Is it time to rethink how neuropsychological tests are used to diagnose mild forms of HIV-associated neurocognitive disorders? Impact of false-positive rates on prevalence and power
Department of Neurology, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, United States; Division of Geriatrics and Division of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States; Center for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya
Background: Between 0 and 48% of normal HIV-uninfected individuals score below threshold neuropsychological test scores for HIV-associated neurocognitive disorders (HAND) or are false positives. There has been little effort to understand the effect of varied interpretations of research criteria for HAND on false-positive frequencies, prevalence and analytic estimates. Methods: The proportion of normal individuals scoring below Z score thresholds drawn from research criteria for HAND, or false-positive frequencies, was estimated in a normal Kenyan population and a simulated normal population using varied interpretations of research criteria for HAND. We calculated the impact of false-positive frequencies on prevalence estimates and statistical power. Results: False-positive frequencies of 2-74% were observed for asymptomatic neurocognitive impairment/mild neurocognitive disorder and 0-8% for HIV-associated dementia. False-positive frequencies depended on the definition of an abnormal cognitive domain, Z score thresholds and neuropsychological battery size. Misclassification led to clinically important overestimation of prevalence and dramatic decreases in power. Conclusions: Minimizing false-positive frequencies is critical to decrease bias in prevalence estimates and minimize reductions in power in studies of association, particularly for mild forms of HAND. We recommend changing the Z score threshold to ≤-1.5 for mild impairment, limiting analysis to 3-5 cognitive domains and using the average Z score to define an abnormal domain. © 2013 S. Karger AG, Basel.
article; cognition; false negative result; false positive result; HIV associated dementia; human; Kenya; major clinical study; mild cognitive impairment; neuropsychological test; prevalence; scoring system; adult; Article; disease classification; false positive result; Cognition Disorders; False Positive Reactions; HIV Infections; Humans; Neuropsychological Tests
K01TW008764, FIC, Fogarty International Center; K01TW008764, NIH, National Institutes of Health; NIH, National Institutes of Health; NCI, National Cancer Institute; NIDA, National Institute on Drug Abuse; NIMH, National Institute of Mental Health