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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 Washington, DC: June 18, 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 Washington, DC: June 18, 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 if Impairment Cognition Memory loss Concentration Mental slowing Comprehension Behavior Apathy Depression Agitation, Mania Motor Unsteady gait Poor coordination Tremor

  6. Fluctuation in Cognitive Status HIV- HIV+ Antinori 2007 Neurology

  7. 21% Developed impairment after 48 weeks of HAART Brain Impairment and HIV 39% Impaired Robertson K, et al. AIDS. 2007

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

  9. 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

  10. Neuropsychological Assessment Battery (NAB) • Memory • Judgment • Driving (Attention/Executive) • Bill Pay (Language and calculations) • Map (Spatial ability)

  11. Total NAB Performance Total NAB across groups ANI did not differ from MND, but both ANI and MND performed more than 2 SD below controls.

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

  13. 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

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

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

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

  17. Aging Worldwide HIV Prevalence in age > 50 HIV and aging – Preparing for the Challenges Ahead, NEJM 2012

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

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

  20. 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

  21. 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

  22. Apo E4 and CognitionUCSF HIV Over 60 Cohort

  23. Where do we go from here?Treatment options • Antiretroviral treatment considerations • Treatments for neurodegenerative disorders? • Exercise • Cognitive stimulation • Treatment of morbidities • Safety in the home/ advanced planning

  24. 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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