An Overview of the Causes, Symptoms, Stages, and Treatments for Alzheimer’s Disease

Alzheimer’s disease is the most common form of dementia, a condition characterized by the severe loss of global cognitive abilities in people who harbored no prior cognitive impairments. It can be the result of a brain injury or exist as a progressive condition that results in long-term decline from damage or disease in the body. While Alzheimer’s disease can develop very differentially for each individual, there are many common symptoms and the disease tends to occur in three separate stages. Currently, there is no known cure for Alzheimer’s, which is always fatal, those afflicted with the disease will suffer significant cognitive and motor impairments as their symptoms worsen throughout its progression.

The actual causes of Alzheimer’s disease are still uncertain. Currently, research proposes three new theories for the cause of Alzheimer’s disease. The first is the Beta-Amyloid Theory. Research by Fullwood, Hayashi, and Allsop (2006) found a common trait of Alzheimer’s is the presence of sticky plaques attached to the outside of neurons as well as stringy tangles inside. While most people tend to develop plaques and tangles on their nerve cells as they get older, Alzheimer’s patients develop more of them. Specifically, research findings have pinpointed that Alzheimer’s patients appear to produce an abundance of a sticky protein known as ‘beta-amyloid,’ which is a fragment of a much larger protein called the amyloid precursor protein (APP). These beta-amyloid fragments are produced when special enzymes called ‘secretatses’ react with APP. When there is an abundance of sticky beta amyloids, they form the plaques observed on the surface of neuron cells in Alzheimer’s patients. These plaques and tangles develop predictably, typically beginning in brain areas associated with learning and memory before spreading to other parts of the brain. As the plaques continue growing, the neuron gets inflamed. This inflammation triggers a response from the body’s immune system, which ends up killing nerve cells. Despite these findings, scientists are still unsure about the exact role that the plaques and tangles play in the onset and progression of the disease (Fullwood et al., 2006). Many researchers hypothesize that they somehow block communication between nerve cells, which results in a severe disruption of cellular activities considered crucial for the cell's survival.

The second theory is Apoe Theory, in which a recently discovered gene known as Apolipoprotein E (APOE4) on chromosome 19 is thought to be responsible for making people susceptible to the onset of Alzheimer’s disease. This gene, though present at birth, may not manifest itself until an individual is at least 65 years old and is associated with an increased risk for the common late-onset case of Alzheimer’s (Small et al., 1997). However, just because an individual has the APOE4 gene does not mean the person will automatically develop Alzheimer’s disease (Black, 2002). Furthermore, people without the APOE4 gene can still develop Alzheimer’s disease.

The third theory is the Tau Theory. According to research by Oddo et al. (2009), this theory states that a molecule, known as ‘tau,’ assembles microtubules that play a role in supporting the structure of the nerve cells. Chemical changes that occur in the nerve cells cause excessive amounts of phosphate ions to become attached to the microtubules strands, which then causes the tau molecules to change shape. The altered shape then results in the inability of these molecules to hold the microtubules in the proper alignment. As a result of the high concentrations of these long filaments, the structures begin to twist and fold into themselves improperly. Eventually, they become tangled and form aggregations, which have toxic effects on the cell (Oddo et al., 2003). This causes the nerve cells to subsequently shrink and die.

Other current research studies have indicated that several genetic and environmental factors may be responsible for the development of Alzheimer’s disease (Black, 2002). These risk factors include previous head injuries, lower levels of education, and other undefined genes that would increase an individual’s susceptibility. Genetic mutations on chromosomes 1, 14, and 21 are associated with a rare and early onset of the disease. Additionally, some forms of late-onset Alzheimer’s are to chromosome 12. Some research also supports a higher prevalence of the disease in females in comparison to males (Small et al., 1997). Understanding the cause of Alzheimer’s disease would be useful for making an earlier diagnosis and potentially even halting the progression of the disease.

Alzheimer’s disease usually begins during the late years of life, generally after a person has reached age 60. Roughly, 6% to 8% of all adults over 65 years of age have developed the disease. However, the prevalence of the disease doubles every 5 years after the age of 60 years. Therefore, by the time an individual has reached age 85 or older, the prevalence of the disease has increased to nearly 30% of the population in that age group (Small et al., 1997). Alzheimer’s disease occurs in three different, distinct stages beginning with early-stage, progressing to middle-stage, and finishing with end-stage. After receiving a diagnosis, the average life expectancy is about eight to ten years (Black, 2002). However, the rate at which the disease progresses varies for each individual.

Early-stage Alzheimer’s is characterized by symptoms such as short-term memory loss, temporary spatial disorientation, aphasia, apraxia, groping of words, and small errors in judgment and executive functioning. However, during the earliest stages, patients are usually still able to function independently and keep up with most of their daily activities (Shankle &Amen, 2004). Patients will have tremendous difficulties in learning any information and will struggle to retain it for more than just a few minutes. As the disease progresses, the ability to learn new information will become increasingly impaired until eventually even the patient's access to older and more distant memories will be lost. Impaired cognition will be one of the first and most visible symptoms to friends and family members of an Alzheimer’s patient as the individual starts to have trouble managing their finances and medications, planning meals, using a telephone and driving without becoming lost or confused. The early stage of Alzheimer’s is also marked by significant changes in behavior and mood (Small et al., 1997). Patients start to exhibit signs of irritability, anxiety, depression, or may experience alterations in their personalities.

The next stage, or middle-stage, usually occurs about two to three years after the first symptom. Symptoms of this stage include lapses in memory, loss of cognitive functions, and difficulties with language. The onset of psychiatric and behavioral symptoms will continue during this stage, making it increasingly difficult for patients to have the ability to follow simple conversations or understand even the simplest of instructions (Shankle & Amen, 2004). Eventually, the perpetual progression of these symptoms will cause patients to gradually lose their basic sense of personal identity. Patients will begin to fall victim to delusions and hallucinations, which can make them act aggressively towards others. Many patients end up wandering aimlessly during this stage, often forgetting where they are going or becoming very lost and confused.

The last stage of Alzheimer’s is marked by a sharp decline in neuro-musculoskeletal and motor performance. Patients lose their ability to walk and eventually will be unable to sit up without assistance. Additionally, they also lose control of their bladder and bowel movements. During this stage, the disease finally starts to affect the patient’s brain stem, which causes basic processes such as respiration and digestion to cease. As a result, patients usually stop eating and will spend most of their time sleeping. Their hands and feet will start to feel cold due to a lack of blood flow to their extremities. During their final moments, their breathing will become more constrained and shallow until the patient is unresponsive (Shankle & Amen, 2004). As soon as patients are completely unresponsive, their breathing stops completely.

Currently, there is no cure for Alzheimer’s disease and no method of therapy will be able to stop or reverse the progressive cognitive decline. Treatment of Alzheimer's disease is mostly focused on managing the symptoms so the patient suffers the least amount of disruption and discomfort possible. Some pharmacologic treatments and psychosocial therapy techniques have been shown to be successful in providing some relief for the depression, psychosis, and agitation that often accompany Alzheimer’s. Additionally, some pharmacotherapy may be able to produce cognitive improvements in many patients, especially during the early stage of the disease (Small et al., 1997). Cholinesterase inhibitors are the only current treatment available for the cognitive impairment caused by Alzheimer’s disease. They improve central cholinergic neurotransmission.

There are five main drugs approved for treating Alzheimer’s in most countries. These drugs are beneficial for limiting the decline of cognitive abilities when they are prescribed early enough. Donepezil is non-competitive acetylcholinesterase, reversible inhibitor that is able to improve cholinergic neurotransmission by delaying the breakdown of acetylcholine that is released into the synaptic cleft. Another drug, memantine, works as an NMDA receptor antagonist. This means that it blocks the harmful effects of pathologically elevated levels of glutamate. High glutamate levels have been shown to lead to significant neuronal dysfunction. Other drugs such as galantamina, rivastigmine, and tacrine also work as reversible, non-competitive cholinesterase inhibitors that are typically used to treat mild to moderate cases of the disease (Cappell et al., 2010). They may also aid in slowing down the progression of the disease so that patients may have more time before entering the late stage of Alzheimer’s.

Another way to fight the impairment of cognition in Alzheimer’s patients is through social activities and interaction. Research indicates that by engaging in frequent social activities, the cognitive decline associated with old age and Alzheimer’s may be prevented or delayed. As the symptoms of Alzheimer’s progress, it becomes increasingly difficult for patients to socialize. However, the brain needs socialization. Without constantly engaging in thought-provoking activities, the brain will not be required to produce the necessary neurotransmitters, which subsequently leads to even more reduction of acetylcholine neurotransmitters (Small et al., 1997). The brain is a muscle, and just like any other muscle, it needs to be exercised to maintain its abilities.

Current research findings suggest that immunization may also be an effective form of treatment or even lead to the discovery of a potential cure for the disease. Dr. Stefan Lichtenthaler of the German Center for Neurodegenerative Diseases theorizes that proteases could be useful for preventing and treating Alzheimer’s disease. Proteases are enzymes that work as a pair of molecular scissors in the body by cleaving proteins apart. There are roughly 600 different proteases that are present within the human body, which control a vast array of biological and medical processes. One protease, a-secretase, has recently been linked to the prevention of the molecular processes that lead to Alzheimer’s disease. One member of the a-secretase family, known as the ADAM10 gene, has been the most promising. Reduced ADAM10 activity, usually a result of mutations on the gene, seems to be connected with an increased risk for Alzheimer’s disease. Many patients with late-onset forms of Alzheimer’s Disease have been found to have reduced ADAM10 activity in their blood and cerebrospinal fluid (Lichtenthaler, 2011). Since it is possible to stimulate the production of ADAM10, this could indicate a possible treatment in the future.

References

Black, I. (2002). The Changing Brain: Alzheimer's Disease and Advances in Neuroscience. Oxford: Oxford University Press.

Coppel, J., Herrmann, N., Cornish, S., & Lanctot, K. (2010). The Pharmacoeconomics of Cognitive Enhancers in Moderate to Severe Alzheimer's Disease. CNS Drugs, 24(11), 909-927.

Fullwood, N., Hayashi, Y., & Allsop, D. (2006). Plasma Amyloid-β Concentrations In Alzheimer's Disease: An Alternative Hypothesis. The Lancet Neurology, 5(12), 1000-1001.

Lichtenthaler, S. (2011). ADAM10: Potential ‘Molecular Scissors’ for the Treatment of Alzheimer’s Disease. Future Neurology, 6(1), 1-4.

Oddo, S., Akbari, Y., Mattson, M. P., Metherate, R., Kayed, R., Golde, T. E., et al. (2003). Triple-Transgenic Model Of Alzheimer's Disease With Plaques And Tangles Intracellular Aβ And Synaptic Dysfunction. Neuron, 39(3), 409-421.

Shankle, W. R., & Amen, D. G. (2004). Preventing Alzheimer's: prevent, detect, diagnose, treat, and even halt Alzheimer's disease and other causes of memory loss. New York: G.P. Putnam's Sons.

Small, G., Teri, L., Gwyther, L., Finkel, S., Ferris, S., Dekosky, S., et al. (1997). Diagnosis and Treatment of Alzheimer Disease and Related Disorders: Consensus Statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society. The Journal of the American Medical Association, 278(16), 1363-1371.