Metabolic Syndrome is Associated with Neurocognitive Deficits in Persons Living with HIV

Transcription

1 Metabolic Syndrome is Associated with Neurocognitive Deficits in Persons Living with HIV Jessica L. Montoya, Ph.D. Postdoctoral Fellow Department of Psychiatry, UC San Diego 9 th International Workshop on HIV & Aging September 13, 2018

2 Metabolic Syndrome (MetS) and Neurocognitive Function Increased risk for MetS among people living with HIV (PLHIV) MetS has been linked to neurocognitive impairment in the general population Among PLHIV, components of MetS (diabetes, central obesity) have been associated with neurocognitive impairment (Fabbiani et al., 2013; McCutchan et al., 2012; Valcour et al., 2005, 2006) Impact of MetS, as a whole, on neurocognitive function might be greater than the sum of components individual effects Risk factors (meet 3 of 5) Increased waist circumference Men Women Raised triglycerides Low concentrations of HDL-C Men Women Elevated blood pressure Elevated fasting glucose Defining Level >102 cm (>40 in) >88 cm (>35 in) 150 mg/dl <40 mg/dl <50 mg/dl 130/ 85 mmhg 110 mg/dl National Cholesterol Education Program s (NCEP) Adult Treatment Panel III (ATP III) identification of MetS

3 AIM 1 Hypothesis: The association between MetS and neurocognitive deficits will be stronger among PLHIV than HIVpersons AIM 2 Hypothesis: Even after accounting for covariates, the association between MetS and neurocognitive deficits among PLHIV will be significant Aims & Hypotheses

4 Methods 201 adults (109 PLHIV and 92 HIV-) from the Multi-dimensional Successful Aging cohort study participated» Inclusion criteria: between age 35-65, English-speaking, capable of providing informed consent» Exclusion criteria: history of non-hiv neurological disorder, current psychotic disorder, history of learning disability Participants completed standardized neuromedical and neurobehavioral assessments» MetS: presence of three or more of the metabolic risk factors determined by laboratory assessment (phlebotomy and anthropometric measurement) and current medication use

5 Neurocognitive Assessment Comprehensive neurocognitive test battery» 7 neurocognitive domains: verbal fluency, executive functioning, speed of information processing, verbal learning, recall, working memory, and complex motor skills» WRAT-4 reading test: estimate of premorbid functioning Domain deficit scores (DDS)» Derived from demographically-corrected T-scores» Range from 0 (no impairment) to 5 (severe impairment) Global deficit score (GDS)» Measures the severity of neurocognitive deficits across the 7 domains

6 Participant Characteristics PLHIV (n=109) HIV- (n=92) p-value Demographics Age, M (SD) 50.5 (8.5) 51.1 (7.7).61 Education, M (SD) 13.9 (2.4) 15.1 (2.3) <.001 Sex (% male) 83.5% 69.6%.02 Race/ethnicity (%).02 Non-Hispanic White 53.2% 69.6% Non-Hispanic Black 19.3% 14.1% Hispanic 19.3% 15.2% Other 8.3% 1.1% WRAT-4 Reading Scaled Score, M (SD) (13.9) (13.7).02 Metabolic Syndrome (%) 39.5% 20.7%.004

7 HIV Disease Characteristics PLHIV (n=109) Estimated years of infection, median [IQR] 18.4 [ ] On antiretroviral therapy (%) 97.2% Detectable plasma RNA (%) 7.4% Current CD4 (cells/mm 3 ), median [IQR] 629 [ ] Nadir CD4 (cells/mm 3 ), median [IQR] 176 [45 323] AIDS (%) 59.6%

8 Greater Impairment Global Deficit Scores MetS and Neurocognitive Function MetS significantly associated with GDS among PLHIV (p=.03) but not among HIV- persons (p=.93) 0,80 0,70 0,60 * 0,50 0,40 0,30 Without MetS With MetS 0,20 0,10 0,00 PLHIV HIV-

9 Greater Impairment Effect Size on DDS MetS and Neurocognitive Function in PLHIV MetS continued to be significantly associated with GDS (p<.05), even after accounting for covariates (i.e., estimated premorbid functioning, nadir CD4) PLHIV with MetS had lower scores in the domains of complex motor skills (p=.04) and learning (p=.04) compared to PLHIV without MetS 0,5 0,4 * * 0,3 0,2 0,1 0 Verbal Fluency Exec SIP Learn Recall Working Memory Motor

10 Greater Impairment Global Deficit Scores MetS Components and Neurocognitive Function in PLHIV 1 0,9 0,8 0,7 * * 0,6 0,5 0,4 0,3 No Yes 0,2 0,1 0 Elevated WC Elevated Triglycerides Reduced HDL-C Elevated BP Diabetes Diabetes (p=.02) but not elevated triglycerides (p=.23) remained significantly associated with GDS in a multivariable model controlling for nadir CD4 and WRAT-4 reading

11 Discussion Presence of MetS was higher among PLHIV than HIV- persons and was significantly associated with global neurocognitive deficits among PLHIV» HIV may worsen the impact of MetS on neurocognitive function, potentially by systemic inflammation and decreased blood brain barrier integrity The neurocognitive domains of complex motor skills and learning seemed to drive the association between MetS and global neurocognition among PLHIV Among MetS components, diabetes and elevated triglycerides were significantly associated with global neurocognitive deficits among PLHIV Implications: early identification of PLHIV at risk for MetS and implementation of preventative approaches may help lessen development of MetS and its potential impact on neurocognitive function among PLHIV

12 Acknowledgements Co-authors» Beverly Yu» Elizabeth Pasipanodya» Raeanne C. Moore» Sara Gianella» Allen McCutchan» Ronald Ellis» Dilip V. Jeste» David J. Moore» Maria J. Marquine NIH Support» R01-MH099987» K23-MH105297» K23-MH107260» T32-DA031098