Medicamentous treatment of Alzheimer's disease and dementia
Prof. Judith Aharon-Peretz, Prof. Ramit Ravona
With an increase in life expectancy, the number of people suffering from cognitive decline and dementia is steadily increasing.
Dementia describes a clinical condition in which loss of cognitive functions and/or changes in behavior cause functional deterioration in everyday life. Dementia can be caused by various causes, most often, as a result of degenerative-inflammatory processes in brain tissue and/or cumulative damage to brain vessels. For the overwhelming majority of patients suffering from dementia, there is still no treatment that can lead to a cure or complete cessation of the deterioration of cognitive and behavioral functions. In a minority of cases, dementia is the result of infectious, inflammatory and immune processes that damage brain tissue. Correct diagnosis and quick treatment in these cases can lead to a reversible process and ideal recovery. A medical diagnosis is necessary for the identification of various factors of cognitive decline and changes in behavior, as well as for the identification of situations that may exacerbate cognitive and behavioral disorders and a condition that, with proper treatment, may be reversible.
Among the diseases that cause dementia, Alzheimer's disease is the most common, but not the only one. Most of the drugs available today are intended for patients suffering from Alzheimer's disease. Medicines for the treatment of other diseases that cause dementia are still in research.
Often, at the beginning of Alzheimer's disease, it is characterized by memory impairment. Later, disorders in the area of language functions and orientation, disorders in behavior, difficulties in planning and difficulties in making decisions will be added. Gradually, difficulties are added to everyday functions. From a patho-anatomical point of view, the disease is characterized by deposits of protein material, beta-amyloid, which accumulates in the cortex of the brain and forms a "plaque", around which the skeletons of destroyed brain cells and inflammatory cells are concentrated. In addition, in amyloid deposits around blood vessels and when brain cells are lost, neurofibrillary tangles are formed, which are formed as a result of tau protein deposition with its excessive phosphorylation. These processes disrupt the ability of brain cells to contact each other and process information necessary for standard cognitive behavioral processes.
In addition to amyloid and tau-protein deposits, pathological protein deposits can be noted in the brain of most people suffering from dementia (as a result of Alzheimer's disease or another degenerative pathology). Often also damage to blood vessels occurs. Clinical manifestations usually reflect the totality of brain pathologies.
The methods of treating Alzheimer's disease offered today - both clinical and research - are based on knowledge about brain pathology accumulated over many years and causing cell damage, as well as a lack of substances responsible for the transmission of information (neurotransmitters) between brain cells. Pathological processes appear many years before cognitive decline occurs, and are not necessarily accompanied by the appearance of dementia. Researchers hope that in the future it will be possible to find the causes of various early brain pathologies, and offer treatment even before brain tissue is damaged.
Since the cause (or causes) of Alzheimer's disease (and other diseases that cause cognitive decline and dementia) is not clear, and since the pathology of the brain in most dementia diseases is combined, today the therapeutic approach includes preventive measures and the study of known risk factors, as well as the balance of damage caused by impaired activity of neurotransmitters. Recently, a treatment was proposed that tries to balance known pathologies (deposition of protein in brain tissues).
Balance of risk factors : Risk factors for vascular diseases - such as hypertension, high lipid levels and diabetes - are recognized risk factors for Alzheimer's disease and vascular diseases of the brain. It is assumed that they are also risk factors for other diseases that cause cognitive decline and dementia. Correct treatment of these diseases can delay and possibly even prevent cerebral vascular pathology and the onset of dementia. Cognitive and physical activity for approximately 150 minutes per week can also delay the onset of the disease.
Treatment of symptoms caused by a decrease in the level of neurotransmitters ( neuromediators ).
These treatment methods are called symptomatic because they treat clinical symptoms and usually do not significantly change the cause of the disease.
Symptomatic treatment of Alzheimer's disease includes treatment that strengthens the cholinergic system, treatment that suppresses the glutamatergic system, and treatment of behavioral disorders.
Preparations that strengthen the cholinergic system : the goal of some neurons affected by Alzheimer's disease is to provide cholinergic innervation to the cerebral cortex. It was found that in animals this innervation affects the processes of concentration and memory. A substance released by cholinomimetic nerve endings is called acetylcholine. Alzheimer's disease is caused by a lack of acetylcholine, which worsens as dementia progresses. Preparations Donepezil (Aricept, Asante, Memorit, Donepezil), Rivastigmine (Exelon in capsules and patches) and Galantamine (Reminil) increase the level of acetylcholine in the brain, delaying its decay. Acetylcholine naturally breaks down by means of a catalyst called acetylcholinesterase. The above-mentioned preparations inhibit this catalyst, and therefore are called acetylcholinesterase inhibitors. Among the common side effects of these drugs, it is possible to note nausea, diarrhea and increased sweating, which usually depend on the dose. A gradual increase in the dose and/or transition to another inhibitor or drug used in another way - for example, patches - are useful for avoiding these symptoms. Clinical studies demonstrated a positive influence on the functions of attention, concentration and memory in patients with Alzheimer's disease undergoing treatment. The effect of preparations lasts about two years, and sometimes even longer. Treatment may delay the need for hospitalization of the patient in a patronage institution. The moderate effectiveness of these drugs was also proven among patients suffering from vascular dementia and dementia with Lewy bodies. Acetylcholinesterase inhibitors are approved in Israel only for the treatment of Alzheimer's disease, they are included in the drug basket and are sold under different commercial names.
Medicines that modulate the action of glutamate : Мемантин (Мемокс, Абикса, Намада, Аксура). Memantine inhibits NMDA receptors and suppresses the pathological influence of elevated glutamate levels on brain cell function. Glutamate is necessary for the implementation of cognitive processes in general, and also for learning and memory in particular, however, when its concentration exceeds the necessary norm, it becomes a toxin that destroys brain cells and disrupts their functioning. Memantin regulates the level of glutamate, not disrupting its action, which is necessary for learning and memory processes. In clinical trials conducted on people, it was found that treatment with memantine slows the decline of cognitive functions and improves behavioral disorders in patients suffering from moderate to severe dementia. General side effects: pain in the stomach, diarrhea, anxiety. This drug is not included in the medication basket. Hospital insurance companies partially participate in the payment of the drug, as a rule, at the expense of additional insurance.
Preparations for balancing recognized pathologies in Alzheimer's disease inhibit and reduce the accumulation of amyloid proteins and tau proteins. The first drug approved by the FDA is Aduhelm (Aducanumab). The drug was approved in an accelerated process. It is still used in research. The drug Lecanemab (Lecanemab) was approved by the American FDA as part of the usual process, and became the first among new drugs that are considered to change the course of the disease and are approved for use in diagnosed patients suffering from Alzheimer's disease. The clinical results of the studies, in which the effectiveness of the preparations was tested, demonstrated a small clinical but statistically significant effect among patients who underwent treatment in the early stages of the disease. This treatment did not stop the progression of the disease and did not restore the lost cognitive functions, however, it was able to slow down the cognitive and functional decline of abilities for several months after undergoing the treatment. The preparations are monoclonal antibodies that act on the beta-amyloid protein and significantly reduce its concentration in the brain. The effectiveness of preparations for other diseases that cause dementia has not been verified. Among the frequent side effects during drug treatment can be attributed cerebral edema, usually in a mild clinical form, and small hemorrhages in the brain tissue. Also, it became known that two patients, who were simultaneously taking anti-coagulant drugs, died as a result of cerebral hemorrhage. The researchers assumed that, probably, this complication was connected with the reception of the above-mentioned anticoagulant preparations.
These drugs are not approved for treatment in Israel and are not included in the medication basket.
Additional drugs that reduce the concentration of amyloid proteins and/or tau proteins and/or suppress the inflammatory processes occurring in the brain of patients are at the stage of research.
Prescription drugs and food additives:
Екстрак лицьев растение гинкго двулопастного : гинкго двулопастный has a beneficial influence on the system of neuromediators. In Israel, the drug Egb761 - Cerbonin - a dosed and high-quality extract of the leaves of the Ginkgo biloba plant - has been registered as a prescription drug for the treatment of cognitive decline among the elderly. This substance is relatively safe to use. Былі повены данные о склености к броемдениемим. Tserbonin is not included in the basket of medicines in Israel. Food additives ginkgo двулопастного can be purchased without a prescription.
phosphatidylserine (phosphatidylserine): sold in Israel as a food additive. This substance was tested in several studies with the participation of elderly people who complained of cognitive decline, as well as among persons with moderate cognitive decline and those diagnosed with dementia. Some studies demonstrated a slight improvement in the results of cognitive tests and everyday functions. This substance is relatively safe to use. Phosphatidylserine is not included in the medicine cabinet in Israel.
To date, the clinical effectiveness of additional food supplements has not been verified.
Preparations for the treatment of mental and behavioral symptoms. Psychic and behavioral symptoms - such as depression, apathy, absent-mindedness, hallucinations, anxiety, anxiety, etc. d. - very common in all types of dementia, and often even precede memory impairment or other cognitive functions. These symptoms may be the result of various factors – the disease itself, an emotional reaction to the disease, environmental factors (e.g., the behavior of loved ones), other diseases (e.g., urinary tract infections), pain, discomfort, and boredom. The first stage of dealing with these symptoms is non-medicinal in nature and includes clarifying the development of symptoms (gradual or acute development), checking the patient's state of health and environment, as well as identifying factors that can amplify or weaken symptoms.
Existing drugs were developed mainly for the treatment of other diseases. Among patients suffering from dementia, these drugs are less effective and may cause side effects. Their use should be considered only when non-medicinal treatment methods have been exhausted, and take into account the potential damage that can be caused to the patient, taking into account the patient's suffering and the consequences of his behavior among others.
Below is a specific link to medication treatment of common types of behavioral disorders in dementia, or disorders that cause the most suffering.
Medicinal treatment of depression in patients with dementia : research conducted so far among patients suffering from depression in the course of dementia does not adhere to a single method of treatment with antidepressants. Also, there is no sufficient information regarding the optimal duration of treatment. The decision on pharmacological intervention should be based on the degree of depression, the patient's health, other drugs he is taking, and the depressive symptoms he is showing.
Options for treating anxiety in patients with dementia include antidepressants, antipsychotic drugs (such as Risperidone, Olanzapine, etc.), or sedatives from the benzodiazepine family (such as Lorivan or Vaben). These drugs are often effective, but associated with risk (falls, elevated risk of death or stroke, deterioration of cognitive status), so their use must be compared with the relatively expected benefit. Recently, the antipsychotic drug Brexipiprazole was approved for the treatment of anxiety among patients suffering from Alzheimer's disease. Rules and considerations applicable to other antipsychotic drugs among patients with dementia also apply to this drug.
Cannabis: The Ministry of Health recently approved the use of medical cannabis (preparations rich in CBD, but not THC) for the treatment of patients with dementia who suffer from severe behavioral disorders that do not respond to conventional treatment methods. This treatment received only minor support, and it was based on several small studies.
Sleep disturbance : despite the lack of justification in the literature regarding the use of sleeping pills among patients with dementia, in practice, drugs from the benzodiazepine family (e.g., Bondormin), other families (e.g., Zolpidem), melatonin, antipsychosomatic drugs (e.g., Seroquel) or antidepressants (e.g., Mirtazonal (Miro)) are often used in practice. Causes of sleep disorders (for example, shortness of breath from heart failure) or non-observance of sleep hygiene (in view of prolonged sleep).
The above description is only a brief description and cannot replace the diagnosis or the choice of the appropriate treatment by the attending physician.
Предупреждение! Medicines are provided exclusively according to the doctor's prescription.
