Supplementary Material for: Efficacy of combined herbal and Western medicine based on Traditional Chinese Medicine for mild cognitive impairment and dementia in Parkinson’s disease: A systematic review and meta-analysis

Introduction: This systematic review aimed to assess the clinical evidence supporting the combination of syndrome differentiation (SD)-based herbal medicine (HM) and Western medicine (WM) in treating Parkinson’s disease (PD)-mild cognitive impairment (PD-MCI) and -dementia (PDD). Methods: Ten electronic bibliographic databases were searched from inception to March 4, 2024, for randomized controlled trials (RCTs) comparing SD-based HM plus conventional therapies with conventional therapies alone for PD-MCI and PDD. Two authors independently screened and selected studies and extracted data related to trial quality, characteristics, and results. The mean difference (MD) was used to analyze continuous variables, and meta-analysis was performed using Reviewer Manager 5.4 software. The risk of bias was assessed using the Cochrane Risk of Bias Tool. Results: For the 15 articles selected for review, 12 trials were included in the meta-analysis: 9 comprising 688 patients with PD-MCI and 3 comprising 264 patients with PDD and with a type of SD, such as “blood stasis and stirring wind” or “deficiency of the liver–kidney.” The meta-analysis showed significant differences favoring HM plus WM with respect to the Montreal Cognitive Assessment score for PD-MCI (MD=2.30, 95% confidence interval [CI; 1.40, 3.19]; p<0.00001, I2=76%) and PDD (MD=3.14, 95% CI [0.48, 5.81]; p=0.02, I2=82%) compared with WM alone. Improvement of cognitive impairment treated using “deficiency of the liver–kidney” SD-based HM plus WM in PD-MCI was more beneficial than that treated using WM alone. Conclusions: SD-based HM may serve as an adjunctive treatment for PD-MCI and PDD, improving cognitive function and alleviating PD symptoms. No severe adverse event was observed in the HM plus WM group, suggesting that HM may be safe for patients with cognitive impairment in PD. However, evidence regarding the efficacy of HM based on SD for PD-MCI and PDD is of poor quality, and all studies were conducted in China. Thus, and rigorous, multicenter, and international RCTs are required.