Neuroimaging correlates of metabolic variables in HIV: The CHARTER Study.

Type: Poster
Title: Neuroimaging correlates of metabolic variables in HIV: The CHARTER Study.
Authors: Archibald S, Fennema-Notestine C, McCutchan JA, FitzSimons C, Ances B, Wolfson T, Jernigan T, Ellis RJ, Collier A, McArthur J, Morgello S, Simpson D, Marra C, Gelman B, Clifford D, Grant I, for the CHARTER Group
Date: 07-15-2011
Abstract:Background: Metabolic variables have recently been shown to correlate with the size of brain structures in a variety of populations. Given that HIV disease is often accompanied by metabolic abnormalities, we examined the structural correlates of metabolic factors in HIV-infected participants from the multi-site CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. We anticipated that high BMI, diabetes, atherogenic lipid profiles and hypertension might be associated with low gray matter volumes and abnormal white matter. Methods: Of 223 HIV+ participants who had metabolic data and brain morphometry, most were male (80%), currently on anti-retroviral therapy (78%), and relatively young (mean age of 44). The MRI exam included a multi-channel protocol that was analyzed using a semi-automated segmentation methods that measures volumes of cerebral white, cortical gray, subcortical gray, abnormal white, and ventricular and sulcal CSF. The metabolic variables examined included: body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure (diastolic and systolic), random blood glucose levels and diagnosis of diabetes. Data was examined using a simultaneous multiple regression model that controlled for scanner, age, gender, ethnicity, cranial vault, and nadir CD4. Each metabolic variable was added separately to this model to predict each MR variable. Results: Greater BMI was associated with smaller cortical gray (t=-4.1, p<.001) and larger cerebral white (t=4.25, p<.001) volumes. Higher total cholesterol (C) levels were associated with smaller cortical gray volumes (t=-2.3, p<.05); higher LDL-C was associated with larger cerebral white volumes (t=2.54, p<.05), while higher HDL-C levels were associated with increased sulcal CSF (t=2.5, p<.05). Higher glucose levels were associated with increased volumes of abnormal white matter (t=2.7, p<.01). Similarly diabetes predicted larger abnormal white volumes (t=2.3, p<.05) as well as increased ventricular size (t=2.4, p<.05). Blood pressure was not significantly associated with any brain volume measures. Summary: Elevated BMI, cholesterol, and glucose or diabetes correlated with altered brain structure in this study. The association of metabolic factors predisposing to atherosclerosis with white matter enlargement and edema is suggestive of vascular pathology. Alternatively, initiation of ART could increase both these metabolic factors and white matter inflammation during immune recovery. While many of these effects are found in HIV-uninfected populations, additional contributions of metabolic factors to brain damage in HIV infection may accelerate onset and severity of brain dysfunction. Further investigations of the effects of antiretroviral treatments on these associations are warranted.