Dementia in Alzheimer's disease

Primary degenerative dementia of the Alzheimer's type, or dementia in Alzheimer's disease, is the most common form of primary degenerative dementias of late age with a gradual onset in presenile or old age, a steady progression of memory disorders, higher cortical functions up to the total disintegration of intelligence and mental activity in general, as well as a characteristic complex of neuropathological signs.

Examples of diagnosis formulation taking into account ICD-10

Late-onset Alzheimer's disease (senile dementia of the Alzheimer's type) with other symptoms, predominantly delusional; stage of moderate dementia.

Early-onset Alzheimer's disease (presenile dementia of the Alzheimer's type) without additional symptoms; severe dementia stage.

Alzheimer's disease of mixed type (with signs of vascular dementia) with other symptoms, mainly depressive; stage of mild (easy) dementia.

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Epidemiology of dementia in Alzheimer's disease

Alzheimer's disease is the most common cause of dementia in the elderly and old age. According to international studies, the prevalence of Alzheimer's disease after 60 years doubles with each five-year period, reaching 4% at 75, 16% at 85 and 32% at 90 years and older. According to an epidemiological study of mental health of the elderly population conducted in Moscow, 4.5% of the population aged 60 and older suffer from Alzheimer's disease, and the age-specific incidence rates increase with the age of those examined (in the age group 60-69 years, the prevalence of the disease was 0.6%, at the age of 70-79 years - up to 3.6% and at the age of 80 years and older - 15%). The prevalence of Alzheimer's disease among elderly women is significantly higher compared to men of the same age.

Alzheimer's disease is the most common cause of dementia in the Western Hemisphere, accounting for more than 50% of cases. The prevalence of Alzheimer's disease increases with age. Women are more likely to develop the disease than men. There are more than 4 million people with Alzheimer's disease in the United States. The annual direct and indirect costs of the disease reach $90 billion.

The prevalence of Alzheimer's disease among people aged 65, 75 and 85 years is 5, 15 and 50%, respectively.

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Causes of Dementia in Alzheimer's Disease

Genetically determined ("familial") forms of Alzheimer's disease account for no more than 10% of cases of the disease. Three genes responsible for their development have been identified. The amyloid precursor gene is located on chromosome 21: presenilin-1 on chromosome 14 and presenilin-2 on chromosome 1.

Mutations in the amyloid precursor gene are responsible for 3-5% of all presenile familial forms of Alzheimer's disease (inheritance is autosomal dominant), mutations in the presenilin-1 gene are detected in 60-70% (mutations in this gene are characterized by complete penetrance, the disease always manifests itself between the ages of 30 and 50). Mutations in the presenilin-2 gene are extremely rare and they cause the development of both early and late familial forms of the disease (they are characterized by incomplete penetrance).

The role of mutations or polymorphisms of presenilin genes in the development of sporadic cases of late Alzheimer's disease (senile dementia of the Alzheimer's type) remains insufficiently understood. The recently identified e4-isomorphic variant of the apolipoprotein E gene is currently considered the main genetic risk factor for the development of late Alzheimer's disease.

Numerous neurohistological and neurochemical studies performed to date have established several cascades of biological events occurring at the cellular level that are presumably involved in the pathogenesis of the disease: disruption of beta-amyloid conversion and T-protein phosphorylation, changes in glucose metabolism, excitotoxicity, and activation of lipid peroxidation processes. It has been suggested that each of these cascades of pathological events or their combination may ultimately lead to structural changes that underlie neuronal degeneration and are accompanied by the development of dementia. 

Alzheimer's Dementia - What's Happening?

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Signs of Dementia in Alzheimer's Disease

According to diagnostic guidelines developed by international expert groups and in accordance with the WHO-approved ICD-10, the lifetime diagnosis of Alzheimer's disease is based on the presence of several obligatory signs.

Obligatory lifetime diagnostic signs of Alzheimer's disease:

• Dementia syndrome.
• Multiple cognitive deficits are a combination of memory disorders (impaired memorization of new and/or recall of previously learned information) and signs of at least one of the following cognitive impairments:
  • aphasia (speech impairment);
  • apraxia (impaired ability to perform motor activity despite intact motor functions);
  • agnosia (inability to recognize or identify objects despite intact sensory perception);
  • violations of intellectual activity itself (its planning and programming, abstraction, establishment of cause-and-effect relationships, etc.).
• A decrease in the patient's social or professional adaptation compared to its previous level due to memory and cognitive impairment.
• The onset of the disease is subtle and progresses steadily.
• During a clinical examination, it is necessary to exclude other diseases of the central nervous system (for example, cerebrovascular diseases, Parkinson's or Pick's disease, Huntington's chorea, subdural hematoma, hydrocephalus, etc.) or other diseases that can cause dementia syndrome (for example, hypothyroidism, vitamin B12 or folic acid deficiency, hypercalcemia, neurosyphilis, HIV infection, severe organ pathology, etc.), as well as intoxication, including drug-induced.
• Signs of the above-mentioned cognitive impairments should be detected outside of states of clouded consciousness.
• Anamnestic information and clinical examination data exclude a connection between cognitive disorders and any other mental illness (for example, depression, schizophrenia, mental retardation, etc.).

The use of the listed diagnostic criteria has made it possible to increase the accuracy of lifetime clinical diagnosis of Alzheimer's disease to 90-95%, but reliable confirmation of the diagnosis is only possible with the help of data from a neuromorphological (usually postmortem) study of the brain.

It should be emphasized that reliable objective information about the development of the disease often plays a much more important role compared to numerous laboratory and/or instrumental research methods. However, none of the intravital paraclinical studies, including CT/MRI data, have high specificity and undoubted diagnostic significance.

The neuromorphology of Alzheimer's disease has now been studied in detail.

Typical morphological signs of Alzheimer's disease:

• atrophy of brain matter;
• loss of neurons and synapses;
• grayulovacuolar degeneration; 
• gliosis;
• the presence of senile (neuritic) plaques and neurofibrillary tangles;
• amyloid angiopathy.

However, only senile plaques and neurofibrillary tangles are considered as key neuromorphological signs of diagnostic significance.

Complaints from the patient himself or his relatives about memory impairment and other intellectual functions, as well as data on the patient’s obvious maladaptation in professional activities and/or everyday life should force the doctor to perform a series of sequential actions to clarify their presumed nature.

Only a combination of reliable anamnestic data, features of the clinical picture of the disease, dynamic monitoring of its course with the exclusion of other possible causes of dementia by clinical and paraclinical methods [general somatic, neurological, laboratory and neurointrascopic (CT/MRI) examination] allow a lifetime diagnosis of Alzheimer's disease to be made.

The questions that a doctor should ask a relative or other person who knows the patient well concern, first of all, the patient’s impairments of various cognitive functions, primarily memory, speech, orientation, writing, counting and intellectual functions proper, as well as the performance of habitual types of professional and everyday activities, etc.

Disorders of functional activity of patients

Disorders in instrumental activities:

• professional activity;
• finance;
• housekeeping;
• handling correspondence;
• independent travel (trips);
• use of household appliances;
• hobby (playing cards, chess, etc.).

Self-care disorders:

• choosing appropriate clothes and jewelry;
• putting on clothes;
• hygiene procedures (toilet, haircut, shaving, etc.).

When questioning a person who knows the patient well, attention should also be paid to identifying signs of psychopathological and behavioral disorders that accompany dementia at one or another stage of its development. Information about the presence of certain manifestations of the disease should be found out in the absence of the patient, since relatives may hide this information due to fears of causing psychological trauma to the patient.

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Psychopathological and behavioral disorders in Alzheimer's disease

Psychopathological disorders:

• affective disorders (usually depressive);
• hallucinations and delirium:
• anxiety and fears;
• a state of amnestic confusion.

Behavioral disorders:

• aspontaneity;
• sloppiness;
• aggressiveness;
• disinhibition of drives;
• excitability; wandering;
• sleep-wake rhythm disorder.

The information obtained and the data of the initial examination of the patient allow for the primary differentiation of dementia syndrome - the distinction between dementia and depressive pseudo-dementia, as well as between dementia and disorder of consciousness, which makes it possible to correctly plan further tactics for managing the patient. If the anamnestic data and clinical picture correspond to the diagnostic signs of depression, the patient should be referred for consultation to a psychiatrist to clarify the diagnosis and prescribe antidepressants. If confusion or delirium is suspected, the patient should be urgently hospitalized to identify the possible cause of the disorder of consciousness (intoxication, including drug intoxication, acute or exacerbation of a chronic somatic disease, subarachnoid hemorrhage, etc. are possible) and provide emergency medical care.

After excluding impaired consciousness or depression, a more detailed assessment of the patient's cognitive abilities should be performed - several simple neuropsychological tests should be performed (for example, an assessment of the mental state using the MMSE scale and a clock drawing test, which allows one to identify disturbances of optical-spatial activity - one of the most characteristic and early manifestations of Alzheimer's type dementia syndrome). A detailed neuropsychological examination is usually necessary only at an early stage of the disease, when it is necessary to differentiate Alzheimer's disease from a slight (mild) decline in cognitive functions or age-related forgetfulness.

At the initial diagnostic stage, it is also necessary to conduct a generally accepted physical and neurological examination and perform the necessary minimum of laboratory tests: a complete blood count, a biochemical blood test (glucose, electrolytes, creatinine and urea, bilirubin and transaminases), determine the level of vitamin B12 and folic acid, thyroid hormones, erythrocyte sedimentation rate, conduct studies to diagnose syphilis, human immunodeficiency virus (HIV) infection.

Neurological examination of patients at the stage of mild and even moderate dementia usually does not reveal pathological neurological signs. At the stage of moderately severe and severe dementia, reflexes of oral automatism, some symptoms of Parkinsonism syndrome (amimia, shuffling gait), hyperkinesis, etc. are revealed.

If, after completion of the diagnostic examination and re-evaluation of cognitive functions, there remains a suspicion of Alzheimer's disease, it is advisable to refer the patient for consultation with specialists in the field of psycho- and neurogeriatrics.

Instrumental diagnostics

Of the instrumental methods for diagnosing Alzheimer's disease, CT and MRI are the most widely used. They are included in the diagnostic standard for examining patients suffering from dementia, as they allow identifying diseases or brain damage that may be the cause of its development.

Diagnostic CT/MRI signs confirming the diagnosis of Alzheimer's dementia include diffuse (frontal-temporal-parietal or, in the early stages, temporo-parietal) atrophy (reduction in volume) of the brain matter. In senile dementia, Alzheimer's type, damage to the white matter of the brain in the periventricular zone and the area of the semi-oval centers is also detected.

Diagnostically significant linear CT/MRI signs that allow us to differentiate Alzheimer's disease from age-related changes:

• increased interhooking distance compared to the age norm; widening of the perihippocampal fissures;
• A decrease in the volume of the hippocampus is one of the early diagnostic signs of Alzheimer's disease.
• The most diagnostically significant functional characteristics of brain structures in Alzheimer's disease:
• bilateral decrease in blood flow in the temporoparietal regions of the cortex according to single-photon emission computed tomography (SPECT): atrophy of the temporal lobes and decreased blood flow in the temporoparietal regions of the cortex according to CT and SPECT.

Dementia in Alzheimer's Disease - Diagnosis

Classification

The modern classification of Alzheimer's disease is based on the age principle.

• Early-onset Alzheimer's disease (before age 65) (Alzheimer's disease type 2, presenile dementia of the Alzheimer type). This form corresponds to classical Alzheimer's disease and is sometimes referred to in the literature as "pure" Alzheimer's disease.
• Late-onset (after 65 years) Alzheimer's disease (Alzheimer's disease type 1, senile dementia of the Alzheimer's type).
• Atypical (combined) Alzheimer's disease.

The main clinical forms of the disease differ not only in the age of patients at the onset of the disease (especially since the age of the onset of the first symptoms is, as a rule, impossible to accurately determine), but also have significant differences in the clinical picture and features of progression.

Atypical Alzheimer's disease, or mixed dementia, is characterized by a combination of features of Alzheimer's disease and vascular dementia, Alzheimer's disease and Parkinson's disease, or Alzheimer's disease and dementia with Lewy bodies.

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Variants of dementia

• Alzheimer's type dementia
• Vascular dementia
• Dementia with Lewy bodies
• AIDS dementia
• Dementia in Parkinson's disease
• Frontotemporal dementia
• Dementia in Pick's disease
• Dementia in progressive supranuclear palsy
• Dementia in Entinton's disease
• Dementia in Creutzfelig-Jakob disease
• Dementia in normal pressure hydrocephalus
• Toxic substance induced dementia
• Dementia in brain tumors
• Dementia in endocrinopathies
• Dementia due to nutritional deficiency
• Dementia in neurosyphilis
• Dementia due to cryptococcus
• Dementia in multiple sclerosis
• Dementia in Hallervorden-Spatz disease

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Psychological correction (cognitive training)

This type of therapy is very important for improving or maintaining the cognitive abilities of patients and maintaining their level of daily activities.

Providing care for people with Alzheimer's disease and other forms of dementia in later life

It is recognized in most economically developed countries as one of the most important problems of health care and social care systems. This has helped to create a system of providing care to patients with dementia and their families, the main features of which are the continuity of support for the patient and his family at all stages of the disease and the inseparable interaction of different types of medical care and social services. This care is initially provided by a general practitioner, then patients are referred to various outpatient diagnostic units. If necessary, they are hospitalized in short-term diagnostic departments of psychogeriatric, geriatric or neurological hospitals. After diagnosis and treatment, the patient receives the necessary treatment on an outpatient basis, sometimes in day hospitals under the supervision of a psychiatrist or neurologist. For a longer stay, patients are hospitalized in a psychiatric hospital only in the case of the development of productive psychopathological disorders that do not respond to outpatient treatment (severe depression, delirium, hallucinations, delirium, confusion). If patients, due to severe cognitive impairment and social maladjustment, cannot live independently (or if family members cannot cope with care), they are placed in psychogeriatric boarding schools with permanent medical care.

Unfortunately, in Russia there is no such system of providing medical and social care to patients suffering from dementia. Patients can be examined in psychiatric or neurological (rarely in specialized psychogeriatric) clinics or hospitals, as well as in outpatient consultative units of these institutions. Outpatient long-term care is provided in psychiatric dispensaries, and inpatient care is provided in geriatric departments of psychiatric hospitals or in psychoneurological boarding schools. In Moscow and some cities of Russia, psychogeriatric consultative and therapeutic care is organized in the primary health care link, geriatric offices with a semi-hospital in a psychiatric dispensary and outpatient consultative and diagnostic units based on a psychiatric hospital.

In the initial period of the disease, patients may be dangerous to others due to disinhibition of drives or delusional disorders. With the development of severe dementia, they are dangerous both to others and to themselves (accidental arson, opening gas taps, unsanitary conditions, etc.). Nevertheless, if it is possible to provide care and supervision, it is recommended to leave patients with Alzheimer's disease in their usual home environment for as long as possible. The need to adapt patients to a new environment, including a hospital one, can lead to decompensation of the condition and the development of amnestic confusion.

The hospital places special emphasis on ensuring the correct regimen for patients and caring for them. Caring for maximum activity of patients (including occupational therapy, exercise therapy) helps in combating various complications (pulmonary diseases, contractures, loss of appetite), and proper skin care and caring for the neatness of patients can prevent bedsores.

Alzheimer's Dementia - Treatment

Differential diagnosis of dementia in Alzheimer's disease

At the final stage of the diagnostic process, the nosological nature of the dementia syndrome is clarified. Differential diagnostics are carried out between Alzheimer's disease and age-related memory loss or mild cognitive decline syndrome ("questionable dementia"), other primary neurodegenerative processes (Parkinson's disease, dementia with Lewy bodies, multisystem degeneration, frontotemporal dementia (Pick's disease), Creutzfeldt-Jakob disease, progressive supranuclear palsy, etc.). It is also necessary to exclude dementia syndrome secondary to the main disease. According to various sources, there are from 30 to 100 possible causes of cognitive impairment in the elderly (secondary dementia).

The most common causes of secondary dementia are:

• cerebrovascular diseases;
• Pick's disease (temporofrontal dementia);
• brain tumor;
• normal pressure hydrocephalus;
• TBI (subarachnoid hemorrhage);
• cardiopulmonary, renal, hepatic failure;
• metabolic and toxic disorders (chronic hypothyroidism, vitamin B12 deficiency, folic acid deficiency);
• oncological diseases (extracerebral);
• infectious diseases (syphilis, HIV infection, chronic meningitis);
• intoxication (including drug-induced).

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Vascular dementia

Most often, Alzheimer's disease must be differentiated from vascular dementia. In this case, the analysis of objective anamnestic data is of particular importance. Acute onset of the disease, previously suffered transient cerebrovascular accidents with transient neurological disorders or short-term episodes of clouding of consciousness, stepwise increase in dementia, as well as changes in the severity of its symptoms over a relatively short period of time (even within one day) indicate a probable vascular genesis of the disease. Identification of objective signs of cerebral vascular disease and focal neurological symptoms increases the likelihood of this diagnosis. Vascular dementia is also characterized by uneven damage to higher cortical functions and impairment of subcortical functions.

To recognize vascular dementia and differentiate it from Alzheimer's disease, it is useful to use the appropriate diagnostic scales (in particular, the Hachinski ischemic scale). A score of more than 6 points on the Hachinski scale indicates a high probability of vascular etiology of dementia, while less than 4 points indicate Alzheimer's disease. However, CT/MRI examination of the brain provides the most significant assistance in differential diagnostics with vascular dementia. Multi-infarct vascular dementia is characterized by a combination of focal changes in the density of the brain matter and mild expansion of both the ventricles and subarachnoid spaces; vascular dementia in Binswanger encephalopathy is characterized by CT/MRI signs of pronounced damage to the white matter of the brain (leukoaraiosis).

Pick's disease

The distinction from Pick's disease (temporofrontal dementia) is based on certain qualitative differences in the structure of the dementia syndrome and the dynamics of its development. Unlike Alzheimer's disease, Pick's disease already at the early stages exhibits profound personality changes with aspontaneity, impoverishment of speech and motor activity or silliness and disinhibition. as well as stereotypical forms of activity. At the same time, the main cognitive functions (memory, attention, orientation, counting, etc.) remain intact for a long time, although the most complex aspects of mental activity (generalization, abstraction, criticism) are impaired already at the initial stage of the disease.

Cortical focal disorders also have certain features. Speech disorders predominate - not only obligatory, but also early manifestations of the disease. Its gradual impoverishment occurs, speech activity decreases to "apparent dumbness" or speech stereotypes, stereotypical statements or stories "standing turns" appear, which in the later stages of the disease are the only form of speech. In the late stages of Pick's disease, complete destruction of speech function (total aphasia) is characteristic, while the symptoms of apraxia appear quite late and usually do not reach the severe degree characteristic of Alzheimer's disease. Neurological symptoms (except for amimia and mutism) are usually absent even in the late stages of the disease.

Neurosurgical diseases

Great importance is attached to the timely differentiation of Alzheimer's disease from a number of neurosurgical diseases (space-occupying lesions of the brain, normal-pressure hydrocephalus), since an erroneous diagnosis of Alzheimer's disease in these cases does not allow the timely use of the only possible surgical treatment method to save the patient.

Brain tumor. The need to differentiate Alzheimer's disease from a brain tumor usually arises if certain cortical disorders predominate in the early stages of the disease, outpacing the rate of progression of memory impairment and intellectual activity proper. For example, appropriate differential diagnostics must be carried out if, with relatively mild dementia, severe speech impairments occur, while other higher cortical functions remain largely intact and can only be detected with a special neuropsychological examination, as well as if, with mild speech impairments and moderate cognitive decline, distinct impairments in writing, counting, reading, and/or agnostic symptoms occur (predominant damage to the parietal-occipital regions of the brain).

In differential diagnostics, it is taken into account that in Alzheimer's disease there are no general cerebral disorders (headache, vomiting, dizziness, etc.) and focal neurological symptoms. The appearance of general cerebral and focal neurological symptoms or epileptic seizures in the early stages of the disease casts doubt on the diagnosis of Alzheimer's disease. In this case, it is necessary to perform neuroimaging and other paraclinical studies to exclude a neoplasm.

Hydrocephalic dementia, or normal pressure hydrocephalus, is the most well-known curable form of dementia, in which timely shunt surgery provides a high therapeutic effect and eliminates the symptoms of dementia in almost half of the cases.

The disease is characterized by a triad of disorders: gradually progressing dementia, gait disturbances, and urinary incontinence, with the last two signs appearing, unlike Alzheimer's disease, at relatively early stages of the disease. However, in some cases, not all symptoms of the "triad" are presented evenly. As a rule, intellectual and memory disorders in normotensive hydrocephalus are manifested by disturbances in memorization and memory for recent events, as well as disturbances in orientation, whereas in Alzheimer's disease they are usually more total (not only memorization and memory for recent events suffer, but also past knowledge and experience).

In contrast to the emotional safety of patients with early-onset Alzheimer's disease, patients with normotensive hydrocephalus are characterized by indifference, emotional dullness, and sometimes disinhibition. Patients with normotensive hydrocephalus usually have no disturbances of praxis and speech, and a peculiar gait develops (slow, with stiff, widely spaced legs).

Indications for consultation with other specialists are determined depending on the presence of concomitant diseases in the patient. If a brain tumor, normal-pressure hydrocephalus, or subarachnoid hemorrhage is suspected, a neurosurgeon consultation is necessary.

After completing the diagnostic examination, it is necessary to determine the functional stage (severity) of dementia caused by Alzheimer's disease, using, for example, the scale of assessment of severity of dementia or the scale of general deterioration of cognitive functions. After this, the tactics of patient management are developed and, first of all, the most adequate and accessible type of drug treatment is selected for him, and the possibility of using rehabilitation methods (cognitive and functional training, creation of a "therapeutic environment", etc.) is also assessed.

Treatment of dementia in Alzheimer's disease

Since the etiology of most cases of Alzheimer's disease has not yet been established, etiotropic therapy has not been developed. The following main areas of therapeutic intervention can be identified:

• compensatory (replacement) therapy, which is aimed at overcoming neurotransmitter deficiency;
• neuroprotective therapy - the use of drugs with neurotrophic properties and neuroprotectors; correction of free radical disorders, as well as calcium metabolism, etc.;
• anti-inflammatory therapy;
• psychopharmacotherapy of behavioral and psychotic disorders;
• psychological correction (cognitive training).

Compensatory (replacement) treatment

Compensatory therapeutic approaches are based on attempts to compensate for neurotransmitter deficiency, which is considered to play a leading role in the pathogenesis of memory and cognitive impairment.

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Cholinergic therapy

The most effective approach to cholinergic therapy for Alzheimer's disease is based on the use of acetylcholinesterase inhibitors.

Ipidacrine is a domestic acetylcholinesterase inhibitor, which also has the ability to activate the conductivity of nerve fibers. The drug improves intellectual and mnestic functions (according to the results of test assessment), increases the spontaneous activity of the patient with a simultaneous positive effect on the organization of behavior, reduces manifestations of irritability, fussiness, and in some patients - also manifestations of amnestic confusion. The initial daily dose is 20 mg (in two doses), then it is increased over 2-4 weeks to therapeutic (40-80 mg / day in two doses). The duration of the course of treatment should be at least 3 months. It is necessary to monitor the heart rate due to the possibility of bradycardia.

Rivastigmine is a representative of a new generation of acetylcholinesterase inhibitors - a pseudo-reversible inhibitor of acetylcholinesterase of the carbamate type, which has a selective effect on acetylcholinesterase in the central nervous system. The drug is recommended for the treatment of patients with mild and moderate Alzheimer's dementia. The peculiarity of the drug's use is the selection of the optimal individual therapeutic dose (the maximum tolerated dose for a given patient in the range from 3 to 12 mg / day in two doses). The optimal therapeutic dose is selected by gradually increasing the initial dose monthly (by 3 mg per month), which is 3 mg / day (1.5 mg in the morning and evening). The drug can be combined with other drugs, often necessary for elderly patients. The duration of therapy should be at least 4-6 months, although in most cases (with good tolerance and effectiveness) long-term use of the drug is necessary.

Currently, a new dosage form for cholinesterase inhibitors has been registered for the first time in the USA, Canada and ten European countries – the Exelon patch (a transdermal therapeutic system containing rivastigmine).

The use of the Exelon patch allows maintaining a stable concentration of the drug in the blood, while improving the tolerability of treatment, and a greater number of patients can receive the drug in therapeutic doses, which in turn leads to improved efficiency. The patch is glued to the skin of the back, chest and shoulder girdle, while ensuring gradual penetration of the drug through the skin into the body over 24 hours.

The severity and frequency of side effects from the gastrointestinal tract, often observed when using cholinesterase inhibitors, are significantly reduced when using the Exelon patch: the number of reports of nausea or vomiting is three times less than when using Exelon capsules. The effect of the Exelon patch is comparable to that when using Exelon capsules in maximum doses, the target dose of the drug (9.5 mg / 24 hours) was well tolerated by patients.

The unique drug delivery system provides a much simpler route of administration for both the patient and caregiver, and improves efficacy by rapidly achieving an effective dose with minimal side effects. The patch allows for easy monitoring of the patient's treatment needs, while the patient continues to lead a normal life.

Galantamine is an acetylcholinesterase inhibitor with a dual mechanism of action. It enhances the effects of acetylcholine not only through reversible inhibition of acetylcholinesterase, but also through potentiation of nicotinic acetylcholine receptors. The drug is registered for the treatment of patients with mild to moderate dementia in Alzheimer's disease. The recommended therapeutic doses are 16 and 24 mg / day in two doses. The initial dose of 8 mg / day (4 mg in the morning and evening) is prescribed for 4 weeks. If well tolerated, from the 5th week, the daily dose is increased to 16 mg (8 mg in the morning and evening). If insufficient effectiveness and good tolerability, from the 9th week of treatment, the daily dose can be increased to 24 mg (12 mg in the morning and evening). The duration of treatment should be at least 3-6 months.

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Use of Reminyl (galantamine) for the treatment of dementia

Galantamine (Reminyl) belongs to a new generation of acetylcholinesterase (AChE) inhibitors with a unique dual mechanism of action, which includes inhibition of AChE and allosteric modulation of nicotinic cholinergic receptors, which enhances the effect of acetylcholine on nicotinic receptors.

Experimental studies have shown that galantamine has neuroprotective properties that are realized through a-nicotinic acetylcholine receptors. It protects neurons from the neurotoxic effects of glutamate and beta-amyloid in vitro and increases their resistance to anoxia.

Galantamine (Reminyl) has a positive therapeutic effect in Alzheimer's disease and mixed dementia. Domestic and foreign clinical studies have proven that the drug improves cognitive functions and behavior in patients with mild and moderate dementia.

The effect of galantamine in mixed dementia has been evaluated in numerous trials. Good tolerability of galantamine and relative stability of cognitive impairment during long-term therapy (24-36 months) in elderly patients with mixed dementia have also been demonstrated. There is evidence that the initial improvement in cognitive functions is maintained for at least a year.

In a double placebo-controlled study by M. Raskind et al. (2004) studying the effectiveness of galantamine in patients with Alzheimer's disease under long-term therapy (36 months), it was found that in mild to moderate dementia, in 80% of cases the rate of dementia progression slows down by approximately 50% compared to the placebo group. Thus, galantamine significantly delays the progression of Alzheimer's disease.

The earlier galantamine therapy for dementia is started, the better the prognosis, which indicates the importance of its timely diagnosis. Various studies have noted that patients who received continuous pharmacological treatment from the onset of the disease generally have a better long-term prognosis.

It has also been shown that after 5 months of therapy with galantamine, patients' daily activities on the ADL scale significantly improve, and this does not depend on the initial level of dementia.

Galantamine therapy not only improves the quality of life of patients, but also facilitates care for them, reduces the burden, including psychological, on the caregiver. The data presented are confirmed by the results of the work, which analyzed the effect of galantamine on behavioral disorders. It was found that galantamine therapy slows the progression of Alzheimer's disease and mixed dementia. It is well tolerated by patients, allowing to significantly reduce the burden on the patient's relatives associated with caring for him, as well as reduce the cost of treatment. It is reasonably considered the drug of first choice in the treatment of Alzheimer's dementia.

Donepezil is a piperidine derivative, a highly specific, reversible, central acetylcholinesterase inhibitor with high bioavailability and a long half-life, which allows the drug to be administered once a day. Its efficacy has been confirmed in multicenter, double-blind, placebo-controlled studies in patients with mild to moderate dementia. Treatment begins with a dose of 5 mg once a day (in the evening); if well tolerated, after 4 weeks the daily dose is increased to 10 mg (once in the evening). The duration of therapy should be 3 months or more until the therapeutic effect is exhausted.

Glutamatergic therapy

In recent years, convincing evidence has been obtained of the involvement of not only the cholinergic system, but also other neurotransmitter systems, primarily the glutamatergic system, in the neurodegenerative process underlying Alzheimer's disease.

Memantine is a modulator of the glutamatergic system, which plays an important role in learning and memory processes, and has neuroprotective activity. It has successfully passed clinical trials in Russia, as well as in the United States and a number of European countries. The drug is indicated for the treatment of patients with both mild and moderate dementia, as well as severe dementia due to Alzheimer's disease. In addition to improving cognitive functions, the drug has a positive effect on motor disorders, leads to an increase in the level of spontaneous activity of patients, improved concentration and an increase in the pace of intellectual activity.

In patients with severe dementia, self-care skills (using the toilet, eating, self-care) improve, and the severity of behavioral disorders (aggression, anxiety, apathy) decreases. Good tolerability of the drug and the absence of serious side effects have been established. Its daily dose is 20 mg (10 mg in the morning and afternoon). Treatment begins with a dose of 5 mg (once in the morning), every 5 days the daily dosage is increased by 5 mg (in two doses) until a therapeutic dose is reached. The course of treatment should be at least 3 months.

Nootropics

Piracetam, a pyritinol that improves brain metabolism and cognitive function by stimulating the release of acetylcholine, has not been shown to have significant positive effects in the treatment of Alzheimer's dementia. Moreover, high doses of these drugs may have a negative effect due to possible neurotransmitter depletion.

Vascular drugs

Until recently, there was no reliable data on the therapeutic effects of vascular drugs. However, when studying the clinical efficacy of nicergoline in Alzheimer's disease, a statistically significant improvement in the condition of patients was found according to three different assessment scales after 6 and 12 months of its use. The therapeutic effect of the drug is associated with its ability to increase cerebral blood flow and improve energy metabolism in the hungry brain. In standard doses (30 mg / day, 10 mg 3 times a day), the drug did not cause serious side effects, Nicergoline is recommended as an additional therapy for older patients and in the presence of combined Alzheimer's and vascular dementia.

Neurotrophic drugs

Based on the evidence obtained in the last decade of the involvement of neurotrophic growth factor deficiency in the pathogenesis of primary neurodegenerative diseases (primarily Alzheimer's disease), a neurotrophic therapeutic strategy has been developed. Since it has been established that the nerve growth factor and some other neurotrophic growth factors prevent the development of apoptosis of brain cells, the use of neurotrophic drugs is of great importance in the neuroprotective therapy of Alzheimer's disease. On the one hand, they enhance the functional activity and protection of still intact neurons and synapses, and on the other, they improve cognitive functions. Despite significant experimental achievements in this area, there are still no drugs available for peripheral administration containing the nerve growth factor and capable of penetrating the blood-brain barrier.

Cerebrolysin

The discovery of neurotrophic effects of Cerebrolysin, similar to the activity of nerve growth factor, has generated new interest in this drug, which has been widely used in neurology for many years to treat stroke and other forms of cerebrovascular diseases. Cerebrolysin consists of amino acids and biologically active neuropeptides with low molecular weight. It regulates brain metabolism, exhibits neuroprotective properties and unique neuron-specific activity. The drug slows down the process of abnormal amyloidogenesis, prevents the activation of neuroglial cells and the production of inflammatory cytokines, inhibits apoptosis of brain cells and promotes the formation of stem cells (neuron precursors), dendrite growth and synapse formation, thus preventing the implementation of pathogenetic mechanisms leading to neurodegeneration and neuronal death in Alzheimer's disease.

Unlike the nerve growth factor, Cerebrolysin oligopeptides easily overcome the blood-brain barrier, exerting a direct effect on the neuronal and synaptic systems of the brain under conditions of peripheral administration of the drug.

The effectiveness of a course of Cerebrolysin therapy for the treatment of Alzheimer's disease has been proven with intravenous administration of 20-30 ml of the drug in 100 ml of 0.9% sodium chloride solution (20 infusions per course). The initial dose of the drug is 5 ml per 100 ml of 0.9% sodium chloride solution; then, over the next 3 days, it is gradually increased (by 5 ml daily) to the recommended therapeutic dose. A course of Cerebrolysin treatment once or twice a year is part of a complex of combined pathogenetic therapy for patients with mild to moderate dementia in Alzheimer's disease in combination with cholinergic or glutamatergic drugs.

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Antioxidants

Oxidative stress is currently considered one of the main causes of various neurodegenerative processes, including Alzheimer's disease. There are two alternative directions in the development of antioxidant therapy for Alzheimer's disease: the use of "external" antioxidants (exogenous or endogenous origin) and stimulation of intracellular antioxidant systems. Research into the effectiveness of a number of "external" antioxidants (vitamin E and its synthetic analogues, ginkgo biloba leaf extract, selegiline, etc.) has not yielded unambiguous results.

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Anti-amyloid therapeutic strategies

Anti-amyloid therapy targeting the key pathogenetic mechanism of Alzheimer's disease (abnormal amyloidogenesis) is currently still in the development or clinical trial phase.

Main directions of therapy:

• reduction of beta-amyloid formation from precursor protein;
• slowing down the transition of beta-amyloid from soluble to aggregated (neurotoxic) form;
• elimination of beta-amyloid aggregates with neurotoxic properties.

A fundamentally new direction in the development of anti-amyloid treatment for Alzheimer's disease is based on the idea of reducing the content of beta-amyloid in the brain by repeated immunization of APP-transgenic mice with serum containing human beta-amyloid. Such immunization leads to the production of antibodies to beta-amyloid, which can facilitate the removal of deposits of this protein from the brain. Another approach is associated with the peripheral administration of antibodies against the beta-amyloid peptide (passive immunization).

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Anti-inflammatory and hormone replacement therapy

Anti-inflammatory (non-steroidal anti-inflammatory drugs) and hormone replacement therapy (estrogen preparations) are still in the clinical study stage. The basis for the development of the corresponding types of therapy was epidemiological data indicating that people who took anti-inflammatory (non-steroidal) or estrogen preparations for a long time had a significantly lower incidence of Alzheimer's disease.

Due to productive psychopathological disorders and behavioral disorders, difficulties may arise in examining patients, conducting treatment and rehabilitation measures, and caring for patients, so their treatment takes on special significance.

Psychopathological and behavioral symptoms are more often an indication for hospitalization of patients with Alzheimer's disease than cognitive impairment. Behavioral disorders (aimless activity, attempts to leave home, aggression, etc.) significantly worsen the quality of life of both the patients themselves and their caregivers, and also statistically significantly increase the costs of maintaining the patients.

In the treatment of patients with dementia, it is extremely important to correctly assess the origin of psychotic symptoms, in particular the state of confusion. Delirium, confusion and other psychotic states of the exogenous type usually develop in patients suffering from dementia under additional influences, most often with intercurrent somatic diseases or exacerbation of chronic diseases, as well as as a result of drug or other intoxications. Each case of the occurrence of disorders of the exogenous type requires mandatory thorough (with the necessary clinical and laboratory studies) clarification of its cause and its elimination by appropriate therapeutic measures.

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Diagnosis of mental disorders and treatment of patients

In Alzheimer's disease, psychopharmacological drugs should be used with great caution. Inappropriate prescription of psychotropic drugs can cause aggravation of dementia symptoms and even development of amnestic confusion. Most often, such effects are accompanied by the use of drugs with an ancholinergic effect [for example, tricyclic antidepressants (TA)], as well as neuroleptics, beta-blockers, benzodiazepines and sedative hypnotics, therefore avoidance (if possible) of prescription of such drugs is one of the principles of drug treatment of Alzheimer's disease.

Neuroleptics should be used only in patients with severe behavioral or psychotic symptoms, and drugs that do not have a cholinergic effect can be prescribed. TA is contraindicated in such patients, and benzodiazepine derivatives, including hypnotics, can be prescribed for a short time. Neuroleptics are used only in cases of severe aggression: 20-100 mg/day of thioridazine is prescribed as monotherapy or in combination with serotonin reuptake inhibitors. Short-term administration of haloperidol (at a dose of 2.5 mg intramuscularly 2 times a day) is possible only in a hospital setting in case of severe agitation and aggression (no more than 3-5 days).

Atypical antipsychotic drugs have significant advantages over traditional neuroleptics, since in low but clinically effective doses for elderly patients they practically do not cause extrapyramidal and cholinergic side effects.

Risperidone is prescribed in a dose of 0.5 mg to 1 mg/day. If necessary, the dose can be increased to 1.5-2 mg/day (in 2 doses). Quetiapine is prescribed in a dose of 25 to 300 mg/day (the optimal dosage is 100 to 200 mg/day) in two doses (morning, evening).

These drugs are prescribed for 3-4 weeks, after the cessation of psychotic and behavioral disorders, their doses are gradually (over the course of 1-2 weeks) reduced, and then discontinued. If, against the background of discontinuation or reduction of the dose, psychotic symptoms reappear or intensify, treatment is continued at the previous therapeutic dose.

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How to Prevent Alzheimer's Dementia?

Prevention of Alzheimer's disease has not yet been developed. Risk factors for its development include advanced age, secondary cases of dementia in the elderly in the family, the presence of the apolipoprotein E gene; probable factors include traumatic brain injury and thyroid disease, low education and advanced age of the mother at the time of the patient's birth; presumptive factors include long-term exposure to stress factors, increased concentration of aluminum in drinking water.

Smoking, long-term use of nonsteroidal anti-inflammatory drugs and estrogens, and regular consumption of small amounts of alcohol may act as factors that reduce the likelihood of developing the disease.

Course and prognosis of dementia in Alzheimer's disease

The natural history of Alzheimer's disease is characterized by a steady decline in cognitive and "non-cognitive" functions. The average time from diagnosis to death is 9 years, but this is extremely variable. Ultimately, the patient becomes bedridden and requires full care. Death often occurs from intercurrent illnesses (eg, pneumonia). More rapid mortality is observed in older individuals, men, patients with more severe impairment of daily life activities, more severe dementia, and more severe aphasia. Race, marital status, and educational level do not significantly affect survival. Algorithms have been developed that can, based on clinical data, predict future life expectancy or the moment when it becomes necessary to place the patient in a nursing home. They also allow one to assess the impact of pharmacotherapy on survival and quality of life.