Chicken. Tiger. Elephant. Monkey. Cheetah. Parrot. Parakeet. Eagle. Condor ... switch cluster cluster switch cluster switch. Subcortical Profile. Cortical Profile.
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
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
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
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
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)
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
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
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 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 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
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)
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
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