Background:  Low nadir CD4 cell count and the apolipoprotein E4 (ApoE4) allele are known risk factors for HIV-related neurocognitive impairment. ApoE4 is also predictive of development or progression of Alzheimer’s disease. The severity of dementia in HIV infection has been correlated to diffusion alterations within the corpus callosum, and in Alzheimer’s disease, with regionally specific atrophy of the same structure. We hypothesize that volumetric changes in callosal regions may correlate with nadir CD4, presence of an ApoE4 allele, and neurocognitive deficits.

Methods:  A total of 17 HIV-seropositive men over age 50 (8 with at least 1 ApoE4 allele; 9 without ApoE4) prospectively underwent T1-weighted structural magnetic resonance imaging at 3.0 Tesla, clinical and neuropsychological tests, and ApoE4 genotyping. Nadir CD4 count was determined by patient self-report and confirmed as possible. We utilized FreeSurfer software to parcellate corpus callosum into five segments. Analysis of co-variance was used to study the effects of callosal volumes on cognitive domains in which neuropsychological test performance differed significantly (p <0.05) between ApoE4⁺ and non-ApoE4 groups. Independent variables were age, education, ApoE4 group status, and callosal segment volume. Regional volumes that were associated with cognitive deficit were examined for correlation with nadir CD4.

Results:  Education, viral load and current CD4 count did not differ significantly between ApoE4⁺ and non-ApoE4 groups. Reductions of normalized total and regional callosal volume in ApoE4 carriers did not reach significance. Significant ApoE4-associated impairment included diminished visuospatial function and non-verbal memory, which showed effects at significant or trend (p <0.1) levels of splenium (posterior), genu (anterior), and central corpus callosal volume. Age and education did not contribute significantly to the model. Lower nadir CD4 correlated with decreased splenium (p = 0.048, R = 0.712) and genu (p = 0.040, R = 0.730) volumes in ApoE4 carriers only.

Conclusions:  HIV-seropositive individuals possessing at least one ApoE4 allele are more vulnerable to effects of low nadir CD4 count, which may contribute to region-specific corpus callosum atrophy and thereby to cognitive impairment. Early ART may be more vital for these patients than for those without the allele.