Istinye University, Faculty of Medicine, Department of Clinical Sciences, Department of Pharmacology and Clinical Pharmacology
"Alzheimer's disease, seen especially in people aged 65 and over, causes progressive damage to neurons in various parts of the brain, causing progressive impairments in learning and memory. It is the most common neurodegenerative disease and one of the major causes of death in elderly people in the world, and there is no effective, complete treatment for this disease."
Description
Dementia is a clinical syndrome characterised by the progressive loss of two or more of the following cognitive (mental) functions: memory, language, personality and behaviour, executive and visuospatial function, instrumental performance abilities and/or basic activities of daily living. Alzheimer's Disease (AD), also known as Alzheimer-type dementia, is a progressive neurodegenerative disease characterised by memory loss and cognitive dysfunction and is the most common cause of dementia and the most common neurodegenerative disease.
History
AD was first described at the beginning of the last century, in 1906, by a German psychiatrist and neuropathologist named Alois Alzheimer in a patient (Auguste Deter) he met in 1901. Alois Alzheimer, who studied his patient with memory loss and bizarre behaviours for many years, examined the brain tissues after the patient's death and discovered the indicators of neuron damage in the brain, defined as “amyloid plaques” and “neurofibrillary tangles” in Kraepelin's laboratory, which constitute the basic pathophysiology (disturbances in mechanical, physical or biochemical functions that cause the disease) of AD, which will be greatly elucidated in the following years and will be named after him. However, it was only in the 1980s that beta amyloid (Aβ) peptides in plaques and tau protein in neurofibrillary tangles, the two main indicators of neuron damage underlying AD, were identified at the molecular level. It has been discovered that many factors such as a decrease in the number and function of neurons called cholinergic neurons, that have important functions in learning and memory, excessive stimulation of neurons called glutamergic neurons, which play an important role in learning and memory, neuroinflammation (inflammation in the central nervous system), oxidative stress (damage due to free radicals) contribute to AD, and research continues intensively to determine the underlying causes of the disease and to treat this disease until today.
Epidemiology (frequency of occurrence)
AD causes progressive memory loss and eventually disabilities in communication and basic daily activities and is one of the major causal factors of death in elderly people worldwide. AD mostly affects older adults. The risk of AD increases as a person passes the age of 65. Approximately one in 13 people aged 65-84 years and one in three people aged 85 years and older are living with AD. The number of people with AD worldwide is approximately 50 million and is estimated to increase to 150 million by 2050. Dementia is the seventh leading cause of death globally and a major cause of disability and dependency among elderly people, and as AD contributes to 60-70% of all cases of dementia worldwide, it is a social and economic global burden.
Medical tests for the diagnosis of Alzheimer's disease
Currently, there is no single test to determine whether a person has AD. Physicians use diagnostic tools in combination with medical history and other information, including neurological examinations, cognitive (mental) and functional assessments, brain imaging (magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET)) and cerebrospinal fluid or blood tests to make an accurate diagnosis. In addition, there are also ongoing researches to detect AD by retinal imaging in the eye and in saliva and skin, and these tests are considered to be emerging tests and biomarkers.
For this purpose, health professionals review the person's medical history, including psychiatric history and history of cognitive and behavioural changes. Information is obtained about current and past medical problems and concerns, as well as the medications the person is taking. The doctor will also ask about any significant medical conditions affecting other family members, including whether they have AD and other dementias, as AD can be genetically transmitted.
Treatment approaches
Although it was discovered more than a century ago and intensive studies have been carried out for many years to define the disease, to elucidate its processes and to treat it, unfortunately, there is still no drug or treatment method that can definitively treat AD.
The drugs used for the treatment of AD are extremely limited and there are basically “four drugs” in this field and the treatment with these drugs is classified as “symptomatic treatment” and they do not completely cure the disease and do not completely treat the damage to the neurons in the brain. Three of these four drugs are “anticholinesterase” drugs (donepezil, rivastigmine and galantamine) that increase the cholinergic activity in the brain, and one “NMDA noncompetitive antagonist” (memantine), which noncompetitively antagonises (inhibiting the biological response that occurs when the receptor is stimulated) N-methyl-D-aspartate (NMDA) receptors, a receptor subtype of glutamergic neurons, in order to reduce the excessive function of glutamergic neurons in the brain. Anticholinestreases (donepezil, rivastigmine and galantamine) are approved for the symptomatic treatment of mild to moderate Alzheimer's-type dementia and NMDA noncompetitive antagonist (memantine) is approved for the symptomatic treatment of moderate to severe Alzheimer's-type dementia.
Donepezil and galantamine are available as tablets and rivastigmine as capsules, solution and skin patches. Memantine is available in tablet and solution forms, and a newer combination form of memantine and donepezil is also available and is used for the treatment of moderate to severe Alzheimer's-type dementia.
As these drugs cannot cure AD, there has been an increased interest in disease-modifying drugs, including monoclonal antibodies (antibodies (immune cells) against a disease agent that are designed (cloned) to destroy it) that target pathophysiological (disease-causing mechanical, physical or biochemical dysfunctions) markers of AD (e.g. many monoclonal antibodies targeting Aβ plaques (e.g. aducanumab, lecanemab)). However, no clear efficacy has been achieved in clinical trials with newer drugs such as aducanumab and lecanemab, and concerns have been raised about their side effects and hence safety. In addition, although many drug trials have been conducted over the decades targeting the various disease development pathways of AD, the results have been unsatisfactory and there is still no effective and validated treatment that effectively halts the progression of AD.
To prevent AD, careful management of body mass index (BMI) and body weight, regular physical exercise (especially by adults over 65 years of age), actions that stimulate cognitive (mental) activities such as reading and playing chess, not smoking and not being in environments where tobacco is used, limiting alcohol intake, adequate and good quality sleep, avoiding diabetes with a healthy lifestyle, avoiding atherosclerosis with a healthy lifestyle and use of medication when necessary, taking precautions against cardiovascular diseases such as atrial fibrillation (uncoordinated and very rapid contraction of the atria of the heart), being careful against hypertension (high blood pressure) and orthostatic hypotension (low blood pressure that occurs when standing after sitting or lying down), being healthy and strong in old age, getting as much education as possible in early life, keeping the mind calm and avoiding daily stress are given as preliminary clinical suggestions in current scientific publications.
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