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Open Access 01-07-2017 | Review

Increasing Precision of Clinical Diagnosis of Alzheimer's Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data

Authors: Marwan N. Sabbagh, Lih-Fen Lue, Daniel Fayard, Jiong Shi

Published in: Neurology and Therapy | Special Issue 1/2017

Abstract

Establishing the in vivo diagnosis of Alzheimer’s disease (AD) or other dementias relies on clinical criteria; however, the accuracy of these criteria can be limited. The diagnostic accuracy is 77% for a clinical diagnosis of AD, even among experts. We performed a review through PubMed of articles related to specific diagnostic modalities, including APOE genotyping, cerebrospinal fluid (CSF) testing, fludeoxyglucose F 18 positron emission tomography (PET), amyloid PET, tau PET, computed tomography (CT), single-photon emission CT, magnetic resonance imaging (MRI), and B12 and thyroid-stimulating hormone screening, to determine the specificity and sensitivity of each test used in the clinical diagnosis of AD. We added a novel immunomagnetic reduction assay that provides ultrasensitivity for analyzing the levels of plasma tau and beta amyloid 42 (Aβ₄₂). The sensitivity and specificity of the current diagnostic approach (structural CT or MRI with screening labs) remain low for clinical detection of AD and are primarily used to exclude other conditions. Because of limited diagnostic capabilities, physicians do not feel comfortable or skilled in rendering a clinical diagnosis of AD. Compounding this problem is the fact that inexpensive, minimally invasive diagnostic tests do not yet exist. Biomarkers (obtained through CSF testing or PET imaging), which are not routinely incorporated in clinical practice, correlate well with pathologic changes. While PET is particularly costly and difficult to assess, CSF measures of tau and beta amyloid are not costly, and these tests may be worthwhile when the tiered approach proposed here warrants further testing. There is a need for developing bloodborne biomarkers that can aid in the clinical diagnosis of AD. Here we present a streamlined questionnaire-enriched, biomarker-enriched approach that is more cost-effective than the current diagnosis of exclusion and is designed to increase clinical confidence for a diagnosis of dementia due to AD.

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Title: Increasing Precision of Clinical Diagnosis of Alzheimer's Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data
Authors: Marwan N. Sabbagh
Lih-Fen Lue
Daniel Fayard
Jiong Shi
Publication date: 01-07-2017
Publisher: Springer Healthcare
Published in: Neurology and Therapy / Issue Special Issue 1/2017
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI: https://doi.org/10.1007/s40120-017-0069-5

At a glance: The STEP trials

Springer Medicine

Increasing Precision of Clinical Diagnosis of Alzheimer's Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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