Skip to main content Accessibility help
Hostname: page-component-568f69f84b-l2zqg Total loading time: 0.557 Render date: 2021-09-22T03:45:28.041Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "metricsAbstractViews": false, "figures": true, "newCiteModal": false, "newCitedByModal": true, "newEcommerce": true, "newUsageEvents": true }

HIV-1–Associated Cognitive-Motor Disorders: A Research-Based Approach to Diagnosis and Treatment

Published online by Cambridge University Press:  07 November 2014


The diagnosis of human immunodeficiency virus type 1 (HIV-1)–associated cognitive-motor disorder—either minor cognitive-motor disorder (MCMD) or HIV-1-associated dementia (HAD)—is fraught with potential pitfalls for the clinician. Before making such a diagnosis, clinicians should exclude other etiologies by using neuroimaging, lumbar puncture, and serum chemistries to screen for opportunistic and non-opportunistic infections of the brain and meninges. Clinicians should also consider psychoneurotoxicity (caused from the use of psychoactive substances and prescribed medications) and psychopathology, such as mood, anxiety, and other disorders. In addition, a thorough medical history and physical examination, including a complete neurologic and neuropsychiatric mental status examination, are necessary for an accurate diagnosis. There is also a need for standardized neuropsychological and functional status tests, since the diagnostic criteria for these disorders are partly based on these criteria. Treatment targets should include subclinical cognitive-motor impairment and neuroprotection, as well as MCMD and HAD. Currently, zidovudine remains the best proven treatment for these disorders, but other nucleoside reverse transcriptase inhibitors, as well as nonnucleoside reverse transcriptase inhibitors and protease inhibitors, show promise, and selected agents from these classes are being tested in clinical trials. Other areas that should be investigated are the modulation of inflammatory mediators (such as tumor necrosis factor α), neurotransmitter manipulation (especially of dopamine), and nutritional interventions.

Grand Rounds
Copyright © Cambridge University Press 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


1.Gabuzda, D, Olshevsky, V, Bertani, P, et al.Identification of membrane anchorage domains of the HIV-1 gp160 envelope glycoprotein precursor. J Acq Immun Defic Syndr. 1991;4:3440.Google ScholarPubMed
2.Petito, CK, Roberts, B. Evidence of apoptotic cell death in HIV encephalitis. Am J Pathol. 1995;146:11211130.Google ScholarPubMed
3.Fujimura, RK, Goodkin, K, Petito, CK, et al.HIV-1 proviral DNA load across neuroanatomical regions of individuals with evidence for HIV-1 associated dementia. J AIDS Hum Retrovirol. 1997;16:146152.Google Scholar
4.Montagnier, L. Lymphadenopathy-associated virus: from molecular biology to pathogenicity. Ann Int Med. 1985;103:689693.CrossRefGoogle ScholarPubMed
5.Shapshak, P, Fujimura, RK, Srivastava, , et al.Dementia and the Neurovirulence of HIV-1. CNS Spectrums. 2000;5(4):3142.CrossRefGoogle ScholarPubMed
6.Ho, DD, Pomerantz, RJ, Kaplan, JC. Pathogenesis of infection with human immunodeficiency virus. New Engl J Med. 1987;317:278286.Google ScholarPubMed
7.Gallo, RC. Human tumor and immunodeficiency viruses. AIDS Res Hum Retrovir. 1987;3(suppl):187196.CrossRefGoogle ScholarPubMed
8.Centers for Disease Control. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Morb Mort Wkly Rep. 1992;41(No.RR-17):119.Google Scholar
9.Vanhems, P, Dassa, C, Lambert, J, et al.Comprehensive classification of symptoms and signs reported among 218 patients with acute HIV-1 infection. J AIDS. 1999;21:99106.Google ScholarPubMed
10.Perelson, AS, Neumann, AU, Markowitz, M, et al.HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996;271:15821586.CrossRefGoogle ScholarPubMed
11.American Academy of Neurology AIDS Task Force (Working Group). Nomenclature and research definition for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology. 1991;41:778785.CrossRefGoogle Scholar
12.McNair, DM, Kahn, RJ. The cognitive difficulties scale. In: Thomas, Crook, Steven, Ferris, and Raymond, Bartus, eds. Assessment in Geriatric Psychopharmacobgy. New Canaan, CN: Mark Powley Associates; 1983:137143.Google Scholar
13.Wu, AW, Rubin, HR, Mathews, WC, et al.A health status questionnaire using 30 items from the Medical Outcomes Study: preliminary validation in persons with early HIV infection. Med Care. 1991;29:786798.CrossRefGoogle ScholarPubMed
14.Wilkie, FL, Goodkin, K, Zuilen, MH, et al.Cognitive Effects of HIV-1 Infection. CNS Spectrum. 2000;5(5):3351.CrossRefGoogle ScholarPubMed
15.Goodkin, K, Wilkie, FL, Concha, M, et al.Subtle neuropsychological impairment and minor cognitive-motor disorder in HIV-1 Infection: neuroradiological, neurophysiological, neuroimmunological, and virological correlates. Neuroimaging Clin No Amer. 1997;7:561579.Google ScholarPubMed
16.Shapshak, P, Segal, SM, Crandall, KA, et al.Independent evolution of HIV type 1 in different brain regions. AIDS Res Hum Retrovir. 1999;15(9):811820.CrossRefGoogle ScholarPubMed
17.Berger, JR, Kumar, M, Kumar, A, et al.Cerebrospinal fluid dopamine in HIV infection. AIDS. 1994;8:6771.CrossRefGoogle Scholar
18.Sardar, AM, Czudek, C, Reynolds, GP. Dopamine deficits in the brain: the neurochemical basis of parkinsonian symptoms in AIDS. Neuroreport. 1996;7:910912.CrossRefGoogle Scholar
19.Mirsattari, SM, Power, C, Nath, A. Parkinsonism with HIV infection. Movement Disorders. 1998;13:684689.CrossRefGoogle ScholarPubMed
20.Gisslen, M, Larsson, M, Norkrans, G, et al.Tryptophan concentrations increase in cerebrospinal fluid and blood after zidovudine treatment in patients with HIV type 1 infection. AIDS Res Hum Retroviruses. 1994;10:947951.CrossRefGoogle ScholarPubMed
21.Navia, BA, Khan, A, Pumarola-Sune, T, Price, RW. Choline acetyltransferase activity is reduced in the AIDS dementia complex. Ann Neurol. 1986;20:142.Google Scholar
22.Concha, M, Rabinstein, A. Central nervous system opportunistic infections in HIV-1 infection. CNS Spectrums. 2000;5(4):4360.CrossRefGoogle ScholarPubMed
23.Harrington, WJ, Miller, GA, Kemper, RR, et al.HTLV-I associated leukemia/lymphoma in South Florida. J of AIDS. 1991;4:284289.Google ScholarPubMed
24.Chang, L, Miller, BL, McBride, D. et al.Brain lesions in patients with AIDS: H1 MR spectroscopy. Radiology. 1995;197:525531.CrossRefGoogle Scholar
25.Clifford, DB, Yiannoutsos, C, Glicksman, M, et al.HAART improves prognosis in HIV-1-associated progressive multifocal leukoencephalopathy. Neurology. 1999;52:623625.CrossRefGoogle Scholar
26.Berger, JR, Levy, RM, Flomenhoft, D, et al.Predictive factors for prolonged survival in AIDS-associated PML. J Neurovirol. 1998;4(3)(abstract):342.Google Scholar
27.Hall, CD, Dafni, U, Simpson, D, et al.Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. AIDS Clinical Trials Group 243 Team. N Engl J Med. 1998;338:13451351CrossRefGoogle Scholar
28.Khouzam, HR, Donnelly, NJ, Ibrahim, NF. Psychiatric morbidity in HIV patients. Can J Psychiatry. 1998;43:5156.CrossRefGoogle ScholarPubMed
29.Maj, M. Organic mental disorders in HIV-1 infection. AIDS. 1990;4:831840.CrossRefGoogle ScholarPubMed
30.Atkinson, JH, Grant, I, Kennedy, CJ, et al.Prevalence of psychiatric disorders among men infected with human immunodeficiency virus. Archives of General Psychiatry. 1988;45:859864.CrossRefGoogle ScholarPubMed
31.Williams, JB, Rabkin, JG, Remien, RH, et al.Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. II. Standardized clinical assessment of current and lifetime psychopathology. Arch Gen Psychiatry. 1991;48:124130.CrossRefGoogle ScholarPubMed
32.Perry, NM. Alcohol use in HIV patients: what we don't know may hurt us. Int J STD AIDS. 1999;10:561571.Google Scholar
33.Perretta, P, Nisita, C, Zaccagnini, E, et al.Psychopathology in 90 consecutive human immunodeficiency virus-seropositive and acquired immune deficiency syndrome patients with mostly intravenous drug use history. Compr Psychiatry. 1996;37:267272.CrossRefGoogle ScholarPubMed
34.Goodkin, K. Psychiatric disorders in HIV-spectrum illness. Tex Med. 1988;84(9):5561.Google ScholarPubMed
35.Lyketsos, CG, Hoover, DR, Guccione, M, et al.Changes in depressive symptoms as AIDS develops. The Multicenter AIDS Cohort Study. Am J Psychiatry. 1996;153:14301437.Google ScholarPubMed
36.Goodkin, K, Blaney, NT, Tuttle, RS, et al.Bereavement and HIV infection. Intl Rev Psychiatry. 1996;8:201216.CrossRefGoogle Scholar
37.Goodkin, K, Blaney, NT, Feaster, DJ, et al.A randomized controlled trial of a bereavement support group intervention in human immunodeficiency virus type 1-seropositive and seronegative homosexual men. Arch Gen Psychiatry. 1999;55:5259.CrossRefGoogle Scholar
38.Rush, AJ, Weissenburger, J, Vinson, DB, et al.Neuropsychological dysfunctions in unipolar nonpsychotic major depressions. J Affect Disord. 1983;5:281287.CrossRefGoogle ScholarPubMed
39.Channon, S, Green, PS. Executive function in depression: the role of performance strategies in aiding depressed and non-depressed participants. J Neurol Neurosurg Psychiatry. 1999;66:162171.CrossRefGoogle ScholarPubMed
40.Asthana, HS, Mandal, MK, Khurana, H, et al.Visuospatial and affect recognition deficit in depression. J Affect Disord. 1998;48:5762.CrossRefGoogle ScholarPubMed
41.Dolan, RJ, Bench, CJ, Brown, RG, et al.Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow. Psychol Med. 1994;24:849857.CrossRefGoogle ScholarPubMed
42.Nemeroff, CB, Krishnan, KR, Reed, D, et al.Adrenal gland enlargement in major depression. Arch Gen Psychiatry. 1992;49:384387.CrossRefGoogle ScholarPubMed
43.Sheline, YI, Wang, PW, Gado, MH, et al.Hippocampal atrophy in recurrent major depression. Proc Nat Acad Sci USA. 1996;93:39083913.CrossRefGoogle ScholarPubMed
44.Wilkie, FL, Goodkin, K. Cognitive Function in HIV-1 infection. In: Goodkin, K, Visser, APh, eds. Psychoneuroimmunology: Stress, Mental Disorders and Health. Washington, DC: American Psychiatric Press; 2000:231290.Google Scholar
45.Bell, JE, Donaldson, YK, Lowrie, S, et al.Influence of risk group and zidovudine therapy on the development of HIV encephalitis and cognitive impairment in AIDS patients. AIDS. 1996;10:493499.CrossRefGoogle ScholarPubMed
46.Goodkin, K, Shapshak, P, Metsch, L, et al.Cocaine abuse and HIV-1: Epidemiology and neuropathogenesis. Ann Neurol. 1999;45:816821.Google Scholar
47.Fletcher, JM, Page, JB, Francis, DJ, et al.Cognitive correlates of long-term cannabis use in Costa Rican Men. Arch Gen Psychiatry. 1996;53:10511057.CrossRefGoogle ScholarPubMed
48.Sidtis, JJ, Gatsonis, C, Price, RW, et al.Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled clinical trial. Ann Neurol. 1993;33:343349.CrossRefGoogle Scholar
49.Montforte, A, Musicco, M, Galli, M, et al.Italian mutlicentre study of didanosine compassionate use in advanced HIV infection. Eur J Microb Infect Dis. 1997;16:135142.CrossRefGoogle Scholar
50.McIntyre, K, Torres, R, Luck, D, et al.Pilot study of zidovudine (AZT) and zalcitabine (ddC) combination in HIV-associated dementia. Tenth International Conference on AIDS. Book of Abstracts, Yokohama, Japan, 8/8-8-12-94, #PB-0233, v.1, p. 201, 1994.Google Scholar
51.Thomas, SA, Segal, MB. The transport of the anti-HIV drug, 2N,3N-didehydro-3N-deoxythymidine (d4T), across the blood-brain and blood-cerebrospinal fluid barriers. Br J Pharmacol. 1998;125:4954.CrossRefGoogle Scholar
52.Brew, BJ, Brown, SJ, Catalan, J. et al. Safety and efficacy of abacavir (ABC, 1592) in AIDS dementia complex (study CNAB 3001). Abstracts of XIIth Int Conf on AIDS. Geneva, Switzerland: Int AIDS Society, Abstract #561/32192, p. 559, 1998.Google Scholar
53.Brew, BJ, Dunbar, N, Druett, JA, Freund, J, Ward, P. Pilot study of the efficacy of atevirdine in AIDS dementia complex. AIDS. 1996;10:13581360.CrossRefGoogle ScholarPubMed
54.Stahle, L, Martin, C, Svensson, JO, et al.Indinavir in cerebrospinal fluid of HIV-1 infected patients. Lancet. 1997;350:1823.CrossRefGoogle ScholarPubMed
55.Martin, C, Sonnerborg, A, Svensson, JO, et al.Indinavir-based treatment of HIV-1 infected patients: efficacy in the central nervous system. AIDS. 1999;13:12271232.CrossRefGoogle ScholarPubMed
56.Galgani, S, Narciso, P, Balestra, P, et al.Nimodipine + ZDV in patients with ADC. Tenth International Conference on AIDS. Book of Abstracts, Yokohama, Japan, 8/8-8-12-94, #PB-0248, v.1, p. 205, 1994.Google Scholar
57.Navia, BA, Dafni, U, Simpson, D, et al.A phase I/II trial of nimodipine for HIV-related complications. Neurology. 1998;51:221228.CrossRefGoogle Scholar
58.Heseltine, PNR, Goodkin, K, Atkinson, JH, et al.Randomized, double-blind placebo-controlled trial of Peptide T for HIV-associated cognitive impairment. Arch Neurol. 1998;55:4151.CrossRefGoogle ScholarPubMed
59.Rosen, MI, Bridge, TP, O'Malley, SS, et al.Peptide T treatment in HIV-positive intravenous drug users. Am J Addictions. 1992;1(4):332338.CrossRefGoogle Scholar
60.Simpson, DM, Dorfman, D, Olney, RK, et al.Peptide T in the treatment of painful distal neuropathy associated with AIDS: results of a placebo-controlled trial. Neurology. 1996;47:12541259CrossRefGoogle ScholarPubMed
61.Albers, GW, Saenz, RE, Moses, JA. Tolerability of oral dextromethorphan in patients with a history of brain ischemia. Clin Neuropharm. 1992;15(6):509514.CrossRefGoogle ScholarPubMed
62.Polles, A, Griffith, JL. Dextromethorphan-induced mania. Psychosomatics. 1996;37(1):7173.CrossRefGoogle ScholarPubMed
63.Black, RS, Barclay, LL, Nolan, KA, et al.Pentoxifylline and cerebrovascular dementia. J Am Geriatrics Soc. 1992;40:237244.CrossRefGoogle ScholarPubMed
64.Dinarello, CA, Gelfand, JA, Wolff, SM. Anticytokine strategies in the treatment of systemic inflammatory response syndrome. JAMA. 1995;269(14):18291835.CrossRefGoogle Scholar
65.Strassman, G, D'Alessandro, F, Fong, M, et al.Suramin blocks the binding of interleukin-1 to its receptor and neutralizes IL-1 biological activities. Int J Immunopharmacol. 1994;16(11):931939.CrossRefGoogle Scholar
66.Cheson, BD, Levine, AM, Mildvan, D, et al.Suramin therapy in AIDS and related disorders. JAMA. 1987;258:13471351.CrossRefGoogle ScholarPubMed
67.Mapou, RL, Law, WA, Wagner, K, et al.Neuropsychological effects of interferon alfa-n3 treatment in asymptomatic human immunodeficiency virus-1-infected individuals. J Neuropsychiatry Clin Neurosci. 1996;8:7481.Google ScholarPubMed
68.Schiffito, G, Sacktor, N, Marder, K, et al.Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurology. 1999;53:391396.CrossRefGoogle Scholar
69.Fernandez, F, Adams, F, Levy, JK. Cognitive impairment due to AIDS-related complex and its response to psychostimulants. Psychosomatics. 1988;29(1):3846.CrossRefGoogle ScholarPubMed
70.Kieburtz, KD, Epstein, LG, Gelbard, HA, et al.Excitotoxicity and dopaminergic dysfunction in the acquired immunodeficiency syndrome dementia complex. Arch Neurol. 1991;48:12811284.CrossRefGoogle ScholarPubMed
71.Dana Consortium. A randomized, doubleblind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment. Neurology. 1998;50:645651.CrossRefGoogle Scholar
72.Wilkie, FL, Goodkin, K, Eisdorfer, C, et al.Mild cognitive impairment and risk of mortality in HIV-1 infection. J Neuropsychiatry Clin Neurosci. 1998;10:125132.CrossRefGoogle ScholarPubMed
73.Singer, EJ, Wilkins, J, Syndulko, K, et al.Cerebrospinal fluid (CSF) biogenic amines increase and cortisol levels decrease after zidovudine (AZT) therapy in subjects with the AIDS dementia complex (ADC), in Neurological and Neuropsychological Complications of HIV Infection. Program and Abstracts. Monterey, CA, Kenness Canada, Inc, 1990, p 145Google Scholar
74.Baldewicz, TT, Brouwers, P, Goodkin, K, et al.Nutritional Contributions to the CNS Pathophysiology of HIV-1 Infection and Implications for Treatment. CNS Spectrums. 2000;5(4):6172.CrossRefGoogle ScholarPubMed
75.Campa, A, Shor-Posner, G, Indacochea, F, et al.Mortality risk in selenium-deficient HIV-positive children. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20:508513.CrossRefGoogle ScholarPubMed
76.Semba, RD, Graham, NMH, Caiaffa, WT, et al.Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type 1 infection. Arch Intern Med. 1993;153:21492154.CrossRefGoogle ScholarPubMed
77.Graham, NM, Sorenson, D, Odaka, N, et al.Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS. J Acquir Immune Defic Syndr. 1991;4:976980.Google ScholarPubMed
Cited by

Send article to Kindle

To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

HIV-1–Associated Cognitive-Motor Disorders: A Research-Based Approach to Diagnosis and Treatment
Available formats

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

HIV-1–Associated Cognitive-Motor Disorders: A Research-Based Approach to Diagnosis and Treatment
Available formats

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

HIV-1–Associated Cognitive-Motor Disorders: A Research-Based Approach to Diagnosis and Treatment
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *