Meyer A.-C.L., John Boscardin W., Kwasa J.K., Price R.W.
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
Meyer, A.-C.L., Department of Neurology, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, United States, Center for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya; John Boscardin, W., Division of Geriatrics and Division of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, United States; Kwasa, J.K., Center for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya; Price, R.W., Department of Neurology, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, United States
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