Assessing Cognitive Functioning in People Living With HIV (PLWH): Factor Analytic Results From CHARTER and NNTC Cohorts

Abstract

Background: Single summary scores, such as the Global Deficit Score, are often used to classify overall performance on neuropsychological batteries. The factor structure of test scores that underlie Global Deficit Score in studies of people living with HIV (PLWH) was assessed to determine whether individual test scores loaded onto a unitary factor to summarize performance.

Setting: Secondary data analysis on baseline data of PLWH from National NeuroAIDS Tissue Consortium and CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Study.

Method: Primary analyses included testing model structure and fit of neuropsychological test scores with confirmatory and exploratory factor analyses. Secondary analyses involved receiver operating characteristic curves, and associations with psychosocial and medical variables.

Results: Participants with confounds were excluded, leading to 798 (National NeuroAIDS Tissue Consortium) and 1222 (CHARTER) cases. When confirmatory factor analysis models were structured to be consistent with theoretically-based cognitive domains, models did not fit adequately. Per exploratory factor analyses, tests assessing speeded information processing, working memory, and executive functions loaded onto a single factor and explained the most variance in both cohorts. This factor tended to be associated with age, estimated premorbid ability, and aspects of substance use history. Its relation to age, in context of demographically corrected neuropsychological scores, suggested accelerated aging.

Conclusion: Results indicate that individual neuropsychological tests did not load exactly onto expected domains, suggesting another framework for future analyses of cognitive domains. The possibility of a new index, and its use to assess cognitive impairment in PLWH, is suggested for further diagnostic and prognostic purposes.

Figure 1.. Final confirmatory factor analysis for CHARTER (A) and NNTC (B).

Standardized factor loadings are presented. As detailed in the tables, this current model has satisfactory fit per multiple indices of overall model fit for both studies. Abbreviations for neuropsychological tests above are HVLT-R = Hopkins Verbal Learning Test-Revised, BVMT-R = Brief Visuospatial Memory Test-Revised, WMS-III = Wechsler Memory Scale, Third edition, PASAT = Paced Auditory Serial Addition Test, WAIS-III = Wechsler Adult Intelligence Scale – Third edition.

Figure 2.. CEF average T-score and DDS distribution, and comparisons with Frascati and GDS.

(A) Frequency distributions of CEF average T-scores in both NNTC and CHARTER reveal a good fit to a Gaussian distribution. (B) Frequency distributions of CEF DDS, with the majority for both NNTC and CHARTER having values between 0.0 and 0.2. (C) CEF average T-scores compared to Frascati diagnosis for NNTC and CHARTER. Red lines indicate median and interquartile range. One-way ANOVA for both revealed significance (p<0.001). Tukey’s multiple comparison tests were p<0.0001 between all conditions except ANI vs. MND, which for NNTC p=0.0001, and CHARTER p=0.0005. (D) CEF DDS compared to Frascati diagnosis for NNTC and CHARTER. Red lines indicate median and interquartile range. The nonparametric Kruskal-Wallis test was used given the distribution of the data, and revealed significance (p<0.0001) for both. Dunn’s multiple comparison tests were p<0.0001 between all conditions except ANI vs. MND, which for NNTC p=0.0002, and CHARTER p=0.0147, and for CHARTER only ANI vs HAD p=0.0001, and MND vs HAD p=0.0361. (E) ROC curves for NNTC and CHARTER, comparing GDS with the CEF average T-scores and DDS to diagnose impairment (using the Frascati criteria) for NNTC, CHARTER, and the combined cohorts. The area under the curve (auc) is indicated. (F). Frequency distribution of CEF average T-scores and DDS in unimpaired subjects from the combined NNTC and CHARTER cohorts. For the average T-scores (left) the cut-off at 1.5 SD below the mean is indicated, and for DDS (right) the cut-off at 0.5 is indicated.