Victor G. Valcour, MD Professor of Geriatric Medicine University of California San Francisco

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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.
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HIV-associated Neurocognitive Disorders (HAND)
Neuropsychological Testing Function
Mild Neurocognitive Impairment (MND) Mild-moderately impaired in at least two cognitive domains Typically mild to moderate impairment
HIV-associated Dementia (HAD) More severely impaired in at least two cognitive domains Typically more severe impairment
Asymptomatic Neurocognitive Impairment (ANI) Any degree of impairment in at least two cognitive domains No identified impairment
Antinori et al Neurology 2007
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Cognitive Impairment in HIV
HIV Asymptomatic Neurocognitive Impairment
Mild Neurocognitive Disorder (MND)
HIV-associated Dementia (HAD)
HIV infection
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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
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Clinical Features of Impairment
Cognition Memory loss Concentration Mental
slowing Comprehension
Behavior Apathy Depression Agitation, Mania
Motor Unsteady gait Poor coordination Tremor
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Brain Impairment and HIV
39 Impaired
Robertson K, et al. AIDS. 2007
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Cognitive Diagnoses Pre-HAART and Post-HAART Eras
HAD
MND
NL
ANI
Asymptomatic Neurocognitive Impairment accounts
for about 70 of non-confounded cases
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Composite neuropsychological testing performance

• HIV Negative Controls (CO), HIV Normal Cognition
  (HIV-NL), asymptomatic impairment (ANI), and
  symptomatic impairment (SNI MND HAD)

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Objective Measures of Everyday Function
Grant et al CROI 2012
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Is the Cognitive Impairment Real?DTI measures in
HIV vs. controls
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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
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Conversion to Symptomatic Impairment
Conversion to symptomatic

• 347 subjects, 90 months of follow-up

CROI 2012 Grant et al CHARTER Cohort
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Poor Proxy Networks in HIV

• Data from the HIV Over 60 Cohort indicates poor
  proximity of informants.

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Age Distribution of HIV in the US
Extrapolation of CDC data through 2008
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Who are they?

• Mostly aging with HIV
• 11 of new infections among 50
• Heterogeneity
• Multimorbidity, polypharmacy, /- frailty

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HIV Over Age 60

• Nearly 100 adherent cant compare to younger
  cohorts
• More symptomatic impairment
• Survival tendencies

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UCSF HIV Over 60 CohortPredictors of Cognitive
Impairment

• Correlated to CI

• NOT Correlated to CI

• CD4 T-lymphocyte nadir
• Diabetes
• Apo E4 genotype
• Monocyte effectiveness (ME) score

• Age and duration of HIV
• Current CD4 T-lymphocyte count
• Plasma Viral load
• Non-diabetes CVD risk factors
• CNS penetration effectiveness score (CPE)

CI Cognitive Impairment, CVD cardiovascular
disease plt0.10
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(No Transcript)
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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
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Apo E4 and CognitionUCSF HIV Over 60 Cohort
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Where do we go from here?Treatment options

• Antiretroviral treatment considerations
• Treatments used for neurodegenerative disorders?
• Exercise
• Cognitive stimulation
• Treatment of comorbidities

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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
  Alzheimers disease