AIDS as a cause of dementia in the elderly

It has been recognized that AIDS can present initially as dementia without other neurological or clinical manifestations. In addition, HIV-contaminated blood transfusions in the elderly seem to be underreported. Because of these findings, dementia in the elderly may be misdiagnosed as Alzheimer's disease or other causes of senile dementia. This paper reports on one patient who presented with a diagnosis of Alzheimer's disease and was later found to have AIDS.     

The acquired immunodeficiency syndrome (AIDS) dementia complex

The acquired immunodeficiency syndrome (AIDS) dementia complex is a frequent and devastating complication of infection with human immunodeficiency virus-type 1 (HIV-1). Features of the AIDS dementia complex include decreased memory, the inability to concentrate, apathy, and psychomotor retardation. Typical neuropathologic findings include gliosis, focal necrosis of neurons, perivascular inflammation, formation of microglial nodules, multinucleated giant cells, and demyelination. That HIV-1 is the direct cause of this neurologic syndrome is strongly supported by the available evidence. In addition, several studies have identified the monocyte-macrophage as the predominant cell type in the brain infected with HIV-1. However, the mechanisms by which the infected monocytes-macrophages mediate neurologic dysfunction and destruction have not been elucidated.     

Nitric oxide synthase expression and apoptotic cell death in brains of AIDS and AIDS dementia patients

OBJECTIVES: To determine the occurrence and cellular localization of inducible nitric oxide synthase (iNOS), NOS activity and its association with cell death in brains of AIDS and AIDS dementia complex (ADC) patients. DESIGN AND METHODS: Post-mortem cerebral cortex tissue of eight AIDS patients, eight ADC patients and eight control subjects was processed for iNOS immunocytochemistry, NADPH-diaphorase activity staining as an index of NOS activity, and in situ end-labelling to detect cell death. RESULTS: iNOS-positive cells were present in the white matter of 14 out of 16 AIDS and ADC patients, whereas two out of eight control subjects showed iNOS-positive cells. iNOS immunoreactivity was exclusively localized in activated macrophages and microglial cells that both showed NADPH-diaphorase activity. In addition, NADPH-diaphorase activity, not related to iNOS immunoreactivity, was observed in astrocytes in both white and grey matter of AIDS and ADC patients. All AIDS and ADC patients, and only one control subject showed characteristic features of apoptotic cell death. CONCLUSIONS: Different forms of NOS are present in microglial cells and astrocytes of AIDS and ADC patients but are largely absent in control subjects. Although more NOS-expressing cells occur in ADC than in AIDS patients, apoptotic cell death was found in both patient groups to the same extent. We postulate that NO production in brains of AIDS patients results in cumulative cortical cell loss, which becomes neurologically evident at later stages of disease and is expressed as ADC.     

Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex

This review will discuss emerging evidence for the possibility that AIDS dementia complex (ADC) has changed in the era of highly active antiretroviral therapy (HAART). The consequences of not considering these possibilities at the patient level and at the level of research are considerable. Data will be discussed that are derived from epidemiological studies, neuropsychological and positron emission tomography studies, as well as analyses from the abacavir ADC trial. These will then be assessed to develop the concept that there are now different forms of ADC: an inactive form, a chronic variety and a 'transformed' variant. Whereas the latter relates to the compounding influence of a number of other processes on ADC, such as hepatitis C, particular discussion will focus upon Alzheimer's disease and whether HIV may lead to Alzheimer-like changes. It is certainly recognized that some of the concepts discussed here are highly speculative.     

Neuropsychological characterization of the AIDS dementia complex: a preliminary report

The AIDS dementia complex (ADC) is a frequent complication of advanced HIV infection. In order to better define the neuropsychological character and progression of the ADC, four groups of subjects were studied with a battery of neuropsychological tests: an HIV-seronegative comparison group (n = 20), asymptomatic HIV-seropositive patients (n = 16), newly diagnosed AIDS patients (n = 44) and AIDS patients who were referred for neurological consultation (n = 40). Results showed significant reductions in performance in the two AIDS groups, with impairment being most prominent in tests that assessed motor speed and fine control, concentration, problem solving and visuospatial performance. This pattern of neuropsychological dysfunction is consistent with the characterization of the ADC as a subcortical dementia.     

Reversal of apparent AIDS dementia complex following treatment with vitamin B12

Abstract. The human immunodeficiency virus (HIV)-associated dementia complex is characterized by difficulties in concentration and memory followed by apathy, social withdrawal and motor dysfunction. Decreased serum vitamin B₁₂ levels occur in up to 20% of patients with acquired immune deficiency syndrome (AIDS) and may adversely contribute to the haematologic and neurologic dysfunction which is frequently attributed to the human immunodeficiency virus. We describe a patient with AIDS who presented with an apparent advanced AIDS dementia complex. There was an associated low serum vitamin B₁₂ resulting from malabsorption due to low gastric intrinsic factor secretion. Following treatment with vitamin B₁₂ the symptoms resolved over a 2-month period. We believe that the AIDS dementia complex represented a reversible adverse synergistic interaction between the human immunodeficiency virus and vitamin B₁₂ deficiency.     

Changes to AIDS dementia complex in the era of highly active antiretroviral therapy.

OBJECTIVES: To determine the protective efficacy of highly active antiretroviral therapy (HAART) against AIDS dementia complex (ADC) relative to other initial AIDS-defining illnesses (ADIs), Australian AIDS notification data over recent years were examined. METHODS: All initial ADIs in Australia over the period 1992-1997 were included. Three initial ADI groups were established: ADC; other predominantly central nervous system (CNS) ADIs (toxoplasmosis and cryptococcosis); and non-CNS ADIs. For each ADI grouping, the proportion of total ADls, and median CD4 cell count in the pre-HAART era (1992-1995) were compared with the HAART era (1996 and 1997). RESULTS: Initial ADls peaked in Australia in 1994 (n = 1049), with a gradual decline to 1996 (n = 722), and a marked decline in 1997 (n = 367). ADC constituted 4.4% of initial ADIs over the period 1992-1995, but increased after the introduction of HAART to 6.0% in 1996 and 6.5% in 1997 (P = 0.02). In contrast, the proportion of other CNS ADIs (1992-1995, 8.1%; 1996, 6.0%; 1997, 8.2%; P = 0.41) was stable over the period 1992-1997. The median CD4 cell count at ADC diagnosis increased from 70/mm3 in 1992-1995 to 120/mm3 in 1996 and 170/mm3 in 1997 (P = 0.04). Although the median CD4 cell count also increased significantly over this period for both other CNS ADIs (40-60/mm3; P = 0.02), and non-CNS ADIs (60-70/mm3; P = 0.02), the increase was small. CONCLUSION: A proportional increase in ADC compared with other ADIs and a marked increase in the median CD4 cell count at ADC diagnosis have occurred since the introduction of HAART in Australia. These changes suggest that HAART has a lesser impact on ADC than on other ADIs, with the poor CNS penetration of many antiretroviral agents a possible explanation.     

盐酸多奈哌齐治疗艾滋病痴呆综合征认知功能疗效分析

目的 探讨盐酸多奈哌齐治疗艾滋病痴呆综合征认知功能的临床疗效.方法 将纳入的艾滋病痴呆综合征患者随机分为治疗组和对照组.治疗组给予抗病毒治疗(ART)合并盐酸多奈哌齐片治疗,对照组给予ART治疗.治疗前后进行国际人类免疫缺陷病毒相关性痴呆量表(IHDS)、简易智能精神状况检查表(MMSE)和药物不良反应量表(TESS)...     

Elevated cerebrospinal fluid neurofilament light protein concentrations predict the development of AIDS dementia complex

The light subunit of neurofilament protein (NFL) is a sensitive indicator of central nervous system axonal injury. We retrospectively identified 9 subjects participating in a longitudinal cohort study who developed acquired immunodeficiency syndrome dementia complex (ADC) and who had had a lumbar puncture performed within 2 years before presentation. Elevated cerebrospinal fluid (CSF) NFL concentrations were found in 7 (78%) of the 9 case patients who later developed ADC, compared with 9 (33%) of 27 CD4 cell count-matched HIV-1-infected control subjects. By contrast, no differences were found in CSF HIV-1 RNA or neopterin concentrations between the 2 groups. CSF NFL may prove to be a useful predictive marker for ADC.     

Prevention of AIDS dementia by HAART does not depend on cerebrospinal fluid drug penetrance

The impact of the cerebrospinal fluid (CSF) penetrance properties of different highly active antiretroviral therapy (HAART) regimes on cognitive processing in AIDS dementia is still undetermined. We therefore designed a retrospective cross-sectional and prospective longitudinal analysis of event-related potentials in HIV-infected patients with different combinations of HAART or without antiretroviral treatment. A total of 353 consecutive patients without secondary CNS manifestation of HIV infection were enrolled in the cross-sectional study and 135 consecutive patients without secondary CNS manifestations of HIV infection were enrolled in the longitudinal study. HAART in different combinations (n = 306) or no antiretroviral treatment (n = 47) was given for at least 6 months in the retrospective cross-sectional study. HAART in different combinations (n = 110) or no antiretroviral treatment (n = 25) was given for 1 year in the prospective longitudinal study. We evaluated the latency and amplitude of the P3 component of visually evoked event-related potentials and mean choice reaction time as measures of cognitive processing. Patients receiving HAART had decreased P3 latencies as compared to those patients not receiving HAART but P3 latency and P3 amplitude were not correlated with the amount of CSF penetrance of the different HAART combinations in either statistical analysis. However, mean choice reaction time was significantly correlated with the amount of CSF penetrance. In HIV-infected patients, the CSF penetrance properties of HAART do not have any significant influence on cognitive processing as measured by event-related potentials.     

Methods for detecting early signs of AIDS dementia complex in asymptomatic HIV-1-infected subjects.

OBJECTIVES: To determine the optimal diagnostic procedures for identifying early signs of AIDS dementia complex (ADC) in asymptomatic HIV-1-infected individuals, in order to prevent further cognitive function impairment by early treatment. DESIGN: Study patients had been referred electively and consecutively to hospital; all had been referred for the first time and gave informed consent. Inclusion criteria were (1) lack of history and/or symptoms of psychosis and neurological disorders; (2) lack of active viral, protozoan or fungal pathology; (3) abstinence from heroin and/or cocaine for at least 6 months before baseline evaluation. SETTINGS: Subjects were seen at the L. Spallanzani Hospital for Infectious Diseases, Rome, Italy between March 1989 and March 1991. PARTICIPANTS: Eighty-two asymptomatic HIV-1-infected subjects: 41 drug users, 27 homosexuals and 14 heterosexuals. MAIN OUTCOME MEASURES: All subjects were evaluated using Wechsler-Bellevue I, Benton C form and Bender tests. Thirty-nine subjects underwent single-photon emission computed tomography (SPECT) and 12 magnetic resonance imaging (MRI). The immunological status of each subject was determined. RESULTS: On psychometric testing, 23 out of the 82 (28%) asymptomatic subjects had a mental decay percentage (MD%) > or = 20%. Cerebral perfusion abnormalities were detected in 31 out of 39 (79.48%) subjects who underwent SPECT; MRI abnormalities were observed in seven out of 12 (58%) subjects. Twelve out of 23 subjects with MD% > or = 20, 15 out of 29 subjects with SPECT abnormalities and four out of seven patients with MRI abnormalities had total CD4+ lymphocyte counts > or = 500 x 10(6)/l. CONCLUSIONS: The high incidence of abnormal SPECT and of MD% > or = 20 in asymptomatic HIV-1-infected patients, and the lack of correlation between immunological status and degree of mental decay, SPECT and MRI abnormalities raise many questions about subclinical HIV-1 neurological disease.