Neurocognitive Impairment Among Cryptococcal Meningitis Survivors in Uganda, a Prospective Cohort Study

Abstract

Background: Neurocognitive impairment in HIV-associated cryptococcal meningitis survivors remains poorly characterized. We sought to identify risk factors associated with sustained neurocognitive impairment.

Methods: Cryptococcal meningitis survivors from the ASTRO-CM trial underwent neurocognitive assessment at 12 weeks. A composite quantitative neurocognitive performance score (QNPZ-8) was calculated as a mean of 8 independent z-scores. Participants were classified by QNPZ-8 score as having mild (QNPZ-8 ≥-1), moderate (-2 < QNPZ-8 < -1), or severe (QNPZ-8 ≤-2) impairment compared with the reference cohort of HIV-negative Ugandan adults. We compared differences in baseline demographics and clinical and laboratory variables by impairment categories.

Results: One hundred fifty-two participants completed ≥5 of the 8 neuropsychological tests and were included in the analysis. Overall, 37% (57/152) exhibited mild (QNPZ-8 ≥-1), 37% (56/152) moderate (-2 < QNPZ-8 < -1), and 26% (39/152) severe impairment (QNPZ-8 ≤-2). The overall mean QNPZ-8 score (SD) of -1.4 (0.82) denoted moderate neurocognitive impairment at 12 weeks. At baseline, lower weight (P = .03), Glasgow Coma Scale score <15 (P = .03), and education ≤7 years (P < .001) were more frequently observed among those with severe neurocognitive impairment at 12 weeks. Education ≤7 years (odds ratio, 6.13; 95% CI, 2.96-12.68; P < .001) and Glasgow Coma Scale score <15 (odds ratio, 2.61; 95% CI, 1.23-5.57; P = .013) were associated with moderate or severe neurocognitive impairment.

Conclusions: Neurocognitive impairment is prevalent at 12 weeks post-treatment in HIV-associated cryptococcal meningitis. Education level and Glasgow Coma Scale score <15 are associated with worse neurocognitive performance. Our findings underscore the need to further evaluate the impact of cryptococcal meningitis on neurocognitive outcomes.

Keywords: HIV; central nervous system infections; cryptococcal meningitis; neurocognitive assessment; neurocognitive impairment.

Figure 1.

Neurocognitive Z-scores by individual domain score and overall QNPZ-8. Individual domain z-scores are represented as mean and 95% CI. Z-scores have been adjusted so that higher scores reflect better performance. QNPZ-8 score is represented as mean and 95% CI and a boxplot of the median and interquartile range. Abbreviations: AVLT, auditory verbal learning recall; QNPZ-8, composite quantitative neurocognitive performance score.