Alzheimer's is a neurodegenerative disease (gradual destruction of neurons) that leads to dementia (progressive and irreversible loss of cognitive functions such as memory, language, thought, among other things).  It's a fatal disease and is the most common form of dementia (60-70% of dementia cases are of Alzheimer's).

 

The impact of dementia on the environment where we live

• Of the 200,000 Portuguese people with dementia, 60-70% suffer from Alzheimer's disease.

• "7.3 million European citizens suffer from one of the several forms of dementia."

Associação Alzheimer Portugal.Noticias:Informações para os jornalistas: Fact-sheet,Retirado de  Fact-Sheet | Associação Alzheimer Portugal (último acesso a 1 de novembro de 2020,16h21)

• Dementia is currently the fifth leading cause of death in the world.

 

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Types of Alzheimer

There’s two types of Alzheimer:

1. Sporadic Alzheimer´s disease, which usually occurs in people with 65 years or more, but could affect people of any age. Of the two types of Alzheimer's, this is the most common and could or not affect people who could have cases of history of Alzheimer's disease in their families. From the late beginning, it looks like it doesn't exist heredity in sporadic Alzheimer's disease.

2. Familiar Alzheimer´s disease is characterized by being genetically transmitted from a generation to another. "If one of the parents has a gene mutated, each child will have 50% of chances of inheriting it. The gene´s presence means the possibility of the person develop Alzheimer usually between 40 and 60 years-old." 

 

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Symptoms

The main symptoms that affect a patient with Alzheimer's disease are:

• Memory loss that disrupts daily life;

• Challenges in planning or solving problems;

• Difficulty completing familiar tasks at home, at work or for leisure;

• Confusion with time or place;

• Trouble understanding visual images and spatial relationships;

• New problems with words when speaking or writing;

• Misplacing things and losing the ability to retrace steps;

• Decreased or poor judgment;

• Withdrawal from work or social activities;

• Changes in mood and personality including apathy and depression.

 

The different stages of Alzheimer's disease

There are three phases which characterize the life of a patient who suffers Alzheimer:

• The initial phase is characterized by the symptoms mentioned above.

• The moderate phase is recognized by the aggravation of the symptoms:

- Difficulty in recognizing family and friends;

- getting lost in known environments;

- Hallucinations, inappetence, weight loss, urinary incontinence;

- Difficulties with speech and communication;

- Movements and repetitive speech;

- Sleep disorders;

- Problems with routine actions;

- Progressive dependence;

- Vacancy;

- Start of motor difficulties.

• The advanced phase is characterized mainly by total dependence:

- Total dependence;

- Increasing immobility;

- Urinary and fecal incontinence;

- Tendency to assume fetal position;

- Mutism;

- Restricted to armchair or bed;

- Presence of pressure ulcers (sores);

- Progressive weight loss;

- Frequent urinary and respiratory infections;

- End of communication.

 

Memory Loss

We can say that the symptom that most characterizes this disease is memory loss. As a consequence of this symptom, these patients sometimes run safety risks, have difficulties communicating, and sometimes behaving. There are different types of memory loss:

Episodic memory consists on forgetting recent episodes, such as if someone says they go to the café, within a few minutes the patient no longer remembers what he was told, however, episodes of the past are quite present. "Memories of ancient events, although not very affected, tend to interfere with current activities. This can result in the person performing routines from the past, which no longer matter."

Semantic memory is known for the difficulty of communicating with people, since these patients do not remember the meanings of words, for example, the word car.

The memory of procedure is characterized by the forgetfulness of how to perform some routine activities, such as dressing, also by the forgetfulness of conducting their mental actions, for example playing chess.

 

 

Risk factors

• Age

• Dementia family history

• Female

• Tobacco, coronary heart disease, atherosclerosis, treated diabetes, obesity, high cholesterol, high pressure etc...

• Low sociocultural level

• History of head injuries

• Small cranial perimeter

• Down Syndrome

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Prevention

As prevention to Alzheimer's disease, I´m going to present some measures which could reduce the risk of developing this disease:

• Keep your brain active;

• Have a healthy diet;

• Practice physical exercise;

• Do checks up regularly;

• Participate in social activities;

• Don’t smoke, drink in moderation; 

• Sleep well;

• Protect the head from injury;

 

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Non-specific Alzheimer's disease injuries

There are two injuries in the brain which are important to detect if a person could be suffering from Alzheimer, although they aren´t specific injuries of the disease: 

• The senile plates are found mainly in the cerebral cortex, have in their constitution a nucleus of amyloid substance and a crown of axons associated with glial cells (auxiliary cells that support the functioning of the central nervous system). The protein β - amyloid is present on amyloid substance, this protein derivate from a precursor protein, APP (Amyloid Precursor Protein).  

• Neurofibrillary degeneration is characterized by abnormal neurofilaments arranged in pairs of helix filaments (PHF), this injury is marked by anti-t-PHF antibodies. In this injury is present an abnormal protein denominated tau(τ), which is hyperphosphorylated.

 

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Chromosomes

Chromosome 21 (APP)

As I had already mentioned, the toxic amyloid protein is originated from the Amyloid Precursor Protein. The protein that forms the senile plates (toxic amyloid) is encoded on chromosome 21. The people who suffer from down syndrome, also known as trisomy 21 present a mutation where they have one more copy on chromosome 21, so these produce 1.5 times more protein, making them more likely to have Alzheimer´s. 

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Chromosomes 1 and 14

Preseline 1 associated with chromosome 14 and preseline 2 mapped on chromosome 1 are very similar structure proteins, but there are many doubts as to their functions. However, they are two proteins associated with the rare form of Family Alzheimer's Disease (transmitted from generation to generation.

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Chromosome 19

The gene that is located on chromosome 19 has so far been the most studied. In men these genes are presented in three forms types 2, 3, and 4. "Everyone has two Apolipoprotein genes: they can be of the same type (2.2; 3.3 or 4.4), or a combination of two types (2.3; 2.4; 3.4). It has been discovered that people with at least one type 4 gene and especially those with two (4.4) have an increased risk of developing Alzheimer's disease earlier than other people with other types of Apolipoprotein E. Nevertheless, half of the 85-year-olds who have 2 copies of apolipoprotein E type 4 have no symptoms of Alzheimer's at that age." 

Researchers have not yet figured out why it happened, but they claim that those with type 2, especially type 2:2, "seem to be protected from the development of AD (Alzheimer's disease)". 

 Associação Alzheimer Portugal. Doença de Alzheimer: Demência: Demência e Hereditariedade, Retirado de Demência e Hereditariedade | Associação Alzheimer Portugal (último acesso a 5 de dezembro de 2020,14h56)

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Treatment / medicines

Although Alzheimer's is an increasingly common disease, especially in older people, it’s not yet known any treatment, even while being the target of many studies.

Memantine is a medicine that has as a function the decrease of symptoms. It is an NMDA glutamate receptor antagonist drug. When there are extremely high concentrations of glutamate (neurotransmitter), there will be a big entrance of calcium on the brain cells, which will, consequently, cause damage. The memantine is in charge of connecting these receptors, blocking the glutamate, preventing excessive calcium intake. 

Cholinesterase inhibitors have as their role the delay of disease’s progression and the decrease of symptoms. 

Acetylcholine is a neurotransmitter that plays an important role in memory.  

In Alzheimer's patients, the acetylcholine is presented by very low values, due to enzymes (cholinesterases) which deteriorate this neurotransmitter. These cholinesterase inhibitors, as indicates by the name, are going to prevent/inhibit the cholinesterases from destroying acetylcholine, so these could be communicated between the nerve cells and improve or stabilize symptoms. 

There are 3 cholinesterase inhibitors licensed for use in Portugal: the Donepezil, the Rivastigmine (that could be taken by capsules, by a liquid solution, or by a transdermal patch), and finally Galantamine.

The cognitive, behavioral, mood, and motor function changes, not specific to AD, lead to an Alzheimer's patient also need to take pharma codes for their symptomatic control, use of non-specific medications such as antipsychotics, antidepressants, anxiolytics, etc. 

There are other therapeutics to be studied, however, there are still many contraindications, like estrogen treatment, anti-inflammatory medicines, folate and vitamin B12, vitamin E, statins, Gingo Biloba, and Brahmi. 

 

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Grey matter and white matter

These two matters present themselves with a role in our central nervous system. Grey matter is the grouping in the spinal cord and brain, dendrites, and cell bodies of neurons. These agglomerations thus have grey color. Gray matter has the function of "controlling the muscular system and sensory perception of individuals".

The white matter is characterized by the coating of myelin in the axons, this substance gives it a whitish color. This matter has the responsibility to "transmit different messages quickly within the gray matter, thus causing the commands to be answered in a short time."

Our brain consists of these two masses, the grey is more in a peripheral (cortex) part and the white part in a more central part. If the white mass suffers an injury there will be demyelination (damage caused to the myelin sheath, leads to a decrease in white mass), as a consequence, the person may begin to have some slowness in his thought, something that is very characteristic of this disease and that is visible in an image of a brain of AD patients. This phenomenon is common in many other pathologies such as dyslexia, ADHD, etc.

 

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Diagnosis

At the moment, there is no specific test that can determine if a person suffers from Alzheimer's, the diagnosis is made by excluding other diseases that the patient may have that could cause the symptoms he presents. This exclusion is made through various physical tests, such as blood and urine tests to detect other possible diseases, X-rays, an electroencephalogram (EEG), Computed Axial Tomography (CT), analysis of the Raquidiano Liquid or Magnetic Resonance (the decrease in the cortex and the hypothalamus, evidence of cell death). 

There are also other exams performed by specialists, such as neurologists or psychiatrists, for example neuropsychological examinations (“to identify the conserved capacities and assess problematic areas, e.g: the comprehension and discernment”), examinations of mental state (“to assess intellectual functions which could be affected by dementia, ex: memory, reading, writing, and calculus abilities"), psychiatric assessments ("to identify treatable disorders that may mimetize dementia, e.g: depression, and monitor psychiatric symptoms that may occur along with dementia, e.g: anxiety and delusions"). 

Associação Alzheimer Portugal. Doença de Alzheimer: Demência Precoce, Retirado de  Demência Precoce | Associação Alzheimer Portugal (último acesso a 5 de novembro de 2020, 17h42)

 

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Curiosity

The ignorance of the causes that lead people to suffer from this disease, causes the scientific community to seek relationships with other aspects that are part of human life. While the research was being done on possible causes, some scientists came across the herpes virus present in the brain of these people, this caused a further investigation of this situation, but the theories are very controversial. This herpes virus is not the typical cold sores virus.