hiv center for clinical and behavioral studies at ny state psychiatric institute and columbia...

HIV CENTER for Clinical and Behavioral Studiesat 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 30th, 2011HIV Center Grand Rounds


What is HAND?(HIV-Associated Neurocognitive Disorder)

HIV has affinity for CNS and crosses blood brain barrier Cortical and subcortical brain regions affected1,2

Neurotoxic effects and inflammatory response

Disrupts neurocognitive functions3,4: Attention and concentration Motor speed and coordination Learning/Memory Planning and organization

Neurocognitive impairment disrupts activities of daily living5-9

Adherence Finance management Employment Driving


What is HAND?

Manifests as HAND10

Asymptomatic Neuropsychological Impairment (ANI) Minor Neurocognitive Disorder (MND) HIV-Associated Dementia (HAD)

HAND highly prevalent among PLWH in developed countries11-13

Up to 60% have some form (typically milder form) HAD 1% - 10%

Milder HAND associated with mortality and progression to HAD14,15

Becoming more important as PLWH live longer


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


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


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 HAND22

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


How is HAND Detected?

From International HIV Dementia Scale


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


Detecting HAND in South Africa

Neurocognitive screening challenging in South Africa Few tools culturally validated with culturally appropriate norms

Neuropsychological test performance negatively influenced by23-26

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 Africa27-29


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


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


Demographics

N= 78 39 HIV+ and 39 demographically matched HIV-

All Xhosa- and/or English-speaking Black South Africans from townships

Age: 29.62 (SD=5.75)

Education: 10.81 (SD=1.38)

Gender: 70% (n=55)

Some Employment: 22% (n=17)


ResultsMoCA Domain Score Comparisons

Table 2. Between groups Comparison on the MoCA

HIV- (n=39) HIV+ (n=39)

Mean SD Mean SD t p

Total Score (unadjusted for education) 21.67 2.00 18.62 4.39 3.95 .000

Visuospatial/Executive 3.82 .64 2.62 1.50 4.62 .000

Naming 2.33 .74 1.79 1.08 2.57 .012a

Attention 4.18 1.21 3.36 1.46 2.70 .009a

Semantic Fluency (Animal Naming) 16.92 3.33 11.92 4.59 5.42 .000

Abstraction .93 .42 .78 .62 1.47 .147

Delayed Recall 3.72 .97 3.92 1.46 -.73 .467

Orientation 5.69 .52 5.69 .66 .71 1.00

aBonferonni Corrected (p<.005)


ResultsMoCA Individual Item Comparisons

Table 3. Between Groups Comparison of Correct Responses on Individual MoCA items

HIV- (n=39) HIV+ (n=39) % N % N χ2 p

Visuospatial/Executive

Trail Making 90% 35 51% 20 13.87 .000

Cube Copy 21% 8 13% 5 .83 .362

Clock Contour 100% 39 82% 32 7.69 .006a

Clock Numbers 87% 34 64% 25 5.64 .018a

Clock Hands 85% 33 51% 20 9.95 .002

Object Naming

Lion 100% 39 80% 31 8.91 .003a

Rhinoceros 49% 19 38% 15 .83 .361

Camel 85% 33 62% 24 5.28 .022a

Attention

Digits Forward 69% 27 72% 28 .06 .804

Digits Backward 72% 28 49% 19 4.34 .037a

Tapping 92% 36 92% 36 0 1.00

Serial 7’sb 31% 12 10% 4 5.03 .025

Language Animal Fluency 100% 39 49% 19 26.90 .000

Abstraction

Train-Bicycle 87% 34 64% 25 5.64 .018a

Watch-Ruler 5% 2 10% 4 .72 .395

Total Score ≤23 Education Adjusted 54% 21 80% 31 5.77 .016a

aBonferoni Corrected


ResultsComparison 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)

Mean SD Mean SD Mean SD Mean SD

Trail Making .90 .31 .87 .34 .56 .50 .27 .45

Cubeb .21 .41 .71 .46 .46 .50 .25 .43

Clock 2.72 .51 2.65 .65 2.16 .82 1.56 .98

Namingb 2.33 .74 2.88 .36 2.64 .58 2.19 .82

Memory 3.72 .97 3.73 1.27 1.17 1.47 .52 1.03

Digits Spanb 1.41 .68 1.82 .44 1.83 .43 1.49 .62

Tapping .92 .27 .97 .18 .93 .26 .67 .47

Serial 7’sb 1.85 .90 2.89 .41 2.65 .65 1.82 1.12

Abstractionb .92 .42 1.83 .43 1.43 .68 .99 .80

Orientationc 5.69 .52 5.99 .11 5.52 .84 3.92 1.73

*MoCA norms from North American older adults


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


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


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)


References

1. Wiley, C. A., Masliah, E., Morey, M., Lemere, C., DeTeresa, R., Grafe, M., et al. (1991). Neocortical damage during HIV infection. Annals of Neurology, 29(6), 651-657. doi: 10.1002/ana.410290613

2. Nottet, H. S. L. M., & Gendelman, H. E. (1995). Unraveling the neuroimmune mechanisms for the HIV-1-associated cognitive/motor complex. Immunology Today, 16(9), 441-448. doi: 10.1016/0167-5699(95)80022-0

3. Grant, I. (2008). Neurocognitive disturbances in HIV. International Review of Psychiatry, 20(1), 33-47. doi: doi:10.1080/09540260701877894

4. Heaton, R. K., Grant, I., Butters, N., White, D. A., & et al. (1995). The HNRC 500: Neuropsychology of HIV infection at different disease stages. Journal of the International Neuropsychological Society, 1(3), 231-251.

5. Gorman, A., Foley, J., Ettenhofer, M., Hinkin, C., & van Gorp, W. (2009). Functional Consequences of HIV-Associated Neuropsychological Impairment. Neuropsychology Review, 19(2), 186-203. doi: 10.1007/s11065-009-9095-0

6. Heaton, R. K., Marcotte, T. D., Mindt, M. R., Sadek, J., Moore, D. J., Bentley, H., et al. (2004). The impact of HIV-associated neuropsychological impairment on everyday functioning. Journal of the International Neuropsychological Society, 10(3), 317-331.

7. Hinkin, C. H., Castellon, S. A., Durvasula, R. S., Hardy, D. J., Lam, M. N., Mason, K. I., et al. (2002). Medication adherence among HIV+ adults: Effects of cognitive dysfunction and regimen complexity. Neurology, 59(12), 1944-1950.


References

8. Marcotte, T. D., Wolfson, T., Rosenthal, T. J., Heaton, R. K., Gonzalez, R., Ellis, R. J., et al. (2004). A multimodal assessment of driving performance in HIV infection. Neurology, 63(8), 1417-1422. doi: 10.1212/01.wnl.0000141920.33580.5d

9. van Gorp, W. G., Rabkin, J. G., Ferrando, S. J., Mintz, J., Ryan, E., Borkowski, T., et al. (2007). Neuropsychiatric predictors of return to work in HIV/AIDS. Journal of the International Neuropsychological Society, 13(1), 80-89. doi: http://dx.doi.org/10.1017/S1355617707070117

10. Antinori, A., Arendt, G., Becker, J. T., Brew, B. J., Byrd, D. A., Cherner, M., et al. (2007). Updated research nosology for HIVassociated neurocognitive disorders. Neurology, 69, 1789-1799.

11. Dore, G. J., McDonald, A., Li, Y., Kaldor, J. M., & Brew, B. J. (2003). Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS, 17(10), 1539-1545. doi: http://dx.doi.org/10.1097/00002030-200307040-00015

12. Sacktor, N., Lyles, R. H., Skolasky, R., Kleeberger, C., Selnes, O. A., Miller, E. N., et al. (2001). HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990-1998. Neurology, 56(2), 257-260.

13. Simioni, S., Cavassini, M., Annoni, J.-M., Rimbault Abraham, A., Bourquin, I., Schiffer, V., et al. (2010). Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS, 24(9), 1243-1250 1210.1097/QAD.1240b1013e3283354a3283357b.

14. Ellis, R., Langford, D., & Masliah, E. (2007). HIV and antiretroviral therapy in the brain: neuronal injury and repair. Nat Rev Neurosci, 8(1), 33-44.


References

15. Vivithanaporn, P., Heo, G., Gamble, J., Krentz, H. B., Hoke, A., Gill, M. J., et al. (2010). Neurologic disease burden in treated HIV/AIDS predicts survival. Neurology, 75(13), 1150-1158. doi: 10.1212/WNL.0b013e3181f4d5bb

16. Joska, J., Westgarth-Taylor, J., Myer, L., Hoare, J., Thomas, K., Combrinck, M., et al. (2010). Characterization of HIV-Associated Neurocognitive Disorders Among Individuals Starting Antiretroviral Therapy in South Africa. AIDS and Behavior, 1-7. doi: 10.1007/s10461-010-9744-6

17. Robertson, K. R., Nakasujja, N., Wong, M., Musisi, S., Katabira, E., Parsons, T. D., et al. (2007). Pattern of neuropsychological performance among HIV positive patients in Uganda. BMC Neurology, 7, 8.

18. McArthur, J. C., & Brew, B. J. (2010). HIV-associated neurocognitive disorders: is there a hidden epidemic? AIDS, 24(9), 1367-1370 1310.1097/QAD.1360b1013e3283391d3283356.

19. Power, C., Selnes, O. A., Grim, J. A., & McArthur, J. C. (1995). HIV Dementia Scale: A Rapid Screening Test. JAIDS Journal of Acquired Immune Deficiency Syndromes, 8(3), 273-278.

20. Sacktor, N. C., Wong, M., Nakasujja, N., Skolasky, R. L., Selnes, O. A., Musisi, S., et al. (2005). The International HIV Dementia Scale: A new rapid screening test for HIV dementia. AIDS, 19(13), 1367-1374.


References

21. Nasreddine, Z. S., Phillips, N. A., Bedirian, V., Charbonneau, S., Whitehead, V., Collin, I., et al. (2005). The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment. Journal of the American Geriatrics Society, 53(4), 695-699. doi: http://dx.doi.org/10.1111/j.1532-5415.2005.53221.x

22. Koski, L., Brouillette, M. J., Lalonde, R., Hello, B., Wong, E., Tsuchida, A., et al. (2011). Computerized testing augments pencil-and-paper tasks in measuring HIV-associated mild cognitive impairment*. HIV Medicine, no-no. doi: 10.1111/j.1468-1293.2010.00910.x

23. Manly, J. J., Byrd, D. A., Touradji, P., & Stern, Y. (2004). Acculturation, reading level, and neuropsychological test performance among African American elders. Applied Neuropsychology, 11(1), 37-46.

24. Manly, J. J., & Espino, D. V. (2004). Cultural influences on dementia recognition and management. Clinics in Geriatric Medicine, 20(1), 93-119.

25. Manly, J. J., Jacobs, D. M., Touradji, P., Small, S. A., & Stern, Y. (2002). Reading level attenuates differences in neuropsychological test performance between African American and White elders.[erratum appears in J Int Neuropsychol Soc 2002 May;8(4):605]. Journal of the International Neuropsychological Society, 8(3), 341-348.

26. Manly, J. J., Touradji, P., Tang, M. X., & Stern, Y. (2003). Literacy and memory decline among ethnically diverse elders. Journal of Clinical & Experimental Neuropsychology, 25(5), 680-690.


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), 95-101. doi: doi:10.1089/apc.2010.0292

28. 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), 282-286.

29. 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), 62-64.

hiv center for clinical and behavioral studies at ny state psychiatric institute and columbia...

Documents