Alzheimer's Disease

Many people believe that dementia and Alzheimer’s disease are one and the same and use the terms interchangeably, but this is simply not true. While the term “dementia” refers to a general decline in mental abilities, which could be associated with several disease conditions, Alzheimer ’s disease is the most common cause of dementia.

The incidence and prevalence of Alzheimer’s disease increase dramatically with age. Approximately 80 per cent of people with dementia are above the age of 75.

Nearly two-thirds of people with dementia are women, likely reflecting lifespan and biological factors. Approximately two-thirds of caregivers are also women.

The overall lifetime risk of Alzheimer's disease at age 65 is about 21 per cent for women and close to 12 per cent for men.

What changes can I expect?

The symptoms and progression of the disease vary greatly from one person to the other. Symptoms of Alzheimer’s disease will become progressively worse over time. In the very early stages, the person may need assistance with activities such as preparing meals, banking, transportation, managing a home and finances.

The person can experience early and prominent deficits in memory, with varying degrees of language, reasoning and decision-making and visuospatial difficulties.

Common symptoms include:

• Loss of memory of recent events, asking repetitive questions or repeating oneself. Symptoms can also include frequently missing appointments or forgetting to pay bills on time, misplacing personal items, and progression to poor long-term memory as dementia advances to later stages.
• Language difficulties such as difficulty finding the right words or names of common objects, a tendency to use wrong words and difficulties understanding complex sentences in the earlier stages of the disease. These language difficulties would also become more prominent with time.
• Visuospatial challenges: The person might experience issues with navigation or way-finding, difficulty locating things in plain sight, or difficulty recognizing object or faces.

Other symptoms can include:

• Reasoning and problem solving
• Making decisions
• Organizing, multi-tasking, maintaining focus, easily distractable
• Getting confused with time and place
• Difficulties using devices or technology
• Problems with numbers and calculations

In the later stages of the disease, assistance will be needed for activities of daily living such as eating, personal hygiene, grooming, dressing and bathing. 

Behaviour changes can also be apparent and can progress from anxiety, depression and frustration in the earlier stages to hallucinations, delusions, suspicions about family/professional caregivers, apathy and sometimes aggression. This can be challenging for caregivers.

In the later stages, the person with Alzheimer's disease might have difficulty recognizing family members, have difficulty swallowing and walking.

Average life span following a diagnosis varies between 8-15 years and is impacted by multiple factors such as age at diagnosis, gender, presence of psychotic symptoms, presence of motor symptoms and coexisting medical conditions.

What changes happen in the brain with Alzheimer's disease?

The hallmark of Alzheimer’s disease is the appearance of plaques and tangles in the brain.

Plaques are an abnormal collection of Beta-amyloid protein in the spaces between the neurons (or nerve cells). Tangles are twisted strands of Tau protein that collect inside the nerve cells.
These plaques and tangles affect the ability of the nerve cells to communicate with each other and ultimately cause the nerve cells to die. This can result in shrinkage of the affected parts of the brain.

There is a loss of connections between nerve cells and a decrease in the level of neurotransmitters in the brain, such as Acetylcholine, that help in transmitting messages from one nerve cell to the other. 

An area called the Hippocampus, located deep in the temporal lobe of the brain is the first to be affected in Alzheimer’s disease.

This part of the brain is involved in learning and memory, which accounts for why the loss of memory of recent events is often the first symptom of Alzheimer’s disease.

These changes are progressive and spread slowly to other parts of the brain. 

The symptoms of Alzheimer’s disease and the course of symptoms that appear is different from one person to another. It depends on the parts of the brain affected and the rate of progression of the disease.

It’s believed that plaques and tangles start developing in the brain at least 15 years prior to the onset of symptoms.

What causes these plaques and tangles to form?

Researchers around the world are working hard to identify this. What triggers the formation of plaques and tangles in the brain is not very clear, though several theories have been proposed. An interplay of multiple factors including genetics, environmental factors, lifestyle, and overall health is suspected.

Recent research points to chronic inflammation as a major factor in the development of Alzheimer’s disease. Infection in the mouth and gut is also believed to play a role, indicating a potential gut-brain connection as well.

Research is ongoing in this field.

What are the risk factors for Alzheimer's disease?

• Environmental and lifestyle risk factors:
   
  • Population-based studies provide strong evidence that the risk of late-life cognitive impairment and dementia is modified by medical conditions, lifestyle choices and environmental factors. Vascular risk factors, sleep disorders, traumatic brain injury and depression are associated with an increased risk of Alzheimer’s disease. Studies show that the role of vascular risk factors actually varies at different stages of life. Therefore, high blood pressure, high cholesterol and obesity in midlife have a stronger association with Alzheimer’s disease, than in late life. Diabetes throughout life has been recognized as a risk factor as well.
     
  • Research has shown we can lower our risk through increased physical and cognitive activity (years of formal education),; social engagement and following a healthy plant-based diet such as the Mediterranean diet, throughout our life span. Avoiding smoking and limiting alcohol consumption also help you lower the risk of Alzheimer’s disease.
     
• Genetic or family risk factors:
   
  • The majority of cases of Alzheimer's disease are not inherited or caused by genetic factors.
     
  • There are some genetic risk factors that play a role in both the familial variety of Alzheimer's disease as well as the more common late-onset variety of Alzheimer's disease.
     
  • Purely familial Alzheimer’s disease accounts for less than 1 per cent of all cases. It is attributed to mutations in any one of genes Pre-Senilin 1 (PSEN1), Pre-Senilin 2 (PSEN2), and Amyloid Precursor Protein (APP) that are situated on chromosomes 14, 1 and 21 respectively. These three mutations lead to aberrant cleavage or aggregation of the amyloid precursor protein. Symptoms of this type of Alzheimer’s disease can manifest before the age of 65 (early/young-onset) and is more rapidly progressive. This type of dementia accounts for 11 per cent of early-onset dementia that appears in people younger than 65 years.
     
• Late-onset Alzheimer's disease:
   
  • This is the more common type of Alzheimer's disease and constitutes over 95 per cent of all cases. Late-onset Alzheimer's disease is a complex genetic disorder, with an estimated heritability of 60 - 80 per cent. It typically affects those over 65 years of age and progresses slowly. A well-known factor is advancing age. 26 risk genes have been identified that contribute to the overall risk of developing late-onset Alzheimer's disease. Therefore, a polygenic risk does exist for Alzheimer's disease. Of these, the strongest risk gene is the APOE gene on chromosome 19, which encodes the brain's major cholesterol transporter.
     
  • APOE gene occurs in three forms (alleles) APOE E2 (about 8.4 per cent of the population), APOE E3 (77.9 per cent of the population), and APOE E4 (13.7 per cent of the population). APOEE4 is associated with an increased risk of AD, while APOEE2 is protective, and APOEE3 is neutral. Having one copy of APOEE4 is associated with roughly three times higher risk of AD compared to those without the risk gene; whereas having two copies of APOEE4 gene is associated with roughly 10-12 times higher risk. Each copy of APOEE4 reduces the age of onset of symptoms by a decade.
     
  • Female carriers of APOEE4 are at an increased risk compared to male carriers, particularly between the ages of 65 and 75.

How is Alzheimer's disease diagnosed?

There is no single, conclusive test for Alzheimer's disease or any other types of dementia. A diagnosis is usually made by excluding other causes that present with similar symptoms.

A diagnosis is made based on investigating a person's medical history, a physical assessment, blood tests, imaging and cognitive assessments.

A physician will first take a detailed history from the person with symptoms/concerns about dementia and from family members, if available. This will be followed by a thorough physical examination and blood tests to rule out conditions such as infections, vitamin deficiencies, thyroid problems and the side-effects of medication.

Following the initial blood tests, the physician may refer the person to a specialist. The specialist may be a neurologist, a physician in geriatric medicine or a general psychiatrist or a geriatric psychiatrist.

The person's memory will be assessed, initially with questions about recent events and past memories. Their memory and thinking skills may also be assessed in more detail by a psychologist. A brain scan may also be carried out to get some information to identify any changes taking place in the brain.

• There are different types of scans, including computerised tomography (CT), magnetic resonance imaging (MRI) and Positron Emission Tomography (PET) scans.
• A CT scan may show conditions such as a tumour, fluid in the brain, shrinkage of the brain, and vascular changes to a small extent.
• The MRI of the brain would show the above conditions in greater detail and even show changes associated with any strokes in the brain.
• An amyloid PET scan will show plaques in the brain. This is of limited diagnostic significance however, as many cognitively normal older adults have amyloid plaques and they may never develop Alzheimer’s disease.
• FDG (Glucose) PET scan, which shows glucose metabolism in different parts of the brain is more beneficial for diagnostic purposes. It also helps to distinguish between Alzheimer’s disease and frontotemporal dementia.

At the end of these investigations, the physician is able to make a diagnosis of dementia and narrow down the most probable type of dementia.

Is there a cure? What kind of treatment is available?

Unfortunately, at this time, there is no known cure for Alzheimer’s disease, but medications are available to help control the symptoms.

These medications include Cholinesterase inhibitors such as Aricept (Donepezil), Exelon (Rivastigmine), Reminyl (Gallantamine), and Ebixa (Memantine). However, these medications do not stop or slow the progression of the disease. They help to control symptoms for a variable period of time.

Aricept, Exelon and Reminyl are recommended for mild-to-moderate Alzheimer’s disease. They help to restore the level of neurotransmitters (Acetyl Choline) in the brain that enables the nerve cells to function more efficiently. The level of Acetyl Choline in the brain is found to be low in individuals with Alzheimer’s disease. 

Side effects of Aricept, Exelon, and Reminyl are found to be mild and may include nausea, vomiting, diarrhoea, insomnia, fatigue, drowsiness, and loss of appetite. An Exelon patch is now available that helps reduce gastrointestinal symptoms.

Ebixa is an NMDA receptor agonist and works by decreasing the level of glutamate in the brain. Its side effects include dizziness, headaches, and tiredness, and rarely confusion, and hallucinations.

Research has shown that giving Aricept in combination with Ebixa leads to better control of symptoms and slows down the progression of symptoms.

http://www.alzheimers.org.uk/site/scripts/download_info.php?downloadID=1093

*This content is provided for informational purposes only and is not to be used for diagnosis or treatment of any type of dementia or its symptoms. Any mention of pharmaceutical interventions or treatments is not an endorsement by the Alzheimer Society of Calgary. This information is apt to change at any time without notice. For medical advice, please contact your physician.