Which drug for Alzheimers disease should be administered beginning at the time of diagnosis

Overview

What is Alzheimer's disease?

Alzheimer’s disease is a brain disorder that cannot be stopped or reversed. The disease severely affects memory, thinking, learning and organizing skills and eventually affects a person’s ability to carry out simple daily activities. Alzheimer’s disease is not a normal part of the aging process.

Alzheimer’s is a disease whose symptoms worsen over time. In fact, scientists believe the disease process may go on for 10 years or longer before the first symptoms of Alzheimer’s disease appear.

When memory problems do begin to be noticeable, they are often identified as mild cognitive impairment (MCI). At this stage, intellectual function is affected but the ability to function and live independently remain intact as the brain compensates for disease-related changes.

In some people, MCI can hold steady at this stage. However, people with MCI are at high risk for progressing to dementia. Alzheimer’s disease is the most common form of dementia. (Dementia can also be due to a variety of reasons such as Parkinson’s disease, dementia with Lewy bodies, vascular dementia, frontotemporal dementia and more.) With dementia, in contrast to MCI, daily function is affected.

As dementia due to Alzheimer’s disease progresses to late stages, affected individuals cannot carry on a conversation, recognize family and friends, or care for themselves.

How common is Alzheimer’s disease?

Alzheimer’s disease is the most common cause of dementia (accounting for 60 percent to 80 percent of cases). Alzheimer’s disease is the sixth leading cause of death in the United States.

One in 10 people older than 65 and nearly half of people older than 85 have Alzheimer’s disease. Alzheimer’s disease can also affect people in their 40s. The percentage of people who have Alzheimer’s disease rises every decade beyond the age of 60. According to the Alzheimer's Association, with the aging of the population and without successful treatment, there will be 14 million Americans and 106 million people worldwide with Alzheimer’s disease by 2050.

Symptoms and Causes

What causes Alzheimer’s disease?

Alzheimer’s disease is caused by the abnormal build-up of proteins in the brain. The build-up of these proteins — called amyloid protein and tau protein — leads to cell death.

The human brain contains over 100 billion nerve cells as well as other cells. The nerve cells work together to fulfill all the communications needed to perform such functions as thinking, learning, remembering, and planning. Scientists believe that amyloid protein builds up in the brain cells, forming larger masses called plaques. Twisted fibers of another protein called tau form into tangles. These plaques and tangles block the communication between nerve cells, which prevents them from carrying out their processes. The slow and ongoing death of the nerve cells, starting in one area of the brain (usually in the area of the brain that controls memory) then spreading to other areas, results in the symptoms seen in patients with Alzheimer’s disease.

What are the symptoms of Alzheimer’s disease?

Symptoms of Alzheimer’s disease vary from person to person and worsen over time. Symptoms of the disease include:

• Memory loss. This is usually one of the first symptoms of Alzheimer’s disease.
• Putting objects in odd places
• Confusion about events, time and place
• Repeating questions
• Trouble managing money and paying bills
• Trouble performing/taking longer to perform familiar tasks
• Getting lost/wandering
• Not being able to sleep
• Changes in personality and behavior including agitation, anxiety and aggression
• Having groundless suspicions about family, friends and caregivers
• Poor judgment or reasoning
• Trouble recognizing family and friends
• Difficulty learning and remembering new information/recent events
• Difficulty performing multistep tasks, such as dressing or cooking
• Having hallucinations, delusions or paranoia
• Difficulty speaking/finding the right words
• Difficulty reading, writing and working with numbers
• Difficulty walking
• Difficulty swallowing

For more information on the stage of disease, click here.

Diagnosis and Tests

How is Alzheimer’s disease diagnosed?

These tests are used to diagnose Alzheimer’s disease or to rule out other medical conditions that cause symptoms similar to Alzheimer’s disease:

• Medical history. The physician will ask about current and past medical conditions, medications the patient is taking, and family history of Alzheimer’s disease or other memory disorders.He or she will also check all current vital signs (blood pressure, heart rate, temperature, pulse rate) and conduct a neurologic exam (check reflexes and coordination, eye movement, speech and sensation).
• Blood and urine tests. These are standard lab tests conducted to rule out other causes of symptoms including blood counts, vitamin levels, liver and kidney function, mineral balance, and thyroid gland function tests.
• Mental status testing. These tests include tests of memory, problem solving, focus, counting, and language skills. This type of testing can also monitor the progress of Alzheimer’s disease.
• Neuropsychological testing. This exam includes tests to assess attention, memory, language, the ability to plan and reason, the ability to change behavior, as well as personality and emotional stability. This type of testing can also monitor the progress of Alzheimer’s disease.
• Spinal tap. Also called a lumbar puncture, this test checks for the tau and amyloid proteins that form the plaques and tangles seen in the brains of people with Alzheimer’s disease.
• Brain imaging tests:
  • Computed tomography (CT). This scan reveals physical changes in the structure of brain tissue seen in the later changes of Alzheimer’s disease, including decrease in the size of the brain (atrophy), widening of the indentations of the brain tissues, and enlargement of the fluid-filled chambers of the brain.
  • Magnetic resonance imaging. This scan can also show brain atrophy. In addition, it can identify strokes, tumors, the buildup of fluid on the brain, and other structural damage that can cause symptoms similar to Alzheimer’s disease.
    • fMRI (functional MRI). This is a type of MRI that measures brain activity in a select area by detecting changes in blood flow. This test is being used by researchers to see how the brain changes at different stages of Alzheimer’s disease. It is also being used to evaluate treatments for Alzheimer’s disease before a person has symptoms.
  • Positron emission tomography. This scan shows the abnormal brain activity in a person affected by Alzheimer’s disease. It can also help diagnosis Alzheimer’s disease versus other forms of dementia.
    • Amyloid PET. This scan shows the buildup of amyloid protein in the brain.
    • FDG PET. This scans shows how well brain cells use glucose. A decline in the absorption of glucose is a sign of Alzheimer’s disease.

Management and Treatment

Which medicines are used to treat Alzheimer’s disease?

There is no cure for Alzheimer’s disease, but available medications temporarily slow the worsening of dementia symptoms and help with behavioral problems that may appear during the course of the disease.

Four medications representing two drug classes are currently approved by the Food and Drug Administration (FDA) to treat the symptoms of Alzheimer’s disease. These drugs are the cholinesterase inhibitors and a NMDA antagonist.

Cholinesterase inhibitors. The cholinesterase inhibitors are all approved to treat the symptoms of mild to moderate Alzheimer's disease (AD). Cholinesterase inhibitors include:

• Donepezil (Aricept®) (also FDA-approved to treat moderate to severe disease)
• Rivastigmine (Exelon®) and Exelon patch
• Galantamine (Razadyne®)

These drugs work by blocking the action of acetylcholinesterase, the enzyme responsible for destroying acetylcholine. Acetylcholine is one of the chemicals that helps nerve cells communicate. Researchers believe that reduced levels of acetylcholine cause some of the symptoms of Alzheimer's disease. By blocking the enzyme, these medications increase the concentration of acetylcholine in the brain. This increase is believed to help improve some memory problems and reduce some of the behavioral symptoms seen in patients with Alzheimer’s disease.

These medications do not cure Alzheimer’s disease or stop the progression of the disease. The most common side effects of these drugs are nausea, diarrhea, and vomiting. Some people may have loss of appetite, insomnia or bad dreams.

NMDA antagonist. Memantine (Namenda®) is approved by the FDA for treatment of moderate to severe Alzheimer's disease. It blocks the neurotransmitter glutamate from activating NMDA receptors on nerve cells, keeping the cells healthier. This medication works differently than the cholinesterase inhibitors. Memantine can be taken alone or taken together with a cholinesterase inhibitor.

Patients with moderate to severe Alzheimer's who were treated with memantine performed better in studies measuring the common activities of daily living such as eating, walking, toileting, bathing, and dressing compared with patients taking placebo. Patient with lower functioning may benefit the most.

• Summary of medications to treat the symptoms of Alzheimer’s disease. The four current medications approved for Alzheimer’s disease have shown modest effects in preserving brain function. They may help lessen or stabilize the symptom of Alzheimer’s disease for a period of time. Due to the side effects of these drugs – especially the gastrointestinal effects -- doctors and patients should talk about their use before prescribing them. Also, these drugs should be stopped when dementia reaches advanced stages.

Managing behavior changes. Medications are available to treat some of the common behavioral symptoms of Alzheimer’s disease. For example, antidepressant drugs can be used to treat anxiety, restlessness, aggression and depression. Anti-anxiety drugs can be used to treat agitation. Anticonvulsants are sometimes used to treat aggression. Antipsychotics can be used to treat paranoia, hallucinations, and agitation. Some of the side effects of these drugs include confusion and dizziness, which can increase the risk of falls. Therefore these drugs are typically used either for short periods of time, only when behavioral problems are severe, and only after safer and/or other non-drug therapies have been tried first.

What newer medications are under study?

All currently approved medications target Alzheimer’s disease after it develops. Scientists are currently researching ways to stop or slow the progress of Alzheimer’s disease before it starts.

Some of the drugs in late-stage investigation are called monoclonal antibodies. These drugs target the amyloid protein that builds up in brain cells. They work by attaching to the amyloid proteins as they float in the brain and remove them, before they form into the plaques and tangles that interfere with the brain’s ability to properly function.

These drugs are still in clinical trials and are several years away from Food and Drug Administration approval in the United States. Early results have been mixed, with some trials showing no improvement in brain function; others showing a slight improvement (less brain function decline). Despite the mixed results, researchers are excited about this new potential method to modify the disease process.

Prevention

What are some risk factors for Alzheimer’s disease?

Risk factors for the development of Alzheimer’s disease include:

• Age. Increasing age is the primary risk factor for developing Alzheimer’s disease.
• Genetics (runs in families). There is a certain gene, apolipoprotein E (APOE) that is associated with late-onset Alzheimer’s disease. Other genes have been associated with early-onset Alzheimer’s disease.
• High blood pressure
• High cholesterol
• Diabetes
• Smoking
• Obesity

Researchers believe the presence of the last five risk factors mentioned above might reduce the clearance of amyloid protein from the brain, which then increases the risk of developing Alzheimer’s disease. In particular, the presence of a number of these risk factors at the same time and while the person is in his or her 50s is associated with a higher risk of Alzheimer’s disease.

There may be some ways to reduce the risk of mental decline. In general, living a healthy lifestyle protects the body from strokes and heart attacks and is believed to also protect the brain from cognitive decline. Scientists can’t absolutely prove the cause and effect of the following factors, but studies have shown a “positive association.”

• Stay mentally active. Play board games, read, do crossword puzzles, play a musical instrument, audit courses at a local community college, do other hobbies that require “brain power.”
• Get physically active. Exercise increases blood flow and oxygen to the brain, which may directly affect brain cell health. Wear protective head gear if engaging in activities that increase the risk of a head injury.
• Stay socially active. Regularly talk with friends and family, join in on group activities (such as worship services, exercise classes, choir, book clubs)
• Follow the Mediterranean or DASH diet or another healthy diet that includes antioxidants. Consume beverages that contain alcohol in moderation — no more than one drink per day for women and no more than two per day for men.

Outlook / Prognosis

What is the outlook for people with Alzheimer’s disease?

Alzheimer’s disease gets worse over time and is ultimately fatal. Persons with Alzheimer’s disease live, on average, four to eight years after diagnosis. Some patients can live as long as 20 years after diagnosis. The course of the disease varies from person to person.

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