Alzheimer's disease

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900,000 people suffer from the disease in France

The disease is roughly twice as common in women as in men

Alzheimer's disease accounts for 70% of dementia syndromes

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Causes and effects

Alzheimer's disease is often suspected when a person presents with a dementia syndrome because it accounts for 70% of these disorders. It develops over several years and is detected when sufferers gradually become dependent and struggle with daily activities, such as washing, dressing and finding their way around.

How does the disease develop?

Alzheimer's disease is caused by a progressive degeneration of neurons, starting in the hippocampus (a brain structure essential for short-term memory). Several regions of the brain are then affected and the disease gradually spreads to the entire brain.
What causes this degeneration?

  • The amyloid beta peptide. It is naturally present in the brain. In the case of Alzheimer's disease, it builds up abnormally and forms amyloid or senile plaques. This build up is toxic for nerve cells.
  • The tau protein. While the amyloid plaques are formed, this protein – which structures neurons – is altered causing in turn a loss of neuronal structure, neurofibrillary degeneration and the death of nerve cells. This degeneration is very gradual and years can pass before symptoms appear.

Risk factors

The main risk factor for Alzheimer's disease is age.

But genetic makeup also has a part to play. Several genes are thought to be linked to an increased susceptibility to the disease (amyloid peptide metabolism genes, or genes involved in inflammation or communication between neurons, etc.). Conversely, it appears that some genes protect against the disease.

The environment also seems to play a part. The disease may be more likely in inactive people, those who have had repeated anesthetics, or those with untreated cardiovascular risk factors (diabetes, high blood pressure, etc.). But the environment can have a positive impact on a "cognitive reserve". It is thought that the function of lost neurons can be compensated by stimulating the brain, and the appearance of early symptoms and/or their severity can be delayed by study, a stimulating job or an active social life.

There are several stages of dementia associated with the disease:

  • Mild: Only part of the hippocampus is affected. The person suffers from memory lapses which may seem harmless but they worsen over time.
  • Moderate: Different regions of the brain are affected. The person gradually loses their independence, and has trouble recognizing family and friends.
  • Severe: The brain lesions multiply. Memories are lost and the person becomes almost completely dependent on others for daily activities.

Epidemiology

According to the World Health Organization (WHO), 50 million people suffer from dementia in the world and almost 10 million new cases are reported each year. It is also estimated that 5 to 8% of people over 60 are affected by dementia.
As there is currently no curative treatment, the total number of people living with dementia could reach 82 million in 2030 and 152 million by 2050. In 2015, the total societal cost of dementia in the world was estimated at $818 billion, i.e. 1.1% of the world's gross domestic product (GDP).
In France, the situation is just as alarming. 900,000 people suffer from the disease but if we consider the impact it has on carers, 3 million people are directly affected. €9.9 billion is allocated to medical and medico-social care for Alzheimer's disease in France. Finally, if there are no new avenues for therapy, Alzheimer France estimates that one in four French people over the age of 65 will be affected by the disease in 2020.

Diagnosis

Although there is no cure for Alzheimer's disease, it is possible to slow down its progression. It is therefore essential to get an early diagnosis to gain access to current drug therapies and receive advice on prevention and stimulating memory. Early diagnosis can also enable patients to make arrangements for the future while they are still able to think clearly and make decisions.

The French National Health Authority (HAS) recently published a guide for good diagnosis practices for health professionals. It features the different steps for diagnosing the disease.
Most often, people consult their family physician following subjective complaints from family, friends or themselves regarding certain aspects of daily life: memory loss, difficulty completing certain tasks, getting lost or losing track of time or mood swings for example.
The family physician is therefore the first contact. S/he will question the patient to rule out other causes of the symptoms described by the patient. S/he will then refer them for screening. Screening involves neuropsychological tests that assess certain aspects of memory and the completion of simple tasks. Imaging is also used to visualize the atrophy of certain brain structures (hippocampus) or the presence of amyloid plaques.

Treatment and prevention

Alzheimer's disease is a real health and societal burden for all countries with an aging population because there is currently no cure.

Four drugs are available on the market (HAS source) – donepezil, rivastigmine, galantamine and memantine. These molecules do not cure patients but slow the progression of the disease or improve certain behavioral disorders. Some improvement is observed in thought, memory, communication and daily activities.

As patients get lost and lose track of time, it is a stressful disease for sufferers and also carers and family members. Various therapeutic measures can improve the daily lives of patients. These measures are based on acknowledging the psychological impact of the disease and offering activities that improve everyday life for patients and their relationships with others (family and carers). Possible activities include those involving art (painting, sculpture, writing, music, theater, etc.), the body (light gymnastics exercises, tai chi, sophrology, relaxation, etc.) and of course cognition (memory workshops, etc.).

At the Institut Pasteur

Membrane trafic and Pathogenesis Unit, led by Chiara Zurzolo. This units studies degenerative illnesses progression mecanisms and the role of  TNTs. In Alzheimer disease, they focus on degradation mecanisms  and amyloid agregates propagation mecanisms in order to find new therapeutic targets.

Integrative Neurobiology of Cholinergic Systems Unit, led by Uwe Maskos.
This unit studies the role of nicotinic receptors in Alzheimer's disease. As an initial target of amyloid beta peptide, these receptors could be part of a new therapeutic approach.

Antibody Engineering Platform, led by Pierre Lafaye.
Scientists from this platform have developed two new types of antibody that are capable of detecting extracellular (amyloid plaques) and intracellular (neurofibrillary tangles caused by the tau protein) targets, which are typical of Alzheimer's disease.


November 2020

 

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