.2019.05.006. Epub 2019 Aug 6.

Authors

Jin-Tai Yu¹, Jie-Qiong Li², John Suckling³, Lei Feng⁴, An Pan⁵, Yan-Jiang Wang⁶, Bo Song⁷, Shan-Liang Zhu⁸, De-Hu Li⁸, Hui-Fu Wang², Chen-Chen Tan², Qiang Dong⁹, Lan Tan², Vincent Mok¹⁰, Paul S Aisen¹¹, Michael M Weiner¹²; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: jintai_yu@fudan.edu.cn.
² Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
³ Department of Psychiatry, University of Cambridge, Cambridge, UK; Medical Research Council and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Cambridgeshire and Peterborough NHS Trust, Cambridge, UK.
⁴ Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁶ Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China.
⁷ College of Information Science and Technology, Qingdao University of Science and Technology, Qingdao, China.
⁸ Research Center for Mathematical Modeling, School of Mathematics and Physics, Qingdao University of Science and Technology, Qingdao, China.
⁹ Department of Neurology and Institute of Neurology, WHO Collaborating Center for Research and Training in Neurosciences, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
¹⁰ Gerald Choa Neuroscience Centre, Lui Che Woo Institute of Innovative Medicine, Therese Pei Fong Chow Research Center for Prevention of Dementia, Division of Neurology, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
¹¹ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
¹² Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; Department of Radiology, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA.

PMID: 31399333
DOI: 10.1016/j.jalz.2019.05.006

Abstract

Introduction: We aimed to estimate the frequency of each AT(N) (β-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group.

Methods: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively.

Results: Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-.

Discussion: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials.

Keywords: Alzheimer's disease; Biomarker; Prognosis; Research framework.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Alzheimer Disease* / diagnostic imaging
Alzheimer Disease* / pathology
Amyloid beta-Peptides / metabolism
Biomarkers*
Brain / pathology
Cross-Sectional Studies
Disease Progression*
Female
Humans
Longitudinal Studies
Male
Positron-Emission Tomography
Prodromal Symptoms*
Prognosis
tau Proteins / metabolism

Substances

Amyloid beta-Peptides
Biomarkers
tau Proteins

Grants and funding

CAPMC/ CIHR/Canada