Alzheimer’s disease is a progressive form of senile dementia, leading to a complete loss of cognitive abilities, developing mainly after 60-65 years. Clinically manifested by a gradual and constantly progressive disorder of cognitive abilities: attention, memory, speech, praxis, gnosis, psychomotor coordination, orientation and thinking. The diagnosis of Alzheimer’s disease allows a thorough collection of anamnesis, PET of the brain, the exclusion of other types of dementia using EEG, CT or MRI. Treatment is palliative, includes medication (cholinesterase inhibitors, memantine) and psychosocial (art therapy, psychotherapy, sensory integration, presence simulation) therapy.
G30 Alzheimer’s disease
Alzheimer’s disease got its name from the name of a German psychiatrist who first described it in 1906. The incidence on average ranges from 5 to 8 people per 1000 population, which is about half of all cases of dementia diagnosis. Globally, according to 2006 data, the number of patients with Alzheimer’s disease amounted to 26.5 million people. There is a clear trend of increasing morbidity, which makes the problem of diagnosis and treatment of this pathology one of the important tasks of modern psychiatry and neurology.
There is a significant correlation between the incidence of Alzheimer’s type dementia and age. So, in the age group of 65 years, there are about 3 cases of the disease per 1000 people, and among people aged 95 years, there are already 69 cases per 1000. The prevalence rate of this pathology in developed countries is much higher, since their population has a longer life expectancy. Among women, Alzheimer’s disease is more common than among men, which is partly attributed to their higher life expectancy compared to men.
Until now, the etiopathogenesis of Alzheimer’s type dementia remains a mystery for scientists and practitioners in the field of medicine. No connection has been established with any external factors triggering Alzheimer’s disease. It is only known that the morphological substrate of the disease is the formation of intra-neuronal neurofibrillary plexuses and cerebral accumulations of beta-amyloid, the so-called “senile plaques”, which leads to degeneration and death of neurons. There is also a decrease in the level of choline acetyltransferase. These features formed the basis of 3 main hypotheses trying to explain how Alzheimer’s disease develops.
The older is the cholinergic theory of the occurrence of the disease, linking it with acetylcholine deficiency. However, the results of clinical studies have shown the inability of acetylcholine preparations to at least partially or temporarily stop Alzheimer’s disease. The amyloid hypothesis of the development of the disease has existed since 1991. According to it, the basis of pathology are accumulations of beta-amyloid. Interestingly, the gene encoding the beta-amyloid precursor protein is part of the 21st chromosome, the trisomy of which is the basis of Down syndrome. At the same time, all patients with Down syndrome who have reached the age of 40 have Alzheimer-like pathology.
The predisposing factors for the synthesis of pathological beta-amyloid are the insufficiency of mitochondrial oxidation processes, a more acidic reaction of the intercellular medium, and an increased number of free radicals. Deposits of pathological amyloid are noted both in the cerebral parenchyma and in the walls of cerebral vessels. It should be noted that such deposits characterize not only Alzheimer’s disease, they are observed in cerebral hematomas of congenital genesis, Down syndrome and in normal aging processes.
According to the third hypothesis, Alzheimer’s disease is associated with the death of neurons as a result of the accumulation of hyperphosphorylated tau protein in them, the strands of which stick together and form tangles. According to the tau hypothesis, protein accumulation is associated with a defect in its structure; the formation of plexuses causes the disintegration of intra-neuronal transport, which in turn leads to disruption of signal transmission between neurons, and then to their destruction. On the other hand, the formation of neurofibrillary tangles is also observed in other cerebral degenerations (for example, in progressive supranuclear paralysis and frontotemporal atrophy). Therefore, many researchers deny the independent pathogenetic significance of tau protein, considering its accumulation as a consequence of the mass destruction of neurons.
Among the possible causes triggering Alzheimer’s disease is the synthesis of pathological apolipoprotein E. The latter has an affinity for amyloid protein and participates in the transport of tau protein, which may underlie the typical morphological changes of the disease described above.
According to many researchers, Alzheimer’s disease is genetically determined. 5 main genetic sites have been identified, which are associated with the development of the disease. They are located on chromosomes 1, 12, 14, 19 and 21. Mutations in these loci lead to disorders of the protein metabolism of cerebral tissues, resulting in the accumulation of amyloid or tau protein.
In typical cases, Alzheimer’s disease manifests in people older than 60-65 years. It is extremely rare to find cases of an early form of the disease that occur in the period from 40 to 60 years. Alzheimer’s type dementia is characterized by an inconspicuous and prolonged onset, steady progression without periods of improvement. The main substrate of the disease is disorders of higher nervous functions. The latter include: short-term and long-term memory, mindfulness, spatial-temporal orientation, psychomotor coordination (praxis), the ability to perceive various aspects of the external world (gnosis), speech, control and planning of higher neuropsychic activity. Alzheimer’s disease is divided into 4 clinical stages: pre-dementia, early, moderate and severe dementia.
Pre – dementia
At the stage of pre-dementia, subtle cognitive difficulties arise, often revealed only during detailed neurocognitive testing. From the moment of their appearance to the verification of the diagnosis, as a rule, 7-8 years pass. In the vast majority of cases, memory disorders for recent events or information received the day before come to the fore, significant difficulties if necessary to remember something new. Some problems with executive functions: cognitive flexibility, ability to concentrate, planning, abstract thinking and semantic memory (difficulty remembering the meaning of some words) usually go unnoticed or are “written off” to the patient’s age and the physiological aging processes occurring in his brain structures. At the stage of pre-dementia, apathy may be observed, which is a typical neuropsychiatric symptom that is persistently present at all stages of the disease.
The low severity of the symptoms of pre-dementia makes it possible to attribute it to the preclinical stage of the disease, after which more pronounced cognitive changes develop that characterize Alzheimer’s disease itself. A number of authors refer to this stage as mild cognitive disorders.
Progressive deterioration of memory leads to such pronounced symptoms of its violation that it becomes impossible to attribute them to the processes of ordinary aging. As a rule, this is the reason for the assumption of the diagnosis of “Alzheimer’s disease”. At the same time, different types of memory are violated to varying degrees. Short—term memory – the ability to remember new information or recent events – suffers the most. Such aspects of memory as the unconscious memory of previously learned actions (implicit memory), memories of distant life events (episodic memory) and facts learned long ago (semantic memory) suffer little. Memory disorders are often accompanied by symptoms of agnosia — disorders of auditory, visual and tactile perception.
In some patients, executive function disorders, apraxia, agnosia or speech disorders come to the fore in the clinic of early dementia. The latter are characterized mainly by a decrease in the rate of speech, depletion of vocabulary, and a weakening of the ability to express their thoughts in writing and orally. However, at this stage, during communication, the patient quite adequately operates with simple concepts.
Due to disorders of praxis and movement planning when performing tasks using fine motor skills (drawing, sewing, writing, dressing), the patient has a clumsy appearance. In the stage of early dementia, the patient is still able to independently perform many simple tasks. But in situations that require complex cognitive efforts, he needs help.
Progressive inhibition of cognitive functions leads to a significant decrease in the ability to perform independent actions. Agnosia and speech disorders become obvious. Paraphasia is noted — the loss of the grammatical structure of speech and its meaning, since patients are increasingly using incorrect words instead of forgotten words. This is accompanied by a loss of writing skills (dysgraphy) and reading skills (dyslexia). The growing disorder of praxis deprives the patient of the ability to cope even with simple everyday tasks, such as dressing, undressing, self-eating, etc.
In the stage of moderate dementia, there are changes in long-term memory, previously unaffected by the disease. Memory disorders progress to such an extent that patients do not even remember their closest relatives. Neuropsychiatric symptoms are characteristic: emotional lability, sudden aggressiveness, tearfulness, resistance to care; vagrancy is possible. Approximately 1/3 of patients with Alzheimer’s disease have a false identification syndrome, etc. manifestations of delirium. There may be urinary incontinence.
The speech of patients is reduced to the use of individual phrases or single words. In the future, speech skills are completely lost. At the same time, the ability to perceive and maintain emotional contact with others remains for a long time. Alzheimer’s disease in the stage of severe dementia is characterized by complete apathy, although sometimes aggressive manifestations can be observed. Patients are exhausted both mentally and physically. They are unable to perform even the simplest actions on their own, have difficulty moving and eventually stop getting out of bed. There is a loss of muscle mass. Due to immobility, complications such as congestive pneumonia, bedsores, etc. develop. It is the complications that ultimately cause a fatal outcome.
One of the main areas of diagnostic search is the collection of anamnesis and complaints. Since the patient himself often does not notice the changes taking place with him in the early stages of the disease, and with the development of dementia he cannot adequately assess his condition, the survey should be conducted among his relatives. Of great importance are: the inability to accurately determine the onset of cognitive abnormalities, indications of the gradual and steadily progressive nature of the aggravation of symptoms, the absence of a history of cerebral diseases (encephalitis, intracerebral tumor, brain abscess, epilepsy, chronic ischemia etc.) and traumatic brain injuries.
It is quite difficult to diagnose Alzheimer’s disease in the pre-dementia stage. During this period, only extended neuropsychological testing can reveal some disorders of higher nervous functions. During the study, patients are asked to memorize words, copy shapes, perform complex arithmetic operations, read and retell what they read.
In order to exclude other diseases that can lead to the development of dementia, a neurologist conducts a neurological examination, prescribes additional examinations: EEG, REG, Echo-EG, CT or MRI of the brain. Of particular importance in confirming the diagnosis is the detection of beta-amyloid deposits during brain PET with the introduction of Pittsburgh compound B. Recently, it has been proven that another marker of the disease can be the detection of tau protein or beta-amyloid in cerebrospinal fluid taken for analysis by lumbar puncture.
Differential diagnosis of Alzheimer’s type dementia is carried out with vascular dementia, parkinsonism, dementia with Lewy bodies, dementia with epilepsy, and other neurological pathology.
Alzheimer’s disease treatment
Unfortunately, currently available treatments are unable to cure Alzheimer’s disease or slow down its course. All attempts at therapy are essentially palliative and can only slightly alleviate the symptoms.
The most recognized drug regimens include memantine and anticholinesterase drugs. Memantine is an inhibitor of glutamate receptors, the excessive activation of which characterizes Alzheimer’s disease and can lead to the death of neurons. There is a moderate effect of memantine in moderate and severe dementia. When taking it, side effects are possible: dizziness, confusion, headache, hallucinations.
Cholinesterase inhibitors (rivastigmine, donepezil, galantamine) have shown moderate efficacy in attempts to treat Alzheimer’s disease in the stage of early and moderate dementia. Donepezil can be used for severe dementia. The use of cholinesterase inhibitors in the pre-dementia stage could not prevent or slow down the development of symptoms. Side effects of these medications include: bradycardia, weight loss, anorexia, muscle spasms, gastritis with increased acidity.
In cases where Alzheimer’s disease is accompanied by antisocial behavior, antipsychotics may be prescribed to stop aggression. However, they can cause cerebrovascular complications, an additional decrease in cognitive functions, motor disorders and, with prolonged use, increase the mortality of patients.
Along with pharmacological methods, psychosocial methods of treating patients with Alzheimer’s disease are used. Thus, supportive psychotherapy is aimed at helping patients with early dementia adapt to their disease. In the stages of more pronounced dementia, art therapy, sensory room, memory therapy, presence simulation, sensory integration, validation therapy are used. These techniques do not lead to clinically significant improvement, however, according to many authors, they reduce anxiety and aggressiveness of patients, improve their mood and thinking, mitigate individual problems (for example, urinary incontinence).
Prognosis and prevention
Unfortunately, Alzheimer’s disease has a disappointing prognosis. The steadily progressive loss of the most important functions of the body leads to death in 100% of cases. After diagnosis, the average life expectancy is 7 years. Less than 3% of patients live for more than 14 years.
Since Alzheimer’s disease is an important social problem in developed countries, many studies have been conducted to determine the factors that reduce the likelihood of its development. However, such studies provide contradictory data and there is still no solid evidence of the preventive value of at least one of the factors under consideration.
Many researchers tend to consider intellectual activity (love of reading, passion for chess, solving crosswords, proficiency in several languages, etc.) as a factor delaying the onset of the disease and slowing its progression. It is also noted that the causal factors of the development of cardiovascular pathology (smoking, diabetes mellitus, increased cholesterol levels, hypertension) cause a more severe course of Alzheimer’s type dementia and may increase the risk of its occurrence.
In connection with the above, in order to avoid Alzheimer’s disease and slow down its course, it is recommended to lead a healthy lifestyle, stimulate thinking and exercise at any age.