Alzheimer’s Disease – Diagnosis, Symptoms, and Treatment

What is Alzheimer’s Disease?

Alzheimer’s disease is a form of dementia, a condition that results in a gradual decline in brain function. It is the most common form of dementia in the United States.  It usually begins with the loss of memories surrounding recent events – then progresses to forgetting where you are, the time and date, and familiar faces and names.  Eventually, Alzheimer’s affects the core regions of the brain and results in impaired mobility, difficulty swallowing, and an inability to perform basic self-care tasks.  Alzheimer’s disease is a major cause of disability and death in the United States.

What Causes Alzheimer’s Disease?

Alzheimer’s is caused by the gradual destruction of neurons in the brain. This occurs due to the formation of plaques made of abnormal protein, known as amyloid plaques. The destruction of neurons and the formation of plaques is associated with decreased levels of acetylcholine in the brain which contributes to the gradual loss of awareness and memory. 

The exact cause of Alzheimer’s and what leads to the disease is unknown. It is thought that this condition results from a combination of genetic and environmental factors that when combined in certain individuals result in disease. Genes such as apolipoprotein E-e4 (APOE-e4) have been identified as a risk factor.  Abnormalities in genes coding the following proteins are also associated with increased risk:

• Amyloid precursor protein (APP)
• Presenilin-1 (PS-1)
• Presenilin-2 (PS-2)

The most common risk factors for Alzheimer’s disease include:

• Family history
• Certain genetic mutations
• Advanced age
• Traumatic brain injury
• Stroke

How Common is Alzheimer’s Disease?

Alzheimer’s disease is the most common cause of dementia. It is estimated that more than 5 million people are currently living with Alzheimer’s in the United States. This condition is most common in those over the age of 65, it is estimated that the risk of developing Alzheimer's doubles every 5 years over the age of 65. As the population of the United States is living longer this disease is becoming more common and affecting more lives. 

Early-onset Alzheimer’s is rare but is seen in some individuals with genetic conditions, heavy use of recreational drugs, and those with a history of traumatic brain injuries. The most common condition that is associated with early-onset Alzheimers is trisomy 21, also known as Down syndrome. 

Signs and Symptoms

The signs and symptoms of Alzheimer’s are progressive, commonly beginning with minor changes in memory and progressing to include a wide variety of changes that reduce the individual's ability to function. Some of the most common symptoms include:

• Memory loss
• Loss of time and space perception
• Impaired language
• Impaired cognition
• Changes in behavior
• Intellectual dysfunction – an inability to plan or judge appropriately
• Impaired mobility

Patients with moderate to severe Alzheimer’s usually become dependent on others due to their inability to feed, prepare food, bathe, dress, and perform other activities of daily living.  Patients eventually develop issues with swallowing that leads to food and drink entering the lungs while eating. This is known as aspiration and leads to infections within the lungs that can result in death. Other patients with severe Alzheimer's rapidly decline due to being bedridden and unable to eat, passing away from natural causes sometime after their diagnosis. 

Diagnosis

Alzheimer’s disease is diagnosed based on a history that suggests memory loss or a decrease in mental functioning, cognitive tests that objectively assess memory and mental status, and laboratory tests that are used to exclude other conditions. 

Alzheimer’s disease is a form of dementia.  When you have symptoms such as memory loss - your doctor will first screen you with a memory test called the mini-mental status examination (MMSE) or Montreal Cognitive Assessment (MoCA).  These tests are focused on simple tasks that the majority of individuals can complete unless a condition that impairs memory or mental functioning is present. They involve recalling where you are, the date, drawing objects, naming objects, repeating words, remembering words, and drawing basic shapes.  If your score does not meet a certain cut-off value, this is highly suggestive of dementia.

Individuals who screen positive for dementia are typically referred for formal neuropsychological testing, this is a much longer and more complete version of the screening tests mentioned above.  They also typically receive a brain MRI to rule out other causes of memory loss such as stroke, tumors, or bleeding within the brain.

 

The lab tests ordered in individuals suspected of having Alzheimer's are focused on ruling out other causes of dementia. The primary goal of these tests is discovering any causes of dementia that are reversible. The most common causes of reversible dementia are:

• Thyroid disease
• Vitamin B12 deficiency
• Alcohol abuse
• Infectious diseases (HIV, syphilis)
• Wilson disease
• Medication side effects

Alzheimer’s Disease Medication and Treatment

Alzheimer’s disease cannot be cured, however, there are many interventions that can slow the progression of the disease, increase the safety of those suffering from it, and help family members cope with having a loved one suffer from a neurological disease. 

Patients with Alzheimer's disease will generally be treated in their primary care physician’s clinic. A neurologist will be involved but visits with them will be infrequent unless symptoms are rapidly progressing or become severe. 

The first step in the treatment of Alzheimer’s is addressing any of the reversible causes of dementia listed above and regular monitoring to ensure that none of them develop, which would rapidly accelerate the overall decline in mental function. 

Second, your doctor will discontinue any medications that would worsen the symptoms of dementia. Some over-the-counter medications such as antihistamines for allergies (e.g. Benadryl), benzodiazepines for anxiety (e.g. Ativan and Valium), and tricyclics for depression and migraines (e.g. Amitriptyline and Imipramine) can dramatically worsen any form of dementia. 

There are certain medications that have shown to have a modest benefit in improving memory and quality of life in individuals with mild to moderate Alzheimer’s disease.  The most commonly prescribed drugs include:

• Namenda (memantine)
• Aricept (donepezil)
• Exelon (rivastigmine)
• Razadyne (galantamine)

These medications generally work by increasing acetylcholine levels in the brain.  Remember that Alzheimer’s disease is associated with low levels of acetylcholine in certain brain regions, which contributes to symptoms such as memory loss. By increasing the amount of acetylcholine in the brain some people see an improvement in their symptoms of Alzheimer’s. These medications are much more effective early in the course of Alzheimer’s and the greatest benefit is seen when starting these medications shortly after the symptoms of Alzheimer's begin. 

 

References:

1. Lawler E, Avila A. Alzheimer’s Disease: Monotherapy vs. Combination Therapy. Am Fam Physician. 2017 Apr 1;95(7):452. - https://www.aafp.org/afp/2017/0401/p452.html
2. Pierce AL, Bullain SS, Kawas CH. Late-Onset Alzheimer’s Disease. Neurol Clin. 2017 May;35(2):283-293. - https://www.ncbi.nlm.nih.gov/pubmed/28410660