Alzheimer's Disease: Causes, Symptoms, Diagnosis, Treatment & Prevention


Alzheimer's Disease is said to be the most common kind of dementia. While the symptoms are often quite mild at the onset of the disease, they gradually progress to take on a more severe form.

Alzheimer's Disease (AD) is a neurodegenerative disease. It was in the year 1906 that Dr Alois Alzheimer found out certain alterations in the brain tissue of a woman who had succumbed to mental illness.

While living, the woman had displayed symptoms that included unpredictability in behaviour, memory loss, and language troubles. On examination of her brain tissue after death, many tangled fibre bundles and abnormal clumps were found. This condition came to be later known as Alzheimer's Disease.

Many cellular changes take place in the brain of a person with AD. The beta-amyloid protein (involved in Alzheimer's) comes in various molecular forms. These get collected between neurons. These are formed from the breakdown of a larger protein known as the amyloid precursor protein. In the brain of a person with AD, there are abnormal levels of this protein which are clumped together to form plaques. These plaques are formed between neurons eventually disrupting the cell functionality.

A number of theories have been put forward to account for why some people are more predisposed to getting AD than the rest.

Advanced age: The advancement in age is believed to be the major risk factor for AD .

Dysfunction of the immune system : There is a close connection between the functioning of the central nervous system and the immune system . The Neuroinflammation Hypothesis deals with the dysregulation of the central nervous system's immune response as a major causative factor for the onset of neurodegenerative diseases. Neuroinflammation is increasingly being recognized as a major cause of AD.

Environmental factors: It has been found that various environmental factors, such as aluminium, diet, exposure to viruses can also lead to the onset of AD . In terms of diet, while total calorific intake, as well as dietary fat, have been found to be contributing factors for AD, consumption of fish has been seen to reduce the risk of AD significantly. Aluminium has been linked to neurological damage and various studies have established an undeniable link between AD and aluminium.

Viral infections cause inflammation, which in turn might lead to neurological damage resulting in AD . Other environmental factors such as malnutrition or head injury have also been found to have led to AD in certain cases .

Genetic factors: Genetics plays a crucial role in the predisposition of someone towards developing AD. It has been found that rare mutations in some genes can lead to early-onset familial AD .

Clinical research has led to the finding that AD is indeed a multifactorial disorder in which both environmental as well as genetic risk factors interact with each other to speed up the normal rate of aging .

On the basis of the age at which AD affects an individual, it can be classified into early-onset Alzheimer's Disease (EOAD) that occurs before 65 years of age, and late-onset Alzheimer's Disease (LOAD) that sets in when the individual is 65 years or more in age. Around 1-5% of the total cases of AD can be said to be EOAD, while the other 95% can be said to be LOAD .

The common symptoms associated with AD are as follows:

Neuropsychiatric symptoms (NPS) such as psychosis, apathy, depression, and aggression are now regarded as the main features accompanying AD. It is also generally seen that the greater the severity of the symptoms, the faster is the decline of cognitive abilities and loss of freedom, even leading to a short survival eventually .

According to the National Center for Biotechnology Information (NCBI), depending on the level of cognitive impairment, AD is classified into preclinical, mild, moderate, and late-stage .

Preclinical AD: The preclinical stage of AD is the asymptomatic phase. In the preclinical stage, cognitive impairment is almost undetectable, and only the pathophysiological changes associated with AD can be detected with the help of biomarkers .

Mild AD: The mild phase of AD is characterized by mild impairments in communicative patterns, memory, and executive ability. Depression is also witnessed in people with mild AD along with a significant reduction in the ability to conduct some advanced daily activities of daily living .

Moderate AD: In the moderate stage of AD, there is a marked decline in cognitive ability, affecting abstract thought and language. The ability for carrying out instrumental activities of daily living is almost completely lost. Another symptom commonly associated with moderate AD is related to mood and behaviour .

Moderate AD is also characterized by other symptoms such as dyspraxia or lack of coordination in fine and gross motor skills, dysgnosia or loss of awareness of self with relation to the environment one finds himself in, and decreased judgement .

As AD progresses from the moderate to severe or late-stage AD, it is usually accompanied by psychotic symptoms, behavioural changes, and social withdrawal .

Late-stage AD: In the late stage of AD, even basic activities such as feeding or dressing oneself can pose a challenge. There is a general overall decline of the patient, with him gradually becoming fully dependent on others .

The most commonly witnessed symptoms of late-stage AD are dysphoria or a condition of dissatisfaction with life in general, reduced motor function, apathy, irritability, agitation, and anxiety .

Do keep in mind that there is no precise definition as such for late-stage AD. The severe or late-stage AD is marked by susceptibility to various life-threatening infections, a severe decline in functioning with most patients being bedbound, severe limitations in communicative as well as cognitive abilities wherein most individuals become mute .

The most severe kind of AD is identifiable with a marked resistiveness on the part of the individual. At this stage, the individual with AD will show great resistance to everyone around him. Also, eating difficulties and incontinence are most pronounced at this stage .

The diagnosis of anyone suspected to be suffering from AD comprises the following steps .

1. A history is taken from someone who can be considered a reliable informant. The history to be taken would include family history, general medical history, neuropsychiatric history, and neurological history.
2. A physical as well as neurological examination.
3. Laboratory tests, such as thyroid function test, complete blood count, etc.
4. Neuroimaging tests, such as computed tomography scan (CT Scan), or magnetic resonance imaging (MRI).

The diagnosis of AD focusses on finding out any functional and cognitive changes, supplemented by a structured history and corroborated by a trustworthy informant .

It is always advisable to conduct a detailed psychiatric and medical analysis, as well as an assessment of substance use history to rule out other factors that might be mistaken for AD - depression, alcohol or substance dependence, medication side effects, or delirium .

The most common cause of dementia, AD is an irreversible neurodegenerative disorder . Identified by memory loss and cognitive impairment, AD is an age-related and progressive disorder.

As an incurable disorder, the therapeutic options available for AD have revolved around reducing the symptoms and checking the rate of progression of damage .

Prevention is undoubtedly a much better solution for tackling AD. Precise diagnosis, as early as possible, is probably the best line of defence. Generally, antidepressants and antipsychotics are given to patients with confirmed AD .

As such, there is no cure for AD. No drug that can either delay or stop the progression of AD has been found. The target of therapy in AD is to inhibit the brain acetylcholinesterase [AChE]. Reversible AChE inhibitors help in improving the life quality of AD patients by treating symptoms that are related to thinking, memory, judgement, language and various other thought processes .

Currently, medications that have been approved by the European Medicines Agency [EMA] and the US Food and Drug Administration [FDA] for administration to individuals with AD are reversible AChE inhibitors such as rivastigmine, galantamine, and donepezil [29] ; and memantine that works as an NMDA receptor antagonist .

Memantine, classed as an NMDA receptor antagonist, is usually prescribed to people with AD. While memantine will not cure AD, it works by decreasing the brain's abnormal activity. The ability to remember and think can be improved with the help of memantine.

The importance of early medical intervention can hardly be overstated, as a delay in seeking medical assistance might lead to non-reversible progression of symptoms .

Various clinical trials and observational studies have found out certain modifiable risk factors for AD, such as physical inactivity, mental inactivity, diabetes mellitus, depression, smoking, and poor diet . To this list of modifiable risk factors were later added obesity, low educational attainment, and hypertension . As per estimates, around one-third of all cases of AD can be understood to have been caused by modifiable risk factors. This fact alone makes the onset of AD preventable in such situations.

The modifiable risk factors for AD can be considered under two broad categories.

Lifestyle habits: Smoking, diet, physical activity, mental activity, social activity, and diet.
Cardiovascular factors: Obesity, hypertension, and diabetes .

Controlling such factors can significantly reduce the risk of someone developing AD with the advancement in age.

In recent years, almost all of the therapeutic trials conducted for AD have met with failure. A primary reason for this failure can be attributed to the clinical trials being conducted at the advanced stages of AD, at a time when irreversible damage has already set in .

பனைமரம் - Panaimaram