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Chester Myers' Nutrition Series HIV-Related Dementia and Nutrition - Is Dementia Curable? Draft copy of publication in Canadian AIDS News. Since writing this article the literature continues to abound in reports of dementia and speculation about its possible origins. Nutrition, the Cinderella of disciplines, continues to be routinely ignored. Definition of dementia taken from the AIDS/HIV Experimental Treatment Directory of the American Foundation for AIDS Research (AmFAR) as reprinted in Body Positive, 1991. HIV and Neurological Symptoms - in the absence of Nutritional Considerations In HIV disease, a number of neurological problems have been associated variously with opportunistic infections, certain treatment drugs, nutritional deficiencies, cytokines produced by the immune system in response to infection, the HIV virus, and psychosocial issues. According to one classification neurological symptoms include dementia (HIVD, also called AIDS dementia complex, ADC), vacuolar myelopathy (VM) and painful sensory neuropathy (PSN). Symptoms can include headache, fever, stiff neck, altered consciousness, seizures, stroke, impairment of speech and/or sight, loss of motor control, change in dream patterns, anxiety, depression, etc. Physical defects in the brain have indicated cysts, abcesses, lesions, hemorrhage, atrophy and other results. Dementia results when there is a chronic impairment of mental capacity. One report estimates that "HIV dementia has an annual incidence of 7% after AIDS development and eventually affects 20% of all HIV-infected persons". In another study, "the estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18", and a third study notes "dementia has been observed in approximately one-fourth of terminally ill patients". It seems that there is general concensus on the progressive nature of neurologic impairment with duration of HIV infection. Opportunistic infections associated with neurological problems have included toxoplasmosis, other parasites, the JC papovavirus which results in progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) encephalitis, cryptococcal meningitis, neurosyphilis, and malignancy. In a number of reports, dementia has been attributed to HIV, and viral burden has been noted to be sometimes substantial in the central nervous system (CNS). Distinct parts of the HIV virus have been associated with dementia. One study of non-HIV infected people notes higher incidences of attempted suicide among male psychiatric patients with low cholesterol levels. Low cholesterol has often been associated with HIV disease. It would be interesting to see if suicide attempts by HIV-infected persons has any correlation with cholesterol. Clinical depression has also been noted to correlate with more rapid decline of T-helper cells; however, that area known as psychoneuroimmunology remains poorly described. Reports of neurological dysfunction are largely speculative with respect to origins, and established associations do not indicate clean-cut cause and effect relationships. The term AIDS-dementia complex has often been used to describe those cases of HIV-related brain disorders that are not traceable to opportunistic infection. In the following, I attempt to explore but a few of the neurologically-related issues related to, or probably related to, nutrition in HIV disease. Nutrition and Neurological Function HIV is paralleled only by certain stages of starvation in its association with multiple nutrient deficiencies. Other diseases of pathological origin are not associated with such malnutrition. Micronutrient deficiencies may result in a number of neurologically-related symptoms: mental confusion (B1, B3, folic acid), anorexia (B1, biotin), irritability (pantothenic acid, magnesium), numbness and tingling of hands and feet (pantothenic acid), depression (biotin, folic acid), degeneration of peripheral nerves (B12), general mental derangement (magnesium). Significantly, these micronutrients are water soluble. It has been noted that in extreme cases of deficiency of some water soluble vitamins that development of symptoms may occur within days or weeks. A recent report from Germany notes that B12 deficiency alone can "lead to impaired bone marrow function, loss of appetite, loss of weight, burning of the tongue, and neurological disorders". (In a sense, it would seem that both loss of appetite and burning of the tongue could also be considered as neurologically-related manifestations.) Deficiency of vitamin E, a fat soluble vitamin, has also been associated with neurological problems. However, overt symptoms may be obvious only after years of deficiency. Nutritionally related issues While several neurological problems in HIV disease have been attributed to nutritional deficiencies, vitamin B12 has received the most attention. In one study of 64 HIV patients, an association was found between dementia, peripheral neuropathy, myopathy, myelopathy and back pain with abnormal B12 metabolism. In studies at the University of Miami it was shown that B12 deficiency is associated with neurologic dysfunction, and that treatment with intramuscular B12 injections give improvement in cognitive function when serum levels were normalized. However, generally, B12 absorption, metabolism and testing for it all seem to be problematic in HIV disease. Even the homocysteine/methylmalonic test, often assumed to give better analytical results for B12 status than the common radioimmune dilution assay, has been discredited as a reliable test in HIV disease. Apparently the inapplicability of the homocysteine test relates to the decreased ability to maintain thiols as a result of the oxidant stress concomitant with HIV infection. A recent French report noted "no clinical or laboratory test abnormalities are reliable for detecting B12" deficiency. At last year's PAAC-affiliated Nutrition and AIDS conference in Philadelphia, several doctors advised that B12 should "just be given", and that it should be given by a non-stomach route such as by intramuscular injection, sublingually, or by "snorting" (of a nasal gel form). Community-based groups have often argued for such B12 administration, and the recommendations in Philadelphia were welcome words for several PHAs who attended. It needs to be noted however, that serum folate levels should be routinely monitored in order that a B12/folate imbalance not result, especially in those who may still store B12 normally, thus attaining unusually high B12 levels in the body. Rick Jones, director of the NuCare Nutrition Support program of New Orleans, notes he has seen lessening of dementia within 48 hours using intramuscular injections of B12. Dr. Gary Bucher, medical director with the program, cautions that not all cases respond to B12 therapy. The regimen used in this program is 2000 micrograms per day for 1 week, and reducing the frequency to a maintenance level of one injection per week in the third week. Vitamin B6 has also been noted to be a likely cause in certain neurological problems. Again, the Miami group has demonstrated an association between low serum B6 levels and "deterioration of performance of tasks related to optimal peripheral psychomotor function. This decrease in reaction time was in contrast to the improvement observed when vitamin B6 status remained adequate." In another study low magnesium was commonly associated with convulsive seizure. At the Philadelphia meeting, magnesium deficiencies were noted to be common with HIV infection. A 1992 report from Germany noted that lack of concentration and memory was restricted mainly to HIV patients who had experienced weight loss. It is likely that specific deficiencies were responsible, although in HIV disease the common occurences of multiple and progressive deficiencies will likely make it difficult to comprehensively find out all specifics. Choline is a conditionally essential nutrient whose synthesis in the body requires the amino acid methionine and vitamn B12, both of which tend to be deficient with HIV disease. It is part of an important neurotransmitter, and required for certain brain function. It is believed to be especially important for learning and memory. When administered to normal young subjects, choline has been observed to result in improvement of memory. In another double-blind, placebo-controlled study, feeding of choline helped ameliorate "tardive dyskinesia, a condition characterized by uncontrollable movements of the face and upper body". Considering its function in the human body and its metabolic requirements in endogenous synthesis, it would seem highly likely that choline deficiency will surface as yet another source of HIV-related neurological problems. The New Orleans NuCare program uses choline, although in some cases night sweats have been noted as side effects. Considering the high prevalence of multiple nutritional deficiencies with HIV disease, and that at least some of these are known to result in neurological problems, one wonders how much noise there has been in the data of those correlations which indicate other factors than nutrition as potential causes. Even more disturbing is the possibility that many neurological problems written off as a dementia complex might be curable with proper nutrition. Several doctors associated with the Physicians Association for AIDS Care noted in the Philadelphia 1994 meeting that they felt that better use of nutrition holds potential for eradication of HIV-related encephalitis. One researcher while noting that "we are failing" in our ability to provide nutritional support, stated that "encephalitis may go away with good nutrition". Use of B vitamin supplements received specific favourable comments in other sessions. Yet another researcher noted that vitamin B12 supplementation has reversed dementia in some cases. Hauntingly, the eminent New York gastroenterologist Dr. Kotler noted that it is essential to "feed them" or "all is lost"! The material in this publication is for information purposes only. It does not endorse any particular treatment program nor strategy; neither is it intended as medical advice nor as a replacement for medical advice. ©This document is copyrighted by Chester Myers. All materials may be reprinted and/or distributed without prior permission. However, reprints may not be edited. References: HIV & Dementia Baker RA, "Treatment Updates from the Harvard-Amsterdam AIDS Conference", BETA, August 1992.
Baum MK, Cure N, Shor-Posner G, "The B-Complex Vitamins, Immune Regulation, Cognitive Function, and HIV-1 Infection", Chapter 7 in Nutrition and AIDS, ed. RR Watson, CRC Press, Boca Raton, 1994. Beach RS, Morgan R, Wilkie F, Mantero-Atienza E, Blaney N, Shor-Posner G, Lu Y, Eisdorfer C, Baum MK, "Plasma Vitamin B12 Level as a Potential Cofactor in Studies of Human Immunodeficiency Virus Type 1 - Related Cognitive Changes", Archives of Neurology 49(1992)501-506. Berger JR, Scott G, Albrecht J, Belman AL, Tornatore C, Major EO, "Progressive multifocal leukoencephalopathy in HIV-1-infected children" AIDS 6(1992)837-839. Brew BJ, "Optimal Treatment of HIV-1-induced CNS Neurological Disorders", CNS Drugs 2(1994)292-300. Burkes RL, Cohen H, Krailo M, Sinow RM, Carmel R, "Low serum cobalamin levels occur frequently in the acquired immune deficiency syndrome and related disorders", European Journal of Haematology 38(1987)141-147. Campione F, Lazzari C, Costigliola P, Ricchi E, Chiodo F, "Sleep Disturbances and Dream Contents during Brain Atrophy in AIDS", VIII International Conference on AIDS, Amsterdam, 1992, abstr. PuB 7087. Carmel R, Karnaze DS, Weiner JM, "Neurologic Abnormalities in Cobalamin Deficiency are Associated with Higher Cobalamin 'Analogue' Values than are Hematologic Abnormalities", Journal Laboratory and Clinical Medicine. 111(1988)57-62 Cohen DB, Glasgow BJ, "Bilateral Optic Nerve Cryptococcosis in Sudden Blindness in Patients with Acquired Immune Deficiency Syndrome", Ophthalmology 100(1993)1689-1694 Cohen KL, Donaldson RM, "Unreliability of Radiodilution Assays as Screening Tests for Cobalamin (Vitamin B-12) Deficiency", Journal of the American Medical Association 244(1980)1942-1945. Coodley GO, "Vitamins in HIV Infection", Chapter 7 in Nutrition and AIDS, ed. RR Watson, CRC Press, Boca Raton, 1994. Coutinho M, Thomas W, "General Psychical Efficiency of HIV-infected People Dependent on their State of Nutrition", VIII International Conference on AIDS, Amsterdam, 1992, abstr. PuB 7126. Dismukes WE, "Management of Cryptococcosis", Clinical Infectious Diseases 17S(1993)S507-S512. Force G, Marguet F, Manicacci M, "Prevalence of Vitamin B12 Deficiency with or without Clinical and Laboratory Test Abnormalities in Patients with Advanced AIDS", abstr. P 024, International Conference on Nutrition and HIV Infection, Cannes, 1995. Gelbard HA, Dzenko KA, Diloreto D, Delcerro C, Delcerro M, Epstein LG, "Neurotoxic effects of tumor necrosis factor alpha in primary human neuronal cultures mediated by activation of the glutamate AMPA receptor subtype: Implications for AIDS neuropathogenesis", Developmental Neuroscience 15(1993)417-422. Hall CA, "Function of Vitamin B12 in the Central Nervous System as Revealed by Congenital Defects", American Journal of Hematology 34(1990)121-127. Hall CA, Chu RC, "Serum homocysteine in routine evaluation of potential B12 and folate deficiency", European Journal of Haematology 45(1990)143-149. Harriman GR, Smith PD, Horne MK, Fox CH, Koenig S, Lack EE, Lane HC, Fauci AS, "Vitamin B12 Malabsorption in Patients with Acquired Immunodeficiency Syndrome", Archives of Internal Medicine 149(1989)2039-2041. Harris PJ, Candeloro P, "HIV-Infected Patients with Vitamin B-12 Deficiency and Autoantibodies to Intrinsic Factor", AIDS Patient Care June, 1991, 125-128. Hofman P, Michiels JF, Saintpaul MC, Galibert A, Marty P, Durant J, Fuzibet JG, Mouroux J, Lefichoux Y, Loubiere R, "Toxoplasmosis in AIDS Patients - A Report of 78 Cases", Annales de Pathologie 13(1993)233-240. Holch A, Opravil M, Moradpour D, Siegenthaler W, Schneider J, Luthy R, "Disseminated Toxoplasmosis in AIDS", Deutsche Medizinische Wochenschrift 118(1993)814-819. Hunt SM, Groff JL, Advanced Nutrition and Human Metabolism, West Publishing Company, New York, 1990. Jautzke G, Sell M, Thalmann U, Janitschke K, Gottschalk J, Schurmann D, Ruf B, "Extracerebral Toxoplasmosis in AIDS - Histological and Immunohistological Findings Based on 80 Autopsy Cases", Pathology Research and Practice 189(1993)428-436. Kieburtz CD, Giang DW, Schiffer RB, Vakil N "Abnormal Vitamin B12 Metabolism in Human Immunodeficiency Virus Infection: Association with Neurologic Dysfunction", Archives of Neurology 48(1991)312-314. Kolhouse JF, Kondo H, Allen NC, Podell E, Allen RH, "Cobalamin Analogues are Present in Human Plasma and can Mask Cobalamin Deficiency because Current Radioisotope Dilution Assays are not Specific for True Cobalamin", New England Journal of Medicine 299(1978)785-792. Kuiken CL, Goudsmit J, Weiller GF, Armstrong JS, Hartman S, Portegies P, Dekker J, Cornelissen M, "Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex", Journal of General Virology 76(1995)175-180. Levitz SM, Tabuni A, Kornfeld H, Reardon CC, Golenbock DT, "Production of Tumor Necrosis Factor Alpha in Human Leukocytes Stimulated by Cryptococcus Neoformans", Infection and Immunity 62(1994)1975-1981. Lindenbaum J, Healton EB, Savage DG, Brust JCM, Garrett TJ, Podell ER, Marcell PD, Stabler SP, Allen RH, "Neuropsychiatric Disorders Caused by Cobalamin Deficiency in the Absence of Anemia or Macrocytosis", New England Journal of Medicine 318(1988)1720-1728. Lindenbaum J, Savage DG, Stabler SP, Allen RH, "Diagnosis of Cobalamin Deficiency: II. Relative Sensitivities of Serum Cobalamin, Methylmalonic Acid, and Total Homocysteine Concentrations", American Journal of Hematology 34(1990)99-107. Lobato MN, Caldwell MB, Ng P, Oxtoby MJ, "Encephalopathy in children with perinatally acquired human immunodeficiency virus infection", Journal of Pediatrics 126(1995)710-715. Mansoor MA, Ueland PM, Svardal AM, "Redox status and protein binding of plasma homocysteine and other aminothiols in patients with hyperhomocysteinemia due to cobalamin deficiency", American Journal of Clinical Nutrition 59(1994)631-635. Marder K, Liu X, Stern Y, Dooneief G, Bell K, Schofield P, Sacktor N, Todak G, Friedman R, Ehrhardt A, Stein Z, Gorman J, Mayeux R, "Neurologic signs and symptoms in a Cohort of homosexual men followed for 4.5 years", Neurology 45(1995)261-267. Marelle L, Raphael M, Henin D, Vazeux R, Schuller E, Piette JC, Poisson M, Gentilini M, Hauw JJ, "AIDS-Related Brain Lymphomas - Clinical Study and Clinico-Pathological Correlations", Revue Neurologique 150(1994)123-132. Mollin DL, Anderson BB, Burman JF, "The Serum Vitamin B12 Level: Its Assay and Significance", Clinics in Haematology 5(1976)521-546. Morgello S, Soifer FM, Lin CS, Wolfe DE, "Central Nervous System Strongyloides-Stercoralis in Acquired Immunodeficiency Syndrome - A Report of 2 Cases and Review of the Literature", Acta Neuropathologica 86(1993)285-288. Powderly WG, "Cryptococcal Meningitis and AIDS", Clinical Infectious Diseases 17(1993)837-842; Squires, K., "Cryptococcosis", PAACNOTES 3(19xx)79-81 & 132. Power C, Johnson RT, "HIV-1 associated dementia: Clinical features and pathogenesis", Canadian Journal of Neurological Sciences 22(1995)92-100. Power C, Mcarthur JC, Johnson RT, Griffin DE, Glass JD, Perryman S, Chesebro B, "Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences", Journal of Virology 68(1994)4643-4649. Power C, Selnes OA, Grim JA, Mcarthur JC, "HIV Dementia Scale: A Rapid Screening Test", Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 8(1995)273-278. Pulliam L, Clarke JA, Mcguire D, Mcgrath MS, "Investigations of HIV-infected macrophage neurotoxin production from patients with AIDS dementia", Advances in Neuroimmunology 4(1994)195-198. Ragnaud JM, Morlat P, Dupon M, Lacoste D, Pellegrin JL, Chene G, "Cerebral Toxoplasmosis in AIDS - 73 Cases", Presse Medicale 22(1993)903-908. Recommended Dietary Allowances, 10th edition, National Academy Press, 1989. Redfield RR, Burke DS, "HIV Infection: The Clinical Picture", The Science of AIDS - Readings from Scientific American Magazine, W. H. Freeman and Company, New York, 1988/1989. Reynolds EH, "Neurological Aspects of Folate and Vitamin B12 Metabolism", Clinics in Haematology 5(1976)661-696. Reynolds EH, Bottiglieri T, Laundy M, Stern J, Payan J, Linnell J, Faludy J, "Subacute Combined Degeneration with High Serum Vitamin-B12 Level and Abnormal Vitamin-B12 Binding Protein - New Cause of an Old Syndrome", Archives of Neurology 50(1993)739-742. Robertson KR, Stern RA, Hall CD, Perkins DO, Wilkins JW, Gortner DT, Donovan MK, Messenheimer JA, Whaley R, Evans DL, "Vitamin-B(12) Deficiency and Nervous System Disease in HIV Infection", Archives of Neurology 50(1993)807-811. Savage, DG, Lindenbaum J, Stabler SP, Allen RH, "Sensitivity of Serum Methylmalonic Acid and Total Homocysteine Determinations for Diagnosing Cobalamin and Folate Deficiencies", The American Journal of Medicine 96(1994)239-246. Scholl U, Knechten H, "Vitamine B12 in the Course of HIV-Infection in Man", abstr. P 087, International Conference on Nutrition and HIV Infection, Cannes, 1995. Schroeder MM, Handelsman L, Torres L, Dorfman D, Rinaldi P, Jacobson J, Wiener J, Ritter W, "Early and Late Cognitive Event-Related Potentials Mark Stages of HIV-1 Infection in the Drug-User Risk Group", Biological Psychiatry 35(1994)54-69. Schwartz RB, Komaroff AL, Garada BM, Gleit M, Doolittle TH, Bates DW, Vasile RG, Holman BL, "SPECT Imaging of the Brain - Comparison of Findings in Patients with Chronic Fatigue Syndrome, AIDS Dementia Complex, and Major Unipolar Depression", American Journal of Roentgenology 162(1994)943-951. Selnes OA, Galai N, Bacellar H, Miller EN, Becker JT, Wesch J, Vangorp W, Mcarthur JC, "Cognitive performance after progression to AIDS: A longitudinal study from the Multicenter AIDS Cohort Study", Neurology 45(1995)267-275. Simpson DM, Tagliati M, "Neurologic Manifestations of HIV Infection", Annals of Internal Medicine 121(1994)769-785. Trotot PM, Sansonetti PJ, Gray F, Bigot JM, Sandoztronca C, "Early Central Nervous System Involvement by the HIV - Detection with Magnetic Resonance Imaging (5 Years Follow-up)", Comptes Rendus de L'Academie des Sciences Series III - Sciences de La Vie - Life Sciences 316(1993)1270-1273. Vanpaesschen W, Bodian C, Maker H, "Metabolic abnormalities and new-onset seizures in human immunodeficiency virus-seropositive patients", Epilepsia 36(1995)146-150. Vongiesen HJ, Arendt G, Neurenjacob E, Prestien K, Jablonowski H, Freund HJ, "A Pathologically Distinct New Form of HIV Associated Encephalopathy", Journal of the Neurological Sciences 121(1994)215-221. Wang F, So Y, Vittinghoff E, Malani H, Reingold A, Lewis E, Giordano J, Janssen R, "Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis", Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 8(1995)75-82. Wesselingh SL, Glass J, Mcarthur JC, Griffin JW, Griffin DE., "Cytokine Dysregulation in HIV-associated Neurological Disease", Advances in Neuroimmunology 4(1994)199-206. Wesselingh SL, Griffin DE, "Local cytokine responses during acute and chronic viral infections of the central nervous system", Seminars in Virology 5(1994)457-463. Wiley CA, Achim C, "Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome", Annals of Neurology 36(1994)673-676. Yeung MC, Pulliam L, Lau AS, "The HIV envelope protein gp120 is toxic to human brain-cell cultures through the induction of interleukin-6 and tumor necrosis factor-alpha", AIDS 9(1995)137-143. "PML: more neurological bad news for AIDS patients", editorial, Lancet 340(1992)943-944. |
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December 1995 | |
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Decisions about particular medical treatments should always be made in consultation with a qualified medical practitioner who is knowledgeable about HIV-related illness and the treatments in question. MORE | |