Dementia with Lewy bodies is a degenerative progressive cerebral lesion characterized by the presence of a large number of intraneuronal pathological inclusions. Clinically manifested by a combination of increasing dementia and mental disorders with symptoms of Parkinsonism, sleep disorders, autonomic dysregulation. Dementia is diagnosed according to clinical criteria, the results of neurological and neuropsychological examination, additionally, MRI, PET of the brain is performed. Therapy is carried out with cholinesterase inhibitors, NMDA antagonists, small doses of levadopa.
G31.8 Other specified degenerative diseases of the nervous system
Lewy corpuscles are called pathological intraneuronal inclusions, the basis of which is alpha-synuclein and ubiquitin. These inclusions, discovered in 1912 by the German morphologist F. Lewy, for a long period, were considered a pathognomonic sign of Parkinson’s disease. Dementia with Lewy bodies (DLB) was first described by Japanese researchers in 1950 as a form of Parkinsonism. In 1984, it was isolated as a separate nosology under the name “Lewy diffuse corpuscle disease”.
In 1995, at the first international symposium devoted to this pathology, diagnostic criteria for the disease designated by the term “dementia with Lewy bodies” were determined. Dementia with Lewy bodies accounts for 10-15% of all dementias, ranks third after Alzheimer’s disease and vascular dementia. Mostly people over the age of 60 get sick. According to various sources, among this age group, the incidence varies between 0.7-5%.
The etiofactors provoking the development of dementia with Lewy bodies have not been established. The morphological basis of the disease is degeneration and death of neurons. Presumably, pathological changes are associated with the inhibition of mechanisms inhibiting apoptosis or activation of factors triggering it. The genetic aspects of the etiology of the disease are carefully studied. 50% of patients are diagnosed with parkinsonism, senile dementia among relatives of the 1st line. However, the clinical polymorphism of dementia with Lewy bodies significantly complicates medical genealogical analysis.
As an example, the case of a Japanese family with a traceable mutation of the Parkin gene described in the literature on neurology can be cited. In accordance with the severity of the genetic defect, family members developed Parkinson’s disease or dementia with Lewy bodies. Opinions are expressed about the genetic predisposition to the development of pathology in old age. Factors that increase the risk of the disease include the e4 allele on the 19th chromosome, mutations in the GBA gene of the 1st chromosome, in the LRRK2 gene of the 12th chromosome, changes in the 2q35-36 locus.
Since a small number of neurons with Lewy corpuscles are found in the cerebral tissues of 35% of elderly people, it is assumed that they are the result of natural aging processes. The mechanism of development of “accelerated” brain aging in patients with dementia with Lewy bodies has not been determined. Assume a significant role in reducing antioxidant systems, activation of the glutamatergic link, which leads to excessive intra-neuronal calcium intake, a change in the charge of the neuron membrane. Hypometabolic changes in the occipital cortex are noted already in the initial period of the disease, which corresponds to the early manifestation of visual-spatial disorders in dementia with Lewy bodies. The spread of the lesion to the black substance and the striatum causes the development of Parkinsonian syndrome, the involvement of stem nuclei — autonomic dysfunction.
Dementia with Lewy bodies symptoms
Clinically, dementia with Lewy bodies includes a wide range of symptoms in the cognitive, mental, motor, and vegetative spheres. During the debut period, neurodynamic disorders are characteristic, manifested by a decrease in the ability to concentrate and hold attention, to plan the performance of complex tasks. Subsequently, the symptoms of visual agnosia quickly join: at first there are errors in recognizing objects, then familiar people, later relatives. In the expanded stage, the patient ceases to recognize even his own reflection in the mirror. A distinctive feature is the early manifestation of visual hallucinations. Memory remains more preserved for a long time, the main manifestations of amnesia are associated with a disorder of searching and reproducing information stored in the brain. Aphasia is not characteristic.
The spectrum of mental disorders includes hallucinatory syndrome (visual, auditory, tactile hallucinations), depression, a sense of the presence of an outsider, dissociative disorders, delirium, delirium, in later stages — psychomotor agitation, apathy. A feature of mental disorders is the fluctuating nature. Episodes of deterioration lasting for minutes or hours up to confusion alternate with light intervals, typically the presence of “good” and “bad” days. In 20% of patients, psychotic disorders are noted only in the final phase of dementia with Lewy bodies.
Motor disorders are represented by extrapyramidal symptoms, in the early stages they are observed in half of the cases. There is a hypokinetic syndrome, increased tone, postural instability, tremor. With the progression of the disease, Parkinsonian symptoms are detected in 80% of cases. Some patients have myoclonia. Vegetative dysfunction is manifested by bradycardia, cardiovascular instability (orthostatic hypotension, tendency to syncope), gastrointestinal dyskinesia (diarrhea, constipation, gastroparesis), dysuric phenomena (nocturia, imperative urges, partial urinary incontinence). There is a violation of the sleep-wake cycle with pronounced daytime hypersomnia, episodes of hyperexcitation in sleep (screaming, motor activity, falling out of bed) are observed.
Progressive dementia, mental disorders lead to the loss of self-service opportunities, patients need constant outside care. Severe complications are associated with incorrect selection of therapy. The administration of dopamine pharmaceuticals, even in moderate dosages, causes an increase in hallucinatory syndrome and psychotic symptoms. The relief of mental disorders with the help of neuroleptics quickly leads to the development of a malignant neuroleptic syndrome. The latter is dangerous with a number of complications that can lead to death: acute respiratory failure, acute renal failure, arrhythmia, myocardial infarction, DIC syndrome, liver failure, sudden cardiac arrest.
Dementia with Lewy bodies is diagnosed mainly clinically. Of fundamental importance is the identification of a combination of the main signs (dementia, visual hallucinations, parkinsonism, autonomic dysfunction, sleep disorders), fluctuation of symptoms, features of the development of the disease (dementia precedes parkinsonism or appears together with it). Instrumental research plays an auxiliary role. The diagnostic list includes:
- Neurological examination. At an early stage, a neurologist reveals slowness of thought processes, difficulty concentrating, and behavioral features. With the development of extrapyramidal dysfunction in the motor sphere, there is a decrease in volume, amplitude of movements, shuffling gait, hypomimia, muscle hypertension by plastic type, tremor, myoclonic phenomena.
- Neuropsychological testing. It is carried out by a psychiatrist or neuropsychologist during a conversation, observation, testing. The examination includes assessment of mental status, determination of the degree of dementia on the Mattis scale, testing of the speed of mental processes. At the beginning of the disease, the patient may hide the presence of visual hallucinations, which makes diagnosis difficult.
- MRI of the brain. The tomographic picture is nonspecific. Cerebral atrophy is diffuse, extremely variable, less pronounced than in Alzheimer’s type dementia. Minor changes in the occipital cortex dissociating from the clinical picture are typical. The damage to the subcortical ganglia is almost total. In order to exclude the vascular genesis of dementia, the study is supplemented by MRI of cerebral vessels.
- PET-CT of the brain. It determines a decrease in neurometabolism and perfusion in the occipital lobes, a pronounced lesion of subcortical structures. Dissociation of weak occipital atrophy according to MRI data with pronounced dysmetabolic processes in this area according to PET results is of decisive diagnostic importance.
- Polysomnography. Identification of signs of psychomotor arousal in the rem sleep phase is a typical feature of neurodegenerative processes. Conducting a study is difficult in view of the mental state of patients.
Differential diagnosis of dementia with Lewy bodies is performed with Alzheimer’s disease, secondary Parkinsonism, Parkinson’s disease, combined with vascular dementia, Pick’s disease and other progressive dementias. Dementia with Lewy bodies differs from Parkinson’s disease by the appearance of Parkinsonism symptoms after the appearance of cognitive impairment, from Peak degeneration by the presence of extrapyramidal dysfunction. Difdiagnosis with Alzheimer’s dementia is the most difficult. The latter is characterized by an older age of debut, a rapid increase in total cognitive disorders (agnosia, apraxia, aphasia), a later development of hallucinatory syndrome, and the severity of atrophic changes on MRI.
Therapy is symptomatic, associated with significant difficulties. Standard antiparkinsonian treatment with levadopa drugs leads to an aggravation of mental disorders, the use of antipsychotic pharmaceuticals leads to the progression of hypokinesia. In this regard, careful careful selection of pharmacotherapy is required. The main directions of therapy are:
- Correction of the cognitive and mental sphere. The drugs of choice are cholinesterase inhibitors (rivastigmine, donepezil). Against the background of their reception, there is an improvement in attention, daily activity, normalization of sleep, a decrease in the severity of hallucinations, aggression. In 25% of cases, treatment is accompanied by pronounced side effects from the gastrointestinal tract. An alternative to anticholinesterase pharmaceuticals are NMDA antagonists (memantine), which significantly weaken mental disorders, but have little effect on cognitive symptoms. Dementia of moderate severity is an indication for the appointment of a combination of these two groups of drugs.
- Therapy of parkinsonism. It is carried out in small doses of levadopa. Antiparkinsonian treatment begins with a significant severity of symptoms that complicate patient care. Dose selection starts from the minimum values, it is recommended in stationary conditions. Since increasing dosages is dangerous by increasing psychotic symptoms, it is rarely possible to bring the dose of the drug taken by the patient to the required therapeutic level. Individual monoamine oxidase inhibitors (rasagiline) used in the course of parkinsonism with “congestions” are relatively safe for dementia with Lewy bodies.
- Non-drug measures. They fall on the shoulders of relatives and medical staff. They include patient care, adequate response to mental disorders, measures to normalize sleep. In most cases, a psychologist’s consultation is recommended to the patient’s relatives to clarify the essence of the disease and its consequences.
The symptomatic therapy described above can somewhat alleviate the condition of patients and care for them, but it cannot stop the progression of the degenerative process. Promising in terms of inhibition of degeneration is the development of medications that block the aggregation of α-synuclein, potentiating the dissolution of the formed intraneuronal inclusions. The search for new methods of treatment is also being conducted in the direction of creating apoptosis inhibiting agents.
Prognosis and prevention
Due to the steadily progressing degenerative process in the cerebral structures, dementia with Lewy bodies is a prognostically unfavorable disease. The life expectancy of patients is within 5-7 years. Patients die from intercurrent infections, cardiovascular, respiratory disorders caused by a violation of central nervous regulation. The lack of information about the etiology of the disease does not allow us to develop effective mechanisms for its prevention.