Medicalising normality? Using a simulated dataset to assess the performance of different diagnostic criteria of HIV-associated cognitive impairment

Title: Medicalising normality? Using a simulated dataset to assess the performance of different diagnostic criteria of HIV-associated cognitive impairment
Authors: Underwood, J
De Francesco, D
Leech, R
Sabin, CA
Winston, A
Item Type: Journal Article
Abstract: Objective The reported prevalence of cognitive impairment remains similar to that reported in the pre-antiretroviral therapy era. This may be partially artefactual due to the methods used to diagnose impairment. In this study, we evaluated the diagnostic performance of the HIV-associated neurocognitive disorder (Frascati criteria) and global deficit score (GDS) methods in comparison to a new, multivariate method of diagnosis. Methods Using a simulated ‘normative’ dataset informed by real-world cognitive data from the observational Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) cohort study, we evaluated the apparent prevalence of cognitive impairment using the Frascati and GDS definitions, as well as a novel multivariate method based on the Mahalanobis distance. We then quantified the diagnostic properties (including positive and negative predictive values and accuracy) of each method, using bootstrapping with 10,000 replicates, with a separate ‘test’ dataset to which a pre-defined proportion of ‘impaired’ individuals had been added. Results The simulated normative dataset demonstrated that up to ~26% of a normative control population would be diagnosed with cognitive impairment with the Frascati criteria and ~20% with the GDS. In contrast, the multivariate Mahalanobis distance method identified impairment in ~5%. Using the test dataset, diagnostic accuracy [95% confidence intervals] and positive predictive value (PPV) was best for the multivariate method vs. Frascati and GDS (accuracy: 92.8% [90.3–95.2%] vs. 76.1% [72.1–80.0%] and 80.6% [76.6–84.5%] respectively; PPV: 61.2% [48.3–72.2%] vs. 29.4% [22.2–36.8%] and 33.9% [25.6–42.3%] respectively). Increasing the a priori false positive rate for the multivariate Mahalanobis distance method from 5% to 15% resulted in an increase in sensitivity from 77.4% (64.5–89.4%) to 92.2% (83.3–100%) at a cost of specificity from 94.5% (92.8–95.2%) to 85.0% (81.2–88.5%). Conclusion Our simulations suggest that the commonly used diagnostic criteria of HIV-associated cognitive impairment label a significant proportion of a normative reference population as cognitively impaired, which will likely lead to a substantial over-estimate of the true proportion in a study population, due to their lower than expected specificity. These findings have important implications for clinical research regarding cognitive health in people living with HIV. More accurate methods of diagnosis should be implemented, with multivariate techniques offering a promising solution.
Issue Date: 11-Apr-2018
Date of Acceptance: 9-Mar-2018
URI: http://hdl.handle.net/10044/1/63270
DOI: https://dx.doi.org/10.1371/journal.pone.0194760
ISSN: 1932-6203
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS ONE
Volume: 13
Issue: 4
Copyright Statement: © 2018 Underwood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
NEUROCOGNITIVE IMPAIRMENT
ANTIRETROVIRAL THERAPY
ERA
POPULATION
PREVALENCE
STATISTICS
INFECTION
DISORDERS
DEMENTIA
CHARTER
AIDS Dementia Complex
Adult
Aged
Cognition
Cognition Disorders
Computer Simulation
Databases, Factual
HIV Infections
Humans
Middle Aged
Models, Statistical
Multivariate Analysis
Neuropsychological Tests
Predictive Value of Tests
Prospective Studies
Reproducibility of Results
Severity of Illness Index
Young Adult
Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) study
Humans
HIV Infections
AIDS Dementia Complex
Severity of Illness Index
Multivariate Analysis
Models, Statistical
Prospective Studies
Reproducibility of Results
Predictive Value of Tests
Cognition
Cognition Disorders
Neuropsychological Tests
Computer Simulation
Databases, Factual
Adult
Aged
Middle Aged
Young Adult
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
NEUROCOGNITIVE IMPAIRMENT
ANTIRETROVIRAL THERAPY
ERA
POPULATION
PREVALENCE
STATISTICS
INFECTION
DISORDERS
DEMENTIA
CHARTER
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: e0194760
Online Publication Date: 2018-04-11
Appears in Collections:Department of Medicine
Faculty of Medicine



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commonsx