The Association Between Comorbidities and Neurocognitive Impairment in Aging Veterans with HIV

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CHAPTER 5 NEUROPSYCHOLOGICAL PROFILE OF ALZHEIMER S DISEASE

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The Association Between Comorbidities and Neurocognitive Impairment in Aging Veterans with HIV Arianna Perra, P syd, Moira Dux, PhD Terry Lee- Wilk, PhD

HIV and HCV in the VA VA is the largest provider of HIV/AIDS & HCV care in the U.S. Over 24,000 Veterans receive care for HIV VISN 5 treats approximately 1600 Veterans with HIV/AIDS Approximately 150,000 Veterans in VHA care with chronic HCV VISN 5 treats approximately 6,000 Veterans with HCV 30% of Veterans with HIV are co-infected with HCV With 50% co-infected in VISN 5

HIV: CNS Infiltration & Impact on Brain

Neurocognitive Disorders PRE-HAART Diagnostic Classifications POST-HAART HIV-Associated Neurocognitive Disorder (HAND) HIV-Associated Dementia (HAD) Asymptomatic Neurocognitive Impairment (ANI) Minor Cognitive Motor Disorder Mild Neurocognitive Disorder (MND) HIV-Associated Dementia (HAD)

Neurocognitive Impairment & HIV: Multifaceted Etiology? Plasma HIV RNA/CSF Viral Load; Viral Escape Demographic Factors CD4: Nadir/Current Neurocognitive Impairment Opportunistic Infections Treatment: prevs. post-cart; CNS Penetration Effectiveness (CPE) Comorbidities: Medical (infectious, noninfectious) & Psychiatric

Role of Comorbidities: The Veterans Aging Cohort Study Index Objective: examine association between VACS Index & neurocognitive impairment (NCI) VACS INDEX Age CD4 count HIV-1 RNA Hemoglobin FIB-4 egfr HCV infection VACS Index significantly correlated with global NCI and all cognitive domains assessed ART status did NOT moderate relationship between VACS and NCI VACS predicted NCI above and beyond HIV-specific characteristics (e.g., nadir CD4, duration of infection)

Current Study Examined relative association of infectious disease (ID)-related factors and non-id comorbidities on neurocognitive impairment (NCI). Predicted that non-id comorbidities would account for significant variance in NCI, above and beyond ID-related markers.

Methods All participants were referred for neuropsychological assessment in the context of cognitive concerns. Data from medical records were extracted to compute infectious disease and non-infectious disease composite scores for each participant.

Neurocognitive Variables Executive Function Trails B; Stroop Interference; Phonemic Fluency (FAS) Processing Speed Trails A; WAIS-III: Digit Symbol Coding & Symbol Search Attention/ Working Memory WAIS-III: Digit Span; WMS-III: Letter-Number Sequencing & Spatial Span Motor Function Grooved Pegboard: Dominant Hand & Non- Dominant Hand Learning & Memory Brief Visuospatial Memory Test (BVMT-R) & Hopkins Verbal Learning Test (HVLT-R): Total Immediate & Delayed Recall

ID Burden Hepatitis C CD4 below 200 # of Infectious Diseases # of Opportunistic Infections Infectious Disease Burden Detectable HIV Viral Load Length of Diagnosis

Non-ID Health Burden Vascular Metabolic Cancer Vitamin Deficiency Non-ID Health Burden Neurologic Immune Kidney Dysfunction

Participants Ethnicity HCV Coinfection African American Caucasian Mono-HIV Coinfected Age: 55.9 +/- 9.8 years Education: 12.1 +/- 2.2 years

Analyses **Hierarchical multiple regression analyses were conducted to assess relative contribution of ID and non-id markers to NCI DV Step 2 Cognitive Factors Non-ID Factor Step 1 ID Factor

Results Domain Learning/Memory R 2 =0.17, p < 0.05 Attention/Working Memory R 2 =0.22, p < 0.05 Processing Speed R 2 =0.21, p < 0.05 The reverse relationship was not supported ID factors did NOT account for significant variance

Role of Metabolic Function Exploratory zero-order correlations were conducted between neurocognitive scores and markers of metabolic function Elevated dispersion in A1c values was associated with worse performance on measures of learning/memory (r = -0.34, p<0.05), and attention/working memory (r = -0.38, p<0.05)

Conclusions Our data suggest that non-id comorbidities are a driving force behind neurocognitive impairment in patients with HIV HgbA1c was associated with worse performance on memory and attention measures Take home points NCI is not exclusively attributable to HIV-related factors, and is more strongly associated with other comorbidities The factors influencing NCI in patients with HIV are potentially modifiable Communication with providers and patients regarding potential causes of NCI and available interventions is critical

Future Directions Continue to explore the association between comorbidities and NCI in patients with HIV Refine ID and non-id factor scores Evaluate the role of mental health comorbidities Examine the influence of specific demographic factors Exercise study Compare the impact of a 16-week aerobic exercise intervention on markers of physical and neurocognitive function among 3 groups of older (50+), African American Veterans: HIV+/ART+ vs. HIV+/ART- vs. HIV-

Questions? Thank you! Emails: Arianna.Perra@va.gov Moira.Dux@va.gov Terry.Lee-Wilk@va.gov