Efficacy and safety of anti‐amyloid‐β immunotherapy for Alzheimer's disease: a systematic review and network meta‐analysis

Abstract

To review the optimality and safety of different anti‐Amyloid‐β(Aβ) immunotherapies for Alzheimer's disease (AD). Published randomized controlled trials were comprehensively reviewed from electronic databases (Cochrane library, Embase, Pubmed, and Google scholar). Pooled outcomes as mean difference or odds ratio values with 95% confidence interval were reported. The network estimates with confidence and predictive intervals for all pairwise relative effects was evaluated. Optimal intervention was ranked by benefit‐risk ratio based on the surface under the cumulative ranking curve. Eleven eligible RCTs from 9 literatures, including 5141 patients and 5 interventions were included. The quality of evidence was rated low in comparisons. For efficacy, in terms of Mini‐Mental State Examination, aducanumab and solanezumab are significantly effective than placebo. For safety, in terms of Amyloid‐Related Imaging Abnormalities (ARIA), bapineuzumab and aducanumab are significantly worse than placebo. There were no significant differences in outcomes of Alzheimer's disease Assessment Scale‐Cognitive subscale, Disability Assessment for Dementia, Adverse Events, and mortality. Given the clinical therapeutic effects of anti‐Aβ immunotherapies for AD, aducanumab and solanezumab improve the cognitive function, while aducanumab and bapineuzumab may increase the risks of ARIA.

Functional brain architecture is associated with the rate of tau accumulation in Alzheimer’s disease

“…Our findings have important clinical implications: Knowledge of future tau spread can be critical for predicting clinical disease progression, since the level of tau is the strongest predictor of cognitive impairment and cognitive decline in AD 36,37 . Here, blocking tau spread by targeting neural activity related mechanisms of tau spread could be a promising target for attenuating AD progression 21 , especially in view of the limited clinical efficacy of anti-amyloid trials 38,39 .…”

In search of Alzheimer’s disease treatment methods: trends of clinical trials

“…Kre ne zu ma bas -hu ma ni zuo tas mo nok lo ni nis IgG4 an ti kû nas, su si jun gian tis su dau ge liu ag re guo to ami loi do for mø (oli go me ri ne ir fib ri li ne for ma, se ni li në mis plokð telë mis) ir pa si þy min tis þe mu afi nið ku mu mo no me ri nëms be ta ami loi do for moms [34]. Jis bu vo su kur tas pa ða lin ti be ta ami loi do san kau pas, pa ska ti nant efek to ri niø mik rogli jos làs te liø funk ci jas, sti mu liuo jant fa go ci to zae, bet vengiant uþ de gi mi niø ci to ki nø ið sky ri mo ir va zo ge ni nës edemos [31,34].…”

“…Jis bu vo su kur tas pa ða lin ti be ta ami loi do san kau pas, pa ska ti nant efek to ri niø mik rogli jos làs te liø funk ci jas, sti mu liuo jant fa go ci to zae, bet vengiant uþ de gi mi niø ci to ki nø ið sky ri mo ir va zo ge ni nës edemos [31,34]. Efek ty vu mo ty ri muo se ste bë ta, kad di des nës vais to do zës yra efek ty ves nës, ir ðiuo me tu at lie ka mi III fazës kli ni ki niai ty ri mai (CREAD, CREAD2 ir ki ti) pro dromi nei AL, leng vai ir vi du ti nio sun ku mo AL bei au to so miniu do mi nan ti niu bû du pa vel di mai AL gy dy ti [14].…”

“…Ma no ma, kad tai lems jø kie kio ma þë ji mà ar neut ra lizuos jø tok sið ku mà [34]. Ðiuo me tu at lie ka mas II fa zës tyri mas.…”

“…Adu ka nu ma bo, se lek ty viai vei kian èio ag reguo tà ami loi dà, tei gia mi re zul ta tai pa re mia ami loi do kaska dos hi po te zae. Nors ir ne sëk min gi, ki tø vais tø ty ri mai sutei kë þi niø apie kiek vie no vais to vei ki mo me cha niz mà ir ga li mai at ei ty je pla nuo ja mà vais tø de ri ni mà, vei kiant ke lis pa to ge ne zi nius pro ce sus [34,35].…”