Additive Effects of Aging and HIV Infection on ... - Virology Education

Combined Effects of Aging and HIV Infection on Semantic Verbal Fluency: A View of the Cortical Hypothesis Through the Lens of Clustering and Switching Jennifer E. Iudicello, Ph.D. Training in Research on Addictions in Interdisciplinary NeuroAIDS (TRAIN) HIV Neurobehavioral Research Program University of California, San Diego 2nd International Workshop on HIV & Aging Baltimore, Maryland HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO HIV NEUROBEHAVIORALndRESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO Presented at the 2 Int. workshop on HIV & Aging, 27 – 28 Oct 2011, Baltimore, USA

Combined effects of HIV & aging on the CNS Accelerate HIV disease progression?

HIV Infection

Exacerbate aging?

Aging

HIV + Aging

Neural Injury

Cognitive Impairment Functional Decline HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO HIV NEUROBEHAVIORALndRESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO Presented at the 2 Int. workshop on HIV & Aging, 27 – 28 Oct 2011, Baltimore, USA

Evidence for the “cortical” hypothesis of HIVassociated neurocognitive disorders (HAND) in older HIV+ adults  Common risk factors » Age, APOE-e4, Lipid metabolism » Amyloid plaques

 Biomarkers » Amyloid beta, Tau

 Neuroanatomy » Temporal regions

40 % HIV-associated Dementia

 Neuropathology

45

35 30 25 20 15 10 5 0 Y APOE4+ Y APOE4- O APOE4+ O APOE4-

Valcour et al., (2004) HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO HIV NEUROBEHAVIORALndRESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO Presented at the 2 Int. workshop on HIV & Aging, 27 – 28 Oct 2011, Baltimore, USA

Using semantic fluency and its component processes to explore the “cortical” hypothesis  Semantic (i.e., category) fluency

» Participants asked to generate as many words as possible within 60 seconds that belong to a specific category (i.e., animals)

 Clustering and switching Clustering

Switching

Production of words within a particular semantic subcategory

Shifting efficiently from one exhausted subcategory to another

Impaired in cortical dementias

Impaired in BOTH cortical and subcortical dementias

(Gruenewald & Lockhead, 1980; Troyer, Moscovitch & Winocur, 1997)

HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO HIV NEUROBEHAVIORALndRESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO Presented at the 2 Int. workshop on HIV & Aging, 27 – 28 Oct 2011, Baltimore, USA

Subcortical Profile

Healthy Adult Cat Dog Rabbit Guinea Pig Cow Horse Sheep Chicken Tiger Elephant Monkey Cheetah Parrot Parakeet Eagle Condor Kangaroo Emu Wallaby Wombat

cluster switch cluster switch cluster switch

Cat Dog Rabbit Guinea Pig Cow Horse Sheep Chicken Tiger Elephant Monkey Cheetah

cluster switch

Cortical Profile Cat Dog Cow Monkey

cluster cluster cluster

switch switch

cluster switch cluster

cluster switch cluster

______________________________________________________________________________________ Total switches: 4

Total switches: 2

Mean cluster size: 3

Mean cluster size: 3

Total switches: 2 Mean cluster size: 0.2


Effects of HIV and aging on clustering and switching: Conflicting hypotheses  Do the combined effects of HIV and aging produce a cortical or subcortical pattern of clustering and switching impairment?

Cortical Pattern

Subcortical Pattern

Poorer switching AND smaller cluster sizes

Poorer switching, but no clustering impairment

Executive dysfunction and degradation of semantic memory

Executive dysfunction

Frontal and temporal systems injury

Frontal systems injury


Participants 

257 participants enrolled at the HNRP » Age (< 40 or ≥ 50 years), HIV serostatus (HIV+/HIV-)



Exclusion criteria » DSM-IV substance dependence within 6 months of evaluation/U-tox positive for illicit drugs (except marijuana) on day of testing » History of neurological (e.g., stroke, seizure disorder, traumatic brain injury) or severe psychiatric conditions (e.g., schizophrenia) » Estimated verbal IQ < 70



Method » Standard category fluency measure (i.e., animal fluency) alongside a comprehensive neuropsychological, psychiatric, and medical evaluation » Clustering and switching scored according to published guidelines by Troyer and colleagues (e.g., Troyer, 2000; Troyer et al., 1997)


Younger Groups

Older Groups

HIV (n=93)

HIV + (n=50)

HIV (n=51)

HIV + (n=63)

Group

Age (years)

32.2 (5.2)

32.8 (4.0)

56.8 (4.9)

58.2 (6.2)

Y+ = Y-, O+ = O-

Education (years)

14.0 (2.2)

14.2 (1.9)

13.4 (2.3)

13.9 (2.6)

-----

Ethnicity (% Caucasian)

66.7%

62.0%

78.4%

74.6%

-----

Sex (% Male)

68.8%

78.0%

74.5%

82.5%

-----

103.4 (10.1)

103.2 (8.7)

100.1 (12.0)

101.5 (11.7)

-----

18.3%

30.0%

24.5%

42.9%

Y-, O- < O+

Hepatitis C Virus (% infected)

5.1%

7.3%

37.5%

25.0%

Y- = Y+, O+ = O-

Vascular Risk (%)

10%

18%

41%

43%

Y- = Y+, O+ = O-

52.0 (35.9)

60.9 (38.1)

53.0 (41.9)

70.8 (40.1)

Y-, O- < O+

Duration of Infection (years)

-----

4.6 (4.5)

-----

10.7 (6.5)

Y+ < O+

Nadir CD4 (cells/µl)

-----

282 (170, 463)

-----

153 (50, 227)

Y+ > O+

Current CD4 (cells/µl)

-----

432 (274, 624)

-----

419 (271, 597)

-----

AIDS (%)

-----

32.0%

-----

71.0%

Y+ < O+

ARVs (%)

-----

37.5%

-----

76.7%

Y+ < O+

Demographic Characteristics

Estimated Verbal IQ Neuropsychological Impairment (%)

Medical Characteristics

Psychiatric Characteristics POMS Total Mood Disturbance

HIV Disease Characteristics


Additive effects of HIV and aging on category fluency 24 ES = -0.70

ES = -0.51

ES = -0.37

HIV-/Y (n=93)

HIV+/Y (n=50)

HIV-/O (n=51)

23 22

Total Correct

21 20 19 18 17 16 15 //

HIV+/O (n=63)

J-T Statistic = 3.03 p = 0.001 HIV NEUROBEHAVIORAL RESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO HIV NEUROBEHAVIORALndRESEARCH PROGRAM | UNIVERSITY OF CALIFORNIA, SAN DIEGO Presented at the 2 Int. workshop on HIV & Aging, 27 – 28 Oct 2011, Baltimore, USA

Additive effects of HIV and aging on switching, not clustering Switching

Mean Cluster Size

12

1,6 ES = -0.70

ES = -0.51

ES = -0.13

Mean Cluster Size

11 Total Switches

ES = 0.00

ES = 0.16

ES = -0.30

HIV-/Y (n=93)

HIV+/Y (n=50)

HIV-/O (n=51)

1,4

10 9 8

1,2 1 0,8 0,6 0,4

7 0,2 6

//

0 HIV-/Y (n=93)

HIV+/Y (n=50)

HIV-/O (n=51)

J-T Statistic = 2.16 p = 0.015

HIV+/O (n=63)

J-T Statistic = -1.37 p = 0.915


HIV+/O (n=63)

Switching, but not clustering deficits in older HIV+ individuals with HAND Mean Cluster Size

Switching 12

1,6 ES = -0.48

ES = -0.21

1,4 Mean Cluster Size

11 Total Switches

ES = -0.32

ES = -0.68

10 9 8

1,2 1 0,8 0,6 0,4

7

0,2

6 //

0 Old HIV(n=51)

Old HIV+ NML Old HIV+ (n=36) HAND (n=27)

Old HIV(n=51)

Old HIV+ NML Old HIV+ (n=36) HAND (n=27)


Cognitive correlates of switching in the older HIV+ group

Category Fluency Switching Spearman's Rho

p-value

Attention/Working Memory

0.349

0.006

Significant independent predictors

Executive Functions

0.244

0.082

p = 0.011

Learning

0.486