Metabolic syndrome, APOE epsilon4 and brain microstructure in HIV-infected individuals.

摘要

Background. As HIV-infected individuals age, metabolic syndrome and apolipoprotein epsilon 4 (APOE epsilon4) allele may have a greater effect on cognition. Using diffusion tensor imaging, we characterize brain microstructure associated with metabolic syndrome and APOE epsilon4 in older HIV-infected individuals on highly active antiretroviral therapy (HAART).;Methods. A convenience sample (N = 22) was obtained from a cohort of HIV-infected subjects ≥ 50 years old who were recruited to study the effect of APOE epsilon4 on cortical metabolism. Evaluations included demographic characteristics, medical history, HIV viral load, CD4+ count, fasting lipid profile, and 2-hour oral glucose tolerance test.;Diffusion-weighted scans were acquired on a Philips 3.0T Achieva scanner. A single-shot echo planar imaging sequence and T2-weighted b0 image were obtained. Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. For FA and MD maps, statistical comparisons were made between groups with multiple comparison correction for the voxelwise tests using the False Discovery Rate p-value ≤ 0.05.;Results. Twenty-two subjects were included. Mean age was 58 years (range 50--73). Most subjects (95%) were on a stable HAART regimen for at least six months. All had CD4+ counts > 200 cells/microL, and a majority of subjects (82%) had undetectable viral loads. Fifty-nine percent had impaired glucose tolerance/diabetes; 50% hypertension; 50% elevated fasting LDL; 36% elevated fasting triglycerides; 64% low fasting HDL; 32% metabolic syndrome; 45% previously or currently smoked tobacco; 40% had at least one APOE epsilon4 allele.;On DTI, subjects with impaired glucose tolerance had significant decreases in FA and increases in MD in the caudate. Those with metabolic syndrome had significant increases in MD in the caudate. Elevated blood pressure or hypertension was associated with significant decreases in FA in the hippocampus and increased MD in the thalamus.;Conclusion. Microstructural changes in the caudate can be detected by using DTI in older HIV-infected individuals on HAART and are associated with impaired glucose tolerance. Further studies are warranted to determine whether these microstructural changes associated with impaired glucose tolerance are seen exclusively in HIV-infected individuals and whether early treatment of impaired glucose tolerance changes brain microstructure.