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Emerging Issues in HIV, Aging, and Cognition

Emerging Issues in HIV, Aging, and Cognition. Victor G. Valcour, MD Professor of Geriatric Medicine University of California San Francisco. From VG Valcour , MD, at Atlanta, GA: April 10, 2013, IAS-USA. HIV-associated Neurocognitive Disorders (HAND). Antinori et al Neurology 2007.

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Emerging Issues in HIV, Aging, and Cognition

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  1. Emerging Issues in HIV,Aging, and Cognition Victor G. Valcour, MDProfessor of Geriatric MedicineUniversity of California San Francisco From VG Valcour, MD, at Atlanta, GA: April 10, 2013, IAS-USA.

  2. HIV-associated Neurocognitive Disorders (HAND) Antinori et al Neurology 2007

  3. Cognitive Impairment in HIV HIV Asymptomatic Neurocognitive Impairment Mild Neurocognitive Disorder (MND) HIV-associated Dementia (HAD) HIV infection

  4. Cognitive Diagnoses Pre-HAART and Post-HAART Eras Pre-cART Post-cART HAD MND ANI NL • Lower incidence • No change in prevalence Modified from Ellis et al, Nat Rev Neurosci 2007 and Grant et al., CROI 2009

  5. Clinical Features of Impairment Cognition Memory loss Concentration Mental slowing Comprehension Behavior Apathy Depression Agitation, Mania Motor Unsteady gait Poor coordination Tremor

  6. 21% Developed impairment after 48 weeks of HAART Brain Impairment and HIV 39% Impaired Robertson K, et al. AIDS. 2007

  7. Cognitive Diagnoses Pre-HAART and Post-HAART Eras HAD MND NL ANI Asymptomatic Neurocognitive Impairment accounts for about 70% of non-confounded cases

  8. Composite neuropsychological testing performance HIV Negative Controls (CO), HIV Normal Cognition (HIV-NL), asymptomatic impairment (ANI), and symptomatic impairment (SNI = MND + HAD) CO HIV-NL ANI SNI

  9. Objective Measures of Everyday Function Grant et al CROI 2012

  10. Is the Cognitive Impairment Real?DTI measures in HIV vs. controls

  11. Imaging Top panel: Correlation between NAB t-scores (y-axis) and corpus callosum volume as a fraction of ICV. Bottom panel: Correlation between NAB t-scores (y-axis) and splenium FA. • Corpus Callosum volume and Fractional Anisotropy (FA) correlate to functional performance on the NAB Regions of significant difference in fractional anisotropy (FA) correlated to NAB z-scores, controlling for age

  12. Conversion to Symptomatic Impairment 347 subjects, 90 months of follow-up Conversion to symptomatic CROI 2012 – Grant et al CHARTER Cohort

  13. Poor Proxy Networks in HIV Data from the HIV Over 60 Cohort indicates poor proximity of informants.

  14. Age Distribution of HIV in the US Extrapolation of CDC data through 2008

  15. Who are they? • Mostly aging with HIV • 11% of new infections among 50+ • Heterogeneity • Multimorbidity, polypharmacy, +/- frailty

  16. HIV Over Age 60 • Nearly 100% adherent – can’t compare to younger cohorts • More symptomatic impairment • Survival tendencies

  17. UCSF HIV Over 60 CohortPredictors of Cognitive Impairment Correlated to CI NOT Correlated to CI Age and duration of HIV Current CD4 T-lymphocyte count Plasma Viral load Non-diabetes CVD risk factors CNS penetration effectiveness score (CPE) • CD4 T-lymphocyte nadir* • Diabetes * • Apo E4 genotype • Monocyte effectiveness (ME) score CI = Cognitive Impairment, CVD= cardiovascular disease *p<0.10

  18. Diffuse plaques in frontal cortex as a factor of duration of HIV In vitro evidence that tat inhibits neprilysin, providing theoretical evidence for increased accumulation of amyloid Rempel, Pulliam et al AIDS 2005

  19. Apo E4 and CognitionUCSF HIV Over 60 Cohort

  20. Where do we go from here?Treatment options • Antiretroviral treatment considerations • Treatments used for neurodegenerative disorders? • Exercise • Cognitive stimulation • Treatment of comorbidities

  21. Conclusions • HAND remains frequent despite cART • Asymptomatic impairment may not be that asymptomatic • Comorbid illnesses are important contributors to impairment, particularly in older age • There are not enough data to determine if older HIV+ patients will be at increased risk for Alzheimer’s disease

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