In the larger sample involved in the neurocognitive analyses, 11 nsHD+ participants were Caucasian (65%), four were African-American (23%), and two were Latino (12%); in the sHD+ group, 18 were Caucasian (66%), eight were African-American (30%), and one was Latino (4%); in the nsLD group, 20 participants were Caucasian (74%), four were African-American (7%), and three were Latino (11%). There were no significant differences between nsHD+ and sHD+ in the frequency of participants with past history of substance abuse or dependence (see ). The most commonly misused illicit substances were cocaine, marijuana, and methamphetamine. In the HD+ group, the average time since criteria were met for substance abuse was 134 months (min = 0, max = 360) and for substance dependence was 73 months (min = 13, max = 300). At the time of evaluation, one nsHD+ (cannabis) and two sHD+ (cocaine and methamphetamine) met current criteria for substance abuse. Similar ethnic percentages and substance abuse/dependence prevalence were apparent for the smaller cohort comprising the brain volumetric analyses. In both neurocognitive and volumetric analyses, a greater percentage of the nsHD+ participants were on HAART than sHD+ participants (P = .05) (see ). Education, estimated premorbid verbal IQ, and alcohol consumption variables were not significantly different between the daily and nearly everyday smokers in the sHD+ group.
Regional brain volumetrics
The MANCOVA comparing nsHD+, sHD+, and nsLD on regional neocortical GM was significant [F(8, 92) = 2.33, P = .025]. ANCOVAs were significant for the frontal [F(2, 48) = 6.17, P = .004, η2 = 0.22], parietal [F(2, 48) = 7.34, P = .001, η2 = 0.20], temporal GM [F(2, 48) = 4.56, P = .015, η2 = 0.25], and for total cortical GM [F(2, 48) = 6.52, P = .003, η2 = 0.21], but not for occipital GM (see ). Follow-up Bonferroni corrected pairwise t-tests indicated sHD+ had significantly lower GM volume than nsLD in the frontal (−7.7%), parietal (−12.1%), and temporal lobe (−7.1%) and for total neocortical GM volume (−8.6%)(P = .001−.020); nsHD+ had lower frontal GM volume than nsLD (−7.1%, P = .027) and showed a trend for lower total neocortical GM (−5.9%, P = .058). In planned contrasts, sHD+ demonstrated a trend for smaller parietal GM than nsHD+ (−5.1%, P = .08). No other significant differences or trends were observed between sHD+ and nsHD+. Covariation for the greater average drinks per month in nsHD+ than sHD+ did not influence findings from comparisons among nsHD+ and sHD+ for brain volumes in any region.
(a) Frontal gray matter volume for all groups. (b) Parietal gray matter volume for all groups. (c) Temporal gray matter volume for all groups. (d) Total neocortical gray matter volume for all groups. Mean ± S.E.M. ICV = Intracranial volume.
The MANOVA for regional WM was significant [F(8, 94) = 2.049, P = .049]. ANOVAs were significant only for the frontal WM [F(2, 48) = 4.56, P = .025, η2 = 0.14], where sHD+ had significantly smaller WM than nsLD (−5.9%, P = .039). The 4.0% lower frontal WM volume in nsHD+ relative to nsLD was not statistically significant (P = .14). The ANOVA for ventricular CSF was significant [F(2, 49) = 5.37, P = .008, η2 = 0.18], where sHD+ had significantly larger volume than nsLD (P = .018).
ANOVAs for caudate, lenticular, thalamus, brain stem, cerebellum volumes, or sulcal CSF volumes indicated no significant group differences on these measures. There were no within-group differences between left and right hemisphere volumes and there were no group by age interactions for any region/structure investigated. No regional volume differences were apparent between the daily-smoking and nearly-daily-smoking participants comprising the sHD+ group.
Neurocognitive, fine motor and postural stability domains
ANOVAs comparing nsHD+, sHD+, and nsLD were significant (P ≤ .01) for AV learning [F(2, 67) = 9.80, P < .001, η2 = 0.22], AV memory-free recall [F(2, 67) = 4.71, P = .01, η2 = 0.15], AV memory-cued recall [F(2, 67) = 8.80, P = .001, η2 = 0.20], cognitive efficiency [F(2, 67) = 11.43, P < .001, η2 = 0.25], executive skills, [F(2, 66) = 7.82, P = .001, η2 = 0.19], visuospatial learning [F(2, 65) = 9.80, P < .001, η2 = 0.23], visuospatial memory [F(2, 66) = 20.56, P < .001, η2 = 0.41], working memory [F(2, 66) = 7.55, P = .001, η2 = 0.18], postural stability [F(2, 65) = 13.35, P = .001, η2 = 0.29], and fine motor skills. Bonferroni corrected pairwise t-tests indicated nsLD were superior to sHD+ on all the foregoing domains (P = .003−.018), and to nsHD+ on all domains (P = .006−.049) except AV learning, AV memory-free recall, and cued AV memory (see ). In planned contrasts, nsHD+ were superior to sHD+ on the domains of AV learning (P = .041), AV memory-free recall (P = .047), AV memory-cued recall (P = .049), and cognitive efficiency (P = .041), with a trend for better fine motor skills (P = .049; nonpredicted comparison; see ). The above contrasts remained significant after covarying for the greater 1-year average drinks per month in nsHD+, indicating the differences between sHD+ and nsHD+ on these domains were not mediated by differences in alcohol consumption over the year prior to enrollment. ANOVAs for visuospatial skills and postural stability were not significant. No differences were apparent on any domain between the daily-smoking and nearly-daily-smoking participants comprising the sHD+ group.
Group performance on neurocognitive and sensorimotor domains
(a) Auditory-verbal learning domain for all groups. Mean ± S.E.M. (b) Auditory-verbal memory domain (free-recall) for all groups. Mean ± S.E.M. (c) Cognitive efficiency domain for all groups. Mean ± S.E.M.
Effects of HIV disease severity on regional brain volumes and neurocognitive and sensorimotor functions
There were no main effects for HAART or CDC symptomatic status for regional brain volumes, neurocognitive/sensorimotor domains and no interactions between HAART or CDC status and smoking status. There were no main effects of viremia for regional brain volumes. Viremic individuals performed significantly worse than those with suppressed viral loads on all neurocognitive and sensorimotor domains (P = .002−.046); however, when covaried for the significantly higher average drinks per day over the week prior to evaluation in the viremic (10.6 ± 4.4 drinks/day) compared with the suppressed group (5.6 ± 2.5 drinks/day) (P = .002), all group differences on neurocognitive and sensorimotor domains were no longer significant. This indicated that alcohol consumption during the week prior to study mediated performance rather than level of viral burden.
Relationships among outcome measures in HD+
In the combined HD+ group (significant P ≤ .008), average number of drinks over past week was inversely related to fine motor skills (r = −0.56, P = .003) with a trend for executive skills (r = −0.48, P = .012). In the individual HD+ groups and the combined HD+ group (i.e., sHD+ and nsHD+), there were multiple moderately strong positive correlations (r = 0.40−0.50, P = .015−.03) between visuospatial learning and memory, visuospatial skills, and parietal, temporal, occipital WM and total lobar WM; however, these relationships did not survive our stringent correction for multiplicity (significant P ≤ .007). No significant relationships were observed among regional brain volumes and alcohol consumption variables; these correlations were generally weak and did not approach statistical significance for the individual groups or the combined HD+ sample. Furthermore, after rigorous correction for multiplicity, regional brain volumes, neurocognitive, or sensorimotor domains were not significantly related to viral load, CD4+ and CD8+ variables, aspartate aminotransferase, alanine aminotransferase, complete blood count variables (e.g., erythrocyte and leukocyte levels, hematocrit, etc), BDI, and duration of dependence on substances other than alcohol in the individual HD+ groups as well as the combined group.