Alzheimer’s disease (AD) is the most common form of dementia. Currently, only symptomatic management is available, and early diagnosis and intervention are crucial for AD treatment. As a recent deep learning strategy, generative adversarial networks (GANs) are expected to benefit AD diagnosis, but their performance remains to be verified. This study provided a systematic review on the application of the GAN-based deep learning method in the diagnosis of AD and conducted a meta-analysis to evaluate its diagnostic performance. A search of the following electronic databases was performed by two researchers independently in August 2021: MEDLINE (PubMed), Cochrane Library, EMBASE, and Web of Science. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to assess the quality of the included studies. The accuracy of the model applied in the diagnosis of AD was determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs). A bivariate random-effects model was used to calculate the pooled sensitivity and specificity with their 95% CIs. Fourteen studies were included, 11 of which were included in the meta-analysis. The overall quality of the included studies was high according to the QUADAS-2 assessment. For the AD vs. cognitively normal (CN) classification, the GAN-based deep learning method exhibited better performance than the non-GAN method, with significantly higher accuracy (OR 1.425, 95% CI: 1.150–1.766, P = 0.001), pooled sensitivity (0.88 vs. 0.83), pooled specificity (0.93 vs. 0.89), and area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) (0.96 vs. 0.93). For the progressing MCI (pMCI) vs. stable MCI (sMCI) classification, the GAN method exhibited no significant increase in the accuracy (OR 1.149, 95% CI: 0.878–1.505, P = 0.310) or the pooled sensitivity (0.66 vs. 0.66). The pooled specificity and AUC of the SROC in the GAN group were slightly higher than those in the non-GAN group (0.81 vs. 0.78 and 0.81 vs. 0.80, respectively). The present results suggested that the GAN-based deep learning method performed well in the task of AD vs. CN classification. However, the diagnostic performance of GAN in the task of pMCI vs. sMCI classification needs to be improved.Systematic Review Registration: [PROSPERO], Identifier: [CRD42021275294].

Alzheimer's disease (AD) is a neurodegenerative disease that severely affects the activities of daily living in aged individuals, which typically needs to be diagnosed at an early stage. Generative adversarial networks (GANs) provide a new deep learning method that show good performance in image processing, while it remains to be verified whether a GAN brings benefit in AD diagnosis. The purpose of this research is to systematically review psychoradiological studies on the application of a GAN in the diagnosis of AD from the aspects of classification of AD state and AD-related image processing compared with other methods. In addition, we evaluated the research methodology and provided suggestions from the perspective of clinical application. Compared with other methods, a GAN has higher accuracy in the classification of AD state and better performance in AD-related image processing (e.g. image denoising and segmentation). Most studies used data from public databases but lacked clinical validation, and the process of quantitative assessment and comparison in these studies lacked clinicians' participation, which may have an impact on the improvement of generation effect and generalization ability of the GAN model. The application value of GANs in the classification of AD state and AD-related image processing has been confirmed in reviewed studies. Improvement methods toward better GAN architecture were also discussed in this paper. In sum, the present study demonstrated advancing diagnostic performance and clinical applicability of GAN for AD, and suggested that the future researchers should consider recruiting clinicians to compare the algorithm with clinician manual methods and evaluate the clinical effect of the algorithm.