In the 21st century

In the 21st century, health is determined by numerous social trends. The economy is globalizing, more and more people are living and working in cities, the pattern of the family is changing, and technology is rapidly evolving. However, aging of the global population is one of the largest social transformations. It is estimated that the percentage of elderly over 60 years will be higher by 56% in the period between 2015 and 2030. An absolute number of people aged 60 and over will grow from 901 million to 1.4 billion during the same period, while the number of people aged 80 and over (“the oldest-old”) will be almost four times higher by 2050, and will grow up to 395 million. Today, most of the elderly live in economically underdeveloped and undeveloped countries, and they will make up 80% of the population by 2050 (United Nations, 2015).
In Europe live more than 160 million people aged 60 and more. It is projectedfor the EU countries that between 2010 and 2060 the portion of people aged 65 and more will almost double, and will increase from 16% to 29%. At the same time, there will be a substantial increase in number of “oldest-old” persons as well; the proportion of people aged 80 and more will triple between 2010 and 2060, with expected number of 64 million persons (Council of Europe Development Bank, 2014).
The same demographic trends are present in the United Kingdom as well, where is projected for the population aged 60 and more increase from 14.6 to 21.9 million between 2014 and 2039 (Government office for Science, 2016).
In the light of demographic changes and prolonged life expectancy, health systems will challenge the increase in prevalence of chronic disabling disease.
Dementia
Even though problems with memory might occur throughout the lifespan, this phenomenon is often referred as the usual side effects of aging. In certain cases, loss of memory can be significant clinical indication of dementia.
Dementia can be referred as a syndrome which is characterized by various cognitive impairments-difficulties with memory, language and problem-solving, with negative impact on activities of daily living. There are various causes of dementia, as well as number of different types of this condition, with Alzheimer’s disease being one of them (Alzheimer’s association, 2017).
It is estimated that in 2010, 46.8 million people worldwide have suffered from dementia syndrome. It is projected that in the year 2030, 74.7 million people will be living with dementia, and in 2050, as many as 134 million people. The world’s total cost of treatment and care for dementia in 2015 was around $ 818 billion and is projected to increase up to $ 2 trillion by 2030. Estimated annual global incidence of dementia is 9.9 million, which means that every 3 seconds somewhere in the world new case of this condition is recorded. Characteristics of this disease, high prevalence and the burden that dementia causes for caregivers, health system and the overall economy puts dementia as one of the top public health priorities (Alzheimer’s Disease International, 2013).
Concerning the fact that between 60-80% cases of dementia are caused by Alzheimer disease, this condition needs specific attention and systematic approach, which includes both health sector as well as other relevant factors (Alzheimer’s Disease International, 2013).
Public health perspective of dementia
The misconception that dementia is an integral part of the aging was probably developed due to the fact that the vast majority of the cases can be found in persons aged 60 years and more. Therefore, a number of dementia cases remains undiagnosed and mistreated. On the other hand, poor understanding of this condition leads to social isolation of both patients and their families. Today dementia is recognized as one of the major causes of disability in the population of elderly persons (World Health Organization and Alzheimer’s Disease International, 2012).
Alzheimer’s disease
Alzheimer’s disease is a degenerative disease of brain cortex and surrounding structures; it is progressive, irreversible, with somatic complications and fatal outcome. Alzheimer’s disease is the most common form of dementia, with aging being the most prominent risk factor for this disease. In most people with this disease, the first symptoms usually occur in the 6th decade of life, but the progression is very rapid. In approximately 5 years from the occurrence of the first symptoms, severe dementia develops. From the moment of diagnosis, the patients live on average 5-10 years. Destruction and death of neurons leads to loss of memory, change in behavior, difficulties and/or problems in performing daily activities. The cause of Alzheimer’s disease is still not fully understood, but today we know that there are two forms of this disease, inherited and sporadic. The inherited form is a very rare autosomal dominant disease occurring very early, before 65 years of age, and it is usually caused by the amyloid-? peptide precursor protein gene or presenilin gene mutations. The sporadic form is the most common form of this disease, but its cause is still unknown.There is still no adequate treatment for Alzheimer’s disease. Therefore, all efforts are aim to slowing down the symptoms and delaying the late stages of the disease (Blennow et al., 2006; Alzheimer’s Association, 2015).

History
AB was first described by Alois Alzheimer in 1906 in Tübingen in a patient Augusta Deter. This lady, born in 1850, had difficulties withmemorizing, as well as altered personality, paranoia, and reading and writing difficulties. Those symptoms were observed when she arrived at the hospital in November 1901. Prior to her death in 1906, Alzheimer noted and described psychotic features (hallucinations),as well as significant deficits in other cognitive domains (dysphasia, dysgnosis and dyspnea). Alzheimer is considered to be the first to correlate described clinical symptoms of the disease with the presence of senile plaques and in particular the neurofibrillary tangles in the brain cortex of the diseased patients. Previously mentioned pathological changes have been demonstrated by the method of silver impregnation by Bielschow, and numerous modifications of this method are still used for the visualization of such pathological changes. After Alzheimer noticed and described a large number of neurofibrillary tangles, along with senile plaques in the cerebral cortex in the brain of patient Johann F. who died in 1910, German psychiatrist Emil Kraepelinconcluded that it was a special disease, and in his book of psychiatry in 1912he called that disease Alzheimer’s (Maurer et al., 1997).
Etiology
The two main hypotheses about the development of Alzheimer disease (amyloid and tau hypothesis) explain the accumulation of senile plaques and neurofibrillary tangles in the brain of the people suffering from this condition. Yet it is still unclear what provokes those pathological clusters in the brain of the patients affected by Alzheimer disease.
According to the amyloid hypothesis, the theory that probably best explains Alzheimer’s disease, as this condition develops, the patient’s brain becomes overweight the formation and precipitation of a pathologically altered protein molecule – beta amyloid between cells, in the form of plaques and thus disturbs the connection between the cells, the synaptic links are interrupted in this way disrupt the transmission of signals between nerve cells. Signals become weaker, therefore in communication between nerve cells transmission of information is altered and, in the final stage, completely compromised. The development of the disease leads to the dying of an increasing number of nerves cells in the brain. In this way, the brain mass decreases up to 20%. If the disease progresses, these changes can be identified using brain imaging (computerized tomography or magnetic resonance).
Some of the etiological mechanisms that are being sought to explain these phenomenons are the toxicity of ?-amyloid deposits and mechanical damage of axons, which compromises axoplasmic transport. The neuron response to such action is the massive production of new axons to bridge the damaged part. In order to make it easier to move and form synapses, young axillary cells and their microtubules need to be less stable than in fully differentiated neurons. This is possible after separating the tau proteins from the microtubule. Enhanced phosphorylation of the tau protein leads to a change in its conformation and separation from the microtubule. One of the possible scenarios might be that amyloid accumulation causes activation of the microglia and inflammatory response (CaiHussain ; Yan, 2014).
In the 1980-ties it was discovered that the senile plaques was composed mainly of ?-amyloid In addition, some of the less represented assumptions that are sought to explain and link all the symptoms and signs with the laboratory findings and results obtained from the structure and brain activity in Alzheimer disease are as follows: hypotheses of oxidative stress, inflammation, mitochondrial and lysosomal function disorders, neurovascular dysfunction and cellular disorders cycle in Alzheimer Disease (Reddy ; Beal, 2005).

The transmission of information in the brain is provided by the nerve fibers that connectbillions of nerve cells. Signals between nerve cells transmittedneurotransmitters. In Alzheimer’s disease there may be a deficiency important neurotransmitters, such as acetylcholine, and in such situation occurs enhanced secretion of another neurotransmitter, glutamate inconcentrations greater than normal. Glutamate has toxic impact to the nerve cells (Alzheimer’s Association, 2015).
Risk factors
There are two basic forms of Alzheimer Disease, sporadic and inherited (family). Family Alzheimer Diseaseis represented with less than 1% of all Alzheimer Disease cases, and among all of them 6% have the early onset, which means occur before 65 years of age. Family Alzheimer Diseaseis confirmed if it is documented by three generations and has a strong genetic basis. On the other hand, the sporadic Alzheimer Diseaseis also called a late-onset Alzheimer Disease. (Brickell et al., 2006).
In most of the cases, Alzheimer’s Disease is caused by several associated factors, such as: genetic factors, environmental impacts, previous illnesses and changes in the brain
due to the aging process.The most important risk factor for the occurrence of sporadic Alzheimer Disease is age and in the context of rapid global population. Other important risk factors for the occurrence of Alzheimer Disease are gender (women more prevalent among people living with Alzheimer Disease) and genetic component. Additional risk factors include head trauma and a lower degree of education (due to reduced “synaptic reserve”), i.e. reduced mental capacity in younger age, arteriosclerosis, and elevated blood pressure. Potential protective factors that might prevent the occurrence of Alzheimer Disease are use of nonsteroidal anti-inflammatory drugs, Mediterranean diet, moderate alcohol consumption, caffeine, homocysteine, vitamin B12 and unsaturated fatty acids (Alzheimer’s Association, 2015).

Clinical features
Alzheimer Disease is neurodegenerative disease which mostly affects people aged 60 years and more. Symptoms of Alzheimer’s dementia vary with each patient in their course, manifestation, and order of appearance. However, there are some typical features of Alzheimer disease. At early stages memory is primarily affected and the rationale for this is the fact that hippocampus is the first region of the brain where neurons are being damaged. As the disease progresses, a patient suffer from difficulties with recovering directly past events, difficulties in performing everyday activities, with unexplained mood swings, loss of initiative, and/or depression and problems in managing in an unknown environment. This is a progressive disease with the fatal outcome (Lama et al., 2017).
Stages of Alzheimer’s disease
Early, mild stage of Alzheimer’s disease
In the first, early stage, memory loss can remain unnoticed and episodes might contribute to minor memory loss. With the disease progression, there is an increasing number of plaques and neurofibrillary fissures, and the ever-growing surface of the cerebral cortex is affected. This stage is characterized by the loss of episodic declarative memory, especially the adoption of new content, followed by the progressive deterioration of capacity for recalling already adopted episodic content. Difficulties in finding the right word in spontaneous speech is usually the first characteristic sign that forces the patient to wander around to find out what he is looking for. Problems in performance of everyday activities, such as dressing, keeping a checklist, finding a desired route, or recalling where things are becoming more frequent, which decreases patient capability for self-care and independent living. There is also a change in mood and behavior. Alzheimer’s disease is most commonly diagnosed at this stage.
Second, moderate stage of Alzheimer’s disease
At this stage the disease spread to areas of the cortex that control speech, reasoning, and conscious thinking. The symptoms become more pronounced and the disease is progressing. This is the longest phase of the disease and can last for a number of years. There is an increased loss of memory and confusion, the patients are less and less aware of their family, friends, and the environment around them. They have more difficulties with talking, writing, reading and organizing thoughts. They are also incapable to learn new things or handle new or unexpected situations. They feel restless, anxious, repeating the same statements or gestures. Hallucinations, illusions, suspicion or paranoia can be represented as well.
Third, severe stage of Alzheimer’s disease
In the last stage of the disease, plaques and nodes are widespread throughout the brain, while the most of the brain tissue is destroyed. The declarative memory is completely lost, both episodic and semantic, and the loss of procedural memory begins as well. Everyday activities become impossible because the patient is no longer able to longer walk, chew, swallow, communicate, control sphincters, and that leads to complete dependency on the care of others. The patient’s physical health deteriorates constantly, which ultimately leads to death. The most common cause of death in people with Alzheimer’s disease is aspiration pneumonia because of the lost function of normal swallowing (Alzheimer’s Association, 2015).
Detection
Sometimes early detection of Alzheimer’s disease is being omitted because of the common misconception that the deterioration of the memory is common for aged persons. However, to determine the presence of this progressive condition it is important to perform a thorough medical and family history assessment, neurological exam and mental status tests to determine cognitive capacity. Those are, among other things, the tests that are performed to determine memory, but also other cognitive functions: speech, ability to thinkand judging, as well as identifying and using the subjects.It is also important to obtain relevant information about cognitive and behavioral changes not just from the patient, but his family members as well. Besides biological markers detection, neuroimaging methods are also used for detection of Alzheimer’s disease.Neuroradiological methods, such as CT(computerized brain tomography) or (MRI) magnetic resonance imaging, usually show strong cerebral cortex diffusion, confirms diagnosis and hypocampal region atrophy( Dubois, Picard &Sarazin, 2009; Alzheimer’s Association, 2015).
Cerebrospinal fluid, i.e. liquor, is the most effectiveindicator of pathological changes in the brain. The main disadvantage of this diagnostic procedure for Alzheimer’s disease is the invasiveness of this method of specimen sampling (lumbar puncture). The analysis of the three proteins in the liquor (A?42, total tau and phosphorylated form of tau) has given the best results and has shown that this test can differentially diagnose people with mild cognitive disorder that will progress in the future in Alzheimer’s disease. A particularly sensitive and specific method for detecting Alzheimer’s disease is the measurement of p-tau / A?42 ratio in liquor. This ratio can be used to distinguish patients with Alzheimer’s disease from healthy controls, and to distinguish patients with Alzheimer’s disease from patients with other forms of dementia. This criterion for differential diagnosis of AB has proven to be effective at the initial stage of the disease. Specific abnormal lipid changes occur in the brain affected by AB. The analysis of phospholipids and other lipids, particularly sulphatides and oxidized sterols in liquor, could potentially lead to the finding of new biomarkers, both for Alzheimer’s disease and other neurodegenerative diseases. In some patients with a positive family history, it is possible to identify a mutation of the appropriate gene (Agrawal ; Biswas, 2015).

Treatment
Contemporary medical science has not yet discovered causal treatment of Alzheimer disease. Therefore the management is based only on the relief of the symptoms of the disease. Such medications increase the production of neurotransmitters, which might temporarily reduce symptoms. The acetylcholine esterase inhibitors comprise a group of medications that affectthe lack of acetylcholinein certain parts of the brain. That group of medications is usually used inearly and middle stage of the disease.The second group of drugs are NMDA (N-metil-D-aspartat)antagonists (activesubstance – memantine) used in the middle and late stages of Alzheimer’s disease.They regulate the function of the hyperexcitatory glutamatergic system, which is responsible for the destruction of nerve cells.
Besides symptomatic therapy, non-pharmacological management is used to maintain cognitive function, which leads to improved capacity for activities of daily living and thus quality of life. There are a whole range of therapies of this kind: music therapy, visual expressiontherapy, movement exercises, behavior therapy, training forpromotion of orientation, cognitive training, validation, therapysocial milieu, etc.The treatment of a social milieu involves conscious adapting to the environment of the patient’s behavior(Duthey, 2013; Alzheimer’s Association, 2015).
Magnetic Resonance Imaging
Physicists Bloch and Purcell are recognized as first authors who performed experimental studies about the nuclear magnetic resonance back in the 1940-ties. However, the clinical use of this diagnostic technique was introduced about 35 years later. Since then, this diagnostic tool has been widely used and appreciated. The basic principle of magnetic resonance imaging relies on the basic physics theory that atomic nucleus is composed of protons and neutrons and has positive charge. The nucleus is spinning around its axis, but that spinning can be affected by external magnetic field (McGowan, 2008; Grover et al, 2015).
MRI represents a highly effective method in diagnostics, treatment planning and monitoring of the condition in a patient with pathological changes in the central nervous system.At the very low cost of performance, the MRI shows greater sensitivity in the representation of soft tissue structures with superior contrast resolution, provides the possibility of multiplanningof the analyzed structures and does not require the use of harmfulionizing K radiation,.Standard Conventional MRI protocol impliesthe use of conventional T2-weighted displays (T2WI) and T1-weighted images (T1WI), inaxial, coronary and sagittal levels. While T2W sequences are more sensitive in the presentation of pathological changes, T1W sequences are better for the observation ofanatomical details.Some of the advanced MRI techniques are as follows: diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI) proton magnetic resonance spectroscopy (1H-MRS), perfusion-weighted displays (PWI), diffusion-tensor imaging (DTI), and functional MR images(fMRI) (Newton &Jolesz, 2007).