Alzheimer's disease is currently the leading cause of dementia, which is a term used to describe the symptoms that are seen when the brain is affected by a particular disease or condition. The German neurologist Alois Alzheimer was the first person to describe the symptoms of Alzheimer's disease, which are seen when ‘plaques' and ‘tangles' accumulate in the brain, leading to the death of brain cells (1). Alzheimer's disease is an age-related disease that primarily affects people over the age of 65 and becomes much more prevalent in the population as people get older. Therefore, Alzheimer's disease is becoming a bigger worry to society as a result of an increasingly aging population. It is predicted that in the USA, 18-20% of the population will be over the age of 65 by the year 2030 (2). It can be seen how the age of the population is changing in the Mann 1995 study, which shows that there is a 68.9% increase in the 65 - 74 age group, an 84.3% increase in the 75 - 79 age group and a staggering 91.7% increase in the people who are of the age 80+ (3). These figures only become worrying in relation to Alzheimer's disease when the prevalence of the disease can be seen in these different age groups of society. The prevalence of Alzheimer's disease is 0.2/100 of the population in the age group 35-59, 0.3/100 in 60-69 year olds, 3.2/100 in 70-79 year olds and 10.8/100 in 80-89 year olds (4). These results show the sharp increase in the prevalence of Alzheimer's disease once people get over the age of 65, and therefore with an increasingly aging population, why Alzheimer's disease is set to burden society with a greater human and economic toll.
AD primarily affects the cerebral cortex of the brain, which commonly tends to be the parietal, temporal and frontal lobes. This gives us a better insight into the reasons behind the symptoms of AD as the frontal lobe controls intelligence, judgment and behaviour; the temporal lobe controls memory and the parietal lobe controls language. Also, the hippocampus and amygdala are two of the primary areas to be affected in AD. They are both areas of the brain that are part of the limbic system and are found inside the medial temporal lobe. The hippocampus plays an important role in the storing of new memories and also in spatial navigation (4). The amygdala plays an important role in the processing of emotional reactions and memories (5). An Alzheimer's diseased brain can vary from extremely atrophic to close to normal. When atrophy is present in the brain, it tends to affect the cerebral cortex with a generalized distribution, however in many cases it may selectively pick out areas such as the hippocampus, amygdala and the medial temporal lobe. However, cases which tend to show severe generalized atrophy, occur in the cases of AD that have an early onset of symptoms as opposed to the cases developing later in life (6).
The earliest clinical symptoms that can be seen in AD are lapses in memory and often problems finding the correct words. As the disease progresses the patient may become more and more confused, will frequently forget names, places, appointments and recent events. Mood swings will become much more apparent with patients swinging between angry/sad and scared/frustrated often at their memory loss. Eventually patients will become more withdrawn with lost confidence and communication problems (7). The problems patients have with their memory is always to do with their short-term memory. For example, a patient may have no problem recalling what they did 30 years ago, however may not be able to recall what they ate for breakfeast. This is because of the damage that is done to the hippocampus and its role in the storing of new memories. However, AD is a disease that often follows a very characteristic process, which has easily identifiable clinical stages. Therefore, the clinical stages of AD have been globally categorized into 7 stages, which range from normality to severe AD. These 7 stages are:
Stage 1: Normal - A patient will be free from any symptoms that cause cognitive and behavioural decline.
Stage 2: Normal aged forgetfulness - A patient will often complain that they can't recall names or recall where they placed things, as well as they could 5 years ago. They may also have problems finding the correct word when speaking. These are often symptoms that would go unnoticed by close friends and family.
Stage 3: Mild cognitive impairment - At this stage people very close to the patient will begin to notice the symptoms. Patients will start to noticeably repeat questions and their ability to perform executive functions will become compromised. Therefore, patients will have difficulty in trying to complete complex occupational and social tasks, like mastering new job skills or trying to plan an event. However, these symptoms will only become evident if the patient is called upon to complete complex social and occupational tasks, in their everyday life.
Stage 4: Mild Alzheimer's disease - This is the stage at which symptoms become evident to family and friends, and even the patient, as the patient begins to forget recent major events such as a recent holiday or a recent family visit. They may also have problems recalling what day, month or even season of the year it is. Nonetheless, they may still be able to recall their current address or the weather outside. Patients begin to lose the ability to do functional jobs, and may need help, in paying bills, cooking meals for the family and even ordering food at a restaurant. Family members will often have to help out. Patients will begin to become more withdrawn and emotionally unresponsive as their cognitive deficits become more noticeable. However, patients at this stage are still generally able to live independently with a little community support.
Stage 5: Moderate Alzheimer's disease - At this stage of AD the problems become so great for patients, that theyare unable to live independently. They will need somebody to ensure they eat properly and that their finances are in order; paying the bills. Patients who are not cared for properly may develop behavioural problems like suspiciousness and anger. The patients' memory problems will come to the extent where they can't recall recent major events. They may begin to forget what the weather conditions were outside, forget their address and may forget the current head principal figure of their country. Some information, like current address, may be loosely held, so that it is remembered at certain times but not at others. Remote memory begins to suffer, as patients may not remember where they went to school. Patients begin to develop calculation difficulties, and may not be able to count down from 20 in 2s. Patients will also have basic functional difficulties, like not being able to choose what clothes to wear.
Stage 6: Moderately severe Alzheimer's disease - At this clinical stage, functional tasks relevant to daily life become so difficult that patients will need constant care. These functional difficulties have been further divided into 5 more substages. At the substage 6a, patients will have problems putting on clothes without help. Patients will tend to put on clothes the wrong way round or inside out. By substage 6b, patients will have trouble bathing on their own, and will need help getting the right temperature on the shower. By substage 6c, patients will have problems going to the toilet correctly. Patients may not know what to do with the toilet paper or where to put it. Substage 6d is reached when the patient has urinary incontinence and 6e is reached with fecal incontinence. Both these problems can be managed with frequent toileting and appropriate clothing and bedding. At the 6th clinical stage of the disease, the cognitive deficits become so severe that patients can no longer recall any recent major events like what the weather outside is or any schools they went to. They may have problems remembering their parents' names or what their job used to be. They may even confuse their partner with a deceased parent. However, they may be able to recall their own name. The patient will have such great calculation problems that they might find it difficult counting down from 10. Changes in patients' emotional and behavioural state begin to become very clear at this 6th stage. This is partly a reaction by a patient to his or her own deficits. Patients will begin to fidget and pace, as they are unable to concentrate on or do any activities. Violent outbursts and threatening behaviour may occur and the patient may become very scared about being left alone, as they recognize their own inability to look after themselves.
Stage 7: Severe Alzheimer's disease - By the time the 7th stage of AD has been reached, the patient will need continual help in order to get through everyday life. The final stage of AD is further divided into 6 functional substages. At stage 7a the patient will only be able to speak a few words, when asked questions. By stage 7b all speech will either be lost or left to a single intelligible word. At stage 7c the ability to walk independently will be lost. However, with proper care the loss of the ability to walk can be postponed. Patients lose the ability to sit up properly, without help in stage 7d, and will often need chairs with arm rests in order to sit up properly. By stage 7e, the ability to smile is lost and by stage 7f patients will have trouble holding their head up without help. The average point of survival of AD sufferers, in the 7th clinical stage, tends to be between the substages 7c and 7d. When entering the 7th clinical stage, patients will tend to show a lot of physical rigidity, especially in joints such as the elbow. Also, the emergence of certain reflexes will occur. These are reflexes that can be seen in infants, but disappear when they become toddlers. Most noticeable are the grasp reflex, sucking reflex and the babinski plantar reflex. The common cause of death in the 7th clinical stage is pneumonia however, patients also become much more vulnerable to heart attacks, strokes and cancer. The mean life expectancy for patients from diagnosis is 7 years (7).
Currently AD is a very difficult disease to get an early diagnosis of because it is difficult to find any biological markers that give away a definite diagnosis. For a diagnosis pathologically, there must be neurofibrillary tangles, neuritic plaques, amyloid angiopathy and neuronal loss in the brain. However, the severity of each of these pathologies can differ greatly in different patients (8). An accurate early diagnosis of AD can be very important because it give the patient and the family the maximum possible time for preparation for future problems, and also medications that are only useful in the early stages of AD (9).