ApoE ε4 Is Associated With Cognition, Brain Integrity, and Atrophy in HIV Over Age 60

Abstract

BACKGROUND There are contradicting reports on the associations between Apolipoprotein E4 (ApoE ε4) and brain outcomes in HIV with some evidence that relationships may be greatest in older age groups. METHODS We assessed cognition in 76 clinically stable HIV-infected participants over age 60 and genotyped ApoE. Sixty-one of these subjects underwent structural brain MRI and diffusion tensor imaging (DTI). RESULTS The median age of the participants was 64 years (range: 60–84) and the median estimated duration of HIV infection was 22 years. Apo ε4 carriers (n=19) were similar to non-carriers (n=57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE ε4 carriers demonstrated greater deficits in cognitive performance in the executive domain (p=0.045) and had reduced fractional anisotropy (FA) and increased mean diffusivity (MD) throughout large white matter tracts within the brain compared to non-carriers. Tensor Based Morphometry (TBM) analyses revealed ventricular expansion and atrophy in the posterior corpus callosum, thalamus, and brainstem among HIV-infected ApoE ε4 carriers compared to ε4-non-carriers. CONCLUSION In this sample of older HIV-infected individuals, having at least one ApoE ε4 allele was associated with decreased cognitive performance in the executive functioning domain, reduced brain white matter integrity, and brain atrophy. Brain atrophy was most prominent in the posterior corpus callosum, thalamus and brainstem. This pattern of cognitive deficit, atrophy and damage to white matter integrity was similar to that described in HIV, suggesting an exacerbation of HIV-related pathology; although emergence of other age-associated neurodegenerative disorders cannot be excluded.

Increased brain-predicted aging in treated HIV disease

“…This fits with evidence from neuroimaging studies that have demonstrated independent effects of aging and HIV on the brain, 10,11,16,19,29 and does not support reports of accelerating effects. 12,21,30 However, these previous studies often included a preponderance of untreated individuals, those with detectable HIV viremia, or younger adults (i.e., <50 years old). These findings are difficult to extrapolate to older, well-treated HIV-positive populations, where the effects of aberrant aging will be more pertinent.…”

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years

“…The HIV-uninfected healthy control participants were selected from a longitudinal cohort of healthy brain aging at our center, as previously described. 23–25 In addition to exclusions described above for the HIV sample, all HIV-uninfected controls denied memory issues or functional complaints due to cognitive impairment, had Mini-mental State Exam scores above 26, Clinical Dementia Rates of 0 and were reviewed at a consensus conference to have normal cognitive function. 26 …”

“…25,34 Similarly, we employed regression models to examine clinical variables including duration of HIV, nadir and proximal CD4 counts. These analyses comprised of two different levels, first assessing relationships between baseline volume and all clinical variables simultaneously, correcting for age, sex and TIV.…”

Differentiating HIV-Associated Neurocognitive Disorders From Alzheimer’s Disease: an Emerging Issue in Geriatric NeuroHIV

“…[40, 41] In HIV-infected participants over age 60, negative associations between ApoE ε4 carrier status and clinical measures of cognitive functioning, brain atrophy and white matter (WM) integrity were noted. [42] In another study ApoE ε4 was found to moderate the expression of amyloid in HAND subjects, although the authors failed to find a direct association between ApoE ε4 carrier status and HAND. [43] Similarly, autopsy findings showed that the presence of diffuse amyloid plaques was associated with HAND among ApoE ε4 carriers, but not in non-ε4 carriers, suggesting that ApoE isoforms differently moderate the association between amyloid aggregation and HAND.…”