Alzheimer’s disease is a degenerative disease that causes a progressive decline in cognitive ability and memory. Gradually, the destruction of nerve cells occurs in areas of the brain related to memory and language. Over time, the affected person has more and more difficulty memorizing events, recognizing objects and faces, remembering the meanings of words, and exercising judgment.

In general, symptoms appear after 65 years of age and the prevalence of the disease increases sharply with age. However, contrary to popular belief, Alzheimer’s disease is not a normal consequence of aging.

Alzheimer’s disease is the most common form of dementia in the elderly; it represents about 65% of dementia cases. The term dementia encompasses, in a very general way, health problems marked by an irreversible decrease in mental faculties.

Alzheimer’s disease is distinguished from other dementias by the fact that it progresses gradually and mainly affects short-term memory in its early stages. However, the diagnosis is not always obvious and it can be difficult for doctors to differentiate Alzheimer’s disease from Lewy body dementia, for example.

Is there a difference between normal aging and Alzheimer’s disease?

Alzheimer’s can be seen as a very accelerated form of aging. In theory, if we lived to be 150 or 160 years old, it is almost certain that we would all have Alzheimer’s. According to the researcher, for Alzheimer’s to occur in your sixties, you have to be predisposed to the disease through heredity, lifestyle, etc.

Prevalence of Alzheimer’s disease

Alzheimer’s disease affects approximately 1% of people aged 65 to 69, 20% of people between 85 and 89, and 40% of people between 90 and 951. According to the Alzheimer’s Association, approximately 5 million people are living with Alzheimer’s disease in the United States.

It is estimated that 1 in 8 men and 1 in 4 women will suffer from it in their lifetime. As women live longer, they are more likely to one day have it.

Due to the prolongation of life expectancy, this disease is becoming more and more common. It is estimated that within 30 years, the number of people affected will nearly triple in the United States.

The brain damage

Alzheimer’s disease is characterized by the appearance of very specific lesions, which gradually invade the brain and destroy its cells, neurons. Neurons in the hippocampus, the region that controls memory, are the first to be affected. It is not yet clear what causes these lesions to appear.

Dr. Alois Alzheimer, a German neurologist, gave his name to the disease in 1906. He was the first to describe these brain lesions, during the autopsy of a woman who died of dementia. He had observed abnormal plaques and tangles of nerve cells in her brain, now considered to be the main physiological signs of Alzheimer’s disease.

Below are the 2 types of damage that appear in the brains of sufferers:

• The excessive production and accumulation of beta-amyloid proteins in certain areas of the brain. These proteins form plaques, called amyloid plaques or senile plaques, which are associated with the death of neurons.
• The “deformation” of certain structural proteins (called Tau proteins). The way neurons are entangled is then changed. This form of injury is called neurofibrillary degeneration.

In addition to these lesions, there is inflammation that contributes to damage to neurons. There is not yet a treatment that can stop or reverse these pathological processes.

Causes of Alzheimer’s disease

The causes of Alzheimer’s disease are not known. In the overwhelming majority of cases, the disease appears due to a combination of risk factors. Aging is the main factor. Risk factors for cardiovascular disease (hypertension, high cholesterol, obesity, diabetes, etc.) also appear to contribute to its development. It is also possible that infections or exposure to toxic products play a role in some cases, but no formal evidence has been obtained.

Genetic factors also play an important role in the onset of the disease. Thus, certain genes can increase the risk of being affected, although they are not the direct cause of the disease. In fact, researchers have found that approximately 60% of people with Alzheimer’s disease carry the Apolipoprotein E4 or ApoE4 gene.

Another gene, SORL1, also seems to be often involved. However, many people carry these genes and will never have the disease, and conversely, some people without these genes can develop the disease.

There are also hereditary forms of the disease but which account for less than 5% of cases. Only 800 families have been listed in the world. Children with a parent who has Alzheimer’s disease in its inherited form have a 1 in 2 risk of having the disease themselves. Symptoms of the familial form appear early, sometimes before the age of 40. However, even if several members of the same family are affected by this disease, it does not necessarily mean that it is an inherited form.

Evolution of of Alzheimer’s disease

Alzheimer’s disease progresses over several years and its progression varies greatly from person to person. We now know that the first lesions appear in the brain at least 10 to 15 years before the first symptoms.

These usually appear after the age of 60. On average, once the disease occurs, life expectancy is 8 to 12 years. The older the disease occurs, the more quickly it tends to get worse. When it manifests around the age of 60 or 65, life expectancy is approximately 12 to 14 years; when it occurs later, life expectancy is only 5 to 8 years. It is currently impossible to stop the progression of the disease.

• Light stage. Occasionally memory loss occurs. Short-term memory – the ability to remember recent information (a new phone number, the words on a list, etc.) is most affected. People with the disease try to overcome their difficulties by resorting to memory aids and to their relatives. Mood changes and slight disorientation in space can also be observed. It is more difficult for the person to find his words and to follow the thread of a conversation. At this point, it is not certain that it is Alzheimer’s disease. Over time, symptoms may remain stable or even decrease.
• Moderate stage. Memory problems get worse. Memories of youth and middle age become less precise but are better preserved than immediate memory. It is increasingly difficult for people with the disease to make choices; their judgment begins to be impaired. For example, it gradually becomes more difficult for them to manage their money and plan their daily activities. The disorientation in space and time becomes more and more evident (difficulty remembering the day of the week, birthdays, etc.…). People with the disease find it increasingly difficult to express themselves verbally;
• Advanced (or terminal) stage. At this stage, the patient loses his or her autonomy. Permanent monitoring or accommodation in a health center becomes necessary. Psychiatric problems may develop, including hallucinations and paranoid delusions, aggravated by severe memory loss and disorientation. Sleep problems are common. Patients neglect their personal hygiene, become incontinent, and find it difficult to eat on their own. If left unattended, they can wander in vain for hours.

Between the moderate and advanced stages, unusual behavioral problems sometimes arise: for example, aggression, atypical, foul language, or changes in personality traits.

The person can die of another disease at any stage of Alzheimer’s. However, in its advanced stage, Alzheimer’s disease becomes a fatal disease, like cancer. Most deaths are caused by pneumonia caused by difficulty swallowing. People suffering from Alzheimer’s disease are at risk of getting saliva or part of what they eat or drink into their airways and lungs. This is a direct consequence of the progression of the disease.

Diagnostic of Alzheimer’s disease

Be careful: just forgetting your keys, an appointment or someone’s name doesn’t mean you have Alzheimer’s disease. This occasional forgetfulness is normal at any age and is usually related to inattention. If they are frequent, they can mask a depressive or anxious state. Only tests done by a doctor can tell if you have a real memory problem. Often, it is family members who are worried about their loved ones and request a consultation.

To make the diagnosis, the doctor will use the results of several medical examinations. First, he or she will ask the patient to find out more about how the memory loss and other daily difficulties manifested themselves. Tests to assess cognitive faculties will then be performed, as appropriate: tests of vision, writing, memory, problem-solving, etc. If memory impairment occurs, even with attentiveness, the patient’s test performance will be abnormal.

In some cases, various medical tests can be performed to rule out the possibility that the symptoms are due to another health problem (vitamin B12 deficiency, poor functioning of the thyroid gland, stroke, depression, etc.).

If deemed necessary, the doctor may also advise the patient to have a brain imaging test (preferably MRI, magnetic resonance imaging) to observe the structure and activity of different areas of the brain. Imaging can show the loss of volume (atrophy) in certain areas of the brain, characteristic of degeneration of neurons.

Hope for early diagnosis

There is a lot of research going on around the world to create tools to diagnose the disease at an earlier stage, when memory loss is mild or even before symptoms appear. This is because the disease sets in insidiously long before the symptoms of dementia appear. Several tests, still experimental, show that it is possible to obtain an early diagnosis: memory tests, brain imaging tests, or even blood or cerebrospinal fluid analyzes.

Symptoms of Alzheimer’s disease

• Short-term memory impairment (unable to remember names of new people, events of the previous hours or days, etc.);
• Difficulty retaining new information;
• Difficulty performing familiar tasks (locking doors, taking medication, finding objects, etc.);
• Language difficulties or aphasia (difficulty finding words, speech less understandable, use of invented or inappropriate words);
• Difficulty following a conversation, a thought process;
• Difficulty or inability to plan (meals, budget, etc.);
• Gradual loss of sense of direction in space and time (difficulty finding the day of the week, remembering the season, birthdays, time of day, inability to find one’s way back);
• Disorders of gestures or apraxia (difficulty writing, buttoning a jacket, using everyday objects, washing…);
• Difficulty grasping abstract concepts and following reasoning;
• Difficulty recognizing objects, faces of relatives (agnosia);
• Gradual impairment of long-term memory (loss of memories of childhood and adulthood);
• Changes in mood or behavior, sometimes aggression or delirium;
• Personality changes;
• Gradual loss of autonomy.

People at risk Alzheimer’s disease

• People aged 60 and over. Age is the main risk factor: the risk of developing the disease doubles every 5 years from the age of 65;
• Women (because they live longer than men);
• People who have a parent or sibling with Alzheimer’s disease. Their risk of being affected in turn is increased by 10% to 30% compared to the rest of the population;
• People whose parents have the inherited familial form of Alzheimer’s disease. Children with an affected parent have a 50% chance of having the disease themselves;
• People of Hispanic and African American descent are more likely to have the disease (up to twice as much).

Risk factors of Alzheimer’s disease

• Systolic hypertension;
• Hypercholesterolemia;
• Diabetes poorly controlled by medication;
• Smoking.
• Factors of less importance
• Severe trauma to the head with loss of consciousness (occurring, for example, among boxers);
• Obesity;
• A personal history of depression.

Prevention of Alzheimer’s disease

Currently, there is no clearly effective way to prevent Alzheimer’s disease. However, certain measures seem to help preserve cognitive faculties and reduce the risk of developing the disease. Here are the most studied.

General measures

It is possible to reduce the risk of suffering from Alzheimer’s disease by intervening medically, paying attention to one’s lifestyle (healthy eating, physical exercise, etc.), and avoiding certain risk factors, such as high blood pressure, diabetes, high cholesterol, and smoking.

Hormone replacement therapy in women going through menopause or taking nonsteroidal anti-inflammatory drugs (such as aspirin and ibuprofen) may provide some protection against Alzheimer’s disease, studies show. But prospective studies on this subject have been negative.

Food

Various studies have been carried out to find out whether a particular diet can prevent Alzheimer’s disease by delaying aging. Here are 3 avenues currently being explored:

• The Mediterranean diet

This type of diet, typical of the countries bordering the Mediterranean, protects against cardiovascular diseases and improves life expectancy. It is distinguished, in particular, by high consumption of olive oil, fruits, vegetables, and fish and by moderate ingestion of red wine.

This diet may help prevent Alzheimer’s disease. A prospective study conducted in 2006 among 2,258 Americans indicates that people whose diet is closest to the Mediterranean diet run a lower risk of suffering from Alzheimer’s disease. The same team of researchers also noticed that this type of diet reduced the mortality associated with the disease.

These observations were confirmed in 2009 by a study carried out on a cohort of 1,796 French people aged 65 and over. According to the study, the Mediterranean diet is associated with less cognitive decline. The scientists partly explain its protective effect on neurons thanks to its high content of antioxidants. Eicosapentaenoic acid (EPA), an omega-3 fatty acid found in fish, appears to be particularly protective;

• Calorie restriction

A low-calorie diet slows aging and increases life expectancy. Scientists wanted to know if the number of calories ingested daily influenced the risk of suffering from Alzheimer’s disease. In a 4-year prospective study published in 2002, US researchers collected data on the dietary intake of 980 people aged 75, on average. During the study, 242 people developed Alzheimer’s disease.

The subjects who consumed the most calories and who had a genetic background that predisposed them to this disease (they carried the ApoE4 gene) were more affected than those who absorbed the fewest calories. Animal studies suggest that calorie restriction increases the resistance of brain neurons to Alzheimer’s disease, Parkinson’s disease, and stroke. It also helps limit normal neuronal loss associated with age;

• A diet rich in antioxidants

Numerous studies confirm that antioxidants reduce the damaging effects of free radicals on neurons. Although there is not yet enough evidence to recommend a specific diet that can prevent Alzheimer’s disease, according to the authors of a scientific literature review, certain foods rich in antioxidants should be favored. The authors emphasize foods rich in folic acid, vitamin B6, and vitamin B12.

Physical activity

The benefit of regular physical activity for the prevention of dementia and cognitive decline has been shown by several epidemiological studies and recent clinical trials. One of them showed that a moderate physical training program, at home (3 sessions of 50 minutes per week, or 20 minutes of walking per day, for 24 weeks), allowed to improve the cognitive performances of people with memory impairment. In addition, adults who exercise regularly appear to be less frequently affected by Alzheimer’s disease.

Mental training

Several recent prospective studies have shown that people who regularly engage in stimulating mental activities (reading, learning, memory games, etc.), regardless of their age, are less likely to suffer from dementia. Let us quote, for example, the case of the famous Nun Study, an epidemiological study focusing on aging and Alzheimer’s disease.

This study has been carried out since 1986 among 678 nuns of the Order of the School Sisters of Notre Dame, a community where the average age is 85 and where many sisters are over 90 years old. In these nuns, who lead healthy lives, eat good food, and have little stress, the rate of Alzheimer’s disease is significantly lower than that of the general population. Significantly, many of them are highly educated and engage in highly demanding intellectual activities for their age.

Thus, keeping an active mind throughout one’s life seems to promote the maintenance and growth of connections between neurons, which would delay dementia. In addition, some believe that a high level of education makes it easier to pass the cognitive tests used to diagnose Alzheimer’s disease. This would allow the effects of the disease to be compensated for longer.

Several ongoing trials are trying to assess the effects of regular mental training in people with early Alzheimer’s disease. However, it appears that the effects of this type of exercise are less marked when cognitive decline has started.

Treatment of Alzheimer’s disease

To this day, there is no cure for Alzheimer’s disease. However, several drugs are in development and are promising. Therapeutic approaches, which are currently in the research stage, aim to tackle the pathological process of the disease with the hope of curing or halting it. In addition, there are drugs that alleviate the symptoms and improve cognitive functioning to some extent.

The effectiveness of treatments is evaluated by the doctor after 3 to 6 months. If necessary, the treatments are then modified. At the moment, the benefits of the treatments are modest and the drugs do not prevent the disease from progressing.

Medicines

The following drugs are prescribed. We cannot know a priori which one will suit the patient best. It can take a few months to find the right treatment. According to studies, after 1 year of medication, 40% of people see their condition improve, 40% are stable and 20% have no effect.

• Cholinesterase inhibitors

They are mainly used to treat mild to moderate symptoms. This family of drugs helps to increase the concentration of acetylcholine in certain areas of the brain (by decreasing its destruction). Acetylcholine allows the transmission of nerve impulses between neurons. People with Alzheimer’s disease have been found to have lower amounts of acetylcholine in the brain because the destruction of their nerve cells reduces the production of this neurotransmitter.

• NMDA receptor antagonist

Memantine hydrochloride (Ebixa®) has been given to relieve moderate or severe symptoms of the disease. This molecule acts by binding to NMDA (N-methyl-D-aspartate) receptors located on neurons in the brain. It thus takes the place of glutamate which, when present in large quantities in the environment of neurons, contributes to the disease. There is no indication, however, that this drug slows down the degeneration of neurons.

Current research

Significant efforts are being invested in the search for new drugs. The main objectives are to:

• Destroy the beta-amyloid protein plaques, by injecting antibodies capable of suppressing them. These plaques are, in fact, one of the most important brain lesions in the disease. Such an antibody has been developed (the name of the molecule is bapineuzumab) and is under clinical evaluation in people with the disease. This approach is called a “therapeutic vaccine”. Another solution tested would be to activate certain brain cells (microglia) to eliminate the plaques in question;
• Replace the neurons. The scientific community has high hopes for replacing neurons destroyed by the disease with transplantation. Nowadays, researchers are able to create cells that resemble neurons from stem cells obtained from human skin. However, the method is not quite perfect. It does not yet make it possible to create neurons which have all the properties of “natural” neurons.

Physical exercise

Doctors strongly encourage people with Alzheimer’s disease to exercise. It improves strength, endurance, cardiovascular health, sleep, blood circulation, and mood, and increases dynamism and energy levels. In addition, physical exercise has particularly beneficial effects for people with this disease:

• it helps to maintain motor skills;
• it gives an impression of meaning and purpose;
• it has a calming effect;
• it maintains the level of energy, flexibility and balance;
• it reduces the risk of serious injury in the event of a fall.

Social support

Seen as a component of treatment, social support for patients is crucial. Doctors advise a variety of strategies for family and caregivers of patients.

• Make regular visits to patients to offer them support, according to their needs;
• Provide them with memory aids;
• Create a stable and calm living structure in the house;
• Establish a bedtime ritual;
• Ensure that their immediate environment presents little danger;
• Make sure they always have a card (or bracelet) in their pocket with an indication of their medical condition, as well as phone numbers in case they get lost.

In conclusion

We must stress the importance of controlling the risk factors for cardiovascular disease because they are modifiable factors that can help in preventing Alzheimer’s disease. The only long-term study that has successfully shown a reduction in new cases of dementia is a study on the treatment of high blood pressure. Prevention of dementia thus becomes an additional reason to maintain optimal blood pressure control throughout adulthood.

Unfortunately, the occurrence of obesity and diabetes in epidemic proportions in our society is likely to increase the risk of developing dementia as we age. Again, a change in lifestyle can reduce the risk.

With regard to developments in research, there is a strong movement to initiate treatments much earlier in Alzheimer’s disease, before the stage of dementia is reached. We know that the disease is detectable in the brain a few years before significant memory problems. Brain imaging will play an increasingly important role in diagnosis. Talk to your doctor for a possible screening.