Li Jiaxuan, Wu Xin, Tan Xin, Wang Shixin, Qu Ruisi, Wu Xiaofeng, Chen Zhouqing, Wang Zhong, Chen Gang
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu Province, China.
Front Aging Neurosci. 2023 Nov 6;15:1257973. doi: 10.3389/fnagi.2023.1257973. eCollection 2023.
This meta-analysis evaluates the efficacy and safety of amyloid-β (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer's disease (AD).
PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023.
We pooled 33,689 participants from 42 studies. The meta-analysis showed no difference between anti-Aβ drugs and placebo in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and anti-Aβ drugs were associated with a high risk of adverse events [ADAS-Cog: MDs = -0.08 (-0.32 to 0.15), = 0.4785; AEs: RR = 1.07 (1.02 to 1.11), = 0.0014]. Monoclonal antibodies outperformed the placebo in delaying cognitive deterioration as measured by ADAS-Cog, Clinical Dementia Rating-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), without increasing the risk of adverse events [ADAS-Cog: MDs = -0.55 (-0.89 to 0.21), = 0.001; CDR-SB: MDs = -0.19 (-0.29 to -0.10), < 0.0001; MMSE: MDs = 0.19 (0.00 to 0.39), = 0.05; ADCS-ADL: MDs = 1.26 (0.84 to 1.68), < 0.00001]. Intravenous immunoglobulin and γ-secretase modulators (GSM) increased cognitive decline in CDR-SB [MDs = 0.45 (0.17 to 0.74), = 0.002], but had acceptable safety profiles in AD patients. γ-secretase inhibitors (GSI) increased cognitive decline in ADAS-Cog, and also in MMSE and ADCS-ADL. BACE-1 inhibitors aggravated cognitive deterioration in the outcome of the Neuropsychiatric Inventory (NPI). GSI and BACE-1 inhibitors caused safety concerns. No evidence indicates active Aβ immunotherapy, MPAC, or tramiprosate have effects on cognitive function and tramiprosate is associated with serious adverse events.
Current evidence does not show that anti-Aβ drugs have an effect on cognitive performance in AD patients. However, monoclonal antibodies can delay cognitive decline in AD. Development of other types of anti-Aβ drugs should be cautious.
PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42023391596.
本荟萃分析评估了靶向淀粉样β蛋白（Aβ）的疗法在延缓阿尔茨海默病（AD）认知功能衰退方面的疗效和安全性。
系统检索了PubMed、EMBASE、Cochrane图书馆和ClinicalTrials.gov，以确定2023年1月18日前发表的相关研究。
我们汇总了42项研究中的33,689名参与者。荟萃分析显示，抗Aβ药物与安慰剂在阿尔茨海默病评估量表认知子量表（ADAS-Cog）方面无差异，且抗Aβ药物与不良事件高风险相关[ADAS-Cog：平均差（MDs）=-0.08（-0.32至0.15），P=0.4785；不良事件：相对危险度（RR）=1.07（1.02至1.11），P=0.0014]。单克隆抗体在延缓认知衰退方面优于安慰剂，这通过ADAS-Cog、临床痴呆评定量表框和（CDR-SB）、简易精神状态检查表（MMSE）以及阿尔茨海默病协作研究日常生活活动量表（ADCS-ADL）来衡量，且未增加不良事件风险[ADAS-Cog：MDs=-0.55（-0.89至0.21），P=0.001；CDR-SB：MDs=-0.19（-0.29至-0.10），P<0.0001；MMSE：MDs=0.19（0.00至0.39），P=0.05；ADCS-ADL：MDs=1.26（0.84至1.68），P<0.00001]。静脉注射免疫球蛋白和γ-分泌酶调节剂（GSM）在CDR-SB中增加了认知衰退[MDs=0.45（0.17至0.74），P=0.002]，但在AD患者中具有可接受的安全性。γ-分泌酶抑制剂（GSI）在ADAS-Cog中增加了认知衰退，在MMSE和ADCS-ADL中也是如此。β-分泌酶1抑制剂（BACE-1）在神经精神科问卷（NPI）结果中加剧了认知衰退。GSI和BACE-1抑制剂引发了安全担忧。没有证据表明活性Aβ免疫疗法、多靶点抗聚集化合物（MPAC）或曲美普明对认知功能有影响，且曲美普明与严重不良事件相关。
目前的证据并未表明抗Aβ药物对AD患者的认知表现有影响。然而，单克隆抗体可延缓AD患者的认知衰退。其他类型抗Aβ药物的研发应谨慎。
PROSPERO（https://www.crd.york.ac.uk/prospero/），标识符CRD42023391596。
