HIV Dementia

HIV dementia is a chronic loss of cognitive abilities as a result of infection of the HIV brain and opportunistic microorganisms.

HIV dementia (AIDS dementia complex) can appear in the late stages of HIV infection. Unlike other types of dementia, it mainly occurs in young people. Dementia can be the result of HIV infection or secondary infection with JC virus, which causes progressive multifocal leukoencephalopathy. Other opportunistic infections (including fungal, bacterial, viral, protozoal) also contribute.

With isolated HIV-associated dementia, pathomorphological changes develop in the subcortical structures as a result of macrophage or microglial cells infiltrating the gray matter of the deep regions of the brain (including basal ganglia, thalamus) and white matter.

The prevalence (prevalence) of HIV dementia in the late stages of HIV infection ranges from 7 to 27%, but 30-40% of patients may have mild cognitive impairment. The frequency of dementia is inversely proportional to the number of CD4 ⁺ cells in the peripheral blood.

AIDS caused by HIV is characterized by CNS damage, which can also be attributed to slow infectious processes in the CNS. The pathogenesis of CNS damage in neuroside is associated with the immediate neurotoxic effect of the virus, as well as the pathological effect of cytotoxic T cells and anti- brain antibodies. Pathomorphologically reveal the atrophy of brain substance with characteristic spongioform changes (spongy of the brain substance) and demyelination in different structures. Especially often such changes are noted in the seminal center, the white matter of the hemispheres and, more rarely, in gray matter and subcortical formations. Along with the pronounced death of neurons, astroglial nodules are observed. For direct brain damage in HIV infection, development of subacute encephalitis with demyelinating sites is characteristic.

Clinically, the so-called HIV-associated cognitive-motor complex, including three diseases :

• HIV-associated dementia:
• HIV-associated myelopathy:
• HIV-associated minimal cognitive-motor disorders.

ICD-10 code

B22.0. The disease caused by HIV, with manifestations of encephalopathy.

Causes of AIDS dementia

It is suggested that AIDS dementia develops as a result of the effects of special neurovirulent HIV strains, toxic effects of gpl20 protein, quinolon acid, stimulation of nitric oxide production and NMDA receptors, oxidative stress, apoptosis, immune reactions with the formation of cytokines and arachidonic acid metabolites, as well as damage and changes in the permeability of the blood-brain barrier. One of the most popular models of neuronal damage is based on the hypothesis that the by-products of inflammatory reactions from the periphery penetrate the blood-brain barrier and exert an excessive stimulating effect on NMDA receptors. This leads to an increase in the intracellular level of calcium, which causes the release of glutamate and hyperstimulation of NMDA receptors of neighboring neurons. In accordance with this hypothesis, antagonists of NMDA receptors and calcium channel blockers can be effective in this disease.

[1], [2]

Symptoms of HIV-dementia

For HIV-dementia (including the AIDS-complex of dementia - HIV-encephalopathy or subacute encephalitis), the psychomotor processes slow down, inattention, memory loss, complaints of forgetfulness, slowness, difficulties in concentrating attention and difficulties in solving problems and reading. Often noted apathy, a decrease in spontaneous activity and social isolation. In some cases, the disease can be expressed in atypical affective disorders, psychoses or seizures. When a somatic examination is detected, tremor, violation of rapid repetitive movements and coordination, ataxia, muscle hypertonia, generalized hyperreflexia, violation of oculomotor functions. With the subsequent progression of dementia, it is possible to attach focal neurological symptoms, motor disorders - extrapyramidal, hyperkinesis, static disorders, coordination of movements and psychomotorics in general. In the period of the expanded picture of dementia, gross affective disorders, frustration of drives and regress of behavior in general are also possible. With the primary localization of the process in the frontal cortex, a variant of dementia with mori-like (durably) behavior is formed.

AIDS dementia is characterized by cognitive, motor and behavioral disorders. The disorder of cognitive functions is represented by the syndrome of subcortical dementia with short-term and long-term memory impairment, slowing down of thinking processes, and attenuation of concentration. Motor symptoms include changes in walking, violation of postural stability, weakness of the limbs, apraxia, changes in handwriting. Of behavioral disorders, emotional lability, a tendency to isolation, apathy are most often encountered. In children, AIDS can cause brain underdevelopment, partial developmental delays, neurological symptoms, and cognitive impairment. This section discusses mainly AIDS dementia in adults.

In view of the absence of biological markers of the disease, the diagnosis of AIDS-dementia is established by elimination. In the cerebrospinal fluid, signs of activation of the immune system, pleocytosis, an increase in the protein level, and the HIV-1 virus are revealed. An auxiliary value in the diagnosis of AIDS dementia is the data of neuroimaging. According to European epidemiological studies, the risk factors for AIDS dementia are a mature age, the abuse of psychoactive substances administered intravenously, homosexuality or bisexualism in men, and a decrease in CD4-lymphocyte count. AIDS dementia develops in one or another stage in 15-20% of AIDS patients, with 7% of people diagnosed with AIDS annually reporting new cases. According to some reports, the survival rate in patients with AIDS dementia is lower than in AIDS patients without dementia. The rate of progression and the clinical manifestations of AIDS dementia are variable. In patients with AIDS dementia, comorbid psychiatric disorders often develop, and these patients are hypersensitive to the side effects of drugs usually prescribed in these conditions.

Diagnosis of HIV dementia

Usually, the diagnosis of HIV dementia is similar to the diagnosis of other types of dementia, except to find out (find) the cause of the disease.

HIV-infected patients with untreated dementia have a poor prognosis (average life expectancy is 6 months), compared with those without dementia. Against the backdrop of therapy, cognitive impairment is stabilizing and there may even be some improvement in health.

If the patient is diagnosed with HIV infection, or if there is an acute change in cognitive function, lumbar puncture, CT or MRI should be performed to detect CNS infection. MRI is more informative than CT, as it allows excluding other causes associated with CNS damage (including toxoplasmosis, progressive multifocal leukoencephalopathy, brain lymphoma). In the late stages of the disease, changes can be detected, which are represented by the diffuse hyperintensity of white matter, atrophy of the brain, expansion of the ventricular system.

[3], [4],

Neuroimaging

Methods of structural and functional neuroimaging can be useful in diagnosing, determining the prognosis and choosing treatment for AIDS dementia. A correlation was found between the severity of AIDS and atrophy of basal ganglia, white matter damage and diffuse atrophy in CT and MRI. Nevertheless, the relationship between neuroimaging and pathomorphological changes is not traced. PET, SPECT, Magnetic Resonance Spectroscopy (MPQ are more sensitive to changes in the basal ganglia and reveal a decrease in cerebral blood flow and metabolic changes in infected patients who do not have clinical manifestations of infection.) In the future, MPC may play an important role in predicting the response to certain medications.

As with other forms of dementia, when suspected of AIDS dementia, it is important to exclude diseases that can worsen the condition, for example, thyroid dysfunction, electrolyte disorders, blood changes, other infections. It is necessary to analyze the medications taken by the patient, since some drugs prescribed for the treatment of AIDS have an adverse effect on cognitive functions. With AIDS, it is often not possible to remove "non-essential" drugs, because the patient for the sake of prolonging life should take constant doses of antiviral drugs and protease inhibitors. People with AIDS often have low levels of vitamin B12. Recognition of this complication is important, since the introduction of a vitamin can reduce the severity of a cognitive defect.

Treatment of AIDS dementia

Treatment of HIV dementia involves the assignment of highly active antiviral drugs that increase the number of CD4 ⁺ cells and improve the cognitive function of patients. Supportive treatment of HIV dementia is similar to that used for other types of dementia.

According to the literature, the antiviral drug zidovudine is effective in AIDS-dementia. In a multicenter, double-blind, placebo-controlled 16-week study, patients with AIDS dementia showed an advantage of zidovudine at a dose of 2000 mg / day before placebo, and the effect of the drug persisted even after further administration of the drug for 16 weeks. Zidovudine is currently considered the drug of choice in AIDS patients (both with and without dementia), because in high doses it can delay the development of AIDS dementia for 6-12 months. However, the use of high doses of zidovudine in some patients is not possible due to the appearance of poorly tolerated side effects.

With AIDS dementia, the combination of zidovudine and didanosine has been shown to be effective, both in sequential and simultaneous administration. In a randomized, but open-label study, there was an improvement in memory and attention in both regimens for 12 weeks. Improvement was more pronounced in patients with initial cognitive impairment. In addition to zidovudine and didanosine, there are currently other reverse transcriptase inhibitors: lamivudine, stavudine, zalcitabine. In recent years, the ability of a combination of zidovudine with protease inhibitors (primarily nevirapine) has been shown to reduce the risk of developing AIDS dementia and improve cognitive function.

Experimental methods of treatment of AIDS dementia

[5], [6], [7], [8]

Ateverdin

A non-nucleoside reverse transcriptase inhibitor was tested in an open trial in 10 patients who were resistant to or were not tolerant to didanosine and zidovudine. The drug was prescribed in a dose of 1800 mg / day in 2 divided doses, the course of treatment was 12 weeks. Of the five patients who completed the study, four showed an improvement in the results of a neuropsychological study or SPECT. The tolerability of the drug was good. Additional tests of the drug are carried out.

[9]

Pentoxifylline

Reduces the activity of tumor necrosis factor alpha (TNF-a) and may be useful in AIDS or AIDS dementia, but no controlled trials of the drug have been conducted.

NMDA receptor antagonists

Memantine is a drug similar in structure to amantadine, and, like it, an NMDA receptor antagonist. It has been shown that memantine has a cytoprotective effect on the culture of cortical neurons infected with the envelope protein of HIV-1 gp 120. Testing of the drug on laboratory animals and humans is necessary. Nitroglycerin is also able to protect neurons from hyperstimulation of NMDA receptors, but no controlled trials of this drug have been conducted.

Peptide T

Peptide T - octapeptide, undergoing tests for AIDS dementia. One patient who took peptide T for 12 weeks had positive changes in PET with fluorodeoxyglucose, which also indicates the important role that functional neuroimaging can play in assessing the effect of drugs in AIDS dementia. Clinical trials of peptide T continue.

Nimodipine

The calcium channel blocker penetrating the blood-brain barrier. It is suggested that nimodipine may attenuate neuronal damage by decreasing the response to stimulation of NMDA receptors with glutamate, but clinical trials of the drug in AIDS-dementia have not been conducted.

Selegiline

MAO type B inhibitor, which, given some studies, due to antioxidant activity, may have a neuroprotective effect in AIDS dementia.

OCR14117

Lipophilic antioxidant, which binds superoxide anionic radicals. In a double-blind, randomized controlled trial, it was noted that, at a dose of 240 mg / day, the drug was tolerated by AIDS dementia patients as well as placebo (The Daba Consortium of HIV Dementia and Related Cognitive Disorders, 1997).

Treatment of behavioral disorders

AIDS dementia is often accompanied by affective disorders (depression, mania or their combination), as well as anxiety, apathy, anergia, demoralization, psychoses, insomnia and other sleep and wakefulness disorders, wandering. An approach to the treatment of these disorders is the use of medication and non-drug measures after a thorough examination and exclusion of concomitant conditions that can serve as their cause. Principles of treatment of noncognitive manifestations of AIDS dementia are the same as in Alzheimer's disease.