Neurocognitive Examination: Screening for Cognitive Problems in HIV

1. Neurocognitive Examination:Screening for Cognitive Problems in HIV Kevin Robertson, Ph.D. Professor, Director of Neuropsychology Neurology, School of Medicine University of North Carolina

2. Overview • HIV enters the CNS within days • Chronic, latent low level infection • Prior to effective treatment (HAART) • 20% developed Dementia • Post HAART era • <5% Dementia • 20+% mild neurocognitive

3. Global Estimates 40 Million HIV+ 30% have some evidence of dementia HIV most prevalent cause of dementia globally (Sacktor et al)

4. Introduction of HAART Introduction of HAART Crypto Toxo 7 PML 6 PCNSL 5 4 3 2 1 0 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 Incidence of Neurologic Complications of HIV Infection: MACS Incidence rate (per 1000 person-years) 35 30 HIVD 25 20 15 10 5 0 '90 '92 '94 '96 '98 '00 Calendar year Sacktor N. J NeuroVirology. 2002;8(supp 2):115-121.

5. PrimaryDiagnostic Revisions • ANI • Asymptomatic Neuropsychological Impairment • MND • Mild Neurocognitive Disorder (MND) • HAD • HIV Associated Dementia or AIDS Dementia Complex

6. Definition • HIV Associated Dementia • Cognitive • (Attention, Learning/Memory loss, Mental Slowing) • Motor • (Response slowing, Poor Coordination, Unsteady Gait) • Behavior • (Apathy, Withdrawn, Irritable, Agitation) • Slow onset, 1 month duration • Not due to delirium from severe illness • Not due to other CNS condition • Functional/occupational impairments

7. “CLASSIC” • Early concentration/memory difficulty • Lose track of conversations • Progress to difficulty with written material • Apathetic appearance, indifference • May look depressed, but generally not, occasional mania, psychosis • Often marked response slowing

8. “CLASSIC” • Generally progressive motor dysfunction with slowing • Gait ataxia, difficulty turning • Progress to cane then wheelchair • Bladder bowel incontinence • Death within weeks/months without treatment

9. Symptom Progression • EARLY LATE • Cognition • Poor Concentration Global Dementia • Forgetfulness • Motor • Slowed fine motor Paraplegia • Clumsiness • Ataxia • Behavior • Apathy Mutism, Coma • Altered personality • “Depressed”

10. Neurocognitive effects of HAART • HAART • Improves neurocognitive functioning • Dementia is less prevalent in HAART era • Do patients on treatment develop neurocognitive disease? • Poor CNS penetration • Viral escape

11. A5001 • ACTG Longitudinal Linked Randomized Trials (ALLRT) • Enrolls patients from ongoing Randomized Clinical Trials • Brief Neurocognitive exam • Trailmaking A/B, Digit Symbol • Current Accrual: 4237/4500

12. International Network Seattle, WA Minneapolis, MN Cincinnati, OH Pittsburgh, PA New York, NY (2) St. Louis, MO Sacramento, CA Columbus, OH Philadelphia, PA Providence, RI Chicago, IL San Francisco, CA Cleveland, OH Rochester, NY Boston, MA Indianapolis, IN Palo Alto, CA Los Angeles, CA (2) Baltimore, MD (2) Pune, India Denver, CO Chapel Hill, NC Dallas, TX Durham, NC Chennai, India Nashville, TN Galveston, TX Birmingham, AL Lilongwe, Malawi Miami, FL San Diego, CA Chiang Mai, Thailand Port-au-Prince, HAITI San Juan, PR Honolulu, Oahu,HI Blantyre, Malawi Havare, Zimbabwe Manguinhos, Brazil Lima, PERU Durban, South Africa Porto Alegre, Brazil Park Town, South Africa

13. Objectives • To estimate the prevalence and incidence of neuropsychological impairment in subjects who have taken HAART

14. Demographics • 1498 Subjects • 54% white 23% African Am. 20% Hispanic • 85% male 15% female • Age: 40 yrs (median) • HIV RNA: 78% < 400 at baseline • CD4+: 421 (median) at baseline • 49% had nadir CD4 < 200

15. Neuropsychological Impairment Prevalence • 43% impaired at baseline • Patients with nadir CD4 < 200 cells had more impairment • p<0.05, after adjusting for race, education, age, gender, and ARV history • 26% of those impaired at baseline became unimpaired with follow-up • median follow up 56 weeks • Treatment effects on HAART?

16. Incidence • Incident Neuropsychological Impairment • 853 initially unimpaired subjects • followed for a median of 93 weeks • 19% (159) became Impaired

17. Conclusions Prevalence relatively common • 43% at entry • Associated with nadir CD4 <200 Incidence • 19% became impaired on treatment Improved 26% Limitations • Screening tests may be less sensitive

18. How Can You RecognizeNeurocognitive Impairment in Your HIV Patients?

19. Awareness Be Aware Ask questions Refer to specialist

20. Memory • “Do you forget things more often than you did a year ago?”

21. Executive Functioning • “Do you notice a change in how well you do math?” • For example, balancing a checkbook, paying bills, figuring out a tip amount

22. Attention or Speed of Information Processing • “Do you notice a change in your ability to pay attention to anything for a long period of time?”

23. Perceptual Motor Abilities • “Do you have trouble doing things that require energy compared to a year ago?” • For example, vacuuming, laundry, groceries, and cooking

24. Summary • Neurocognitive impairment of “today” presents differently from the HIV dementia of the past • The cumulative prevalenceof NIhas risen with the improved survival of HIV+ patients