HIV dementia

HIV dementia is a chronic loss of cognitive ability resulting from infection of the brain with HIV and opportunistic microorganisms.

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

In isolated HIV-associated dementia, pathomorphological changes develop in the subcortical structures as a result of infiltration of the gray matter of the deep parts of the brain (including the basal ganglia, thalamus) and white matter by macrophages or microglial cells.

The prevalence of HIV dementia in the late stages of HIV infection ranges from 7 to 27%, but 30-40% of patients may have moderate cognitive impairment. The incidence 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 neuroAIDS is associated with the direct neurotoxic effect of the virus, as well as with the pathological effect of cytotoxic T-cells and anti-brain antibodies. Pathomorphologically, atrophy of the brain substance with characteristic spongiform changes (spongy brain substance) and demyelination in various structures are detected. Such changes are especially often noted in the semioval center, white matter of the hemispheres and less often in the gray matter and subcortical formations. Along with pronounced neuronal death, astroglial nodules are observed. Direct brain damage in HIV infection is characterized by the development of subacute encephalitis with areas of demyelination.

Clinically, the so-called HIV-associated cognitive-motor complex is noted, which includes three diseases:

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

ICD-10 code

B22.0. HIV disease with manifestations of encephalopathy.

Causes of AIDS Dementia

AIDS dementia is thought to be caused by specific neurovirulent HIV strains, toxic gpl20 protein, quinolone acid, stimulation of nitric oxide and NMDA receptor production, oxidative stress, apoptosis, immune responses producing cytokines and arachidonic acid metabolites, and damage to 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 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 intracellular calcium levels, which causes the release of glutamate and hyperstimulation of NMDA receptors in neighboring neurons. According to this hypothesis, NMDA receptor antagonists and calcium channel blockers may be effective in this disease.

[ 1 ], [ 2 ]

Symptoms of HIV Dementia

HIV-dementia (including AIDS-complex dementia - HIV-encephalopathy or subacute encephalitis) is characterized by slowing of psychomotor processes, inattention, memory loss, complaints of forgetfulness, slowness, difficulty concentrating, and difficulty solving problems and reading. Apathy, decreased spontaneous activity, and social withdrawal are often noted. In some cases, the disease may manifest itself in atypical affective disorders, psychoses, or seizures. Somatic examination reveals tremor, impaired rapid repetitive movements and coordination, ataxia, muscle hypertonia, generalized hyperreflexia, and impaired oculomotor functions. With subsequent progression of dementia, focal neurological symptoms, movement disorders - extrapyramidal, hyperkinesis, static disorders, movement coordination, and psychomotor skills in general may be added. During the period of the developed picture of dementia, severe affective disorders, disorders of drives and regression of behavior in general are also possible. With the predominant localization of the process in the frontal cortex, a variant of dementia with moria-like (foolish) behavior is formed.

AIDS dementia is characterized by cognitive, motor, and behavioral disorders. Cognitive impairment is represented by subcortical dementia syndrome with impairment of short-term and long-term memory, slowing of thought processes, and weakening of concentration. Motor symptoms include changes in gait, impaired postural stability, weakness of the limbs, apraxia, and changes in handwriting. The most common behavioral disorders are emotional lability, a tendency toward isolation, and apathy. In children, AIDS can cause underdevelopment of the brain, partial developmental delays, neurological symptoms, and cognitive impairment. This section mainly discusses AIDS dementia in adults.

Due to the lack of biological markers of the disease, the diagnosis of AIDS dementia is made by exclusion. Signs of immune system activation, pleocytosis, increased protein levels, and the HIV-1 virus are detected in the cerebrospinal fluid. Neuroimaging data are of auxiliary importance in the diagnosis of AIDS dementia. According to European epidemiological studies, risk factors for AIDS dementia include advanced age, intravenous substance abuse, homosexuality or bisexuality in men, and decreased CD4 lymphocyte levels. AIDS dementia develops at one stage or another in 15-20% of AIDS patients, with new cases being registered annually in 7% of people diagnosed with AIDS. According to some data, the survival rate of patients with AIDS dementia is lower than that of AIDS patients without dementia. The rate of progression and clinical manifestations of AIDS dementia are variable. Patients with AIDS dementia often develop comorbid psychiatric disorders and are more sensitive to the side effects of medications commonly prescribed for these conditions.

Diagnosis of HIV-Dementia

Typically, the diagnosis of HIV dementia is similar to the diagnosis of other types of dementia, with the exception of finding out (searching for) the cause of the disease.

HIV-infected patients with untreated dementia have a poor prognosis (average survival is 6 months) compared to those without dementia. With therapy, cognitive impairment stabilizes and some improvement in health may even be noted.

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

[ 3 ], [ 4 ]

Neuroimaging

Structural and functional neuroimaging techniques may be useful in diagnosing, prognosing, and guiding treatment in AIDS-related dementia. Correspondence has been found between AIDS severity and basal ganglia atrophy, white matter lesions, and diffuse atrophy on CT and MRI. However, there is no relationship between neuroimaging and pathological changes. PET, SPECT, and magnetic resonance spectroscopy (MPQ) are more sensitive to changes in the basal ganglia and reveal decreased cerebral blood flow and metabolic changes in infected patients who do not have clinical manifestations of infection. MRS may play an important role in predicting response to certain drugs in the future.

As with other forms of dementia, when AIDS dementia is suspected, it is important to rule out conditions that may worsen the condition, such as thyroid dysfunction, electrolyte imbalances, blood changes, and other infections. The patient's medications should be reviewed, since some drugs prescribed to treat AIDS have an adverse effect on cognitive function. In AIDS, it is often not possible to remove "nonessential" drugs, since the patient must take constant doses of antiviral drugs and protease inhibitors to prolong life. Low levels of vitamin B12 are often found in AIDS patients. Recognizing this complication is important, since administration of the vitamin can reduce the severity of the cognitive deficit.

Treatment of AIDS dementia

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

According to the literature, the antiviral drug zidovudine is effective in AIDS dementia. A multicenter, double-blind, placebo-controlled, 16-week study in patients with AIDS dementia showed the advantage of zidovudine at a dose of 2000 mg/day over placebo, and the effect of the drug was maintained with further use of the drug for 16 weeks. Zidovudine is currently considered the drug of choice in AIDS patients (with or without dementia), since in high doses it can delay the development of AIDS dementia by 6-12 months. However, the use of high doses of zidovudine in some patients is impossible due to the occurrence of poorly tolerated side effects.

In AIDS dementia, the effectiveness of a combination of zidovudine and didanosine has been proven, both with sequential and simultaneous administration. A randomized but open study noted an improvement in memory and attention with both drug regimens for 12 weeks. The improvement was more pronounced in patients with baseline 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) to reduce the risk of developing AIDS dementia and improve cognitive functions has been demonstrated.

Experimental Treatments for AIDS Dementia

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

Ateverdin

A non-nucleoside reverse transcriptase inhibitor, tested in an open-label study in 10 patients who were resistant to or poorly tolerated didanosine and zidovudine. The drug was administered at a dose of 1800 mg/day in 2 divided doses for 12 weeks. Of the five patients who completed the study, four showed improvement in neuropsychological testing or SPECT. The drug was well tolerated. Additional trials of the drug are underway.

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Pentoxifylline

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

NMDA receptor antagonists

Memantine is a drug similar in structure to amantadine and, like it, is an NMDA receptor antagonist. Memantine has been shown to have a cytoprotective effect on a culture of cortical neurons infected with the HIV-1 gp 120 envelope protein. Testing of the drug on laboratory animals and humans is necessary. Nitroglycerin is also capable of protecting neurons from NMDA receptor hyperstimulation, but controlled trials of the drug for this effect have not been conducted.

Peptide T

Peptide T is an octapeptide being tested in AIDS-related dementia. One patient treated with Peptide T for 12 weeks showed positive changes on fluorodeoxyglucose PET, which also points to the important role that functional neuroimaging may play in assessing the effects of drugs in AIDS-related dementia. Clinical trials of Peptide T are ongoing.

Nimodipine

A calcium channel blocker that penetrates the blood-brain barrier. Nimodipine is thought to reduce neuronal damage by reducing the response to glutamate stimulation of NMDA receptors, but clinical trials of the drug in AIDS dementia have not been conducted.

Selegiline

An MAO-B inhibitor which, according to some studies, may have a neuroprotective effect in AIDS-related dementia due to its antioxidant activity.

ORS14117

A lipophilic antioxidant that binds superoxide anion radicals. A double-blind, randomized, controlled study found that at a dose of 240 mg/day, the drug was tolerated by patients with AIDS dementia 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 a combination of both), as well as anxiety, apathy, anergy, demoralization, psychosis, insomnia and other sleep and wakefulness disorders, wandering. The approach to treating these disorders involves the use of drug and non-drug measures after a thorough examination and exclusion of concomitant conditions that can cause them. The principles of treating non-cognitive manifestations of AIDS dementia are the same as for Alzheimer's disease.