The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis
BackgroundThis meta-analysis evaluates the efficacy and safety of amyloid-β (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer’s disease (AD).MethodsPubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published...
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| Format: | Article |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1257973/full |
| _version_ | 1797635765683879936 |
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| author | Jiaxuan Li Xin Wu Xin Tan Shixin Wang Ruisi Qu Xiaofeng Wu Zhouqing Chen Zhong Wang Gang Chen |
| author_facet | Jiaxuan Li Xin Wu Xin Tan Shixin Wang Ruisi Qu Xiaofeng Wu Zhouqing Chen Zhong Wang Gang Chen |
| author_sort | Jiaxuan Li |
| collection | DOAJ |
| description | BackgroundThis meta-analysis evaluates the efficacy and safety of amyloid-β (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer’s disease (AD).MethodsPubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023.ResultsWe 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), p = 0.4785; AEs: RR = 1.07 (1.02 to 1.11), p = 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), p = 0.001; CDR-SB: MDs = −0.19 (−0.29 to −0.10), p < 0.0001; MMSE: MDs = 0.19 (0.00 to 0.39), p = 0.05; ADCS-ADL: MDs = 1.26 (0.84 to 1.68), p < 0.00001]. Intravenous immunoglobulin and γ-secretase modulators (GSM) increased cognitive decline in CDR-SB [MDs = 0.45 (0.17 to 0.74), p = 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.ConclusionCurrent 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.Systematic Review RegistrationPROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42023391596. |
| first_indexed | 2024-03-11T12:24:58Z |
| format | Article |
| id | doaj.art-b614396effef43078df3520f6bb820c4 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-03-11T12:24:58Z |
| publishDate | 2023-11-01 |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-b614396effef43078df3520f6bb820c42023-11-06T10:07:12ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652023-11-011510.3389/fnagi.2023.12579731257973The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysisJiaxuan Li0Xin Wu1Xin Tan2Shixin Wang3Ruisi Qu4Xiaofeng Wu5Zhouqing Chen6Zhong Wang7Gang Chen8Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaDepartment of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaDepartment of Ultrasound, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaDepartment of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, ChinaBackgroundThis meta-analysis evaluates the efficacy and safety of amyloid-β (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer’s disease (AD).MethodsPubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023.ResultsWe 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), p = 0.4785; AEs: RR = 1.07 (1.02 to 1.11), p = 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), p = 0.001; CDR-SB: MDs = −0.19 (−0.29 to −0.10), p < 0.0001; MMSE: MDs = 0.19 (0.00 to 0.39), p = 0.05; ADCS-ADL: MDs = 1.26 (0.84 to 1.68), p < 0.00001]. Intravenous immunoglobulin and γ-secretase modulators (GSM) increased cognitive decline in CDR-SB [MDs = 0.45 (0.17 to 0.74), p = 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.ConclusionCurrent 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.Systematic Review RegistrationPROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42023391596.https://www.frontiersin.org/articles/10.3389/fnagi.2023.1257973/fullAlzheimer’s diseasecognitive impairmentamyloid-βmonoclonal antibodyγ-secretase inhibitorsBACE-1 inhibitors |
| spellingShingle | Jiaxuan Li Xin Wu Xin Tan Shixin Wang Ruisi Qu Xiaofeng Wu Zhouqing Chen Zhong Wang Gang Chen The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis Frontiers in Aging Neuroscience Alzheimer’s disease cognitive impairment amyloid-β monoclonal antibody γ-secretase inhibitors BACE-1 inhibitors |
| title | The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis |
| title_full | The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis |
| title_fullStr | The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis |
| title_full_unstemmed | The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis |
| title_short | The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis |
| title_sort | efficacy and safety of anti aβ agents for delaying cognitive decline in alzheimer s disease a meta analysis |
| topic | Alzheimer’s disease cognitive impairment amyloid-β monoclonal antibody γ-secretase inhibitors BACE-1 inhibitors |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2023.1257973/full |
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