Research Paper Volume 11, Issue 16 pp 6217—6236

Risk estimation before progression to mild cognitive impairment and Alzheimer’s disease: an AD resemblance atrophy index

Lei Zhao1, *, , Yishan Luo1, *, , Darson Lew1, , Wenyan Liu1, , Lisa Au2,3, , Vincent Mok2,3,4,5, , Lin Shi1,2,6, , for the Alzheimer Disease Neuroimaging Initiative7, ,

  • 1 BrainNow Research Institute, Shenzhen, Guangdong Province, China
  • 2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, China
  • 3 Therese Pei Fong Chow Research Centre for Prevention of Dementia, The Chinese University of Hong Kong, China
  • 4 Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong, China
  • 5 Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong, Shatin, China
  • 6 Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, China
  • 7 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:
* Equal contribution

Received: March 26, 2019       Accepted: August 10, 2019       Published: August 29, 2019
How to Cite

Copyright © 2019 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


To realize an individual-level risk evaluation of progression of early Alzheimer’s disease (AD), we applied an AD resemblance atrophy index (AD-RAI) to differentiate the subjects at risk of progression from normal subjects (NC) to mild cognitive impairment (MCI) and from MCI to AD. We included 183 subjects with a two-year follow-up: 50 NC stable (NCs), 23 NC-to-MCI converters (NCc), 50 MCI stable (MCIs), 35 MCI-to-AD converters (MCIc), 25 AD stable (ADs). ANCOVA analyses were used to identify baseline brain atrophy in converters compared with non-converters. To explore the relative merits of AD-RAI over individual regional volumetric measures in prediction of disease progression, we searched for the optimal cutoff for each measure in logistic regressions and plotted the longitudinal trajectories of these brain volumetric measures in converters and non-converters. Baseline AD-RAI performed the best in differentiating NCc from NCs (odds ratio 26.35, AUC 0.740) and MCIc from MCIs (odds ratio 8.91, AUC 0.771). The AD-RAI presented greater increase in the second year for NCc vs. NCs but not for MCIc vs. MCIs. Baseline AD-RAIs were also associated with CSF-based and PET-based AD biomarkers. These results showed the potential of AD-RAI in early risk estimation before progression to MCI/AD at an individual-level.


AD: Alzheimer’s disease; ADNI: Alzheimer’s Disease Neuroimaging Initiative; AD-RAI: AD resemblance atrophy index; ADs: AD stable; AUC: area under the curve of receiver operating characteristics; CSF: cerebrospinal fluid; FLAIR: fluid attenuated inversion recovery; ICV: intracranial volume; IR-FSPGR: inversion recovery-fast spoiled gradient recalled; MCI: mild cognitive impairment; MCIc: MCI-to-AD converter; MCIs: MCI stable; MMSE: Mini-Mental State Examination; MP-RAGE: magnetization-prepared rapid gradient echo; MRI: magnetic resonance imaging; NC: normal control; NCc: NC-to-MCI converter; NCs: NC stable; OR: odds ratio; PET: positron emission tomography; ROC: receiver operating characteristics; WMH: white matter hyperintensity.