Impact of metabolic syndrome and vascular risk factors on age-related neurocognitive decline in HIV.

Type: Published Abstract
Title: Impact of metabolic syndrome and vascular risk factors on age-related neurocognitive decline in HIV.
Authors: Ellis R, Iudicello J, Marquine M, Ghias A, Heaton R, Kao Y, Deutsch R, McCutchan JA
Year: 2013
Publication: 4th International Workshop on HIV and Aging

Background: Despite effective virologic suppression on antiretroviral therapy, microbial translocation and immune activation persist, promoting metabolic disturbances such as insulin resistance and hyperlipidemia. Cross-sectional studies have shown an excess of metabolic syndrome and vascular risk factors (MSVRF) in older individuals with HIV, and these correlate with brain injury and neurocognitive (NC) disorders. This study utilized a longitudinal design to determine whether these metabolic changes exacerbate age-related NC declines in the context of HIV infection.

Methods: Subjects were evaluated at an initial time point (baseline) and again at least 1 year later. MSVRF were ascertained at baseline, including hypertension [HTN], diabetes mellitus [DM], current tobacco smoking [TOB], coronary heart disease [CHD], body mass index [BMI] and hyperlipidemia [HL]). NC performance was evaluated at all time points. To permit age affects to be delineated, NC test scaled scores were used. NC decliners were defined as participants whose subject-specific, mean practice-adjusted scaled score slopes fell below the 10th percentile of the HIV- control sample. Screening mixed effects regression models were performed to identify which MSVRF and MSVRF X age interactions significantly predicted NC decliner status, retaining terms with p < 0.10. MSVRF significant in the screening models were then entered into an overall model and the final model was simplified using backwards selection according to Akaike information criterion (AIC).

Results: Subjects were 634 HIV+ and 107 HIV- adults, primarily men (80%), with mean (±SD) age 42.1 (±9.3) years and total follow-up of 3,305 person-years. Average BMI was lower for HIV+ than for HIV- (26.0 versus 28.1; p = 0.005). HL was more common in HIV+ than HIV- (65% versus 51%; p = 0.008). No significant differences in prevalence were observed for the other MSVRF, including TOB (62% in the combined sample), HTN (16%), DM (9%) and CHD (3%). For the combined HIV+ and HIV- sample, factors associated with worse NC trajectories were older age (OR per year 1.03 [95% CI 1.01, 1.06]), TOB (OR 2.03 [1.26, 3.30]) and interactions for HTN X age and DM X age. At younger ages (less than 48 years) HTN and DM had no or a small protective effect on NC decline, while at older ages, both hypertension and diabetes became increasingly deleterious. Results were similar for the HIV+ only sample; factors predicting worse NC trajectories were age (OR per year 1.02 [096, 1.06], TOB (2.14 [1.27, 3.61] and interactions for HTN X age and DM X age. Again, at younger ages HTN and DM had no or a small protective effect, while at older ages, both factors became increasingly deleterious.

Conclusions: After accounting for age, which was associated with worse NC decline in all models, specific, modifiable MSVRFs (TOB, HTN and DM) were associated with NC decline both in HIV+ and HIV- individuals. The impact of some MSVRFs (HTN, DM) was age-dependent, with increasingly deleterious effects seen in older participants. These findings can inform efforts to determine which modifiable risk factors should be targeted to prevent or ameliorate NC decline in HIV.