Affiliations: [a] Department of Medical Imaging, Peking University Shenzhen Hospital, Shenzhen, China
| [b] Department of Medicine and Therapeutics, Faculty of Medicine, Division of Neurology, Gerald Choa Neuroscience Institute, Lau Tat-chuen Research Centre of Brain Degenerative Diseases in Chinese, Therese Pei Fong Chow Research Centre for Prevention of Dementia, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| [c] Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China
| [d] BrainNow Research Institute, Hong Kong Science and Technology Park, Hong Kong SAR, China
Correspondence:
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Correspondence to: Prof. Vincent Chung Tong Mok, Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. E-mail: vctmok@cuhk.edu.hk and Lin Shi, Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong. E-mail: shilin@cuhk.edu.hk.
Abstract: Background:
Pilot study showed that Alzheimer’s disease resemblance atrophy index (AD-RAI), a machine learning-derived MRI-based neurodegeneration biomarker of AD, achieved excellent diagnostic performance in diagnosing AD with moderate to severe dementia. Objective:
The primary objective was to validate and compare the performance of AD-RAI with conventional volumetric hippocampal measures in diagnosing AD with mild dementia. The secondary objectives were 1) to investigate the association between imaging biomarkers with age and gender among cognitively unimpaired (CU) participants; 2) to analyze whether the performance of differentiating AD with mild dementia from CU will improve after adjustment for age/gender. Methods:
AD with mild dementia (n = 218) and CU (n = 1,060) participants from 4 databases were included. We investigated the area under curve (AUC), sensitivity, specificity, and balanced accuracy of AD-RAI, hippocampal volume (HV), and hippocampal fraction (HF) in differentiating between AD and CU participants. Among amyloid-negative CU participants, we further analyzed correlation between the biomarkers with age/gender. We also investigated whether adjustment for age/gender will affect performance. Results:
The AUC of AD-RAI (0.93) was significantly higher than that of HV (0.89) and HF (0.89). Subgroup analysis among A + AD and A- CU showed that AUC of AD-RAI (0.97) was also higher than HV (0.94) and HF (0.93). Diagnostic performance of AD-RAI and HF was not affected by age/gender while that of HV improved after age adjustment. Conclusions:
AD-RAI achieves excellent clinical validity and outperforms conventional volumetric hippocampal measures in aiding the diagnosis of AD mild dementia without the need for age adjustment.
