Research Paper Volume 13, Issue 13 pp 17237—17252

Association between Alzheimer’s disease genes and trajectories of cognitive function decline in Han Chinese in Taiwan

Tsung-Jen Hsieh1,2, *, , Wei-Ju Lee3,4,5,6,7, *, , Yi-Chu Liao4,7,8, , Chih-Cheng Hsu1, , Yao-Hwei Fang1, , Tzu-Yu Chen1, , Yung-Shuan Lin4,8, , I-Shou Chang9, , Shuu-Jiun Wang4,7,8, , Chao A. Hsiung1, , Jong-Ling Fuh4,7,8, , Alzheimer’s Disease Neuroimaging Initiative #, ,

  • 1 Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan
  • 2 School of Medicine, I-Shou University, Kaohsiung, Taiwan
  • 3 Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
  • 4 Faculty of Medicine, National Yang-Ming University Schools of Medicine, Taipei, Taiwan
  • 5 Dementia Center, Taichung Veterans General Hospital, Taichung, Taiwan
  • 6 Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan
  • 7 Brain Research Center, National Yang-Ming University, Taipei, Taiwan
  • 8 Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
  • 9 National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan
* Equal contribution
# ADNI data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database ( As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at:

Received: October 5, 2020       Accepted: June 8, 2021       Published: July 2, 2021
How to Cite

Copyright: © 2021 Hsieh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Genetic background has been considered one of the important contributors to the rate of cognitive decline among patients with Alzheimer’s disease (AD). We conducted a 4-year longitudinal follow-up study, recruited 255 AD and 44 mild cognitive impairment (MCI) patients, and used a data-driven trajectory analysis to examine the influence of selected AD risk genes on the age for and the rate of cognitive decline in Han Chinese population. Genotyping of selected single-nucleotide polymorphisms in the APOE, ABCA7, SORL1, BIN1, GAB2, and CD33 genes was conducted, and a Bayesian hierarchical model was fitted to analyze the trajectories of cognitive decline among different genotypes. After adjusting for sex and education years, the APOE ε4 allele was associated with an earlier mean change of −2.39 years in the age at midpoint of cognitive decline, the G allele in ABCA7 rs3764650 was associated with an earlier mean change of −1.75 years, and the T allele in SORL1 rs3737529 was associated with a later mean change of 2.6 years. Additionally, the rate of cognitive decline was associated with the APOE ε4 allele and SORL1 rs3737529. In summary, APOE and SORL1 might be the most important genetic factors related to cognitive decline in Han Chinese population.


Aβ: amyloid β; AD: Alzheimer’s disease; ADNI: Alzheimer’s Disease Neuroimaging Initiative; APOE: apolipoprotein E; APP: amyloid precursor protein; BSAD: Biosignature Study of Alzheimer’s Disease; CDR: Clinical Dementia Rating; CSF: cerebrospinal fluid; GWASs: genome-wide association studies; MCI: mild cognitive impairment; MMSE: Mini-Mental State Examination; PCR: polymerase chain reaction; SNPs: single-nucleotide polymorphisms.