Assessment of a Plasma Amyloid Probability Score to Estimate Amyloid Positron Emission Tomography Findings Among Adults With Cognitive Impairment.

Autor:	Hu Y; C 2 N Diagnostics, St Louis, Missouri., Kirmess KM; C 2 N Diagnostics, St Louis, Missouri., Meyer MR; C 2 N Diagnostics, St Louis, Missouri., Rabinovici GD; Departments of Neurology, Radiology & Biomedical Imaging, University of California, San Francisco., Gatsonis C; Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island., Siegel BA; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri., Whitmer RA; Department of Public Health Sciences, University of California, Davis., Apgar C; American College of Radiology, Reston, Virginia., Hanna L; Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island., Kanekiyo M; Eisai, Woodcliff Lake, New Jersey., Kaplow J; Eisai, Woodcliff Lake, New Jersey., Koyama A; Eisai, Woodcliff Lake, New Jersey., Verbel D; Eisai, Woodcliff Lake, New Jersey., Holubasch MS; C 2 N Diagnostics, St Louis, Missouri., Knapik SS; C 2 N Diagnostics, St Louis, Missouri., Connor J; ConfluenceStat, Miami, Florida., Contois JH; C 2 N Diagnostics, St Louis, Missouri., Jackson EN; C 2 N Diagnostics, St Louis, Missouri., Harpstrite SE; C 2 N Diagnostics, St Louis, Missouri., Bateman RJ; Department of Neurology, Washington University School of Medicine, St Louis, Missouri., Holtzman DM; Department of Neurology, Washington University School of Medicine, St Louis, Missouri., Verghese PB; C 2 N Diagnostics, St Louis, Missouri., Fogelman I; C 2 N Diagnostics, St Louis, Missouri., Braunstein JB; C 2 N Diagnostics, St Louis, Missouri., Yarasheski KE; C 2 N Diagnostics, St Louis, Missouri., West T; C 2 N Diagnostics, St Louis, Missouri.
Jazyk:	angličtina
Zdroj:	JAMA network open [JAMA Netw Open] 2022 Apr 01; Vol. 5 (4), pp. e228392. Date of Electronic Publication: 2022 Apr 01.
DOI:	10.1001/jamanetworkopen.2022.8392
Abstrakt:	Importance: The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology. Objective: To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status. Design, Setting, and Participants: This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019. Data were analyzed from May to November 2020. Exposures: Amyloid detected in blood and by positron emission tomography (PET) imaging. Main Outcomes and Measures: The main outcome was the diagnostic performance of plasma Aβ42:40 ratio, together with apoE proteotype and age, for identifying amyloid PET status, assessed by accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Results: All 686 participants (mean [SD] age 73.2 [6.3] years; 368 [53.6%] men; 378 participants [55.1%] with amyloid PET findings) had symptoms of mild cognitive impairment or mild dementia. The AUC of plasma Aβ42:40 ratio for PARIS was 0.79 (95% CI, 0.73-0.85) and 0.86 (95% CI, 0.82-0.89) for MissionAD. Ratio cutoffs for Aβ42:40 based on the Youden index were similar between cohorts (PARIS: 0.089; MissionAD: 0.092). A logistic regression model (LRM) incorporating Aβ42:40 ratio, apoE proteotype, and age improved diagnostic performance within each cohort (PARIS: AUC, 0.86 [95% CI, 0.81-0.91]; MissionAD: AUC, 0.89 [95% CI, 0.86-0.92]), and overall accuracy was 78% (95% CI, 72%-83%) for PARIS and 83% (95% CI, 79%-86%) for MissionAD. The model developed on the prospectively collected samples from PARIS performed well on the MissionAD samples (AUC, 0.88 [95% CI, 0.84-0.91]; accuracy, 78% [95% CI, 74%-82%]). Training the LRM on combined cohorts yielded an AUC of 0.88 (95% CI, 0.85-0.91) and accuracy of 81% (95% CI, 78%-84%). The output of this LRM is the Amyloid Probability Score (APS). For clinical use, 2 APS cutoff values were established yielding 3 categories, with low, intermediate, and high likelihood of brain amyloid plaque pathology. Conclusions and Relevance: These findings suggest that this blood biomarker test could allow for distinguishing individuals with brain amyloid-positive PET findings from individuals with amyloid-negative PET findings and serve as an aid for Alzheimer disease diagnosis.
Databáze:	MEDLINE
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