Cognitive impairment in older HIV-1-seropositive individuals: prevalence and potential mechanisms.

Individuals over 50 years of age comprise 11% of AIDS cases reported to the Centers for Disease Control and Prevention. A higher prevalence of AIDS in older individuals has been reported in certain states including Hawaii (20%) and Florida (13%). Although life expectancy in individuals with AIDS has increased with advances in antiretroviral therapy, it is likely that there are health consequences both of long-term infection and chronic antiretroviral therapy. Given the general increase in neurological disorders with age and the relatively high prevalence of cognitive dysfunction associated with HIV itself, the risk of HIV-associated dementia (HAD) in this aging HIV-seropositive subgroup is of particular concern. Existing data suggest, but have not conclusively demonstrated, increased rates of HAD in older compared with younger seropositive individuals. Preliminary data from the Hawaii Aging with HIV Cohort, a prospective cohort study designed to address this issue definitively, are presented. Factors underlying this hypothesized susceptibility in older individuals are discussed, including a synergy among HAD and other dementias, the role of vascular co-pathology, HIV and age-related immunological changes, and detrimental neuroglial changes that limit the compensatory ability of the aging brain.

[1]  M. Burns,et al.  Case-Control Study , 2020, Definitions.

[2]  K. Marder,et al.  Inter-rater reliability of a clinical staging of HIV-associated cognitive impairment , 2003, Neurology.

[3]  V. Valcour,et al.  HIV-associated dementia and aging , 2002 .

[4]  Ryung S. Kim,et al.  Limited immune restoration after 3 years’ suppression of HIV-1 replication in patients with moderately advanced disease , 2002, AIDS.

[5]  H. Gendelman,et al.  HIV-1-associated dementia: a basic science and clinical perspective. , 2002, The AIDS reader.

[6]  E. Major,et al.  HIV-1 and the brain: connections between HIV-1-associated dementia, neuropathology and neuroimmunology. , 2002, Microbes and infection.

[7]  L. Pulliam,et al.  Changes in monocyte/macrophage neurotoxicity in the era of HAART: implications for HIV-associated dementia , 2002, AIDS.

[8]  A. Kilbourne,et al.  General medical and psychiatric comorbidity among HIV-infected veterans in the post-HAART era. , 2001, Journal of clinical epidemiology.

[9]  C Eisdorfer,et al.  Aging and neuro-AIDS conditions and the changing spectrum of HIV-1-associated morbidity and mortality. , 2001, Journal of clinical epidemiology.

[10]  W. Boscardin,et al.  Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy. , 2001, AIDS.

[11]  Stuart A. Lipton,et al.  Pathways to neuronal injury and apoptosis in HIV-associated dementia , 2001, Nature.

[12]  A. Mocroft,et al.  Influence of age on CD4 cell recovery in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: evidence from the EuroSIDA study. , 2001, The Journal of infectious diseases.

[13]  J. Margolick,et al.  Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study , 2001, AIDS.

[14]  J. Becker,et al.  HIV-associated neurologic disease incidence changes: , 2001, Neurology.

[15]  R. Haubrich,et al.  Cellular restoration in HIV infected persons treated with abacavir and a protease inhibitor: age inversely predicts naive CD4 cell count increase , 2000, AIDS.

[16]  P. Simmonds,et al.  Cerebral Infarction in Adult AIDS Patients: Observations From the Edinburgh HIV Autopsy Cohort , 2000, Stroke.

[17]  K. Feingold,et al.  Infection and inflammation-induced proatherogenic changes of lipoproteins. , 2000, The Journal of infectious diseases.

[18]  C. Franceschi,et al.  Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. , 2000, Blood.

[19]  M. Gill,et al.  Accelerated replicative senescence of the peripheral immune system induced by HIV infection , 2000, AIDS.

[20]  K. Yaffe,et al.  Elevation of CD69+ monocyte/macrophages in patients with Alzheimer's disease. , 2000, Immunobiology.

[21]  D. Clifford,et al.  Human immunodeficiency virus-associated dementia. , 2000, Archives of neurology.

[22]  E. Masliah,et al.  Changes in pathological findings at autopsy in AIDS cases for the last 15 years , 2000, AIDS.

[23]  J. Kaldor,et al.  Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. , 1999, AIDS.

[24]  Rodney W. Johnson,et al.  Increased interleukin-6 expression by microglia from brain of aged mice , 1999, Journal of Neuroimmunology.

[25]  Lars Lannfelt,et al.  HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy , 1998, Nature Medicine.

[26]  Steven Goldman,et al.  Gap-junction-mediated propagation and amplification of cell injury , 1998, Nature Neuroscience.

[27]  I. Akiguchi,et al.  Age‐related changes in the brains of senescence‐accelerated mice (SAM): Association with glial and endothelial reactions , 1998, Microscopy research and technique.

[28]  C. Kane,et al.  Microglia, but not astrocytes, react to sciatic nerve injury in aging rats , 1998, Brain Research.

[29]  M. Esiri,et al.  Prevalence of Alzheimer plaques in AIDS , 1998, Journal of neurology, neurosurgery, and psychiatry.

[30]  J. Cummings,et al.  Alzheimer's disease , 1998, Neurology.

[31]  C. Gall,et al.  Deafferentation-induced increases in hippocampal insulin-like growth factor-1 messenger RNA expression are severely attenuated in middle aged and aged rats. , 1998, Neuroscience.

[32]  R. Mrak,et al.  Enlarged and phagocytic, but not primed, interleukin-1α-immunoreactive microglia increase with age in normal human brain , 1998, Acta Neuropathologica.

[33]  N. Berman,et al.  Microglial Expression of MHC Class II Increases in Normal Aging of Nonhuman Primates , 1998, Neurobiology of Aging.

[34]  T. Morgan,et al.  Age-Related Activation of Microglia and Astrocytes: In Vitro Studies Show Persistent Phenotypes of Aging, Increased Proliferation, and Resistance to Down-Regulation , 1998, Neurobiology of Aging.

[35]  C. Brodie,et al.  Functional IL-4 receptors on mouse astrocytes: IL-4 inhibits astrocyte activation and induces NGF secretion , 1998, Journal of Neuroimmunology.

[36]  D. Griffin,et al.  Perspectives Series : Cytokines and the Brain Cytokines in the Brain during Viral Infection : Clues to HIV-associated Dementia , 1997 .

[37]  E. P. Richardson,et al.  Cerebrovascular Disease , 1997, Current opinion in neurology and neurosurgery.

[38]  G. Shah,et al.  Age-related changes in the blood-brain barrier , 1997, Experimental Gerontology.

[39]  B. Reisberg,et al.  Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) Rating Scale , 1997, International Psychogeriatrics.

[40]  M. McGrath,et al.  Unique monocyte subset in patients with AIDS dementia , 1997, The Lancet.

[41]  V. Yong,et al.  Astrocyte reactivity in neonatal mice: apparent dependence on the presence of reactive microglia/macrophages , 1996, Glia.

[42]  C. Franceschi,et al.  Expansion of cytotoxic CD8+ CD28− T cells in healthy ageing people, including centenarians , 1996, Immunology.

[43]  J. Merrill,et al.  Cytokines in inflammatory brain lesions: helpful and harmful , 1996, Trends in Neurosciences.

[44]  C. Harley,et al.  Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. , 1996, AIDS.

[45]  K. Barron The microglial cell. A historical review , 1995, Journal of the Neurological Sciences.

[46]  D. Stram,et al.  Human immunodeficiency virus type 1 infection: relationship of risk group and age to rate of progression to AIDS. Transfusion Safety Study Group. , 1995, The Journal of infectious diseases.

[47]  D. Fuchs,et al.  Decreased plasma concentrations of HDL cholesterol in HIV-infected individuals are associated with immune activation. , 1994, Journal of acquired immune deficiency syndromes.

[48]  C. Sergeant,et al.  Plasma lipids in HIV‐infected patients: a prospective study in 95 patients , 1994, European journal of clinical investigation.

[49]  J. Becker,et al.  The relationship between age and cognitive impairment in HIV‐1 infection , 1994, Neurology.

[50]  R. Hackler,et al.  Age-related alterations of the blood-brain-barrier (bbb) permeability to protein molecules of different size. , 1993, Zeitschrift fur Gerontologie.

[51]  V. Perry,et al.  Altered antigen expression of microglia in the aged rodent CNS , 1993, Glia.

[52]  Naomi E. Aronson,et al.  Predictors of HIV‐1 Disease Progression in Early‐ and Late‐Stage Patients: The U.S. Army Natural History Cohort , 1992, Journal of acquired immune deficiency syndromes.

[53]  R. Janssen,et al.  Epidemiology of human immunodeficiency virus encephalopathy in the United States , 1992, Neurology.

[54]  K. Feingold,et al.  Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. , 1992, The Journal of clinical endocrinology and metabolism.

[55]  M. Vijaya Lakshmi,et al.  Age-related changes in cerebrospinal fluid protein concentrations , 1991, Journal of the Neurological Sciences.

[56]  Andrew J. Saykin,et al.  Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus‐type 1 (HIV‐1) infection , 1991, Neurology.

[57]  Jonathan O. Harris,et al.  Cerebrovascular disease in AIDS: a case‐control study , 1990, AIDS.

[58]  J. Goedert,et al.  A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. , 1989, The New England journal of medicine.

[59]  B. Truman,et al.  Survival with the acquired immunodeficiency syndrome. Experience with 5833 cases in New York City. , 1987, The New England journal of medicine.

[60]  Toshio Tanaka,et al.  Age-related changes of the function of T cell subsets: Predominant defect of the proliferative response in CD8 positive T cell subset in aged persons , 1987, Mechanisms of Ageing and Development.

[61]  Toshio Tanaka,et al.  Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified tac-positive T cells , 1986, Mechanisms of Ageing and Development.

[62]  E. Sykova Glia and Extracellular Space Diffusion Parameters in the Injured and Aging Brain , 2002 .

[63]  Peter J. S. Smith,et al.  Glial Cell Involvement in Brain Repair and the Effects of Aging , 2002 .

[64]  J. Glowinski,et al.  Intercellular Diffusional Coupling between Glial Cells in Slices from the Striatum , 2002 .

[65]  G. Labourdette,et al.  Gliosis Growth Factors in the Adult and Aging Rat Brain , 2002 .

[66]  K. Williams,et al.  Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. , 2002, Annual review of neuroscience.

[67]  M. Lederman,et al.  Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy. , 2000, The Journal of infectious diseases.

[68]  D. Dziewulska Age-dependent changes in astroglial reactivity in human ischemic stroke. Immunohistochemical study. , 1997, Folia neuropathologica.

[69]  D R Hoover,et al.  Psychomotor slowing in HIV infection: a predictor of dementia, AIDS and death. , 1996, Journal of neurovirology.

[70]  F. Goebel,et al.  Epidemiology of AIDS dementia complex in Europe. AIDS in Europe Study Group. , 1996, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[71]  D. Stram,et al.  Human immunodeficiency virus type 1 infection: relationship of risk group and age to rate of progression to AIDS. Transfusion Safety Study Group. , 1995, The Journal of infectious diseases.

[72]  M. Hatten,et al.  Astroglia in CNS injury , 1991, Glia.

[73]  J Elford,et al.  More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts. , 1991, Journal of acquired immune deficiency syndromes.

[74]  C. Eggers,et al.  The epidemiology of HIV-associated neurological disease in the era of highly active antiretroviral therapy , 2022 .