Slide 1 of 22 IAS–USA Victor G. Valcour, MD Professor of Geriatric Medicine University of...

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IAS–USA

Victor G. Valcour, MDProfessor of Geriatric Medicine

University of California San Francisco

Emerging Issues in HIV,Aging, and Cognition

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 infection

HIV Asymptomatic Neurocognitive

Impairment

Mild Neurocognitive

Disorder (MND)

HIV-associated Dementia

(HAD)

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Cognitive Diagnoses Pre-HAART and Post-HAART Eras

Modified from Ellis et al, Nat Rev Neurosci 2007 and Grant et al., CROI 2009

• Lower incidence• No change in prevalence

Pre-cART Post-cART

HAD

MND

ANI

NL

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Clinical Features of Impairment

CognitionMemory loss

ConcentrationMental slowingComprehension

BehaviorApathy

DepressionAgitation, Mania

MotorUnsteady gait

Poor coordinationTremor

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Brain Impairment and HIV

21% Developed impairment after 48 weeks of HAART

Robertson K, et al. AIDS. 2007

39% Impaired

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Cognitive Diagnoses Pre-HAART and Post-HAART Eras

Asymptomatic Neurocognitive Impairment accounts for about 70% of non-confounded cases

NL ANI

HAD

MND

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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)

-4

-3

-2-2

-1

0

1

2

NP

ZC

om

p S

co

res

CO HIV-NL ANI SNI

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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

Regions of significant difference in fractional anisotropy (FA) correlated to NAB z-scores, controlling for age

0.0015 0.0020 0.0025

-8

-6

-4

-2

0

2

0.4 0.5 0.6 0.7

-3

-2

-1

0

1

2

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

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Conversion to Symptomatic Impairment

347 subjects, 90 months of follow-upCROI 2012 – Grant et al CHARTER Cohort

Con

vers

ion

to s

ympt

om

atic

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Poor Proxy Networks in HIV

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

Control AD HIV NL HIV ANI MND+HAD Sample Size 28 20 35 17 23

Mean Age (Range) 66 (61-70) 70 (60-80) 64 (59-76) 63 (60-79) 65 (60-82)

CDR mean 0.0 0.8 0.1 0.2 0.5

Unable to contact informant

0% 0% 14% 18% 9%

Informant is relative or spouse

86% 95% 40% 24% 43%

Informant lives with subject

75% 70% 40% 18% 39%

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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 – can’t compare to younger cohorts

• More symptomatic impairment• Survival tendencies

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UCSF HIV Over 60 CohortPredictors of Cognitive

Impairment

Correlated to CI

• CD4 T-lymphocyte nadir*

• Diabetes *• Apo E4 genotype• Monocyte

effectiveness (ME) score

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)

CI = Cognitive Impairment, CVD= cardiovascular disease *p<0.10

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Diffuse plaques in frontal cortex as a factor of duration of HIV

Rempel, Pulliam et al AIDS 2005

In vitro evidence that tat inhibits neprilysin, providing theoretical evidence for increased accumulation of amyloid

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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 Alzheimer’s disease

Slide 1 of 22 IAS–USA Victor G. Valcour, MD Professor of Geriatric Medicine University of...

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