PMID- 36208415 OWN - NLM STAT- MEDLINE DCOM- 20221114 LR - 20230719 IS - 1532-5415 (Electronic) IS - 0002-8614 (Linking) VI - 70 IP - 11 DP - 2022 Nov TI - Effectiveness and safety of anti-tau drugs for Alzheimer's disease: Systematic review and meta-analysis. PG - 3281-3292 LID - 10.1111/jgs.18025 [doi] AB - OBJECTIVE: To assess the cognitive effectiveness and safety of tau-targeting drugs for Alzheimer's disease (AD) METHODS: The MEDLINE, Embase, Cochrane Library, PsycINFO, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform databases were searched from inception to 22 November 2021. A systematic review and meta-analysis of randomized controlled trials were performed RESULTS: Thirty-four randomized controlled trials comprising 5549 participants, of which fifteen (51.7%) had a low risk of bias, were included. The meta-analysis showed no differences in the cognitive subscale of the AD: Assessment Scale (ADAS-Cog) between anti-tau drugs and placebo (mean difference [MD]: -0.77, 95% CI: -1.64 to 0.10; minimal important difference 3.1-3.8 points, moderate certainty evidence). For ADAS-Cog, the results subgroup analysis suggested a statistical effect of tau posttranslational modifications on drug inhibition (MD: -0.80, 95% CI: -1.43 to -0.17), which was not seen with tau aggregation inhibitors or immunotherapy (interaction p = 0.24). A total of 11.0%, 5.2%, and 4.8% of drugs inhibiting tau aggregation, immunotherapy, and drugs targeting posttranslational modifications, respectively, had a reduced risk of dropouts due to adverse events (AEs). DISCUSSION: Current evidence suggests that anti-tau drugs are unlikely to have an important impact on slowing cognitive impairment. Although the subgroup analysis suggested that inhibition of tau posttranslational modifications is statistically effective and generally safer because of reduced dropouts due to AEs, the analysis has limited credibility. Additional large-scale and well-designed randomized and placebo-controlled trials will be necessary to explore the benefit of a certain type of anti-tau drug for AD. CI - (c) 2022 The American Geriatrics Society. FAU - Zheng, Xiaoyan AU - Zheng X AD - School of Rehabilitation Sciences, Southern Medical University, Guangzhou, China. FAU - Tang, Yuyuan AU - Tang Y AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Yang, Qinghui AU - Yang Q AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Wang, Shuting AU - Wang S AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Chen, Rouhao AU - Chen R AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Tao, Chenyang AU - Tao C AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zhang, Peiming AU - Zhang P AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Fan, Baochao AU - Fan B AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zhan, Jie AU - Zhan J AD - Postdoctoral Research Station, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Tang, Chunzhi AU - Tang C AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Lu, Liming AU - Lu L AD - Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China. LA - eng GR - 2020B1111100008/Guangdong Provincial R & D Program/ GR - NSFC/82174527/National Natural Science Foundation of China/ GR - NSFC/81873375/National Natural Science Foundation of China/ GR - 2019KYTD203/Scientific Research Team Training Project of GZUCM/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20221008 PL - United States TA - J Am Geriatr Soc JT - Journal of the American Geriatrics Society JID - 7503062 SB - IM CIN - J Am Geriatr Soc. 2023 Jul;71(7):2345-2347. PMID: 37021841 CIN - J Am Geriatr Soc. 2023 Jul;71(7):2342-2344. PMID: 37021845 MH - Humans MH - *Alzheimer Disease/drug therapy MH - *Cognitive Dysfunction/drug therapy OTO - NOTNLM OT - Alzheimer's disease OT - anti-tau drugs OT - meta-analysis EDAT- 2022/10/09 06:00 MHDA- 2022/11/15 06:00 CRDT- 2022/10/08 11:42 PHST- 2022/07/29 00:00 [revised] PHST- 2022/03/06 00:00 [received] PHST- 2022/08/14 00:00 [accepted] PHST- 2022/10/09 06:00 [pubmed] PHST- 2022/11/15 06:00 [medline] PHST- 2022/10/08 11:42 [entrez] AID - 10.1111/jgs.18025 [doi] PST - ppublish SO - J Am Geriatr Soc. 2022 Nov;70(11):3281-3292. doi: 10.1111/jgs.18025. Epub 2022 Oct 8.