Alzheimer's disease (AD) or dementia of Alzheimer's type (DAT) is one of the most common pathologies of the central nervous system and psyche. It usually affects persons in the old age and today an estimated of 500,000 Canadians suffer from Alzheimer’s or related dementia, over 70,000 being under 65 and 50,000 under 60. Neurodegenerative process is accompanied by progressive loss of memory and cognitive abilities decline. AD inevitably leads to death of the patient, and there are still no drugs to prevent or cure this disease. Incidence increases parallel with an increase in life expectancy. Now it is the main cause of death after cardiovascular diseases and cancer. In the research paper, I will outline the main features of the Alzheimer’s disease, as well as the stages of its development. The main purpose of the paper is to analyze the disease, and how it influences Canadians, and, consequently, provide a plan on measures that can be taken by the government in response to the epidemic of the disease.
First the disease was described by Professor Alois Alzheimer in Germany in 1907, in a 55-year-old woman. First, it was considered a relatively rare form of presenile dementia. However, over time it turned out that Alzheimer's disease may begin in adults at any age and is the most common type of dementia in the elderly. This neurodegenerative disorder was named after the doctor, who gave the first description of the major histopathological signs of illness:
accumulation of amyloid plaques and neurofibrillary tangles in the brain tissue (Dubois et al., p. 736).
The disease has characteristic clinical and pathologic features. The main characteristic of Alzheimer’s disease is loss of memory. Besides, the patient suffer from progressing dementia for several years. Like in most common complex diseases, in Alzheimer's disease there is a broad clinical heterogeneity of symptoms. This disease should also be distinguished from other, rarer dementias: vascular, with Lewy bodies, Pick's disease, Huntington's disease, and others. Accurate diagnosis of Alzheimer's disease can only be set on the basis of histopathological examination of postmortem material. (McGeer P. L., McGeer E. G., p. 644)
In their article, Mueller S. G. et al. argue that diagnostic criterion for AD is a set of attributes, namely:
- so-called accumulation of amyloid plaques (conglomerate of sparingly soluble cellular proteins), particularly in blood vessels of the brain; intracellular neurofibrillary tangles;
- mass death of neurons, especially in areas of the hippocampus and temporal lobes of the cerebral cortex responsible for the storage and processing mechanisms of active memory. (Meuller S. G. et al., p. 58)
Detection of four different genes responsible for the development of Alzheimer's disease provides a framework for rapid development of knowledge base about the biological basis of this disease. (Meuller S. G. et al., p. 64)
At the beginning of the disease, memory loss may go unnoticed or mistaken for normal forgetfulness. Cognitive impairment gradually begin to restrict activities of daily living (financial management, professional work, driving, shopping and taking care of the house). Some patients are not aware of these disorders (anosognosia), in other cases, criticism remains intact, which causes severe experiences. Because of the differences in the course of the disease is unknown. Patients get lost in a new environment and can do the same while walking or driving.
At the peak of the disease patients are not able to work, are easily disoriented; they need constant care. At the same time, secular skills and stereotyped behaviors may persist, and a superficial conversation may show no abnormalities. There are possible speech disorders, particularly in understanding another's speech and naming of objects. In some cases, severe aphasia appears early in the disease. Difficulty in finding words and circumlocution sometimes occur even in patients with satisfactory performance of special speech tests. Apart from naming objects, there can be broken fluency, comprehension and repetition of speech. (Mueller S. G. et al. p. 57)
Characteristic are various forms of apraxia: difficult dressing, patients cannot feed themselves, are unable to solve simple puzzles and copy geometric shapes. Violated counting, patients cannot tell the time on the clock (Ringman et al., 2005).
Occasionally there develops cortical blindness, which the patients themselves deny. In such cases, in the course of autopsy gross changes are found in the visual cortex. At later stages, some patients can move independently, but their moving around the house is reduced to aimless wandering; there is possible complete loss of cognitive function (the ability to judgments and inferences, etc.). Often there are hallucinations or delusions. As a rule, they are simple in care and lack quirkiness. For example, patients wrongly suspect a spouse of infidelity, do not recognize old friends, take a visitor for a thief or are scared of their reflection in the mirror. (Mueller et al, p. 59)
Disinhibition and conflict can be replaced by apathy and alienation. There may be disrupted sleep-wake cycle; at night patients can wander around the house, which further complicates their care by relatives. Sometimes there develops shuffling gait and generalized muscle rigidity, movement is slow and clunky, and overall appearance resembles that of patients with Parkinson's disease, but rapid, rhythmic resting tremor is rare.
Late-stage Alzheimer's disease is characterized by muscle rigidity, mutism, urinary incontinence, fecal incontinence, patients are bedridden. Tendon reflexes may be increased, there appears sucking reflex and proboscis reflex. Spontaneous or in response to stimuli (e.g., loud sounds), myoclonic jerking sometimes arise of individual muscles or the entire body. These symptoms cause exclusion of Creutzfeldt-Jakob disease. Unlike it, Alzheimer's disease is characterized by a protracted course. There is a chance of generalized seizures. Death in most cases comes from exhaustion, secondary infection or heart disease (Mueller et al., p. 65).
The recent discovery of several AD genes explains the clinical heterogeneity of AD symptoms. He et al. in the article “Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer's disease” showed that AD is characterized by a common pathological phenotype – progressive dementia, accompanied by the following pathologic features: intracellular accumulation of filaments that form neurofibrillary tangles in neurons; formation in the hippocampus, neocortex, and other brain senile plaques, which consist of several proteins, including alpha-antichymotrypsin, APOE, beta-amyloid, the accumulation of which in the parenchyma occurs during the early development of AD and apparently initiates the formation of protein aggregates; massive loss of neurons, particularly in the hippocampus and temporal lobes of the cerebral cortex – the departments responsible for the storage and processing of active memory. Until now, there is debate about whether the accumulation of tau protein and beta-amyloid are proximate causes that trigger neuronal death, or, conversely, the effects of death. Overall neurodegeneration is followed by further decreased activity of a number of enzymes, in particular, elements of the signal transduction and neurotransmitter systems: choline, norepinephrine, serotonin receptors, nicotinic receptors, glutamate receptors, and somatostatin receptors, possibly due to the loss of the corresponding neurons. Identification of primary molecular disorders in AD is the main and most formidable task, especially as the first histopathological changes in it may occur long before the onset of clinical symptoms. (He Y. et al., p. 4758-4762) There are different clinical forms and, accordingly, AD classification.
The average life expectancy in Alzheimer's disease is 8-10 years, but can range from 1 to 25 years. For unknown reasons, in some cases, the disease progresses slowly and continuously, while in others – there are typical long periods of stabilization.
Major risk factors of AD are older age and family history. With each decade of life there increases the risk of Alzheimer's disease, in the age over 85 from 20 to 40% of individuals suffer from this disease (He, Chen & Evans, 2008). Dementia in relatives suggests familial disease. Being a woman is another risk factor for AD, and is not associated with a higher life expectancy of women. According to unconfirmed reports, the use of estrogens in postmenopausal women reduces the risk of AD development. Some people in the past have suffered a concussion, but the brain injury is unlikely to be a significant risk factor for the disease. It is believed that Alzheimer's is more common among the less educated part of the population. However, the level of education affects only the quality of intelligence tests, and the disease itself is equally common among people with different IQ.
Studies have shown that the risk is lower in those who in adolescence writes well, but these were not verified. It was assumed that Alzheimer's disease may be caused by the accumulation of aluminum and mercury; there was discussed the viral and prion etiology of AD. However, none of these assumptions were confirmed. According to preliminary data, the use of NSAIDs reduces the risk of Alzheimer's disease. Vascular lesions (and amyloid angiopathy often accompanying AD), apparently, are not the cause of the disease.
Simard et al described the beginning of the disease from medical point of view. They said that according to positron emission tomography, metabolic changes in AD first appear in the cortex of the parietal lobe. At autopsy, the greatest changes are found in the hippocampus, temporal lobe cortex and the basal ganglia. Characteristic findings at microscopic examination are amyloid plaques and neurofibrillary inclusions (Simard et al., p. 493). Both these and others are found in the brain in normal aging, but in case of AD their number is significantly increased.
Before diagnosing Alzheimer's disease, there are usually excluded other causes of dementia, including disposable ones: thyroid disease, vitamin deficiency, brain tumor, drug intoxication, drug use, chronic infections and severe depression (depressive pseudodementia). The peculiarity of the disease is that it is almost invisible while brain examination. McGeer and McGeer showed that changes in results of brain scanning are nonspecific, and at the early stages of Alzheimer's disease are absent. Along the progression of Alzheimer's disease, there develops diffuse atrophy of the cerebral cortex, and sighting MRI reveals atrophy of the hippocampus. Slow progression of dementia, normal laboratory values, diffuse cortical atrophy, including the hippocampus, CT or MRI are typical signs of Alzheimer's.
Diagnosis established on the basis of careful analysis of the clinical data is confirmed at autopsy in 85-90% of cases. In other cases, dementia is due to another disease. In the differential diagnosis, their help relatively simple clinical signs. So, expressed gait only at a slight disorder of memory in the early stages of the disease are characteristic of normal pressure hydrocephalus. Resting tremor, hunched posture, mask-like face and hypokinesia indicate Parkinson's disease. Violation of proprioceptive sensitivity and vibration sensitivity in combination with pathological extension reflex is a sign of vitamin B12 deficiency. Epileptic seizures at the early stage of the disease are characteristic of primary and metastatic brain tumors. Prolonged depression in history makes doctors exclude depressive pseudodementia.
One of the characteristic features of the disease that deserves additional attention is the way it affects the family of the patients and the government and what should be done to change the situation for the better. In the paper, it has been already mentioned the way the disease impacts life of a person – when he/she falls ill, the individual gradually stops living normal life and becomes dependent on caregivers and the environment.
As for the family and relatives of AD patients, there are certain common feelings that are well-known to people who got into such a situation. The first of them is guilt – family members feel it due to the way the person was treated in the past, the strange behavior of the person, for losing temper in some situations accompanying such people. Another common reaction is grief and loss (Olazaran et al., p. 163). As dementia means gradual deterioration of the person’s state, we can talk about a few years left for the person to life, and it is not surprising that close people are worried about this situation as well. Family members can also feel anger due to different reasons – some people can fail to help them, AD relatives usually have difficult behavior, which can be very hard to handle, especially when they witness it every single day.
When speaking about the government, it also does not stay aside the problem, as people are worried about the situation, the prospects and the increasing number of AD cases observed today. To help these people, and to change the situation for the better, the following steps can be taken: there should be increased investment in the areas of AD research; constant education of geriatricians and other specialists who can treat the disease is required; improvement in diagnostics and treatment capabilities of specialists dealing with AD; implementation of programs of AD prevention by facilitating extensive physical exercise for people of all ages; support of caregivers and implementing new ways of helping them help AD patients. There has been many researches conducted on development and treatment of the disease, such as the treatment described by Ringman et al.. On of the most significant suggestions is to provide researchers with money and all the necessary equipment to find an effective treatment for the disease.
References
Dubois, B., Feldman, H. H., Jacova, C., DeKosky, S. T., Barberger-Gateau, P., Cummings, J., & Scheltens, P. (2007). Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria. The Lancet Neurology, 6(8), 734-746.
He, Y., Chen, Z., & Evans, A. (2008). Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer's disease. The Journal of neuroscience, 28(18), 4756-4766.
McGeer, P. L., & McGeer, E. G. (2007). NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiology of aging, 28(5), 639-647.
Mueller, S. G., Weiner, M. W., Thal, L. J., Petersen, R. C., Jack, C. R., Jagust, W., & Beckett, L. (2005). Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative (ADNI). Alzheimer's & Dementia, 1(1), 55-66.
Olazaran, J., Reisberg, B., Clare, L., Cruz, I., Pena-Casanova, J., del Ser, T., & Muniz, R. (2010). Nonpharmacological therapies in Alzheimer’s disease: a systematic review of efficacy. Dementia and geriatric cognitive disorders, 30(2), 161-178.
Ringman, J. M., Frautschy, S. A., Cole, G. M., Masterman, D. L., & Cummings, J. L. (2005). A potential role of the curry spice curcumin in Alzheimer’s disease. Current Alzheimer Research, 2(2), 131.
Simard, A. R., Soulet, D., Gowing, G., Julien, J. P., & Rivest, S. (2006). Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease. Neuron, 49(4), 489-502.
