Alzheimer disease is a type of dementia that causes progressive loss of cognitive function. It is characterized by the degeneration of brain tissue, the accumulation of an abnormal protein called beta-amyloid and the development of neurofibrillary tangles.
Hence, the decline is slow and gradual and involves faculties such as memory, thought, judgment and learning ability.
Alzheimer’s disease affects women more than men , in part because women live longer. In addition, the number of people with Alzheimer’s is expected to increase considerably as the proportion of older people in the global population increases.
One of the early signs of the disease is the loss of memories . In fact, recent events are forgotten, a confusional state gradually appears, the alteration of other mental functions, speech disorders and difficulty in carrying out normal daily activities.
However, there is currently no cure. Treatment mostly involves strategies to prolong functional capabilities and may include the use of medications to slow the progression of the disease.
Finally, life expectancy is difficult to predict exactly , but death occurs on average about 7 years after diagnosis.
Alzheimer’s disease: what is it?
The term “dementia” (or major neurocognitive disorder) defines an acquired syndrome, characterized by an evident and significant cognitive decline . This decline may or may not be associated with neuropsychiatric manifestations, the seriousness of which is such as to interfere with the usual course of daily life and with the independence of the affected subject.
In fact, recent studies have shown that dementias are the consequence of a slow and progressive accumulation of neuropathological damage , which begins during adult life and then fully manifests itself with aging. In parallel, the clinical manifestations of these pathologies gradually evolve over time, initially configuring themselves with nuanced cognitive symptoms, up to the onset of full-blown dementia.
But, Alzheimer’s disease represents the leading cause of dementia (about 60% of all cases).
In Italy there are about 600,000 people affected and over three million people directly or indirectly involved in their assistance.
What’s up with the brain?
Macroscopically, the brain of an individual with Alzheimer’s has a variable degree of atrophy based on the clinical stage. Hence, atrophy mainly affects the cerebral cortex and is more marked in the anterior and mesial regions of the temporal lobes (in particular the hippocampus) and parietal. In addition, the brain grooves and ventricles appear enlarged due to the loss of substance (ex vacuo dilatation). Finally, the weight and dimensions of the organ are seriously reduced.
Instead, microscopically, the brain has extracellular deposits and intracellular inclusions defined respectively senile plaques and neurofibrillary tangles .
Alzheimer’s: age percentage
It rarely occurs before the age of 65 , becoming more frequent with advancing age, with the following incidence rates. Age Between:
- 65 and 74 years: 3%
- 75 and 84 years: 17%
- 85 years or over: 32%.
Alzheimer’s disease was first described in 1906 by the German psychiatrist and neuropathologist Alois Alzheimer.
In fact, during the Tübingen psychiatric conference, Alzheimer presented the case of a 51-year-old woman suffering from a form of dementia previously unknown.
Subsequently, in 1910 the German psychiatrist Emil Kraepelin in his treatise “Psychiatry” , described the new form of dementia discovered by Alzheimer, calling it precisely Alzheimer’s disease .
But, in defining the new disease, an Italian researcher, Gaetano Perusini, also played an important role. In fact, Perusini was part of a group of psychiatrists who preferred the anatomical study of patients over psychoanalytic treatments. This was also the Alois Alzheimer line, which followed the guidelines of the purely anatomical school of Emil Kraepelin.
Then, in 1906, in Munich, Perusini flanked Alzheimer’s in the research activity to decipher the particular form of dementia discovered.
In this study, Perusini sensed the action of “a kind of cement that glues the fibrils together”. In fact, almost 80 years in advance, including the presence of the beta-amyloid protein , the substance from which plaques are made, as a “pathological metabolic product”.
Later, this protein was later discovered, thanks to molecular biology, in 1984.
In the world
In fact, in 2010, there were 35.6 million people with dementia with an estimate of an increase of double in 2030 and triple in 2050. So, the new cases each year are about 7 million (1 every 4 seconds) and with a average survival, after diagnosis, of 4-8-years.
Healthcare costs are estimated at approximately $ 600 billion a year , with a progressive increase.
The major risk factor associated with the onset of dementia is age and, in an aging society, the impact of the phenomenon is alarming in size. Furthermore, it is expected that these diseases will quickly become one of the most significant problems in terms of public health.
The female sex is most affected and the prevalence in industrialized countries is about 8% in the over sixty-five years old and more than 20% over the age of eighty.
Despite numerous research projects to identify effective therapies, to date there is still no cure for dementia and Alzheimer’s. The therapeutic strategies available are pharmacological, cognitive and psychosocial. For chronic-degenerative diseases such as dementias, therefore, it appears necessary to define care pathways for an integrated management of the disease.
Alzheimer’s disease: world day
On the occasion of the XXV World Alzheimer Day on 21 September 2018 , the 2018 World Alzheimer Report was presented , entitled “The state of the art of research on dementia”.
This, in summary:
- Every 3 seconds, in the world, a person develops a form of dementia . Globally, dementia affects 47 million people, in Italy around 1,200,000.
- Dementia is the seventh leading cause of death worldwide and there is still no cure.
- Many countries do not yet have adequate diagnostic tools, easy access to clinical studies and specialized doctors and researchers. As the 2016 World Alzheimer’s Report already revealed, most people with dementia around the world have yet to receive a diagnosis, as well as comprehensive and ongoing healthcare.
Alzheimer’s: causes and risk factors
What are the causes of Alzheimer’s? Unfortunately, they are not yet known. In fact, 90% of all cases are sporadic , that is, they occur without inheritance between the generations of a family. Instead, in 10% of cases, the disease occurs in a family form , with the presence of at least two affected subjects among first degree relatives.
But, the genetic factor seems to play an important role. Thus, a parent with Alzheimer’s is 50% likely to pass on the abnormal gene to each child. In addition, about half of these children generally develop Alzheimer’s disease before the age of 65.
In Alzheimer’s disease, we are witnessing the progressive degeneration of some parts of the brain , the loss of nerve cells and the reduction of reactivity towards the chemical messengers that transmit signals between the cells (neurotransmitters).
The level of acetylcholine , a neurotransmitter involved in cognitive functions such as memory and learning, is also quite low.
Abnormal brain tissue
Alzheimer’s disease causes the following abnormalities in brain tissue:
- beta-amyloid deposits : accumulation of beta-amyloid (an abnormal and insoluble protein) since the cells are no longer able to metabolize and remove it
- senile or neuritic plaques : thickening of dead nerve cells around a beta-amyloid nucleus
- neurofibrillary tangles : rolled strands of insoluble proteins in the nerve cell
- high tau levels : an abnormal protein that makes up neurofibrillary and beta-amyloid tangles.
Thus, these anomalies occur with advancing age, within certain levels, in all people, but are much more frequent in those affected by Alzheimer’s disease. However, it is not yet known whether these anomalies directly determine Alzheimer’s disease or whether they are secondary to other pathologies that cause both dementia and abnormalities in the brain tissue.
Risk factors, apart from the advancement of age and the genetic component, there are also aspects related to lifestyle . So, they are largely editable factors like:
- alcohol intake
- vitamin deficiency
- poor physical activity
- reduced mental and social activities.
In addition, diabetes, hypercholesterolemia, hypertension, obesity and dyslipidemia are other risk factors associated with Alzheimer’s, as well as some brain trauma, cerebrovascular disease and vascular disease . Even a low schooling and an unbalanced diet are aspects associated with an increased risk of contracting the disease.
But, some ongoing studies are also investigating the incidence of pollution or exposure to some toxic substances as a possible risk factor.
Main risk factors
There are 7 main risk factors:
- physical inactivity
- low level of education.
Alcohol abuse, brain trauma and vascular pathologies follow.
Instead, the protection factors represent the other side of the coin. Apart from the lack of familiarity with the disease, there are aspects that can somehow protect us:
- high schooling
- healthy food style
- physical and brain training
- good social relationships
- monitor and carefully treat any cardiovascular problems.
Alzheimer coffees are being born in many Italian regions and municipalities . The basic idea is that Alzheimer’s is not only fought with drugs, but also with a coffee, together with their family members, outside the home.
These initiatives offer recreational and socialization activities, important for the maintenance of the cognitive faculties of Alzheimer’s patients, and provide information and orientation support for families. Furthermore, with the support of psychologists, family members and caregivers are helped to understand the evolution of the disease and to better face everyday life.
Born in Holland in 1997, Alzheimer Cafes have spread throughout Europe.
Alzheimer’s disease: symptoms
How does Alzheimer’s disease manifest itself? Clinical history spans a long time span . The progressive accumulation of damage and the consequent inability of the brain to compensate, occur slowly and progressively.
Therefore, there is a long period, between 15 and 30 years , in which the pathology is present, without however any evidence of cognitive impairment. This means that the onset of symptoms occurs late in the course of the disease, preceded by a long asymptomatic phase .
Stages of the disease
In general, the stages of the disease are three:
It corresponds to the asymptomatic phase of the disease, in which all pathogenetic mechanisms are in place, but the extent of the damage is not such as to determine the development of symptoms. This phase completely eludes diagnosis in clinical practice. Instead, it is recognizable in subjects still asymptomatic but carriers of genetic mutations responsible for the onset of the disease, through specific clinical investigations.
It corresponds to the initial symptomatic phase of the disease. The pathology reaches a level of damage that compromises some cognitive functions in a mild way and without interfering in the overall functioning of the individual.
It corresponds to the full-blown phase of the disease. The level of neuropathological alteration is so serious as to compromise many cognitive functions.
Initial stages: symptoms
In the initial state of the disease, the most obvious symptoms can be:
- forgetfulness for recent events, because it is difficult to form a new memory
- personality changes (people can become emotionally less reactive, depressed or unusually fearful or anxious)
- change in language (using simpler words or more words than a specific one)
- insomnia and difficulty falling asleep.
Advanced state of the disease
- difficulty remembering past events (forget the names of friends and family)
- loss of autonomy (assistance with eating, dressing, washing or going to the bathroom may be necessary)
- loss of spatio-temporal orientation (affected people can even get lost in the house)
- increased confusion (which involves the risk of wandering – because the person no longer finds his way home and gets lost – and falls)
- destructive or unsuitable behavior , agitation, irritability, hostility and physical aggression
- total loss of autonomy (you are no longer able to walk or take care of yourself; you may encounter incontinence, difficulty swallowing, loss of language).
The symptoms that occur during the course of the disease can be distinguished into cognitive symptoms and behavioral and psychological symptoms .
The most frequently altered function in Alzheimer’s is memory . Memory deficit for recent events is the pre-eminent clinical feature of the disease, of which it constitutes the clinical onset. So, forgetting where the objects are stored or often repeating the same questions are typical early symptoms .
Instead, the autobiographical memory and that relating to historical events, not recent and long-term, is unchanged.
Disorientation (spatial and temporal)
It occurs constantly throughout the course of the disease. At the beginning, the difficulty is limited to the dates , but with the aggravation of the disease the ability to place oneself and the events experienced in time and space is lost. Therefore, for this reason, there are frequent losses outside the home and, in the most serious cases, even in one’s own home.
Concentration and attention deficit
They are among the earliest symptoms involving learning difficulties . The subject is no longer able to acquire and retain new information.
Language impairment is quite frequent . At the beginning the linguistic function is preserved, but an impoverishment of the vocabulary can be found already in the first clinical interviews (it is difficult to find the words or synonyms). Subsequently, a more complex aphasic syndrome, with a deficiency in naming, repetition and understanding, usually occurs late.
Gnosic, praxic and visuospatial disorders
More difficult to frame, especially outside the highly specialized centers, are disturbances:
- gnosics (difficulty in perception of objects, people, etc.)
For example, visuospatial deficits are often confused with changes in the visus.
Furthermore, the difficulty in recognizing the body and extracorporeal spatial coordinates can compromise walking, with a higher risk of falling .
Behavioral and Psychological Symptoms
These “non-cognitive” symptoms often profoundly affect the course of the disease , with an important impact on the quality of life of the affected person and family members and / or caregivers.
In fact, over 70% of patients, with different modalities and frequency according to the various stages of the disease, develop:
- aggression (verbal and / or physical)
- inappropriate social behavior
- aberrant motor activity
- sleep, eating and sexual behavior disorders.
Although the fluctuations of the symptoms do not characterize the disease, it is not uncommon for the subject to experience a “circadian” worsening that occurs in the late afternoon and in the evening.
Therefore, this phenomenon is called “sunset syndrome” because it is characterized by a worsening of cognitive and behavioral disorders (confusional state, anxiety, restlessness, psychomotor agitation) as the evening hours approach.
Sunset syndrome is found in 65% of patients .
At an advanced stage
In advanced stages of the disease, cognitive impairment is so serious that the patient is no longer able to carry out the basic activities of daily life alone, such as:
- to get dressed
- provide for your physiological needs.
Furthermore, the appearance of incontinence, due to the loss of voluntary control of the sphincters, further compromises the situation. Over time, long-term memory and language are also impaired, as is the ability to understand. Finally, motor deficits and disorders of muscle tone can also occur in the terminal phase . But, dysphagia, dehydration and pneumonia ab ingestis may also occur.
Furthermore, difficulty in walking can be complicated by falls and subsequent fractures. Therefore, the enticement that follows can increase the risk of infections (urinary and respiratory) and worsen constipation, up to the possible intestinal blockage.
The alterations of abstract thinking , which in some cases are already present at the onset of symptoms, with the progression of the disease compromise the ability to plan, criticize and judge. This poses important medico-legal questions because the individual’s decision-making skills are compromised .
Alzheimer’s: diagnosis and prognosis
The clinical diagnosis is mainly based on detection of a cognitive deficit that relates to the memory and at least another function.
So, the presence of these criteria allows you to make a diagnosis , but if only one of these 4 characteristics is missing, we talk about possible Alzheimer’s . For example, this is the case in which cognitive deficits show an atypical trend or occur within a deterioration framework due to the presence of cerebrovascular diseases or in conjunction with symptoms typical of other neurological syndromes:
- motor neuron disease, etc.
Hence, some symptoms can help distinguish Alzheimer’s disease from other dementias. For example, visual hallucinations are more common in Lewy body dementia than Alzheimer’s.
Cerebrospinal fluid analysis
Cerebrospinal fluid analysis , obtained by a lumbar puncture, and positron emission tomography ( PET ) can help diagnose the disease.
However, an exact diagnosis can only be confirmed by taking a sample of brain tissue (after death, during an autopsy) examined under a microscope.
In life, the diagnosis is based on the accurate collection of anamnestic information, general neurological and physical examination, neuroimaging (CT and / or MRI of the brain) and on the evaluation of cognitive functions .
Routine laboratory tests, the dosage of thyroid hormones, vitamin B12 and folic acid, complete the diagnostic process. The collection of the anamnesis must carefully investigate the characteristics of:
- onset of disturbances
- progression mode
- impact on the subject’s autonomy levels.
Assessment of cognitive functions
The evaluation of cognitive functions represents the central moment of the diagnostic phase. Therefore, the administration of tests by neuropsychologists at specialized structures, such as the Centers for Cognitive Disorders and Dementias ( CDCD ), allows to obtain an accurate neuropsychological profile and to describe, both from a qualitative and quantitative point of view, the deficits present .
Finally, the use of standard neuroimaging (CT and / or MRI), allow to exclude other causes of cognitive impairment , such as vascular lesions.
How long can you live with Alzheimer’s? It is difficult to give an exact answer. Generally the disease can last from seven to twenty years, with an average time of 10 years, much depends on the age of diagnosis. However, some medications can slow the disease for a short time, but do not prevent its progression.
Alzheimer’s is defined as the “four A disease” because it involves:
- amnesia : significant memory loss
- aphasia : inability to formulate and understand verbal messages
- agnosia : inability to correctly identify stimuli, recognize people, things and places
- apraxia : inability to correctly perform certain complex voluntary movements, such as dressing.
Phases of the course
Although the course of the disease is unique to each individual, it can generally be divided into three phases.
In the initial phase , memory disorders are prevalent, but speech disorders may also be present. Therefore, the person:
- it is repetitive in expressing itself
- tends to lose objects
- tends to get lost and not find the way home.
In addition, it can manifest emotional alteration, irritability, unpredictable reactions.
Instead, in the intermediate phase , there is a progressive loss of autonomy and continuous assistance is needed.
The severe phase is characterized by the complete loss of autonomy:
- stop eating
- can no longer communicate
- it becomes incontinent
- he is bedridden or wheelchair-bound.
However, the duration of each phase varies from person to person and in many cases one phase may overlap the other.
How is Alzheimer’s treated? To date, no effective drug therapies are available and the disease remains an incurable disease .
How is Alzheimer’s treated? To date, no effective drug therapies are available and the disease remains an incurable disease .
The treatments involve the use of so-called “symptomatic” drugs that alleviate some symptoms without intervening, however, on the pathogenetic mechanisms.
The acetylcholinesterase inhibitors (AChEI) act by increasing the levels of acetylcholine in the brain. Acetylcholine is an important neurotransmitter for correct cognitive functioning. Hence, AChEI action aims to compensate for the functional deficit linked to this impairment.
The molecules used for drug therapy, in the mild and moderate stages of the disease, are:
Instead, memantine is used for the treatment of moderate and severe stages of the disease , although it has shown limited efficacy in promoting the slowing of the progression of symptoms.
But over the past two decades, research has focused on the study of drugs that can interfere with the pathogenetic mechanisms of the disease. Drugs of this type are not symptomatic , but aim to change the course of the disease.
Instead, other research focuses on the body’s immunological response against the disease, trying to develop a vaccine capable of containing the production of beta-amyloid (the peptide that aggregates to form plaques).
However, research is still ongoing.
The poor efficacy of conventional drug therapy and the demonstration that the lack and constant cognitive stimulation during life reduces cognitive reserve and promotes deterioration have pushed researchers also towards non-pharmacological interventions .
These interventions aim :
- increased cognitive performance
- control of behavioral and psychological symptoms of dementia
- improving the quality of life of patients.
However, the effectiveness of these approaches is generally transitory and of modest entity, but if prolonged over time they can bring benefits similar to those of drug therapy .
Cognitive stimulation is among the most used techniques. It is an approach mainly dedicated to social interactions and is generally implemented in the form of group activities.
Then, it is focused on identifying goals to be achieved with respect to cognitive deficits. Therefore, the proposed method is compensatory , that is, a preserved function compensates for the deficient one. In addition, by also involving family members, cognitive stimulation aims to improve the overall functioning of the individual.
Cognitive training involves performing standard tasks designed for various cognitive functions.
The proposed exercises may include the use of pen and paper or be reproduced on the computer.
The difficulty of the exercise is established on the basis of the degree of impairment of the specific cognitive function and modulated on the basis of improvements.
But, the principle is that repeated exercise and practice can improve or maintain an impaired function.
Can Alzheimer’s be prevented by diet? A study carried out by Columbia University researchers and published in Neurology has involved more than 1,200 people, over 65 years of age, without cognitive impairment.
After completing a detailed questionnaire about their eating habits, these people, a year and a half later, were subjected to a blood sample to measure the level of the beta-amyloid protein (main responsible for the formation of plaques typically present in the brain of a Alzheimer’s patient).
Food rich in omega 3 and 6
The study aimed to highlight the existence of a link between this protein and the nutrients present in food, such as:
- saturated fatty acids
- omega 3 and omega 6
- monounsaturated fatty acids
- vitamin E, C, D, B12
- folate and beta carotene.
Hence, it emerged that the more an individual consumes omega 3- rich foods (such as fish, shellfish and dried fruit), the lower the rates of beta-amyloid protein in the blood.
Hence, the Mediterranean diet is particularly suitable for maintaining an active brain, as it is rich in vegetables, fruits and fish.
Alzheimer’s: Avoiding AGEs Foods
Furthermore, it is important to reduce the consumption of meat, aged cheeses and, above all, to avoid pre-cooked foods.
In fact, these foods contain AGEs (Advanced Glication End products) which represent an important risk factor for Alzheimer’s disease.
AGEs are chemicals produced by combining sugars with other molecules such as fats or proteins. In some industrial foods they are added as flavor enhancers , but the greater quantity of AGEs is formed during cooking of the food.
Their formation depends on the temperature and the type of cooking . Therefore, the higher the temperature and cooking time , the greater the formation and accumulation of AGEs. Therefore, grilling, grilling or frying are not recommended if they are habitual, instead favoring stewed, steamed or boiled cooking.
These substances are able to increase the risk of Alzheimer’s, producing alterations at all levels :
- vascular damage
- neuronal damage
- oxidative stress.
Alzheimer: exercise, sport and yoga
Can Sport Reduce Alzheimer’s Risk? Various studies confirm that movement and physical activity help the subject to remain independent for longer, maintaining and stimulating mental and physical abilities, also facilitating night sleep .
So encouraging the affected person to have interests, to stay active, and to make movement can help them lead as normal a life as possible.
According to some research, irisin , a hormone produced in large quantities by muscle tissue during physical-sports activities, would play an important role as a possible antidote to cognitive impairment . In fact, the hormone is present in lower concentrations in people affected by Alzheimer’s.
Hence, sport, by increasing the production of irisin , can contribute to the maintenance of cognitive functions. Even in the presence of accumulations of beta-amyloid, the protein that forms the typical plaques in the brain of people affected by the disease.
The importance of intellectual activity, but above all physical activity , is also confirmed by a study published in Science . Research has shown (on an animal model) how exercise promotes the synthesis of new neurons at the hippocampus level , one of the first brain regions to show signs of disease.
Since it is not currently possible to eliminate beta-amyloid plaques , researchers are attempting new avenues, including the “enhancement” of nerve tissue , to ensure turnover for damaged neurons. The hippocampus, on the other hand, has a peculiarity, that of continuously renewing itself also thanks to the presence of stem cells which, if adequately stimulated, can make up for the loss of other cells.
A 2015 study published in International Psychogeriatrics highlighted the benefits of yoga breathing that can increase the Nerve Growth Factor (NGF) . It is a fundamental protein for the development of the central nervous system, which is significantly reduced in people with Alzheimer’s.
Hence, the researchers asked 20 volunteers to perform yoga breathing and used their saliva samples to measure the level of NGF. Specifically, the volunteers participated in a 20-minute yoga breathing program. At the end of the experiment, 60% of the volunteers showed a marked increase in NGF levels .
Dementias have been recognized as a priority for public health. The progressive aging of the population and the lack of treatment are, in fact, leading to a marked increase in the prevalence and socio-welfare impact of these diseases.
Hence, it becomes essential to identify and activate effective preventive strategies.
Can Alzheimer’s be prevented? In this regard, epidemiological studies have identified a wide range of risk factors for dementia, potentially modifiable such as:
- cardiovascular disorders
- unhealthy lifestyles and habits (reduced physical activity, smoking, alcohol abuse, low schooling, poor social relationships, etc.).
On the contrary, mentally and physically stimulating activities, good social relationships, high level of education and professional complexity, balanced diet regimes (such as the Mediterranean diet) seem to be protective factors towards dementia.
Furthermore, it has recently been highlighted that a considerable number of Alzheimer’s cases worldwide (around a third) can be attributed to seven potentially modifiable risk factors , namely:
- physical inactivity
- low level of education.
Hence, the incidence of the disease could be significantly reduced by implementing public health strategies aimed at reducing the prevalence of these factors. This approach could also be accompanied by a significant reduction in the prevalence of vascular and mixed (degenerative-vascular) dementias , considering that most of the risk and protective factors are also shared by these pathologies.
Alzheimer’s: prevention rules
There are 6 main prevention rules:
- be physically active
- follow a healthy and balanced diet
- not smoking
- take a little alcohol
- train the mind
- check your health.
Alzheimer’s: social costs
According to the latest research the estimated economic impact for Alzheimer’s disease is very high. Above all, if we consider the loss of autonomy of both affected people and family members, often forced to retire early, and health and care costs.
In fact, in addition to hospitalization, it is often necessary to also consider home care and support for families .
After 3-4 years of illness, 24-hour assistance is generally required.
The study took into account both the costs incurred by families and the national health system and therefore by the community.
Average annual cost
The average annual cost estimated to assist Alzheimer’s patients is € 70,587 per capita , including the costs borne by the National Health Service, those that fall directly on families and indirect costs (the assistance costs that weigh on caregivers, patients’ lost income from work, etc.).
Therefore, multiplying it by the number of patients, the figure is considerable: 42.352 billion euros per year, of which 11.364 billion for health and care services.
Furthermore, a large part of these costs is represented by indirect expenses, which in this case almost entirely weigh on the caregivers, that is, the family members who take care of the sick.
In addition to the costs related to medical visits, analysis, purchase of specific drugs, aids and health equipment, etc. it is also necessary to consider the expenses to be incurred to modify their own homes, totally borne by the family.
Compared to previous estimates, the study showed a progressive increase in costs , confirming how much more onerous the burden not only psychological and social but also economic burdens on families to meet the needs of the patient. There is therefore an urgent need to adapt and strengthen the offer of health services.