Background And Objectives: To assess the incidence of amyloid-related imaging abnormalities (ARIA) in clinical trials of anti-β-amyloid (Aβ) immunotherapy and compare the incidence among different agents and clinical characteristics to identify possible predisposing factors for ARIA.
Methods: The PubMed and Embase databases were searched for clinical trials of anti-Aβ immunotherapy published on or before January 12, 2022. Phase 2 or 3 randomized controlled trials reporting detailed data sufficient to assess the incidence of ARIA were selected. The pooled incidences of ARIA and subgroup analyses according to agent and ApoE-4 carrier status were calculated using the DerSimonian-Liard random-effects model. The proportion of symptomatic ARIA cases was also calculated.
Results: In total, 19 eligible studies, including 24 cohorts, were identified and 9,429 patients were analyzed. The overall pooled incidence of ARIA-effusion (E) and ARIA-hemorrhage (H) was 6.5% and 7.8%, respectively. In the subgroup analysis, the incidence of ARIA was different according to the anti-Aβ immunotherapy agent. The cohorts treated with aducanumab had a significantly higher incidence of ARIA-E and ARIA-H (30.7% and 30.0%, respectively; both < 0.001) compared with cohorts from other drugs. In subgroup analysis according to ApoE-4 carrier status, the incidences of ARIA-E and ARIA-H were higher in the ApoE-4 carrier group than those in the ApoE-4 noncarrier group, but there was no statistical significance (ApoE-4 carrier vs noncarrier, ARIA-E: 8.6% vs 6.9%, = 0.663, and ARIA-H: 10.5% vs 6.6%, = 0.398). The pooled proportion of asymptomatic ARIA, detected by routine scheduled MRI surveillances, was 80.4%.
Discussion: The overall incidences of ARIA-E and ARIA-H were 6.5% and 7.8%, respectively, and the pooled proportion of asymptomatic ARIA was 80.4%. The cohorts treated with aducanumab showed a significantly higher incidence of ARIA-E and ARIA-H (30.7% and 30.0%) compared with other drugs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1212/WNL.0000000000201019 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The impact of genetic variability on Alzheimer's therapies: obstacles for pharmacogenetic progress.
Expert Opin Drug Metab Toxicol
January 2025
EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, Bergondo, Corunna, Spain.
Introduction: Genetic load influences the therapeutic response to conventional drugs in Alzheimer's disease (AD). Pharmacogenetics (PGx) is the best option to reduce drug-drug interactions and adverse drug reactions in patients undergoing polypharmacy regimens. However, there are important limitations that make it difficult to incorporate pharmacogenetics into routine clinical practice.
View Article and Find Full Text PDFAmyloid, Tau, and APOE in Alzheimer's Disease: Impact on White Matter Tracts.
Pac Symp Biocomput
December 2024
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Alzheimer's disease (AD) is characterized by cognitive decline and memory loss due to the abnormal accumulation of amyloid-beta (Aβ) plaques and tau tangles in the brain; its onset and progression also depend on genetic factors such as the apolipoprotein E (APOE) genotype. Understanding how these factors affect the brain's neural pathways is important for early diagnostics and interventions. Tractometry is an advanced technique for 3D quantitative assessment of white matter tracts, localizing microstructural abnormalities in diseased populations in vivo.
View Article and Find Full Text PDFMidlife and late-life environmental exposures on dementia risk in the Wisconsin Longitudinal Study: The modifying effects of ApoE.
Alzheimers Dement
December 2024
Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin at Madison, School of Medicine and Public Health, Madison, Wisconsin, USA.
Introduction: Late-life air pollution exposure is associated with an increased risk for dementia, with this effect exacerbated among apolipoprotein E-4 (ApoE-4) carriers. However, whether midlife occupational exposures likewise influence dementia outcomes, and varies as a function of ApoE-4 status is unknown.
Methods: Using data from 3814 participants in the Wisconsin Longitudinal Study (WLS), we employed weighted logistic regression to evaluate associations between midlife occupational respiratory exposures and late-life air pollution on all-cause dementia risk, stratified by ApoE-4 status.
Pure LATE-NC: Frequency, clinical impact, and the importance of considering APOE genotype when assessing this and other subtypes of non-Alzheimer's pathologies.
Acta Neuropathol
November 2024
Sanders-Brown Center On Aging, University of Kentucky, U. Kentucky, Rm 575 Lee Todd Bldg 789 S. Limestone Ave, Lexington, KY, 40536, USA.
Pure limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (pure LATE-NC) is a term used to describe brains with LATE-NC but lacking intermediate or severe levels of Alzheimer's disease neuropathologic changes (ADNC). Focusing on pure LATE-NC, we analyzed data from the National Alzheimer's Coordinating Center (NACC) Neuropathology Data Set, comprising clinical and pathological information aggregated from 32 NIH-funded Alzheimer's Disease Research Centers (ADRCs). After excluding subjects dying with unusual conditions, n = 1,926 autopsied subjects were included in the analyses.
View Article and Find Full Text PDFAPOE 𝜀4-related blood-brain barrier breakdown is associated with microstructural abnormalities.
Alzheimers Dement
December 2024
Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Introduction: Blood-brain barrier (BBB) dysfunction occurs in Alzheimer's disease (AD). Yet, the stage at which it appears along the AD time course and whether it contributes to neurodegeneration remain unclear.
Methods: Older adults (61 to 90 years) from cognitively normal (CN) to mildly cognitively impaired (CI), enriched for APOE 𝜀4 and amyloid positivity, underwent dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and diffusion MRI to measure BBB permeability and brain microstructure.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!