HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Detecting HIV-Associated Neurocognitive Disorder in South Africa: The need for culturally valid screening tools Reuben N. Robbins, Ph.D. June 30 th, 2011 HIV Center Grand Rounds

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University What is HAND? (HIV-Associated Neurocognitive Disorder) HIV has affinity for CNS and crosses blood brain barrier  Cortical and subcortical brain regions affected 1,2  Neurotoxic effects and inflammatory response Disrupts neurocognitive functions 3,4 :  Attention and concentration  Motor speed and coordination  Learning/Memory  Planning and organization Neurocognitive impairment disrupts activities of daily living 5-9  Adherence  Finance management  Employment  Driving

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University What is HAND? Manifests as HAND 10  Asymptomatic Neuropsychological Impairment (ANI)  Minor Neurocognitive Disorder (MND)  HIV-Associated Dementia (HAD) HAND highly prevalent among PLWH in developed countries  Up to 60% have some form (typically milder form)  HAD 1% - 10% Milder HAND associated with mortality and progression to HAD 14,15 Becoming more important as PLWH live longer

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University HAND in South Africa Little known about prevalence and impact of HAND in South Africa  Yet, SA hardest hit by HIV with 5.5 million PLWH Recent study by Joska et al. (2010) 16  70% of younger adults with later stage HIV commencing ART had HAND (N=283)  25% HAD; 45% MND

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University How is HAND detected/diagnosed? Neuropsychological tests that assess deficits in neurocognitive function  Do not detect disease, but rather pattern of impairment typical of the disease  Require stimulus books, forms, stopwatches, etc  Numerous tests and batteries available  Administration must be exact  Performance compared to normative sample Current gold-standard diagnosis requires multi-hour neuropsychological and neurological exam

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University How is HAND detected/diagnosed? Screening for HAND not routine, 17,18 but could help:  Track and monitor  Make most appropriate referrals  Determine when to start ART Current screening tools just for HAD  HIV Dementia Scale (HDS) 19  International HIV Dementia Scale (IHDS) 20  Recent study used Montreal Cognitive Assessment (MoCA) 21 to screen for less severe HAND 22 Need for easy-to-use screening tools in South Africa:  Few neurologists and neuropsychologists, and other experts  Many undetected with HAND  Shift screening demands to lay personnel

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University How is HAND Detected? From International HIV Dementia Scale

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Montreal Cognitive Assessment (MoCA): highest score = 30, ≤25 = mild impairment Multi-hour neuropsychological exam would include many more items like the MoCA, as well as timed tests of processing speed and motor function

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Detecting HAND in South Africa Neurocognitive screening challenging in South Africa  Few tools culturally validated with culturally appropriate norms Neuropsychological test performance negatively influenced by  Low education  Low literacy  Culture differences  Limited test-taking experience  All very common in South Africa International HIV-Dementia Scale and HIV-Dementia Scale validated for use in South Africa 27-29

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Screening in South Africa Dr. Remien’s R34 adherence study (Masivukeni)  Neurocognitive screening tool component  IHDS  Montreal Cognitive Assessment (MoCA)  Grooved Pegboard Recent findings from our research  IHDS suggested 80% of adults on ART likely have HAD (N=65) Abnormalities on the MoCA  Cannot draw cube  Difficulty naming rhinoceros, etc

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Pilot Study Grant through Mount Sinai Institute of NeuroAIDS Disparities  Examine suitability of screening tools in South Africa Methods:  39 demographically matched HIV- and HIV+  Psychiatric screening  Neurocognitive screening  IHDS, MoCA, and Grooved Pegboard  Slight modifications to MoCA, cut-off score ≤23 (not 25)  All assessments available in Xhosa and English  Compare performance on MoCA (total, domain, and item)  Compare HIV- group to MoCA published norms

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Demographics N= 78  39 HIV+ and 39 demographically matched HIV- All Xhosa- and/or English-speaking Black South Africans from townships Age: (SD=5.75) Education: (SD=1.38) Gender: 70% (n=55) Some Employment: 22% (n=17)

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Results MoCA Domain Score Comparisons Table 2. Between groups Comparison on the MoCA HIV- (n=39)HIV+ (n=39) MeanSDMeanSDtp Total Score (unadjusted for education) Visuospatial/Executive Naming a Attention a Semantic Fluency (Animal Naming) Abstraction Delayed Recall Orientation a Bonferonni Corrected (p<.005)

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Results MoCA Individual Item Comparisons Table 3. Between Groups Comparison of Correct Responses on Individual MoCA items HIV- (n=39)HIV+ (n=39) %N%Nχ2χ2 p Visuospatial/Executive Trail Making90%3551% Cube Copy21%813% Clock Contour100%3982% a Clock Numbers87%3464% a Clock Hands85%3351% Object Naming Lion100%3980% a Rhinoceros49%1938% Camel85%3362% a Attention Digits Forward69%2772% Digits Backward72%2849% a Tapping92%3692% Serial 7’s b 31%1210% LanguageAnimal Fluency100%3949% Abstraction Train-Bicycle87%3464% a Watch-Ruler5%210% Total Score ≤23Education Adjusted54%2180% a a Bonferoni Corrected

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Results Comparison to MoCA Norms* Table 4. Comparison of HIV- performance to MoCA published norms MoCA Published Norms HIV- (n=39) Normal Controls (n=90) Mild Cognitive Impairment (n=94) Alzheimer’s (n=93) MeanSDMeanSDMeanSDMeanSD Trail Making Cube b Clock Naming b Memory Digits Span b Tapping Serial 7’s b Abstraction b Orientation c *MoCA norms from North American older adults

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Conclusion MoCA has some potential  Some items discriminate  Some appear to be biased  Norms and cut-off score may not be appropriate Implications  Use “as is” will lead to inaccurate and inflated rates of HAND  Need to make item modifications, develop norms, and determine most accurate cut-off score Future research  Compare against gold standard  Compare expert to lay personnel administration

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University The Future Future project  Develop neurocognitive screening tool for mobile technology (e.g., smartphones and tablets)  To address lack of culturally valid screening tools, and increase capacity for ease of screening by lay personnel  Currently have prototype developed  Completely self-contained: do not need timing device, paper, pencils, etc.  Reduce administration errors: automatically scored  Highly portable  Instant results

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University Acknowledgements Robert Remien, PhD – Scientific Mentor  The Masivukeni Team Mount Sinai Institute of NeuroAIDS Disparities Scholar Grant (PI: Susan Morgello, MD) John Joska, MD – University of Cape Town  Corne Robertson  Teboho Linda HIV Center T32 Postdoctoral Training Fellowship (PI: Theo Sandfort, PhD)  International Elective HIV Center (PI: Anke Ehrhardt, PhD)

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HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University References 27. Joska, J. A., Westgarth-Taylor, J., Hoare, J., Thomas, K. G. F., Paul, R., Myer, L., et al. (2011). Validity of the International HIV Dementia Scale in South Africa. AIDS Patient Care and STDs, 25(2), doi: doi: /apc Singh, D., Sunpath, H., John, S., Eastham, L., & Gouden, R. (2008). The utility of a rapid screening tool for depression and HIV dementia amongst patients with low CD4 counts- a preliminary report. African Journal of Psychiatry, 11(4), Ganasen, K. A., Fincham, D., Smit, J., Seedat, S., & Stein, D. (2008). Utility of the HIV Dementia Scale (HDS) in identifying HIV dementia in a South African sample. Journal of the Neurological Sciences, 269(1-2),

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University

HIV CENTER for Clinical and Behavioral Studies at NY State Psychiatric Institute and Columbia University