Alzheimer's disease

Alzheimer's disease (Alzheimer's disease) is the most common cause of dementia. It is associated with symptoms such as memory loss and orientation problems. You can find out more about symptoms, diagnosis and therapy here

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Alzheimer's disease - briefly explained

Alzheimer's disease is a common cause of the development of dementia. It manifests itself through an increasing loss of mental abilities, such as increasing forgetfulness, difficulties in orientation or language comprehension and changes in personality. The disease is associated with the deposition of certain proteins in the brain, the beta-amyloid and the tau protein. In addition, an immune reaction is observed in the brain. This is followed by loss of function and death of the nerve cells and nerve cell connections. The exact cause of the change in protein has not yet been finally clarified. Alzheimer's disease not only has drastic consequences for those affected, it also often means a considerable burden for relatives and carers. In order to spare the sick and their families as much suffering as possible, it is necessary to make the diagnosis early and treat the symptoms with medication. However, Alzheimer's disease is not curable.

What is Alzheimer's Disease?

Alzheimer's dementia, also known as Alzheimer's disease, is the best-known and most common cause of dementia. According to the international classification of diseases (ICD-10), dementia is an acquired memory and thinking disorder that is so pronounced that it impairs everyday professional and / or private activities. According to this classification system, the disorder must have existed for at least six months.

According to estimates, a good million people in Germany currently suffer from dementia, and it is estimated that 47 million people are affected worldwide. Two thirds of people with dementia have Alzheimer's disease, around 700,000 people. Both sexes are equally prone to developing Alzheimer's disease. However, around 70 percent of people with Alzheimer's disease are female, as the likelihood of developing Alzheimer's disease increases with age. Therefore, experts justify this primarily with the different life expectancy of both sexes. Women currently live an average of six years longer than men. Alzheimer's disease affects around one percent of people over 65, around 15 percent of those over 80 and almost one in three people over 90.

In the latest studies there are increasing indications that the incidence of new cases of dementia has decreased worldwide in recent years. A similar trend can also be seen in Germany, adjusted for age. However, with increasing life expectancy, it is assumed that the disease will increase overall.

The doctor Alois Alzheimer

© W&B

History of Alzheimer's Disease

Alzheimer's disease was first described by the Bavarian neurologist Alois Alzheimer (1864 to 1915) at the beginning of the 20th century. He carried out detailed studies on patients with abnormal behavior and acquired mental deficits. In the course of these examinations, Alois Alzheimer also studied the brains of the deceased patients and linked the results with his observations. The scientist published his findings for the first time in 1906 in a pioneering work that was not recognized worldwide until later. He had succeeded in describing a new, independent clinical picture.

Causes: How does Alzheimer's disease come about?

The exact cause of Alzheimer's disease is not yet known. In the patients, however, there is an increasing number of characteristic protein deposits that were already observed by Alois Alzheimer and that probably play a central role. On the one hand, these are so-called senile plaques, which consist of protein fragments (beta-amyloid peptide). On the other hand, it is about fibrous deposits, the so-called neurofibrillary tangles, which consist of abnormal, clumped / accumulated protein (tau protein with too many attached phosphate groups). In addition, Alzheimer's dementia is associated with an altered concentration of certain messenger substances (neurotransmitters) in the brain. In addition, there is increasing evidence that neuroinflammation, i.e. inflammation in the nervous system due to dysregulation of the immune system, plays an important role in the development of Alzheimer's disease.

  • Beta amyloid and tau protein

Experts assume that a certain protein, the so-called beta-amyloid, plays a central role in the development of Alzheimer's. It is a cleavage product of a larger protein molecule, the function of which is not yet precisely known. Beta-amyloid deposits, so-called senile plaques, are found in particularly high density in the gray matter of the brain of Alzheimer's patients.

The deposits consist of a central amyloid core, which is surrounded by abnormally altered nerve cell processes, reduced synapses (contact points between nerve cells) and activated astrocytes, the most common cell type in the brain. In many patients, the amyloid is also deposited in the wall of small blood vessels. This can worsen their permeability, which affects the oxygen and energy supply to the brain.

It has not been conclusively clarified why the abnormal accumulation of beta amyloid occurs. Because it could be shown that the protein in the human body is produced constantly and throughout life. The highest concentrations are found in the nerve cells (neurons), where beta amyloid is a by-product of a normal metabolic process. While the amyloid deposits are necessary for diagnosis, they are not sufficient on their own. These plaques can also be found in people who have not developed dementia into old age. Nowadays it is assumed that it is less the plaques than structural changes of the amyloid (conformational changes / misfolding or smaller, soluble aggregates, so-called oligomers) that trigger pathological processes.

It is also typical of Alzheimer's disease that synapses are lost and, in the further course, neurons die. This is associated with the formation of abnormally changed protein (tau-protein), which is deposited in the brain in the form of fibers, the fibrils. These are the bundles of neurofibrils already described by Alois Alzheimer.

These tangles, which can be detected within many nerve cells, consist of the so-called tau protein, which is actually a normal component of the cell skeleton. However, in Alzheimer's disease, the tau protein becomes excessively loaded with phosphate groups. This can disrupt stabilization and transport processes in the cell, which ultimately leads to their demise. Misfolded tau protein spreads along with the increase in disease symptoms in connected nerve networks (spreading).

  • Changed messenger substance concentrations

Another characteristic of Alzheimer's dementia is the changed concentration of certain messenger substances (neurotransmitters) in the brain. Above all, these include acetylcholine and glutamate. Both substances are of central importance for the normal function of nerve cells and the transmission of signals between neurons. Since nerve cells perish in different areas of the brain, this leads on the one hand to a deficiency in acetylcholine. On the other hand, excessive glutamate is formed.

  • The role of genes

The question is repeatedly asked whether dementia, especially Alzheimer's disease, is hereditary. The risk of developing Alzheimer's disease is slightly higher in first-degree relatives than in the rest of the population. This type of inheritance is probably based on a large number of genes that create a so-called predisposition - that is, increase the risk of developing Alzheimer's disease. The most common risk gene is the apolipoprotein E gene (ApoE gene) in the epsilon 4 variant, which increases the risk of Alzheimer's disease about three to ten times. In very rare cases Alzheimer's is "firmly" (dominant) anchored in the genes. Several such genes are known so far and anyone who carries such a gene can pass it on to their children.

The diseases inherited with the "fixed Alzheimer's genes" usually occur relatively early from the age of 30. The benefit of genetic tests, which could be used to prove who has the corresponding genetic makeup, has so far been controversial. Among other things, because so far there are no medical measures available that would enable the chronic disease to be cured and safely avert the threat of dementia.

DIAN is currently open to people from families with the dominantly inherited form of Alzheimer's disease. DIAN stands for "Dominantly Inherited Alzheimer Network", an international network for dominantly inherited Alzheimer's disease. It was founded in the USA to better research the genetic forms of Alzheimer's disease and also provides these patients with therapies in studies.

Primary and Secondary Dementia

Dementia diseases are divided into primary and secondary forms. Up to ten percent of all illnesses are secondary dementias. This is understood to mean those that develop, for example, as a result of the effects of drugs, metabolic diseases, vitamin deficiencies or depression. Brain tumors or changes that lead to increased pressure in the brain - such as drainage disorders of the cerebrospinal fluid (CSF) - can cause symptoms of dementia. If the underlying disease is successfully treated, the symptoms of dementia can partially or completely regress.

Primary dementias, on the other hand, start directly from dying tissue in the brain. The primary dementias are so far not curable. Alzheimer's disease is the most common form of primary dementia, followed by the vascular (vascular) forms and mixed dementia (Alzheimer's plus vascular dementia). Other primary dementias are frontotemporal dementia (Pick's atrophy), Lewy body disease and Parkinson’s dementia.

Symptoms: What symptoms does Alzheimer's disease cause?

Mostly it is a conspicuous forgetfulness that raises the question of the onset of dementia in the elderly concerned themselves or in their relatives. If this memory disorder is actually due to Alzheimer's disease, then by this point in time the brain has usually already undergone a gradual change that has lasted for many years. In the process, the processes and connections of nerve cells in the brain die unnoticed and later the nerve cells themselves. The decay leads to the regression of the brain tissue (atrophy). This damage slowly spreads through the brain.

Depending on the damaged area of ​​the brain, the functions and abilities located there decrease. Short-term memory, the ability to do daily routine work, the ability to make judgments and the language are dwindling little by little. The expressions of feeling, behavior, cognition and communication change. In addition, as dementia progresses, patients often lose control of urination and bowel movements.

Characteristic symptoms of Alzheimer's

Even if the symptoms and complaints of a person with dementia are usually very diverse, some characteristic signs can be recognized on closer observation. The following changes in a person should make him or his environment prick up:

  • Forgetfulness, loss of short-term memory, later also long-term memory (affected person keeps repeating the same questions; forgets the current date)
  • Difficulty doing everyday and domestic tasks correctly (a trained housewife suddenly makes mistakes when cooking, washing machine or stove can no longer be operated correctly)
  • Problems expressing themselves linguistically (person can no longer find words; uses substitute words)
  • Loss of orientation about time, space and place (the person affected no longer knows when it is Christmas; can no longer find their way around a strange, later in a familiar environment; walks around at night, sleeps during the day)
  • Decline in judgment
  • Problems with concentration and abstract thinking (affected person can no longer keep an account; can no longer complete a bank transfer)
  • Incorrect assignment of objects and circumstances (affected person puts butter in the wardrobe; goes shopping in a dressing gown)
  • Occasionally, visual disturbances occur despite normal eye function (faces and objects are not recognized, the person concerned reaches out to them)
  • Changes in behavior (affected person is overly suspicious; has sudden, extreme mood swings)
  • Personality disorders (previously balanced person becomes aggressive; develops unfounded fears)
  • Loss of drive (person generally loses interest in current affairs, work and hobbies; withdraws more and more, becomes depressed)

Course of Alzheimer's dementia

The course can be very different from person to person. Alzheimer's disease, however, is a chronically progressive process that has so far been delayed with medication, but cannot be permanently averted. The process can be divided into three stages, each of which - with individual differences - can last for several years:

Symptoms of early Alzheimer's disease

  • Memory and retentiveness disorders
  • Mood swings
  • Problems in performing difficult tasks, loss of performance
  • Loss of precise linguistic expression
  • Ability to work and social contacts significantly reduced

Middle-stage symptoms

  • All intellectual performance losses increase as well as changes in psyche and personality
  • The patient is often still able to lead an independent life to a certain extent, but increasingly needs support in everyday practical matters

Late stage symptoms

  • The patient is no longer able to live without outside help. Personal hygiene alone is no longer possible, the short-term memory is almost completely extinguished

In the initial phase, those affected notice that they are becoming more forgetful, can make bad decisions or are no longer able to fully carry out their daily work. Often this leads to further reactions such as anger, shame, fear or frustration with the consequence of withdrawing further from the social environment. Often the perception of the complaints differs between those affected and relatives. The lack of insight into the symptoms of the disease (anosognosia) can be part of Alzheimer's disease. If physical symptoms and their consequences are added at a later stage, this also worsens the situation: For example, seizures, loss of control over posture (falls) and over the bladder and bowel function and swallowing disorders can occur. The leading cause of death in Alzheimer's patients is infection.

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Diagnosis: how is Alzheimer's disease diagnosed?

According to the traditional doctrine of neuropathologists and coroners, the diagnosis of Alzheimer's disease can only be made with 100% certainty by microscopic examination of the brain after death. Nevertheless, there are now numerous ways to diagnose or exclude a clinically probable Alzheimer's dementia in patients. Advances in biomarker diagnostics mean that conclusions can also be drawn about the underlying cause in living patients.

The following conditions make the presence of Alzheimer's dementia extremely likely if other diseases that may be associated with these or similar symptoms have been excluded:

  • Memory impairment and, in the further course of the disease, usually at least one of the following symptoms: Speech disorders (aphasia), apraxia (patient has a movement disorder, although he is motorically healthy, for example can no longer find his jacket sleeves), agnosia (patient has problems closing objects recognize even though the sense organs are intact), difficulties in planning, solving problems and abstracting
  • Acquired, profound impairment of everyday practical skills (for example, the inability to make a sandwich, go shopping yourself or the like)
  • insidious onset of symptoms
  • persistent persistence of the disturbances
  • progressive course

Basic diagnostics include the following steps:

  • The doctor takes a detailed medical history of the patient (together with relatives / people who know the patient well).
  • This is followed by a physical exam.
  • Standardized tests provide information on intellectual performance and abilities. In addition, it is important to estimate how well the patient is still able to carry out activities of everyday life. Well-known short test procedures are the Mini-Mental-Status-Test (MMST), Montreal Cognitive Assessment Test (MoCA) or the DemTect (dementia detection). The clock test, which can be carried out quickly and easily, in combination with the other short test procedures mentioned, can increase the diagnostic significance. In the case of questionable or mild dementia, detailed neuropsychological test diagnostics are used.
  • Blood tests help rule out other causes of dementia such as infections, vitamin deficiencies, or an underactive thyroid.
  • Examinations of the brain water are now routine in specialized memory consultations. The specific markers (biomarkers) that are typically changed in Alzheimer's disease (beta-amyloid, tau protein) can be determined in the cerebrospinal fluid.

With imaging methods such as computer or magnetic resonance tomography (CT or MRT), preferably MRT, the brain structures can be assessed and indications of brain changes typical of Alzheimer's or other dementia diseases can be found. In addition, using imaging methods, among other things, vascular diseases of the brain can be detected or tumors can be excluded.

Suhlmann watch test

© W & B / Neurolog. Polyclinic Munich-Großhadern

TO THE PICTURE GALLERY

© W & B / Neurolog. Polyclinic Munich-Großhadern

Shulmann watch test

The clock mark test according to Shulmann is a quick test to determine dementia. With this exercise you can get a first impression of the memory function of a person.

The person concerned is asked to draw the face of a clock and enter a given time with the hands, such as "Please draw a clock on which the time 3:35 p.m. can be seen"

© W & B / Neurolog. Polyclinic Munich-Großhadern

Evaluation of the test

There is a point system from one to six, which are awarded according to various criteria such as correct entry of a dial and correct pointer setting. As in the school grading system, one point here means everything was drawn correctly, with four points there are significant restrictions such as missing digits in the clock face, incorrect numbers (> 12) or clearly shifted intervals between the number of hours. With six points it is impossible for the person concerned to draw a clock at all

© W & B / Neurolog. Polyclinic Munich-Großhadern

In the case of dementia, it is increasingly difficult for those affected to enter the correct time or even to draw a clock face

© W & B / Neurolog. Polyclinic Munich-Großhadern

In the further course of the disease, it is impossible for those affected to draw a clock with the hands

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Therapy: How is Alzheimer's disease treated?

Alzheimer's disease cannot yet be cured. However, there are various medications that can help reduce the rate of dementia and improve memory. Various other therapeutic measures can promote the mental abilities of the person affected and alleviate the symptoms. Especially in advanced stages of the disease, it is important to ensure good nursing care for those affected and to relieve the relatives.

  • Non-drug treatment

Non-drug treatment measures make a decisive contribution to improving the symptoms, the quality of life and the independence of the Alzheimer's patient as well as relieving the burden on caring relatives and caregivers. Such measures include, above all, everyday training and aim to stimulate the body and mind.

Different specialists should work together in order to provide the patients with the best possible care. This includes the family doctor, geriatrician, (geronto) psychiatrist, neurologist or neurologist as well as physiotherapists, occupational therapists, speech and language therapists, home care workers and social workers and workers. It is also important to educate and train relatives and caregivers. There are good programs here via self-help groups, but also care support centers and other initiatives, which, in addition to general knowledge about the disease, include management with regard to patient behavior, communication, coping strategies and relief options for relatives as well as integration into the treatment of dementia sufferers.

As sensible non-drug measures have proven themselves and are recommended in the current guidelines: cognitive stimulation, occupational therapy (especially in the home environment), reminiscence procedures (memory maintenance) and physical activation even in the stage of mild dementia. From the stage of moderate dementia, multi-sensory procedures (such as Snoezelen, aromatherapy, touch) are also recommended.

Other useful aspects are the adjustment of the daily routine and the living conditions (milieu therapy), structured leisure activities, consideration of the life story of the individual patient (biography work), special respect and acceptance of the patient as a whole person (validation), treatment of speech disorders (speech therapy), Physiotherapy as well as art and music therapy. And finally, as the disease progresses, the patient increasingly needs nursing help. It has been shown that the use of medical nutrition in the early stages leads to improved memory performance.

  • Medical therapy

The drugs mentioned below, so-called anti-dementia drugs, are used in the therapy of Alzheimer's dementia to improve memory performance and cope with everyday life with individually varying degrees of success. The aim of this treatment is to maintain the independence and quality of life of the dementia patient for as long as possible and to reduce the amount of care required.

Cholinesterase inhibitors

In the early and middle stages, drugs that inhibit the enzyme cholinesterase, which breaks down the messenger substance acetylcholine, are suitable. This means that the neurotransmitter acetylcholine is again increasingly available for signal processing in the brain. The currently used active ingredients in this group are: Donepezil, galantamine, rivastigmine.

For all three remedies, there is evidence of an improvement in brain performance and everyday skills from numerous study results. However, the tablets can also have side effects. Symptoms such as nausea, vomiting, and diarrhea can occur. Such undesirable effects are less and less common when treatment is started with a lower drug dose and then slowly increased. There is evidence that cholinesterase inhibitors can also be effective in the advanced stages of Alzheimer's disease. Further treatment can be useful.

Memantine

The active substance Memantine influences the receptor of the neurotransmitter glutamate in the brain. With Memantine can improve attention and everyday skills - especially in advanced dementia. The tablets should be dosed rather low at the beginning and then the dose should be increased. Side effects of Memantine can include: dizziness, internal and physical restlessness and over-excitability. General shows Memantine fewer side effects than the acetylcholinesterase inhibitors. Memantine is effective in the middle and late stages. The effect of Memantine has not been proven in the early stages of Alzheimer's disease.

Prevention: How can you prevent Alzheimer's disease?

There is no measure that ensures that dementia can be safely prevented. However, a healthy lifestyle also contributes to "brain health". Therefore, general risk factors, which also cause cardiovascular diseases, should be reduced, such as smoking, obesity, high blood pressure, diabetes or physical inactivity. Maintaining social contacts also seems to be of great importance for "brain health".

You can find more information online at:

  • German Alzheimer's Society
  • Alzheimer's Research
  • German Dementia Aid - DZNE Foundation for Brain and Health
  • Germany's Alzheimer's Researcher - Hirnliga e.V.

Prof. Dr. Christine von Arnim

© W & B / Stephan Höck

Our advisory expert:

Professor Dr. med. Christine von Arnim is a specialist in neurology. It bears the additional designations "Clinical Geriatrics" and "Palliative Medicine". She received her clinical and scientific training in Freiburg, Mannheim, Harvard and Ulm and completed her habilitation in Ulm in 2006. Ms. von Arnim headed a research group on Alzheimer's dementia at the Ulm University Clinic and was a senior physician at the Neurology Clinic there. From 2016 to 2019 she was chief physician at the Clinic for Neurogeriatry and Neurological Rehabilitation in Ulm. In 2019 she moved to Göttingen University Hospital as director of the geriatric department.

Swell:

  • Alzheimer's Disease Handbook, Frank Jessen (Ed.), 2018, De Gruyter (Verlag), ISBN 978-3-11-040345-9
  • Press D., MD; Alexander M., MD. "Prevention of dementia", ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (accessed on December 13, 2019)
  • Keene, D.C., MD, PhD; Montine T.J., MD, PHD; Kuller L. H., DrPH. "Epidemiology, pathology, and pathogenesis of Alzheimer's disease," ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (accessed on December 13, 2019)
  • Association of the Scientific Medical Societies in Germany (AWMF), S3 guideline "Dementia", long version - January 2016. Online: https://www.awmf.org/uploads/tx_szleitlinien/038-013l_S3-Demenzen-2016-07.pdf ( accessed on 16.09.2020)
  • Alzheimer Research Initiative e.V., "Alzheimer's Disease". Online: https://www.alzheimer-forschung.de/alzheimer/ (accessed on September 16, 2020)
  • Word Healt Organization, risk reduction of cognitive decline and dementia, WHO GUIDELINES. Online: https://apps.who.int/iris/bitstream/handle/10665/312180/9789241550543-eng.pdf?ua=1 (accessed on September 16, 2020)

Important note: This article contains general information only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor. Unfortunately, our experts cannot answer individual questions.

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