Some aspects of Alzheimer’s disease are still unknown to medicine, precisely because it is a neurodegenerative disease that has no cure. Its cause, diagnosis and treatment are not always precise, which makes it necessary to talk more about the condition. That is why, September 21 was named World Alzheimer’s Day.
In Brazil, at least 1.2 million people live with some form of dementia, and 100,000 new cases are diagnosed each year. Worldwide, the number reaches 55 million, with 10 million new cases per year, according to the World Health Organization (WHO).
According to estimates by Alzheimer’s Disease International, the number of individuals affected by the disease could reach 74.7 million in 2030 and 131.5 million in 2050, due to the aging of the population.
What is Alzheimer’s?
Alzheimer’s is a neurodegenerative, progressive and still incurable disease that affects, in general, people over 65 years of age, being the most common form of dementia in the elderly, explains psychiatrist Adiel Rios, researcher at the University’s Institute of Psychiatry of São Paulo (USP).
The disease sets in when the processing of certain proteins in the central nervous system begins to fail. As a result, fragments of toxic proteins appear inside neurons and in the spaces between them. This toxicity causes progressive loss of neurons in certain regions of the brain, such as the hippocampus, which controls memory, and the cerebral cortex, essential for language, reasoning, memory, recognition of sensory stimuli, and abstract thinking.
“Studies show that the disease is related to the accumulation in the brain of plaques formed by the beta-amyloid protein. Its agglutination between neurons prevents the transmission of signals, impairing all neural activity”, says Rios.
The term dementia is used to describe a set of symptoms that include memory loss, difficulty thinking and language impairment, among others. Despite being the most common cause of dementia, Alzheimer’s disease is not the only one. There are other types of neurodegenerative and cerebrovascular dementia, says Natally Santiago, a neurosurgeon at Hospital San Gennaro.
“Unlike normal brain aging, in Alzheimer’s disease pathological changes occur in the brain tissue, with protein deposition (proteinopathy) and loss of neurons,” explains Santiago.
Causes of Alzheimer’s
It is not yet known what actually causes Alzheimer’s, but it is believed to be genetically determined. According to Santiago, heredity can be considered a risk factor, but without a direct genetic transmission character to all generations.
“It is believed that the transmission of a predisposition to develop it occurs, which together with external (environmental) factors, may or may not trigger the disease”, he said.
Memory loss and behavior change are the first signs of the disease, according to the neurologist. A warning sign, according to her, is when memory loss interferes with personal activities, becomes repetitive and compromises the individual’s routine.
“With the evolution of the disease, memory is significantly compromised, with family members’ inability to recognize, to have autobiographical memories. Behavioral changes also tend to get worse”, he says. Diagnosis is clinical, made by medical evaluation. There is no marker for the disease, and blood tests and imaging help to rule out other possible causes of dementia, explains the neurologist.
In the early stages of Alzheimer’s, progressive memory failures in relation to recent events are the most striking symptoms. Old memories tend to be preserved, according to Rios. “A person can remember in detail events that happened 50 years ago, but he doesn’t remember something that happened yesterday, or a few hours ago,” explains the psychiatrist.
With the progression of the disease, the difficulty in orienting oneself in time and space begins to appear, and the inability to remember the way home, for example. Other symptoms are sleep disorders, restlessness or apathy, and even psychotic conditions, explains the psychiatrist.
In the final stage of the disease, the patient loses the ability to express himself, does not even recognize family members and is no longer able to take care of himself, demanding the presence of full-time caregivers”, says Rios.
The psychiatrist indicates how the main symptoms of Alzheimer’s:
- Memory loss
- Decrease in judgment and criticism
- reasoning difficulty
- Putting objects in an inappropriate place
- Frequent changes in mood and behavior
- Changes in personality, and the loss of initiative to carry out tasks
Risk Factors for Alzheimer’s
The disease was named after the doctor alois alzheimer. In 1906, the neuropathologist performed an autopsy on the brain of a woman who died after experiencing language problems, unpredictable behavior and memory loss.
Dr. Alzheimer discovered amyloid plaques and neurofibrillary tangles, considered the hallmarks of the disease. Know some factors that can contribute to its development:
Age: the probability of developing Alzheimer’s doubles every five years after age 65. For most people, symptoms first appear after age 60 years. Early-onset Alzheimer’s is an uncommon form of dementia that affects people under 65 years of age and usually has a hereditary factor.
Family history: genetics play an important role in an individual’s risk of developing the disease.
Head trauma: there is a possible link between the illness and repeated trauma or loss of consciousness.
Heart health: the risk of vascular dementia increases with heart problems such as high blood pressure, high cholesterol and diabetes.
As Alzheimer’s is still an incurable disease, some medications are indicated to stabilize or reduce the rate of progression of the disease, providing more time with symptom relief, generating better quality of life for patients and their families, says Santiago.
The use of the experimental drug aducanumab, indicated for the early stages of the disease, was approved by the Food and Drug Administration (FDA) – the US regulatory agency equivalent to Anvisa in June 2021. The agency has not approved a new drug for Alzheimer’s since 2003 .
The drug was developed for patients with mild cognitive impairment and is intended to slow the progression of the disease – not just relieve symptoms. Pharmaceutical company Biogen and its Japanese partner Eisai developed aducanumab, given by intravenous infusion to treat early Alzheimer’s disease. In July 2020, Biogen completed its application to the FDA and has been awaiting approval ever since.
This is the first authorization that changes the perspective of treatment against the Alzheimer’s. “The drug acts on the damaged protein in the brain of those who already have the disease”, says Jerusa Smid, coordinator of the Scientific Department of Cognitive Neurology and Aging at the Brazilian Academy of Neurology (ABN).
However, there are controversial factors about aducanumab that still need to be clarified. They involve clinical results and side effects, which should be clarified in phase 4 of the research (which tests the medication on a larger group of people), according to the neurologist.
“There is a lack of data proving the patient’s clinical improvement, in addition to the fact that the medication presents cerebral bleeding as a side effect, considered serious”, says Jerusa.
Other drugs are being studied. In March 2021, the New England Journal of Medicine published a study indicating that Eli Lilly and Company’s experimental intravenous drug, donanemab, may slow cognitive decline in people with the disease.
On July 25, 2018, additional results from an initial clinical trial for an experimental drug, the antibody called BAN2401, showed that it improved cognition and reduced clinical signs of Alzheimer’s. Details about immunotherapy were announced at a press conference during the Alzheimer’s Association’s International Conference that same year.
The first drug used on a large scale and approved by regulatory agencies, in 1993, was tacrine. However, this medicine fell into disuse with the advent of new medications, due to the difficulty in administering it and the risk of complications and adverse effects.
The medications that act on acetylcholine and that are approved for use in Brazil in cases of mild and moderate dementia are rivastigmine, donepezil and galantamine (known as acetylcholinesterase inhibitors or anticholinesterases), according to the Brazilian Alzheimer’s Association (Abraz). “All available in the Unified Health System”, says the ABN neurologist.
“Preventive measures and the use of these medications tend to improve symptoms and delay disease progression, but they definitely do not cure the disease. Alzheimer’s,” says Smid.
How to prevent Alzheimer’s
As until today medicine has not discovered what really causes the Alzheimer’s disease, measures considered to be preventive tend to delay it, not prevent it, explains Smid.
Prevention measures were listed in two meta-analyses (review of several studies) published in the scientific journals The Lancet and Journal of Neurology, Neurosurgery & Psychiatry, in 2020, which analyzed studies on prevention, treatment and care in cases of dementia, especially Alzheimer’s.
Excessive alcohol consumption, sedentary lifestyle, smoking and a nutrient-poor diet, which increases the risk of obesity, diabetes and hypertension are the main risk factors, according to the publication.
These factors, according to experts, need to be avoided with social and educational measures to improve the lives of these groups. “These actions require public health programs and individualized interventions, concluded the researchers from University College London and the University of Plymouth, both in the United Kingdom, who signed the work.
The authors concluded that two-thirds of the most promising interventions focused on lifestyle changes for healthy living, focused on avoiding risk factors for cardiovascular disease, such as high blood pressure and cholesterol levels.
The main preventive actions (by individuals or public authorities) identified by the two meta-analyses included:
- Keeping proper blood sugar and weight under control to prevent diabetes
- Keeping your weight at a healthy level, typically below a Body Mass Index (BMI) of 25
- Get as much school education as possible from childhood onwards.
- Avoid head trauma (such as concussions)
- Staying cognitively active by reading and learning new things
- Prevent or control depression
- manage stress
- Treat “orthostatic hypotension” (recurrent feeling dizzy when standing up)
- Keeping blood pressure under control from age 40 onwards
- Examine the risk of hearing loss throughout life and adopt a hearing aid if necessary (hearing loss is associated with damage to the brain region linked to memory)
- Avoid high levels of homocysteine, an amino acid that can contribute to the formation of clots in blood vessels and damage to arteries (prevention based on supplementation of B vitamins, with medical advice)
- Practice physical exercises
- Manage atrial fibrillation, which is a fast and irregular heart rate due to chaotic electrical signals in the heart (with regular medical monitoring)
- Eat foods with vitamin C or take supplements (citrus fruits such as oranges and acerola; vegetables such as carrots, yellow peppers and red peppers, and vegetables such as kale and broccoli)
- Reduce exposure to air pollution and secondhand tobacco smoke
- avoid alcohol abuse
- Avoid smoking
- have good quality sleep
- Avoid postmenopausal estrogen replacement therapy (this does not apply in cases of early menopause or perimenopause)
- Avoiding the use of dementia medications as prevention
- Combat poverty and racial discrimination