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Methamphetamine dependence increases risk of neuropsychological impairment in HIV infected persons



Both HIV infection and methamphetamine dependence can be associated with brain dysfunction. Little is known, however, about the cognitive effects of concurrent HIV infection and methamphetamine dependence. The present study included 200 participants in 4 groups: HIV infected/methamphetamine dependent (HIV+/METH+), HIV negative/methamphetamine dependent (HIV−/METH+), HIV infected/methamphetamine nondependent (HIV+/METH−), and HIV negative/methamphetamine nondependent (HIV−/METH−). Study groups were comparable for age, education, and ethnicity, although the HIV−/METH− group had significantly more females. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neurobehavioral domains. Rates of neuropsychological impairment were determined by cutoff scores derived from performances of a separate control group and validated with larger samples of HIV+ and HIV− participants from an independent cohort. Rates of global neuropsychological impairment were higher in the HIV+/METH+ (58%), HIV−/METH+ (40%) and HIV+/METH− (38%) groups compared to the HIV−/METH− (18%) group. Nonparametric analyses revealed a significant monotonic trend for global cognitive status across groups, with least impairment in the control group and highest prevalence of impairment in the group with concurrent HIV infection and methamphetamine dependence. The results indicate that HIV infection and methamphetamine dependence are each associated with neuropsychological deficits, and suggest that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms. (JINS, 2004, 10, 1–14.)Note: Dr. Erin D. Bigler served as action editor during the course of this review.


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Reprint requests to: Igor Grant, MD, HIV Neurobehavioral Research Center, 150 West Washington Street, 2nd Floor, San Diego, CA 92103.


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Adams, K.M., Brown, G.G., & Grant, I. (1985). Analysis of covariance as a remedy for demographic mismatch of research subject groups: Some sobering simulations. Journal of Clinical and Experimental Neuropsychology, 7, 445462.
Alhassoon, O.M., Dupont, R.M., Schweinsburg, B.C., Taylor, M.J., Patterson, T.L., & Grant, I. (2001). Regional cerebral blood flow in cocaine- versus methamphetamine-dependent patients with a history of alcoholism. International Journal of Neuropsychopharmacology, 4, 105112.
Atkinson, J.H., Grant, I., Kennedy, C.J., Richman, D.D., Spector, S.A., & McCutchan, J.A. (1988). Prevalence of psychiatric disorders among men infected with human immunodeficiency virus: A controlled study. Archives of General Psychiatry, 45, 859864.
Beck, A.T. & Steer, R.A. (1987). The Beck Depression Inventory. San Antonio, TX: Psychological Corporation.
Benedict, R.H. (1997). Brief Visuospatial Memory Test–Revised. Odessa, FL: Psychological Assessment Resources, Inc.
Benedict, R.H., Schretlen, D., Groninger, L., & Brandt, J. (1998). Hopkins Verbal Learning Test–Revised: Normative data and analysis of inter-form and test–retest reliability. Clinical Neuropsychologist, 12, 4355.
Bing, E.G., Burnam, A., Longshore, D., Fleishman, J.A., Sherbourne, C.D., London, A.S., Turner, B.J., Eggan, F., Beckman, R., Vitiello, B., Morton, S.C., Orlando, M., Bozzette, S.A., Ortiz-Barron, L., & Shapiro, M. (2001). Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Archives of General Psychiatry, 58, 721728.
Bloom, F.E. & Rausch, D.M. (1997). HIV in the brain: Pathology and neurobehavioral consequences (meeting report). Journal of Neurovirology, 3, 102109.
Borkowski, J.G., Benton, A.L., & Spreen, O. (1967). Word fluency and brain damage. Neuropsychologia, 5, 135140.
Czub, S., Koutsilieri, E., Sopper, S., Czub, M., Stahl-Hennig, C., Muller, J.G., Pedersen, V., Gsell, W., Heeney, J.L., Gerlach, M., Gosztonyi, G., Riederer, P., & ter Meulen, V. (2001). Enhancement of central nervous system pathology in early simian immunodeficiency virus infection by dopaminergic drugs. Acta Neuropathologica (Berl), 101, 8591.
Davidson, C., Gow, A.J., Lee, T.H., & Ellinwood, E.H. (2001). Methamphetamine neurotoxicity: Necrotic and apoptotic mechanisms and relevance to human abuse and treatment. Brain Research Reviews, 36, 122.
Deutsch, R., Ellis, R.J., McCutchan, A., Marcotte, T.D., Letendre, S., Grant, I., & the HNRC Group. (2001). AIDS-associated mild neurocognitive impairment is delayed in the era of highly active antiretroviral therapy (HAART). AIDS, 15, 18981899.
Diehr, M.C., Heaton, R.K., Miller, W., & Grant, I. (1998). The Paced Auditory Serial Addition Task (PASAT): Norms for age, education, and ethnicity. Assessment, 5, 375387.
Dore, G.J., Correll, P.K., Li, Y., Kaldor, J.M., Cooper, D.A., & Brew, B.J. (1999). Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS, 13, 12491253.
Durvasula, R.S., Myers, H.F., Satz, P., Miller, E.N., Morgenstern, H., Richardson, M.A., Evans, G., & Forney, D. (2000). HIV-1, cocaine, and neuropsychological performance in African American men. Journal of the International Neuropsychological Society, 6, 322335.
Durvasula, R.S., Miller, E.N., Myers, H.F., & Wyatt, G.E. (2001). Predictors of neuropsychological performance in HIV positive women. Journal of Clinical and Experimental Neuropsychology, 23, 149163.
Eisch, A., O'Dell, S., & Marshall, J. (1996). Striatal and cortical NMDA receptors are altered by a neurotoxic regimen of methamphetamine. Synapse, 22, 217225.
Ernst, T., Chang, L., Leonido-Yee, M., & Speck, O. (2000). Evidence for long-term neurotoxicity associated with methamphetamine abuse. Neurology, 54, 13441349.
Ferrando, S., Goggin, K., Sewell, M., Evans, S., Fishman, B., & Rabkin, J. (1998). Substance use disorders in gay/bisexual men with HIV and AIDS. American Journal on Addictions, 7, 5160.
First, M.B., Spitzer, R.L., Gibbon, M., & Williams, J.B. (1996). Structured Clinical Interview for DSM–IV Axis I Disorders. New York: Biometrics Research Department.
Gladsjo, J.A., Schuman, C.C., Evans, J.D., Peavy, G.M., Miller, S.W., & Heaton, R.K. (1999). Norms for letter and category fluency: Demographic corrections for age, education, and ethnicity. Assessment, 6, 147178.
Golden, C. (1974). Stroop Color and Word Test. Chicago: Stoelting.
Gouzoulis-Mayfrank, E., Schreckenberger, M., Sabri, O., Arning, C., Thelen, B., Spitzer, M., Kovar, K.A., Hermle, L., Bull, U., & Sass, H. (1999). Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. Neuropsychopharmacology, 20, 565581.
Grant, I., Adams, K.M., Carlin, A.S., Rennick, P., Judd, L.L., & Schooff, K. (1978). The collaborative neuropsychological study of polydrug abusers. Archives of General Psychiatry, 35, 10631074.
Grant, I., Atkinson, J.H., Hesselink, J.R., Kennedy, C.J., Richman, D.D., Spector, S.A., & McCutchan, J.A. (1987). Evidence for early central nervous system involvement in the acquired deficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Studies with neuropsychologic testing and magnetic resonance imaging. Annals of Internal Medicine, 107, 828836.
Grassi, M.P., Clerici, F., Perin, C., Zocchetti, C., Cargnel, A., & Mangoni, A. (1995). HIV infection and drug use: Influence on cognitive function. AIDS, 9, 165170.
Grassi, M.P., Perin, C., Clerici, F., Zocchetti, C., Cargnel, A., & Mangoni, A. (1993). Neuropsychological performance in HIV-1-infected drug abusers. Acta Neurologica Scandinavica, 88, 119122.
Gronwall, D.M.A. (1977). Paced auditory serial-addition task: A measure of recovery from concussion. Perceptual and Motor Skills, 44, 367375.
Halstead, W.C. (1947). Brain and intelligence: A quantitative study of the frontal lobes. Chicago, University of Chicago Press.
Haughey, N.J., Nath, A., Mattson, M.P., Slevin, J.T., & Geiger, J.D. (2001). HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. Journal of Neurochemistry, 78, 457467.
Heaton, R.K., Grant, I., Butters, N., White, D.A., Kirson, D., Atkinson, J.H., McCutchan, J.A., Taylor, M.J., Kelly, M.D., Ellis, R.J., Wolfson, T., Velin, R., Marcotte, T.D., Hesselink, J.R., Jernigan, T.L., Chandler, J., Wallace, M., Abramson, I., & the HNRC Group. (1995). The HNRC 500–Neuropsychology of HIV infection at different disease stages. Journal of the International Neuropsychological Society, 1, 231251.
Heaton, R.K., Grant, I., & Matthews, C.G. (1991). Comprehensive norms for an expanded Halstead-Reitan Battery: Demographic corrections, research findings, and clinical applications. Odessa, FL: Psychological Assessment Resources.
Heaton, R.K., Paulsen, J., McAdams, L.A., Kuck, J., Zisook, S., Braff, D., Harris, M.J., & Jeste, D.V. (1994). Neuropsychological deficits in schizophrenics: Relationship to age, chronicity, and dementia. Archives of General Psychiatry, 51, 469476.
Heaton, R.K., Taylor, M.J., & Manly, J.J. (2002). Demographic effects and use of demographically corrected norms with the WAIS–III and WMS–III. In D. Tulsky, D. Saklofske, R.K. Heaton, G. Chelune, R. Ivnik, R.A. Bornstein, A. Prifitera, & M. Ledbetter (Eds.), Clinical interpretation of the WAIS–III and WMS–III (pp. 183210). San Diego, CA: Academic Press.
Hesselgesser, J., Taub, D., Baskar, P., Greenberg, M., Hoxie, J., Kolson, D.L., & Horuk, R. (1998). Neuronal apoptosis induced by HIV-1 gp120 and the chemokine SDF-1alpha is mediated by the chemokine receptor CXCR4. Current Biology, 8, 595598.
Hollander, M. & Wolfe, D.A. (1973). Nonparametric statistical methods. New York: John Wiley & Sons, Inc.
Itoh, K., Mehraein, P., & Weis, S. (2000). Neuronal damage of the substantia nigra in HIV-1 infected brains. Acta Neuropathologica (Berl), 99, 376384.
Iyo, M., Namba, H., Yanagisawa, M., Hirai, S., Yui, N., & Fukui, S. (1997). Abnormal cerebral perfusion in chronic methamphetamine abusers: A study using 99MTc-HMPAO and SPECT. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 21, 789796.
Jernigan, T.L., Archibald, S., Hesselink, J.R., Atkinson, J.H., Velin, R.A., McCutchan, J.A., Chandler, J., Grant, I., & the HNRC Group. (1993). Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. Archives of Neurology, 50, 250255.
Jonckheere, A.R. (1954). A distribution-free k-sample test against ordered alternatives. Biometricka, 41, 133145.
Kløve, H. (1963). Grooved Pegboard. Lafayette, IN: Lafayette Instruments.
Kongs, S.K., Thompson, L.L., Iverson, G.L., & Heaton, R.K. (2000). Wisconsin Card Sorting Test–64 Card Computerized Version. Odessa, FL: Psychological Assessment Resources.
Ladenheim, B., Krasnova, I.N., Deng, X., Oyler, J.M., Polettini, A., Moran, T.H., Huestis, M.A., & Cadet, J.L. (2000). Methamphetamine-induced neurotoxicity is attenuated in transgenic mice with a null mutation for interleukin-6. Molecular Pharmacology, 58, 12471256.
Langford, D., Trinh, T., Everson, A., Adame, A., Grant, I., McCutchan, A., Ellis, R., Marcotte, T., Masliah, E., & the HNRC group. (2002). Selective damage of calbindin immunoreactive neurons in methamphetamine-user HIVE patients. Manuscript submitted for publication.
Lipton, S.A. & Gendelman, H.E. (1995). Dementia associated with the acquired immuno-deficiency syndrome. New England Journal of Medicine, 332, 934940.
Marshall, J., O'Dell, S., & Weihmuller, F. (1993). Dopamine–glutamate interactions in methamphetamine-induced neurotoxicity. Journal of Neural Transmission-General Section, 91, 241254.
Martin, E.M., Sullivan, T.S., Reed, R.A., Fletcher, T.A., Pitrak, D.L., Weddington, W., & Harrow, M. (2001). Auditory working memory in HIV-1 infection. Journal of the International Neuropsychological Society, 7, 2026.
Maschke, M., Kastrup, O., Esser, S., Ross, B., Hengge, U., & Hufnagel, A. (2000). Incidence and prevalence of neurological disorders associated with HIV since the introduction of highly active antiretroviral therapy (HAART). Journal of Neurology, Neurosurgery, and Psychiatry, 69, 376380.
McCann, U.D., Wong, D.F., Yokol, F., Villemagne, V., Dannals, R.F., & Ricaurte, G.A. (1998). Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: Evidence from positron emission tomography studies with [11C]WIN-35,428. Journal of Neuroscience, 18, 84178422.
McKetin, R. & Mattick, R.P. (1997). Attention and memory in illicit amphetamine users. Drug and Alcohol Dependence, 48, 235242.
McKetin, R. & Mattick, R.P. (1998). Attention and memory in illicit amphetamine users: Comparison with non-drug-using controls. Drug and Alcohol Dependence, 50, 181184.
Nath, A., Maragos, W.F., Avison, M.J., Schmitt, F.A., & Berger, J.R. (2001). Acceleration of HIV dementia with methamphetamine and cocaine. Journal of Neurovirology, 7, 6671.
Ohmori, T., Abekawa, T., & Koyama, T. (1996). The role of glutamate in behavioral and neurotoxic effects of methamphetamine. Neurochemistry International, 29, 301307.
Peavy, G., Jacobs, D., Salmon, D.P., Butters, N., Delis, D.C., Taylor, M., Massman, P., Stout, J.C., Heindel, W.C., Kirson, D., Atkinson, J.H., Chandler, J.L., Grant, I., & the HNRC Group. (1994). Verbal memory performance of patients with human immunodeficiency virus infection: Evidence of subcortical dysfunction. Journal of Clinical and Experimental Neuropsychology, 16, 508523.
Pirie, W. (1983). Jonckheere Tests for Ordered Alternatives. In S. Kotz & N.L. Johnson (Eds.), Encyclopedia of statistical sciences, Vol. 4 (pp. 315318). New York: John Wiley & Sons, Inc.
Psychological Corporation. (1997). Wechsler Adult Intelligence Scale–Third Edition. San Antonio, TX: Author.
Rabkin, J.G. (1996). Prevalence of psychiatric disorders in HIV illness. International Review of Psychiatry, 8, 157166.
Rausch, D.M. & Stover, E.S. (2001). Neuroscience research in AIDS. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25, 231257.
Reitan, R.M. & Davison, L.A. (Eds.). (1974). Clinical Neuropsychology: Current status and applications. Washington, DC: V.H. Winston & Sons.
Reyes, M.G., Faraldi, F., Senseng, C.S., Flowers, C., & Fariello, R. (1991). Nigral degeneration in acquired immune deficiency syndrome (AIDS). Acta Neuropathologica (Berl), 82, 3944.
Robins, L., Cottler, L., Bucholz, K., Compton, W., North, C.S., & Rourke, K.M. (1995). Diagnostic Interview Schedule for DSM–IV. St. Louis, MO: Washington University School of Medicine.
Rothrock, J.F., Rubenstein, R., & Lyden, P.D. (1988). Ischemic stroke associated with methamphetamine inhalation. Neurology, 38, 589592.
Rumbaugh, C.L., Bergeron, R.T., Scanlan, R.L., Teal, J.S., Segall, H.D., Fang, H.C., & McCormick, R. (1971). Cerebral vascular changes secondary to amphetamine abuse in the experimental animal. Radiology, 101, 345351.
Rylander, G. (1969). Clinical and medicocriminological aspects of addiction to central stimulating drugs. In F. Sjoqvist & M. Tottie (Eds.), Abuse of central stimulants (pp. 251274). Stockholm: Almqvist & Wiskell.
Sacktor, N., Lyles, R.H., Skolasky, R., Kleeberger, C., Selnes, O.A., Miller, E.N., Becker, J.T., Cohen, B., McArthur, J.C., & the Multicenter AIDS Cohort Study. (2001). HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology, 56, 257260.
Sekine, Y., Iyo, M., Ouchi, Y., Matsunaga, T., Tsukada, H., Okada, H., Yoshikawa, E., Futatsubashi, M., Takei, N., & Mori, N. (2001). Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. American Journal of Psychiatry, 158, 12061214.
Simon, S.L., Domier, C., Carnell, J., Brethen, P., Rawson, R., & Ling, W. (2000). Cognitive impairment in individuals currently using methamphetamine. American Journal on Addictions, 9, 222231.
Simon, S.L., Domier, C.P., Sim, T., Richardson, K., Rawson, R.A., & Ling, W. (2002). Cognitive performance of current methamphetamine and cocaine abusers. Journal of Addictive Diseases, 21, 6174.
Stephans, S. & Yamamoto, B. (1994). Methamphetamine-induced neurotoxicity: Roles for glutamate and dopamine efflux. Synapse, 17, 203209.
Stout, J.C., Ellis, R.J., Jernigan, T.L., Archibald, S.L., Abramson, I., Wolfson, T., McCutchan, J.A., Wallace, M.R., Atkinson, J.H., Grant, I., & the HNRC Group. (1998). Progressive cerebral volume loss in human immunodeficiency virus infection: A longitudinal volumetric magnetic resonance imaging study. Archives of Neurology, 55, 161168.
Substance Abuse and Mental Health Administration. (2000). Treatment Episode Data Set: 1993–1998. Rockville, MD: Substance Abuse and Mental Health Administration.
Taylor, M.J., Alhassoon, O.M., Schweinsburg, B.C., Videen, J.S., Grant, I., & the HNRC Group. (2000). MR spectroscopy in HIV and stimulant dependence. Journal of the International Neuropsychological Society, 6, 8385.
Terpstra, T.J. (1952). The asymptotic normality and consistency of Kendall's test against trend, when ties are present in one ranking. Indigationes Mathematicae, 14, 327333.
Tracey, I., Hamberg, L.M., Guirnaraes, A.R., Hunter, G., Chang, I., Navia, B.A., & Gonzalez, R.G. (1998). Increased cerebral blood volume in HIV-positive patients detected by functional MRI. Neurology, 50, 18211826.
Trites, R.L., Suh, M., Offord, D., Nieman, G., & Preston, D. (1974). Neuropsychological and psychosocial antecedents and chronic effects of prolonged use of solvents and methamphetamines. Paper presented at the International Psychiatric Research Society, Ottawa, Canada.
Volkow, N.D., Chang, L., Wang, G.J., Fowler, J.S., Franceschi, D., Sedler, M.J., Gatley, S.J., Hitzemann, R., Ding, Y.S., Wong, C., & Logan, J. (2001a). Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers. American Journal of Psychiatry, 158, 383389.
Volkow, N.D., Chang, L., Wang, G.J., Fowler, J.S., Leonido-Yee, M., Franceschi, D., Sedler, M.J., Gatley, S.J., Hitzemann, R., Ding, Y.S., Logan, J., Wong, C., & . Miller, E.N. (2001b). Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. American Journal of Psychiatry, 158, 377382.
von Giesen, H.J., Antke, C., Hefter, H., Wenserski, F., Seitz, R.J., & Arendt, G. (2000). Potential time course of human immunodeficiency virus type-1 associated minor motor deficits. Archives of Neurology, 57, 16011607.
White, D.A., Heaton, R.K., & Monsch, A.U. (1995). Neuropsychological studies of asymptomatic human immunodeficiency virus-type 1-infected individuals. Journal of the International Neuropsychological Society, 1, 304315.
Wilkinson, G.S. (1993). The Wide Range Achievement Test–Third Edition. Wilmington, DE: Wide Range, Inc.
Wilson, J.M., Kalasinsky, K.S., Levey, A.I., Bergeron, C., Reiber, G., Anthony, R.M., Schmunk, G.A., Shannak, K., Haycock, J.W., & Kish, S.J. (1996). Striatal and dopamine nerve terminal markers in human, chronic methamphetamine users. Natural Medicine, 2, 699703.
Woody, G.E., Donnell, D., Seage, G.R., Metzger, D., Marmor, M., Koblin, B.A., Buchbinder, S., Gross, M., Stone, B., & Judson, F.N. (1999). Non-injection substance use correlates with risky sex among men having sex with men. Data from HIVNET. Drug and Alcohol Dependence, 53, 197205.


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