Date Published: January 31, 2017
Publisher: Springer US
Author(s): Lewis J. Haddow, Rosanna Laverick, Marina Daskalopoulou, Jeffrey McDonnell, Fiona C. Lampe, Richard Gilson, Andrew Speakman, Andrea Antinori, Pietro Balestra, Tina Bruun, Jan Gerstoft, Lars Nielsen, Anna Vassilenko, Simon Collins, Alison J. Rodger.
We conducted a cross-sectional study in 448 HIV positive patients attending five European outpatient clinics to determine prevalence of and factors associated with neurocognitive impairment (NCI) using computerized and pen-and-paper neuropsychological tests. NCI was defined as a normalized Z score ≤−1 in at least 2 out of 5 cognitive domains. Participants’ mean age was 45.8 years; 84% male; 87% white; 56% university educated; median CD4 count 550 cells/mm3; 89% on antiretroviral therapy. 156 (35%) participants had NCI, among whom 26 (17%; 5.8% overall) reported a decline in activities of daily living. Prevalence of NCI was lower in those always able to afford basic needs (adjusted prevalence ratio [aPR] 0.71, 95% confidence interval [CI] 0.54–0.94) or with a university education (aPR 0.72, 95% CI 0.54–0.97) and higher in those with severe depressive symptoms (aPR 1.53, 95% CI 1.09–2.14) or a significant comorbid condition (aPR 1.40, 95% CI 1.03–1.90).
HIV-1 can cause neurological disease, but severe impairment is rare in HIV positive (HIV+) patients with access to antiretroviral therapy (ART) . A variety of estimates of prevalence of milder neurocognitive impairment (NCI) have been reported in HIV+ patients, exceeding 50% in studies from Western Europe and North America [2–4], but as low as 19% in other studies using broadly similar neuropsychological (NP) definitions [5, 6]. Estimates may vary because of differences in the characteristics of study populations. Most studies have focused on a particular setting (such as clinical trial participants [5, 7, 8], a single country [2–7, 9], or a specific patient group [6, 10]), and many studies have specifically excluded participants with potentially confounding conditions, detectable viral load or low CD4 count [2, 5, 7, 9, 11]. There is a need to study more diverse HIV + populations inclusive of those with typical comorbid conditions to clarify the effects of clinical, psychological and social variables as risk factors. As well as differences between study populations, differences in assessment method may lead to variations in results. Despite efforts to standardize definitions of HIV-associated NCI, for example with the “Frascati criteria”  or with a threshold in global deficit score (GDS) , there may be important differences between measuring instruments. The use of computerized neuropsychological testing batteries is one method that may provide stable and cross-cultural measures of cognitive function [14–17].
In HIV+ patients receiving care at five European HIV clinics, we found that 35% fulfilled standard criteria for at least mild NCI. Of these, a quarter had conditions that confounded a definitive diagnosis of HAND, more than half had no significant decline in daily function, and the remainder (6% of the total sample) had symptomatic HAND. Our estimates of overall prevalence and the proportion with symptomatic impairment are similar to previous estimates [2–4, 7–9], despite important differences in the target population of those studies and the measuring instruments used. The prevalence of self-reported functional decline associated with cognitive difficulties was half that of measured cognitive impairment on the NP battery, and half of the patients perceiving difficulties had normal cognitive function, indicating weak correlation between the two outcomes. The disconnect between objective function and patients’ lived experiences is the subject of a recent study, which concluded that “patient identification of physical versus cognitive causes is poorly associated with objective criteria” . These observations have important implications for classification of HAND in research studies and clinical practice. They also lead to concerns about whether a diagnosis of asymptomatic NCI creates unnecessary anxiety or, as some data suggest [31, 32], heralds future decline.