title: Topographies of Cortical and Subcortical Volume Loss in HIV and Aging in the cART Era.
abstract: OBJECTIVE
  Studies of HIV-associated brain atrophy often focus on a priori brain regions of interest, which can introduce bias. A data-driven, minimally biased approach was used to analyze changes in brain volumetrics associated with HIV and their relationship to aging, viral factors, combination antiretroviral therapy (cART), and gender, and smoking.
  
  
  METHODS
  A cross-sectional study of 51 HIV-uninfected (HIV-) and 146 HIV-infected (HIV+) participants.
  
  
  METHODS
  Structural MRI of participants was analyzed using principal component analysis (PCA) to reduce dimensionality and determine topographies of volumetric changes. Neuropsychological (NP) assessment was examined using global and domain-specific scores. The effects of HIV disease factors (eg, viral load, CD4, etc.) on brain volumes and neuropsychological were investigated using penalized regression (LASSO).
  
  
  RESULTS
  Two components of interest were visualized using principal component analysis. An aging effect predominated for both components. The first component, a cortically weighted topography, accounted for a majority of variance across participants (43.5% of variance) and showed independent effects of HIV and smoking. A secondary, subcortically weighted topography (4.6%) showed HIV-status accentuated age-related volume loss. In HIV+ patients, the cortical topography correlated with global neuropsychological scores and nadir CD4, whereas subcortical volume loss was associated with recent viral load.
  
  
  CONCLUSIONS
  Cortical regions showed the most prominent volumetric changes because of aging and HIV. Within HIV+ participants, cortical volumes were associated with immune history, whereas subcortical changes correlated with current immune function. Cognitive function was primarily associated with cortical volume changes. Observed volumetric changes in chronic HIV+ patients may reflect both past infection history and current viral status.
authors.affiliation: Departments of *Neurology; †Bioengineering; ‡Radiology, Washington University in Saint Louis, St. Louis, MO; and §Hope Center for Neurological Disorders, Washington University in Saint Louis, St. Louis, MO.
authors.forename: Anika
authors.initials: A
authors.lastname: Guha
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Brier
authors.forename: Mario
authors.initials: M
authors.lastname: Ortega
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Westerhaus
authors.forename: Brittany
authors.initials: B
authors.lastname: Nelson
authors.forename: Beau M
authors.initials: BM
authors.lastname: Ances
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D025341:Principal Component Analysis; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents