Alzheimer's disease: symptoms, diagnosis, and treatment approaches

Alzheimer's disease has developed into a major health concern for the elderly population throughout the world. This degenerative brain disorder was first described by Alois Alzheimer in 1907. Today Alzheimer's is one of the most prevalent forms of brain disorders contributing to as much as 50 to 70% of all reported cases of dementia. Over the years the study of early onset Alzheimer's disease (pre-senile AD) has kind of overshadowed the study of late onset Alzheimer in elderly group. However the disease statistics indicate an increasing susceptibility of the older population. Approximately 5% of the population above 65 years of age and around 20% of the people above 85 years of age are affected by Alzheimer's disease. Hence what was previously ignored as an inevitable old age symptom (senile dementia) is now being properly recognized as an illness. This new perspective of AD has resulted in a drastically altered understanding and new approach towards diagnosis and treatment. Let us study the disease in a little detail by analyzing the symptoms and the etiology along with the diagnostic approaches and the currently available treatment methods. In the process we will also briefly discuss some other common forms of dementia and how AD can be differentiated from them.

The Alzheimer's Disease

Alzheimer's is a progressive, degenerative, and irreversible brain disease that stifles the normal cognitive and functional abilities of the affected person. There is a gradual deterioration of the mental faculties, which may ultimately lead to total dysfunction of the brain resulting in the death of the patient. In general the progress of the disease is very slow and steady and this presents considerable difficulty in early identification of the disease. However in some patients there is a sudden and rapid decline in brain function leading to death in a few years. Since the human brain is very adaptive the onset of Alzheimer's disease may not be obvious and it is only when as much as 80% of the brain cells are damaged symptoms are conspicuous. [Bennett, 63]

The main cause for the disease is the destruction of the brain cells particularly in the cortex region. In the first stage of the disease the region in the cerebral cortex that is associated with memory is affected. Then as the disease progresses other regions in the cerebral cortex also undergo progressive deterioration leading to total impairment of functional and cognitive abilities. Though as in any other form of dementia syndrome memory loss is one of the chief and noticeable problems the effect of the disease extends to much more than memory loss and in most of the cases there is a total crippling of the brain functions thereby affecting the individuals ability to relate and respond appropriately to the outside world.

Symptoms of Alzheimer's Disease

As discussed above Alzheimer's disease is characterized by a wide variety of symptoms from memory loss or amnesia, language difficulties, Dyspraxia or difficulties in performing complex tasks to depression and other kinds of psychotic symptoms. It has to be understood that a careful study of the symptoms followed by detailed tests and diagnosis is essential to identify Alzheimer's disease as most of the other kinds of dementia share the same kind of symptoms. This inter-relatedness of the symptoms makes it more difficult to specifically identify the nature of the dementia. Let us discuss each of these in a little detail.

Amnesia

Memory loss (amnesia) is one of the most noticeable and manifest symptom which is fairly common in all forms of dementia. It is observed that amnesia is more pronounced for the latest or the recent events and in many cases the person is able to recollect events that happened long back. This selective loss of memory is attributed to the impairment in storage mechanism of the brain. The most common signs of memory loss include the person's inability to recollect names, making lists even for trivial and routine tasks, repeated phone calls to relatives. The level of memory loss is acute in the later stages of the disease and the patient starts to forget faces and fails to identify his family.

Lovestone, 11]

Language Disorder

This is another predominant trait in Alzheimer's disease. Typically patients have difficulty in finding words and in naming objects. Nominal dysphasia, as the problem is identified is caused by the lesions in the left posterior temporoparietal region of the brain. There is a general loss of expressive ability along with the onset of receptive difficulties. These symptoms can be easily confirmed by subjecting the patient to standard tests such as Mini Mental State Examination (MMSE). [Lovestone, 13]

Dyspraxia

Dyspraxia refers to the difficulties associated with performing complex tasks. Dyspraxia due to Alzheimer's disease is associated with the poor transmission of the messages from the brain to the various organs of the body. Dressing Dyspraxia and 'Ideomotor Dyspraxia' are more pronounced with the patient being unable to dress himself properly and even finding difficulties with the daily grooming activities.

Agnosia and Prosopagnosia

The ability to recognize objects and faces is seriously affected in patents suffering from Alzheimer's disease. In many cases the patients exhibit difficulty in recognizing their own image leading to a medical condition known as autoprosopagnosia. There is also a distinct manifestation of topographical disorientation with the patient being unable to understand the environment. Because of topographical disorientation patients may find difficulty in driving as the disease advances. [Lovestone, 15]

Depression and other Psychotic Symptoms

Depression is a fairly common problem associated with Alzheimer's disease. Physicians have to be careful in their treatment of depression symptoms associated with AD because many of the anti-depressant medications exhibit anticholinergic activity. Incidentally this directly interferes with the cholinergic therapy which is one of the main treatment methods in Alzheimer's Disease. Furthermore there is a marked manifestation of non-cognitive disorders. Frequent mood swings, visual and auditory hallucinations are reported in 50% of all AD patients. Incontinence is another diagnostic symptom, which is fairly common to many other forms of dementia including AD.

Diagnosis

As we discussed earlier Alzheimer's disease does not reveal itself until such time when the disease is moderately advanced. However it is important to have an early diagnosis of the problem to be proactive in treatment and to minimize the severity of the symptoms. Today with the availability of drugs to treat the problem early diagnosis presents us with an opportunity to significantly improve the situation for the patient and to provide effective treatment. Detecting cognitive impairment is the first step in the diagnosis of the disease. But the main difficulty lies in the fact that the general practitioner may not detect AD and even if detected may not correctly attribute it to Alzheimer's disease. Typically a person with AD will have memory loss and a general decline in activity. Once the clinician suspects AD the next step in the diagnostic process is to subject the patient to a cognitive screening test.

Positron Emission Topography

This facility is a highly expensive one and presently restricted only to research institutions. The advantage of PET is that it measures the metabolic rate inside the brain in real time. Using PET it is possible to even identify the minute details such as the number of receptors within particular areas of the brain. This in turn will help us identify defects in cholinergic transmission. [Bennett, 121]

Major causes for Alzheimer's Disease

Amyloid Plaques

There has been enormous amount of research in the field of dementia. Researchers have recently identified one of the important causes for Alzheimer's disease. Autopsy study of the brains of AD patients has revealed the presence of Amyloid plaques between the neurons of the brain. Amyloid and B-Amyloid are two proteins that are synthesized by the body. While in a normal healthy individual these proteins are easily broken down in the case of patients suffering from AD the protein structures seem to accumulate between the neurons forming hard and insoluble plaques. The neurons that immediately surround the plaques degenerate rapidly.

NeuroFibrillary Tangles

Intraneuronal neurofibrillary tangle is another cause for Alzheimer's disease. Biochemical analysis of these NeuroFibrillary tangles has revealed the presence of very high levels of phosporylated neuro protein called TAU. Under normal situation this protein is essential for the transport of nutrients within the neurons. However in the case of AD the abnormally high Phosporylated State of the 'tau' protein leads to neuronal death. The underlying problem for patients is that the above mentioned complications result in a general reduction of cholinergic transmission which is at the core of neurological communication. [American Health Assistance Foundation]

Treatment Methods

Restoring Cholinergic Transmission

Considerable reduction in cholinergic transmission is one of the primary causes for the loss of memory and other associated symptoms of Alzheimer's disease and other kinds of dementia. Hence pharmacological treatment for AD mainly revolves around rectifying this circulatory deficit within the brain. Compounds designed to enhance cholinergic transmission constitute an important part of the treatment plan. Acetylcholine the neurotransmitter of the brain is considerably broken down in-patients suffering from AD and other dementias. The underlying mechanism of the neurotransmitter can be simplified as follows. An electrical impulse generated passes along the nerve and when it reaches the end it triggers the release of chemical messengers known as neurotransmitters which in turn diffuse along the synaptic cleft and react with the specific receptor sites on the organ. Activation at the receptor junction initiates a series of chemical reactions resulting in a specific biological response.

It has to be observed that the above mentioned process of cholinergic transmission is adequately timed and controlled by the body using another enzyme called acetylcholinesterase (AChe). The job of AChe is to breakdown Acetylcholine once the signal transmission is effected between the cells. Currently pharmacological therapy for AD is mainly concerned with two types of drugs. That is drugs which stimulate the release of Acetylcholine using stimulators such as Choline and lecithin alongside the use of drugs like that inhibit the action of acetylcholinesterase are the mainstay treatment mechanisms. In particular the drug Glycerylphosphorylcholine has found to show significant positive results in the neurological parameters of the patients by increasing the levels of Acetylcholine in the brain. Among the cholinesterase inhibitors are drugs such as tacrine (cognex), Donepezil. Exelon etc. [Life Extension, September 2002]

Anti-inflammatory Drugs

Post-mortem studies of the affected brain have clearly indicated inflammation of the brain cells. In tune with this researchers have also turned their attention to anti-inflammatory drugs (ex aspirin) as a protection mechanism against Alzheimer's disease. Other research evidences indicate the role of free radical damage of the brain cells and hence there is also a concurrent research on the use of anti-oxidants for preventing the damage caused by free radicals. Further clinical tests for women has shed new light into the possible cause of the disease. Researchers have testified that post menopausal hormonal changes make women more vulnerable for AD. In this connection the role of oestrogen as a preventive factor is being studied.

Other forms of Dementia

Alzheimer's disease is the most common form of dementia with a prevalence ratio of 2/3. However there are other forms of dementia such as vascular dementia, Lewy body dementia, Fronto-temporal degeneration, etc. The overlapping of the symptoms in many varieties of dementia implies that specific disease prognosis is fraught with difficulties. However from the perspective of the clinician it is important to perform a differential diagnosis of the disease as it has implications for the treatment. One of the main differences between Alzheimer's disease and the other kinds of dementia is the pattern of progression of the disease. Alzheimer's disease is slowly progressive while vascular dementia shows a stepwise progression.

Vascular dementia occurs as a result of repeated strokes. The depletion of oxygen to the brain during a stroke attack may cause irreversible damage to particular areas or cells of the brain. Typically in cases of vascular dementia there are a visible holes in the brain surface. The degree of cognitive impairment is proportional to the volume of brain lost. Furthermore, unlike AD, vascular dementia is not caused due to neurochemical imbalance. Treatment methods usually involve the use of anti-inflammatory drugs to prevent blood coagulation and consequent depletion of nourishment to the brain. [Bennett, 77]

Lewy body dementia on the other hand is kind of fluctuating one wherein noticeable improvement alternates with degeneration. The presence of Lewy bodies (intra neuronal inclusions) in the cortex region of the bran is a characteristic feature of Lewy body dementia. Patients also exhibit wild hallucinations and recover soon after and there is also a symptomatic resemblance to Parkinson's disease. Typically these patients are treated with antipsychotic drugs. [Bennett, 80]

Conclusion

Alzheimer's disease is one of the degenerating forms of brain disorders, which casts considerable emotional strain on the patient as well as the family. The availability of a number of drugs to relieve the symptoms has considerably eased the life for the patient and the caregiver. Research is already underway in discovering the molecular pathogenesis of Alzheimer's disease and in the near future advancements in this area will enable new drug therapies based on mechanisms aimed at preventing the formation of plaques and neurofibrillory tangles within the brain. It is pertinent to mention that caring of patients with Alzheimer's disease involves much more than pharmacological treatment as it is equally important to attend to critical issues such as family management and environmental management. (From the patients viewpoint). This kind of an integrated approach will definitely reduce the stress on the patient and the care giver leading to better management of this debilitating disease.