Systematic Literature Review and Meta-Analysis of Diagnostic Test Accuracy in Alzheimer's Disease and Other Dementia Using Autopsy as Standard of Truth

Article type: Research Article

Authors: Cure, Sandrine^{a; *} | Abrams, Keith^b | Belger, Mark^c | dell'agnello, Grazzia^d | Happich, Michael^e

Affiliations: [a] OptumInsight, Uxbridge, UK | [b] Department of Health Sciences, University of Leicester, Leicester, UK | [c] Lilly Research Centre, Windlesham, Surrey, UK | [d] Medical Department, Eli Lilly, Italy | [e] Lilly Deutschland GmbH, Bad Homburg, Germany

Correspondence: [*] Correspondence to: Sandrine Cure, OptumInsight, 3rd Floor, Beaufort House, Cricket Field Road, Uxbridge, Middlesex, UB8 1QG, UK. Tel.: +44 1895 455385; Fax: +44 1895 520039; E-mail: Sandrine.cure@optum.com.

Abstract: Background:Early diagnosis of Alzheimer’s disease (AD) is crucial to implement the latest treatment strategies and management of AD symptoms. Diagnostic procedures play a major role in this detection process but evidence on their respective accuracy is still limited. Objective:To conduct a systematic literature on the sensitivity and specificity of different test modalities to identify AD patients and perform meta-analyses on the test accuracy values of studies focusing on autopsy-confirmation as the standard of truth. Methods:The systematic review identified all English papers published between 1984 and 2011 on diagnostic imaging tests and cerebrospinal fluid biomarkers including results on the newest technologies currently investigated in this area. Meta-analyses using bivariate fixed and random-effect models and hierarchical summary receiver operating curve (HSROC) random-effect model were applied. Results:Out of the 1,189 records, 20 publications were identified to report the accuracy of diagnostic tests in distinguishing autopsy-confirmed AD patients from other dementia types and healthy controls. Looking at all tests and comparator populations together, sensitivity was calculated at 85.4% (95% confidence interval [CI]: 80.9%–90.0%) and specificity at 77.7% (95% CI: 70.2%–85.1%). The area under the HSROC curve was 0.88. Sensitivity and specificity values were higher for imaging procedures, and slightly lower for CSF biomarkers. Test-specific random-effect models could not be calculated due to the small number of studies. Conclusion:The review and meta-analysis point to a slight advantage of imaging procedures in correctly detecting AD patients but also highlight the limited evidence on autopsy-confirmations and heterogeneity in study designs.

Keywords: Alzheimer's disease, amyloid, biomarkers, diagnosis, emission tomography, magnetic resonance imaging, sensitivity and specificity, tomography

DOI: 10.3233/JAD-131559

Journal: Journal of Alzheimer's Disease, vol. 42, no. 1, pp. 169-182, 2014