Dataset Information

Amyloid Plaques in Retina for Diagnosis in Alzheimer's Patients: a Meta-Analysis.

ABSTRACT: Background: Detection of retinal ?-amyloid (A?) peptide accumulation is a novel diagnostic method for Alzheimer's disease (AD), but there is, as yet, no conclusive evidence of its accuracy. Aim: To identify the diagnostic accuracy of pathological retinal A? detection for AD by a meta-analytic approach. Methods: Electronic and reference searches were conducted to identify studies related to the diagnostic effects of retinal A? detection in AD that met pre-defined inclusion criteria. The QUADAS-2 tool was employed to assess the risk of bias, and Review Manager plus the Open Meta-Analyst were used to perform the data analysis. Results: From 493 unduplicated reports, five studies with small sample sizes were included in this review. Six staining methods were employed. The eligible studies showed extremely broad ranges of sensitivity (0-1.00) and specificity (0.50-1.00) with substantial heterogeneity. The estimates of positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) were also extremely varied (from 0.71 to 11.57 for PLR, from 0.04 to 1.11 for NLR, and from 0.69 to 297.00 for DOR). Conclusions: The limited number of eligible studies and their methodological heterogeneity make it impossible to come to a conclusion whether pathological retinal A? detection is an effective diagnostic tool for AD. More studies, especially large surveys investigating retina A? load with quantitative methods among consecutive or random samples, are needed to determine the accuracy of A? detection for diagnosing AD.

SUBMITTER: Jiang J

PROVIDER: S-EPMC5102884 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Amyloid Plaques in Retina for Diagnosis in Alzheimer's Patients: a Meta-Analysis.

Jiang Jiangling J Wang Hongyan H Li Wei W Cao Xinyi X Li Chunbo C

Frontiers in aging neuroscience 20161110

Background: Detection of retinal β-amyloid (Aβ) peptide accumulation is a novel diagnostic method for Alzheimer's disease (AD), but there is, as yet, no conclusive evidence of its accuracy. Aim: To identify the diagnostic accuracy of pathological retinal Aβ detection for AD by a meta-analytic approach. Methods: Electronic and reference searches were conducted to identify studies related to the diagnostic effects of retinal Aβ detection in AD that met pre-defined inclusion cr ...[more]

PMID: 27891091

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Project description:BACKGROUND:We previously investigated low doses (105 or 225 mg) of gantenerumab, a fully human monoclonal antibody that binds and removes aggregated amyloid-β by Fc receptor-mediated phagocytosis, in the SCarlet RoAD (SR) and Marguerite RoAD (MR) phase 3 trials. Several lines of evidence suggested that higher doses may be necessary to achieve clinical efficacy. We therefore designed a positron emission tomography (PET) substudy to evaluate the effect of gantenerumab uptitrated to 1200 mg every 4 weeks on amyloid-β plaques as measured using florbetapir PET in patients with prodromal to moderate Alzheimer's disease (AD). METHODS:A subset of patients enrolled in the SR and MR studies who subsequently entered the open-label extensions (OLEs) were included in this substudy. Patients were aged 50 to 90 years with a clinical diagnosis of probable prodromal to moderate AD and were included based on a visual read of the original screening scan in the double-blind phase. Patients were assigned to 1 of 5 titration schedules (ranging from 2 to 10 months) with a target gantenerumab dose of 1200 mg every 4 weeks. The main endpoint of this substudy was change in amyloid-β plaque burden from OLE baseline to week 52 and week 104, assessed using florbetapir PET. Florbetapir global cortical signal was calculated using a prespecified standard uptake value ratio method converted to the Centiloid scale. RESULTS:Sixty-seven of the 89 patients initially enrolled had ≥ 1 follow-up scan by August 15, 2018. Mean amyloid levels were reduced by 39 Centiloids by the first year and 59 Centiloids by year 2, a 3.5-times greater reduction than was seen after 2 years at 225 mg in SR. At years 1 and 2, 37% and 51% of patients, respectively, had amyloid-β plaque levels below the amyloid-β positivity threshold. CONCLUSION:Results from this exploratory interim analysis of the PET substudy suggest that gantenerumab doses up to 1200 mg resulted in robust amyloid-β plaque removal at 2 years. PET amyloid levels were consistent with sparse-to-no neuritic amyloid-β plaques in 51% of patients after 2 years of therapy. Amyloid reductions were similar to those observed in other placebo-controlled studies that have suggested potential clinical benefit. TRIAL REGISTRATION:ClinicalTrials.gov, NCT01224106 (SCarlet RoAD) and NCT02051608 (Marguerite RoAD).

Dataset Information

Amyloid Plaques in Retina for Diagnosis in Alzheimer's Patients: a Meta-Analysis.

Publications

Amyloid Plaques in Retina for Diagnosis in Alzheimer's Patients: a Meta-Analysis.

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