Dementia with Levy bodies

Dementia with Levy bodies is a chronic loss of cognitive functions, characterized by the appearance of intracellular inclusions called Lewy bodies in the cytoplasm of cortical neurons. The disease is characterized by a progressive violation of memory, speech, praxis, thinking.

Distinctive clinical features of dementia with Lewy bodies are fluctuations in mental status, transient states of confusion, hallucinations (most often visual), increased sensitivity to neuroleptics. Dementia with Levi bodies is more common in men than in women. Progression of the disease can be more rapid than with Alzheimer's disease.

[1], [2]

Epidemiology

Dementia with Levi bodies is the third in the occurrence of dementia. The onset of the disease is usually observed at the age of over 60 years.

[3], [4], [5], [6], [7], [8], [9], [10],

Pathogenesis

Pathomorphologically, dementia with Lewy bodies is characterized by the presence of changes characteristic of Parkinson's disease (BP) in combination with changes in the Alzheimer's type or without them. In dementia with Levi bodies, Levy bodies are identified in cortical neurons in combination with senile plaques or without Alzheimer's type changes. The term "dementia with Levy bodies" was proposed in 1995 by the International Workshop on this issue. Previously, the disease was designated as a disease of diffuse Levy bodies, senile dementia with Levy bodies, a variant of Alzheimer's disease with Levi bodies.

Cortical Levi bodies - the main pathomorphological sign of dementia with Lewy bodies - are detected in 15-25% of patients with dementia. Pathomorphological studies show that in patients with dementia with Levi bodies, it is often clinically wrong to diagnose Alzheimer's disease.

Disease diffuse Lewy bodies (BDTL) is manifested by dementia, psychotic disorders and extrapyramidal (parkinsonism) symptoms. The combination of dementia, characterized by fluctuations (sometimes sharp) of its severity, psychotic disorders with transient visual hallucinations (more than 90% of patients), unprovoked by antiparkinsonics, and parkinsonism, manifestations of which do not fit into the diagnostic criteria of Parkinson's disease, should serve as a basis for suspicion of the disease diffuse Levi bodies. Disease diffuse bodies Lévy meets more often than is diagnosed.

[11], [12], [13], [14], [15], [16], [17]

Symptoms of the dementia with Levy bodies

Initial cognitive impairments are similar to those of other types of dementia. However, extrapyramidal symptoms differ from those inherent in Parkinson's disease: for dementia with Levi bodies, tremor does not appear in the early stages of the disease, initially there are axial rigidity and gait disturbances, neurological deficits tend to symmetry.

Fluctuation of cognitive functions is a relatively specific symptom of dementia with Levy bodies.

The periods of the patient's stay in an active state, explainable behavior and orientation can be replaced by periods of confusion and lack of response to the questions asked, which usually last for days and weeks, but are then replaced by the ability to come into contact.

The memory suffers, but its deficit is mostly due to a change in the level of wakefulness and a violation of attention, rather than a mere violation of the mnestic processes, so the memories of recent events suffer less than a consecutive memory for numbers (the ability to repeat 7 numbers in direct and 5 in the reverse order) . Excessive drowsiness is common. Visual spatial and visual constructive abilities (tests for designing, drawing clocks, copying figures) suffer more than other cognitive functions. Therefore, dementia with Levy bodies can be difficult to differentiate from delirium, and all patients exhibiting the above symptoms should be examined for delirium.

Visual hallucinations are common and frequent manifestations of the disease, in contrast to benign hallucinations in Parkinson's disease. Auditory, olfactory and tactile hallucinations are less typical.

In 50-65% of patients there is delirium, which is complex, bizarre, which differs from Alzheimer's disease, in which there is often a simple delirium of persecution. Typically, vegetative disorders develop with the occurrence of unexplained syncopal conditions. Vegetative disorders can occur simultaneously with the appearance of a cognitive deficit or after its occurrence. Typical is hypersensitivity to antipsychotics.

[18], [19], [20], [21]

Diagnostics of the dementia with Levy bodies

The diagnosis is established clinically, however sensitivity and specificity of diagnostics are low. The diagnosis is considered (considered) as probable in the presence of 2-3 signs - fluctuations in attention, visual hallucinations and parkinsonism - and as possible in the detection of only one of them. Evidence supporting the diagnosis is repeated falls, syncopal conditions and increased sensitivity to antipsychotics. The overlapping of symptoms of dementia with Lewy bodies and Parkinson's disease can make it difficult to diagnose. In the event that the motor deficiency inherent in Parkinson's disease precedes and is more hostile than cognitive impairment, Parkinson's disease is usually diagnosed. If early cognitive impairment and behavior change predominate, a diagnosis of dementia with Levi bodies is established.

CT and MRI do not reveal any characteristic changes, but are initially useful for establishing other causes of dementia. Positron emission tomography with fluorine-18-labeled deoxy-lyxose and single-photon emission CT (SPECT) with ¹²³ I-FP-CIT (Nw-fluoropropyl-2b-carbomethoxy-Zb- [4-iodophenyl] -tropane) - a fluoroalkyl cocaine derivative It is useful to identify dementia with Lewy bodies, but it is not a routine method of investigation. The final diagnosis requires the autopsy of brain tissue.

Clinical criteria for the diagnosis of disease of diffuse Lewy bodies (BDTL):

• Obligatory trait: progressive decrease in cognitive functions in the form of dementia of the frontal-subcortical type
• Additionally, at least 2 of the following 3 signs are required for the probable diagnosis of diffuse Levy's disease and 1 symptom for a possible diagnosis of diffuse Levy's disease:
  • fluctuations in the severity of the defect in cognitive functions
  • transient visual hallucinations
  • motor symptoms of Parkinson's disease (not associated with taking antipsychotics

To the additional diagnostic criteria for the disease of diffuse bodies, Levy include: increased sensitivity to neuroleptics, repeated falls, syncopal conditions, hallucinations of other modalities.

A reliable diagnosis of Diseases of Levy diffuse bodies is possible only with pathomorphological examination.

Diagnosis of the disease of diffuse Lewy bodies is considered unlikely in the presence of symptoms of a stroke, changes in neuroimaging or in the detection of any other brain diseases or somatic diseases that can explain the observed clinical picture.

[22], [23], [24], [25]

Differential diagnosis

Symptoms that distinguish dementia from Lewy bodies from Alzheimer's disease and Parkinson's disease:

APOE-64 is a risk factor for dementia with Levy bodies. However, in terms of the prevalence of the genotype AROE-64, dementia with Levy bodies is intermediate between Parkinson's disease and Alzheimer's disease. This may indicate that dementia with Levy bodies is a combination of Alzheimer's disease and Parkinson's disease

In patients with dementia with Levi bodies (without concomitant Alzheimer's pathomorphological changes), the age of dementia development is lower, and the disease more often than with combination with alzheimer's changes begins with parkinsonism, which is subsequently followed by dementia. Patients with dementia with Levi body cells perform worse tests for praxis, but more successfully cope with the tests for the reproduction of the stored material, and also have more pronounced fluctuations in the wakefulness level than patients with Alzheimer's disease. Visual hallucinations are more likely to occur with dementia with Levy bodies than with Alzheimer's, although the sensitivity of this feature in the differential diagnosis of dementia with Levy bodies and Alzheimer's disease is poor. Dementia with Levy bodies reveals a lower level of homovanic acid in the cerebrospinal fluid than in Alzheimer's disease, which probably reflects changes in the metabolism of dopamine in dementia with Levy bodies. With dementia with Levy bodies, as in Parkinson's disease, there is a significant decrease in the number of neurons of the black substance producing dopamine.

The severity of dementia in Alzheimer's disease and dementia with Levy bodies correlates with the number of Lewy bodies, a decrease in choline acetyltransferase activity, the number of neurofibrillar glomeruli and neuritic plaques. But, in contrast to Alzheimer's disease, dementia with Levi bodies does not reveal a connection between the severity of dementia and the number of neurofibrillary glomeruli in the neocortex, and also with the level of antisynapto-ficin activity reflecting the synaptic density. With dementia with Levi bodies, there is less tremor of rest, less asymmetry of Parkinson's symptoms, but more severe rigidity than with Parkinson's disease.

Treatment of the dementia with Levy bodies

Dementia with Levi bodies is a progressive disease, the prognosis is bad for him. Treatment is mostly supportive. Rivastigmine at a dose of 1.5 mg orally according to the indications with increasing dose titration, if necessary up to 6 mg, can improve cognitive impairment. Other cholinesterase inhibitors may also be helpful. Approximately one-half of patients respond to the therapy of extrapyramidal symptoms with antiparkinsonian drugs, but at the same time psychiatric manifestations of the disease are aggravated. In the event that the use of antiparkinsonian drugs is necessary, preference should be given to levadopa.

Traditional antipsychotics, even at very low dosages, lead to a sharp exacerbation of extrapyramidal symptoms, and it is better to abandon them.

Treatment of Parkinsonism

Antiparkinsonian drugs in patients with dementia with Levi bodies often cause psychotic disorders. If parkinsonism disrupts the life of the patient, then levodopa preparations may be used to correct it, but on average they are less effective than Parkinson's. In general, the published data on the effectiveness of antiparkinsonian drugs in dementia with Levy bodies is insufficient. To reduce rigidity, baclofen is also suggested.

Treatment of psychotic disorders

Pharmacotherapy of hallucinations and delusional disorders in patients with dementia with Levi bodies is hampered by their hypersensitivity to neuroleptics. With dementia with Levi bodies, treatment with a typical neuroleptic is started at a lower dose, and subsequently it is increased more slowly than with other diseases. Clozapine can be used to treat psychotic disorders, but when taking this drug, regular monitoring of the clinical blood test is necessary. Risperidone was useful in one open-label study, but ineffective in the other. In one study olanzapine reduced the severity of psychotic disorders in patients with dementia with Levy bodies, but often caused confusion and drowsiness, as well as increased symptoms of parkinsonism. Data on the use of other atypical antipsychotics, in particular quetiapine, as well as remoxipride, zotepin, mianserin, and ondansetron in patients with dementia with Levy bodies are not yet available in the literature.

Treatment of depression

About half of patients with dementia with Lewy bodies develop depression. With dementia with Levy bodies, it occurs about five times more often than with Alzheimer's, but with the same frequency as Parkinson's disease. Depression significantly burdens the patient's condition, increases mortality, appealing to health services, but, unlike many other manifestations of dementia with Levy bodies, is treatable. Treatment of depression in patients with sedimentation can also improve cognitive function and reduce apathy.

Pharmacotherapy

The choice of an antidepressant is based mainly on the profile of side effects, since there is no evidence of an advantage in the effectiveness of a drug in patients with dementia with Levy bodies and depression. When choosing an antidepressant, it is important to consider its ability to cause a cholinolytic effect, to interact with other medicines, to cause drowsiness and vegetative disorders.

Electroconvulsive therapy

Clinical trials of the effectiveness of electroconvulsive therapy (ECT) in the treatment of depression in patients with dementia with Levy bodies have not been conducted. Nevertheless, it is shown that ECT can reduce the manifestations of depression and the severity of motor defect in patients with Parkinson's disease. ECT is mentioned as one and the treatment for depression in patients with dementia and in the Practice Guidelines for Dementia Treatment developed by the American Psychiatric Association. Thus, ECT can be used to treat depression and in patients with dementia with Levy bodies. Placement of electrodes, stimulation parameters, frequency of procedures should be selected in such a way as to minimize possible adverse effects on cognitive functions.

[26], [27], [28], [29], [30], [31], [32], [33], [34], [35]

Cholinergic drugs for dementia with Levy bodies

The level of choline acetyltransferase in the neocortex in patients with dementia with Levy bodies is lower than in patients with Alzheimer's disease. Not surprisingly, cholinesterase inhibitors for dementia with Levy bodies on average are more effective than those with Alzheimer's disease. In recent years, double-blind, placebo-controlled clinical trials of cholinesterase inhibitors (rivastigmine, donepezil) have been shown to demonstrate their ability to improve attention and other cognitive functions, and to reduce the severity of behavioral and psychotic disorders, especially in patients with mild to moderate dementia.

[36], [37], [38], [39], [40], [41], [42], [43],

Prospective directions of drug search for dementia with Levy bodies

Since the cognitive defect in dementia with Levy bodies appears to be associated not only with Levy bodies, therapeutic intervention should be directed to other pathological processes, in particular leading to the formation of amyloid plaques or neurofibrillary glomeruli. In connection with the emergence of common criteria for dementia with Lewy bodies, it becomes possible to conduct clinical trials of those drugs that have been developed for the treatment of Alzheimer's disease and Parkinson's disease and are potentially capable of influencing the progression of dementia with Lewy bodies. It is promising to develop means to correct neurochemical imbalance, antioxidants, neuroprotective drugs, drugs that inhibit amyloid production, phosphorylation of tau protein, formation of neurofibrillary glomeruli, synthesis of products of the APOE-e4 gene, anti-inflammatory drugs, glutamate receptor agonists.