Subcortical shape and volume abnormalities in an elderly HIV+ cohort

Over 50% of HIV+ individuals show significant impairment in psychomotor functioning, processing speed, working memory and attention [1, 2]. Patients receiving combination antiretroviral therapy may still have subcortical atrophy, but the profile of HIV-associated brain changes is poorly understood. With parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV+ subjects (4 female; age=65.35 ± 2.21) and 31 uninfected elderly controls (2 female; age=64.68 ± 4.57) scanned with MRI as part of a San Francisco Bay Area study of elderly people with HIV. We also investigated whether morphometry was associated with nadir CD4+ (T-cell) counts, viral load and illness duration among HIV+ participants. FreeSurfer was used to segment the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, accumbens, brainstem, callosum and ventricles from brain MRI scans. To study subcortical shape, we analyzed: (1) the Jacobian determinant (JD) indexed over structures’ surface coordinates and (2) radial distances (RD) of structure surfaces from a medial curve. A JD less than 1 reflects regional tissue atrophy and greater than 1 reflects expansion. The volumes of several subcortical regions were found to be associated with HIV status. No regional volumes showed detectable associations with CD4 counts, viral load or illness duration. The shapes of numerous subcortical regions were significantly linked to HIV status, detectability of viral RNA and illness duration. Our results show subcortical brain differences in HIV+ subjects in both shape and volumetric domains.

[1]  Michael J. Taylor,et al.  The HNRC 500-Neuropsychology of Hiv infection at different disease stages , 1995, Journal of the International Neuropsychological Society.

[2]  Kiralee M. Hayashi,et al.  3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer's disease. , 2006, Brain : a journal of neurology.

[3]  Paul M. Thompson,et al.  Applying tensor-based morphometry to parametric surfaces can improve MRI-based disease diagnosis , 2013, NeuroImage.

[4]  Paul M. Thompson,et al.  Disrupted cerebral metabolite levels and lower nadir CD4 + counts are linked to brain volume deficits in 210 HIV-infected patients on stable treatment☆ , 2013, NeuroImage: Clinical.

[5]  M. Maschke,et al.  Structural gray and white matter changes in patients with HIV , 2011, Journal of Neurology.

[6]  Michael Weiner,et al.  Automated 3d Mapping of Baseline and 12-month Associations between Three Verbal Memory Measures and Hippocampal Atrophy in 490 Adni Subjects and the Alzheimer's Disease Neuroimaging Initiative , 2022 .

[7]  Yaakov Stern,et al.  HIV-associated cognitive impairment before and after the advent of combination therapy , 2011, Journal of NeuroVirology.

[8]  Anne Casey,et al.  Evidence for change , 1998 .

[9]  Christine Fennema-Notestine,et al.  Effects of methamphetamine dependence and HIV infection on cerebral morphology. , 2005, The American journal of psychiatry.

[10]  P. Maruff,et al.  Prevalence and pattern of neuropsychological impairment in human immunodeficiency virus-infected/acquired immunodeficiency syndrome (HIV/AIDS) patients across pre- and post-highly active antiretroviral therapy eras: A combined study of two cohorts , 2011, Journal of NeuroVirology.

[11]  Jean-Marie Annoni,et al.  Cognitive dysfunction in HIV patients despite long-standing suppression of viremia , 2009, AIDS.

[12]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[13]  C A Wiley,et al.  HIV mediates a productive infection of the brain. , 1999, AIDS.

[14]  Bruce J Brew,et al.  Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. , 2004, AIDS.

[15]  Chantal E Stern,et al.  Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise. , 2007, Archives of neurology.