Alzheimer disease

Highlights

Dementia is significant loss of cognitive functions such as memory, judgment, attention, and abstract thinking. Alzheimer disease is the most common form of dementia. It is a progressive brain disease. It affects more than 5 million Americans, and millions more worldwide.

Age is the greatest risk factor for Alzheimer disease. Most people who develop Alzheimer disease are 65 years old or more, and the risk increases with age. People age 85 years and older are largely at risk for Alzheimer disease.

Early symptoms of Alzheimer disease may include:

There is no cure for Alzheimer disease. Drug therapy aims to treat symptoms associated with the disease. The benefit from drugs used to treat Alzheimer disease is typically small. Patients and their families may not notice any benefit.

Patients and their families need to discuss with their doctors whether drug therapy can help improve behavior or functional abilities. They also need to discuss whether or not drugs should be prescribed early in the course of the disease or delayed.

The following drugs are commonly prescribed for treatment of Alzheimer disease:

Introduction

Alzheimer disease (AD) is the most common cause of dementia among older people. Dementia is the medical term for loss of cognitive functions including memory, judgment, attention, and abstract thinking

AD is a progressive and incurable degenerative disease of the brain. AD begins slowly. It first involves the parts of the brain that control thought, memory and language.

The disease slowly attacks nerve cells in all parts of the cortex of the brain and some surrounding structures, thereby impairing a person's abilities to govern emotions, recognize errors and patterns, coordinate movement, and remember. The changes in the brain may begin to develop more than 20 years before symptoms develop. Ultimately, a person with AD loses memory and many other mental functions.

Alzheimer disease

Click on the icon to see an animation of Alzheimer disease.

There are three brain abnormalities that are the hallmarks of the AD process:

Brain

The major areas of the brain have one or more specific functions.

Although no cure has been found for Alzheimer, scientists are making advances in better understanding the disease and how it progresses. The U.S. National Institute on Aging and the Alzheimer's Association has criteria for defining and diagnosing Alzheimer. It classifies the disease into three stages:

Causes

Scientists do not know what causes AD. It may be a combination of various genetic and environmental factors that trigger the process in which brain nerve cells are destroyed.

Genetics certainly plays a role in early-onset Alzheimer, a rare form of the disease that often runs in families. Scientists are also investigating genetic targets for late-onset Alzheimer, which is the more common form.

Apolipoprotein E (ApoE) is the main gene that has been definitively linked to late-onset Alzheimer disease. However, only a small percentage of people carry the form of ApoE (ApoE e4) that increases the risk for late-onset Alzheimer. Other genes or combinations of genes may be involved. Researchers have made some preliminary identifications of other possible gene variants.

Researchers have investigated various environmental factors that may play a role in AD or may trigger the disease process in people who have a genetic susceptibility. Some studies have suggested an association between serious head injuries in early adulthood and Alzheimer development. Lower educational level, which may decrease mental and activity and neuron stimulation, has also been investigated. To date, there does not appear to be any evidence that infections, metals, or industrial toxins cause AD.

Risk Factors

AD is the fifth leading cause of death in American adults age 65 and older. It affects more than 5 million Americans and millions more people worldwide.

Age is the primary risk factor for AD. The number of cases of AD doubles every 5 years beyond age 65. According to the U.S. Alzheimer's Association, nearly 1 in 3 people age 85 years and older have the disease. While less common, AD can also affect younger people. About 200,000 Americans younger than age 65 have early-onset Alzheimer disease.

More women than men develop AD but this is most likely because women tend to live longer than men. According to the Alzheimer's Association, nearly two thirds of patients with AD are women. Women in their 60s are more likely to develop AD during their lifetimes than breast cancer.

African Americans and Hispanics are at greater risk of developing Alzheimer disease than whites. This may be in part because they have a higher prevalence of medical conditions such as high blood pressure and diabetes, which are associated with increased risk for Alzheimer. Genetic factors may also play a role.

Having a first-degree relative (parent, brother, sister) with AD increases your risk for the disease. Having more than one first-degree relative with AD further increases risk.

People who have memory problems and other early symptoms that suggest mild cognitive impairment (MCI) may be at increased risk of later developing AD. However, not everyone who has MCI goes on to have AD.

A history of traumatic brain injury, including a concussion, is a risk factor for AD.

There is growing evidence that diseases that affect the heart and vascular (blood vessel) system increase the risk for AD. The brain requires a steady supply of oxygen-rich blood, which is supplied by a healthy pumping heart and adequate blood flow throughout the body. Conditions associated with heart and circulatory problems include high blood pressure, unhealthy cholesterol levels, and type 2 diabetes. There is some evidence that controlling these conditions may help prevent AD.

Blood pressure

Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.

Cholesterol producers

Click on the icon to see an image of cholesterol producers

Clinical trials have evaluated numerous substances for preventing AD but have not found any of them to be helpful. They included nonsteroidal anti-inflammatory drugs (NSAIDs), statin drugs, estrogen replacement therapy, folic acid supplementation, vitamin E, fish oil supplements, and herbal remedies such as ginkgo biloba.

However, certain lifestyle changes may help in AD prevention:

Symptoms

The early symptoms of Alzheimer disease (AD) may be overlooked because they resemble signs of natural aging. However, extreme memory loss or other cognitive changes that disrupt normal life are not typical signs of aging. In addition, the symptoms of AD do not begin abruptly; they develop gradually and worsen over the course of months or years.

Older adults who begin to notice a persistent mild memory loss of recent events may have a condition called mild cognitive impairment (MCI). MCI may be a sign of early-stage AD in older people. Studies suggest that some, although not all, older individuals who experience such mild memory abnormalities can later develop AD.

Patients may be aware of their symptoms or may be unaware that anything is wrong. The Alzheimer's Association recommends that everyone learn these 10 warning signs of AD:

Diagnosis

AD can only be definitely diagnosed after death when an autopsy of the brain is performed. However, AD is a very active area of research. The goal is to diagnose AD while it is still in its early stages.

Researchers are making progress studying biomarkers, chemical substances that signal changes in the brain associated with AD. In a recent study of biomarkers, scientists found that measuring levels of amyloid beta and tau proteins in brain imaging scans and spinal fluid may help predict the development of AD many years before symptoms begin.

The scientific community is working on standardizing the use of biomarkers to aid in the early detection of AD while it is in its preclinical or mild cognitive impairment stages. Biomarkers may also eventually help doctors evaluate how the disease progresses.

At this time, there is no one test that confirms a diagnosis of AD. Doctors use a variety of tests to make a probable diagnosis of AD.

The doctor will ask about the patient's health history, including other medical conditions the patient has, recent or past illnesses, and progressive changes in mental function, behavior, or daily activities. The doctor will ask about use of prescription drugs (it is helpful to bring a complete list of the patient's medications) and lifestyle factors, including diet and use of alcohol. The doctor will evaluate the patient's hearing and vision, and check blood pressure and other physical signs. A neurological test will also be conducted to check reflexes, coordination, and eye movement.

Blood and urine samples may be collected. They can help the doctor evaluate other possible causes of dementia, such as thyroid imbalances or vitamin deficiencies. Researchers are studying measuring levels of amyloid beta and tau proteins in spinal fluid samples to help identify patients with memory problems who may be at risk for developing AD.

Several psychological tests are used to assess difficulties in attention, perception, memory, language, problem-solving, social, and language skills. These tests can also be used to evaluate mood problems such as depression. Because depression may mimic symptoms of dementia, neuropsychological testing may be useful in determining if symptoms are due to depression, dementia, or both.

Two commonly used tests are the Mini-Mental State Exam (MMSE) and the Montreal Cognitive Assessment (MoCA). These tests use a series of questions and tasks to evaluate cognitive function. For example, the patient is given a series of words and asked to recall and repeat them a few minutes later. In the clock-drawing test, the patient is given a piece of paper with a circle on it and is asked to write the numbers in the face of a clock and then to show a specific time on the clock.

Imaging tests are useful for ruling out blood clots, tumors, or other structural abnormalities in the brain that may be causing signs of dementia. These tests include magnetic resonance imaging (MRI), computed tomography (CT), or positron-emission testing (PET) scans.

Researchers are using MRIs and PET scans to study new approaches to diagnosing AD in earlier stages of the disease. Methods include measuring the volume and shrinkage (atrophy) of brain tissue with MRI and evaluating the brain's use of glucose with PET.

Since 2012, the Food and Drug Administration (FDA) has approved 3 radioactive diagnostic drugs that are used with PET scans to evaluate beta amyloid density. They are florbetapir (Amyvid), flutemetamol (Vizamyl), and florbetaben (Neuraceq). Patients with AD have a high build-up of amyloid plaques in the brain. However, high amyloid plaque density is also found in some patients with normal cognitive function as well as those who have dementias not related to AD. If PET scans using these drugs do not show amyloid accumulation in the brain, a person's symptoms are unlikely due to AD.

AD is the most common cause of dementia. Other causes of dementia in older people can include:

Vascular Dementia

Vascular dementia is primarily caused by either multi-infarct dementia (multiple small strokes) or Binswanger disease (which affects tiny arteries in the midbrain).

Lewy Bodies Variant

Lewy bodies are abnormalities found in the brains of patients with both Parkinson and AD. They can also be present in the absence of either disease; in such cases, the condition is called Lewy bodies variant (LBV). In all cases, the presence of Lewy bodies is highly associated with dementia.

Parkinson Disease

Some of the symptoms of Parkinson and AD can be similar and the diseases may coexist.

Substantia nigra and Parkinson disease

Parkinson disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination. About a third of people with Parkinson disease will develop dementia. However, unlike AD, language is not usually affected in Parkinson dementia.

Frontotemporal Dementia

Frontotemporal dementia (FTD) is a term used to describe a group of disorders that affect the frontal and temporal lobes of the brain. Although some of the symptoms can overlap with AD, people who develop this condition tend to be younger than most patients with AD.

Other Conditions

A number of conditions, including many medications, can produce symptoms similar to Alzheimer. These conditions include severe depression, drug abuse, thyroid disease, vitamin deficiencies, blood clots, infections, brain tumors, and various neurological or vascular disorders.

Treatment

There is no cure for Alzheimer disease (AD) or treatment to stop its progression or reverse the symptoms. Most drugs used to treat Alzheimer are aimed at slowing the rate at which symptoms become worse, and prolonging a person's ability to remain independent. The benefit from these drugs is generally small, and patients and their families may not even notice any benefit.

AD is classified into various stages that range from mild to moderate to severe. In the final stages of AD, the patient is unable to communicate and is completely dependent on others for care.

The lifespan of patients with AD is generally reduced, although a patient may live anywhere from 4 to 20 years after diagnosis. The final phase of the disease may last from a few months to several years, during which time the patient becomes increasingly immobile and dysfunctional.

Most people with AD are cared for at home, largely during the early stages of the disease. Caregiving is an enormous commitment. Support services can greatly improve the quality of life for both caretakers and their patients and make it easier for people to continue caring for patients in their homes. These services include home healthcare aides and adult day care.

As AD progresses, round-the-clock care is largely required. At this point, the family needs to decide whether in-home treatment can be continued or whether placement in a nursing home or assisted living facility is a feasible option. In choosing a facility, it is best to select one that is specialized in the care of people with AD and equipped to meet their needs.

Medications

Most drugs used to treat AD, and those under investigation, are aimed at slowing progression. At this time, there is no cure. In addition, the improvements from some of these drugs may be so modest that patients and their families may not notice any benefit.

The FDA has approved two drug classes to treat the cognitive symptoms of AD:

While these drugs do not have generally serious risks, they can cause a number of bothersome side effects, including indigestion, nausea, vomiting, diarrhea, loss of appetite, muscle cramps, and fatigue.

Patients and caregivers should ask their doctors the following questions about when and if to use these drugs:

Cholinesterase inhibitors are designed to protect the cholinergic system, which is essential for memory and learning and is progressively destroyed in AD. These drugs work by preventing the breakdown of the brain chemical acetylcholine.

The three most commonly prescribed cholinesterase inhibitors for AD are donepezil, rivastigmine, and galantamine:

Side Effects

Common side effects of cholinesterase inhibitors, largely when taken in higher doses, may include nausea, vomiting, diarrhea, and upset stomach. Rivastigmine and galantamine tend to have more side effects than donepezil, and may also cause weight loss and loss of appetite. Cholinesterase inhibitors may increase the risk for gastrointestinal bleeding or ulcers, largely when used with NSAIDs (which can also cause gastric irritation).

Some drugs known as anticholinergics may offset the effects of the AD pro-cholinergic drugs. Such drugs include antihistamines, antipsychotic drugs, and some antidepressants and anti-incontinence drugs.

Effectiveness

Comparative studies have reported little difference in effectiveness among these drugs. In any case, the benefits of these drugs may often not be noticeable in everyday life. Many doctors have reservations about developing additional drugs that affect the cholinergic system since, at best, they only slow progression and do not appear to affect the basic destructive disease process or even the quality of a patient's life.

Memantine (Namenda) is approved for treatment of moderate-to-severe AD. (It does not appear to be effective for mild AD. Cholinesterase inhibitors are used to treat mild-to-moderate stages of the disease.) By blocking NMDA receptors, memantine protects against the overstimulation of glutamate, an amino acid that excites nerves and, in excess, is a powerful nerve-cell killer.

Memantine is prescribed either alone or in combination with donepezil. Studies indicate that memantine may help modestly improve cognitive function and delay the progression of AD for up to 1 year. Side effects are generally mild but may include dizziness, drowsiness, or fainting.

Depression

Antidepressants known as selective serotonin reuptake inhibitors (SSRIs), including fluoxetine (Prozac, generic) and sertraline (Zoloft, generic), may help reduce depression, irritability, and restlessness associated with Alzheimer in some patients.

Apathy

Depression is often confused with apathy. An apathetic patient lacks emotions, motivation, interest, and enthusiasm while a depressed patient is generally very sad, tearful, and hopeless. Apathy may respond to stimulants, such as methylphenidate (Ritalin, generic), rather than antidepressants.

Psychosis

Antipsychotic drugs are used to treat verbally or physically aggressive behavior and hallucinations. Because older antipsychotic drugs, such as haloperidol (Haldol, generic), have severe side effects, most doctors now prescribe newer atypical antipsychotics, such as risperidone (Risperdal, generic) or olanzapine (Zyprexa, generic).

However, these newer antipsychotic drugs can cause serious side effects, including confusion, sleepiness, and Parkinsonian-like symptoms. In addition, studies indicate that their safety risks may outweigh any possible benefits. Studies show that both atypical and older antipsychotics produce a slightly increased rate of death in patients with AD or dementia and that atypical antipsychotics work no better than placebo in controlling psychosis, aggression, and agitation in patients with AD.

The American Psychiatric Association and the American Geriatrics Society recommend against prescribing antipsychotic medication to patients with dementia unless absolutely necessary. They recommend first trying behavioral treatments and controlling changes in the patient's environment and routine.

Disturbed Sleep

Patients with AD commonly experience disturbances in their sleep/wake cycles. Moderately short-acting sleeping drugs, such as temazepam (Restoril, generic), zolpidem (Ambien, generic), or zaleplon (Sonata, generic), or sedating antidepressants, such as trazodone (Desyrel, generic), may be useful in managing insomnia. However, these drugs increase the risk of falling, confusion, and abnormal behavior and must be used with considerable caution and restraint.

Some research suggests that exposure to brighter-than-normal artificial light during the day for patients with normal vision may help reset wake/sleep cycles and prevent nighttime wandering and sleeplessness. Sleep hygiene methods (regular times for meal and bed, exercise, avoiding caffeine) can also be helpful.

Caregiving

Caregivers of people with AD face enormous challenges. Few diseases disrupt patients and their families so completely or for so long a period of time as AD. The following tips may help caregivers better cope with some of the issues and behaviors associated with this disease.

There is no single AD personality, just as there is no single human personality. All patients must be treated as the individuals they continue to be, even after their social self has vanished.

Patients with AD often display abrupt mood swings, and some become aggressive and angry. Some of this erratic behavior is caused by chemical changes in the brain. But it may also be due to the experience of losing knowledge and understanding of one's surroundings, causing fear and frustration that patients can no longer express verbally.

The following recommendations for caregivers may help soothe patients and avoid agitation:

Although much attention is given to the negative emotions of patients with AD, some patients become extremely gentle, retaining an ability to laugh at themselves or appreciate simple visual jokes even after their verbal abilities have disappeared. Some patients may seem to be in a drug-like or "mystical" state, focusing on the present experience as their past and future slip away. Encouraging and even enjoying such states may bring comfort to both the patient and the caregiver.

Hygiene and grooming can be major challenges for caregivers. Many patients resist bathing or taking a shower. Some patients find bathing confusing or frightening. Some spouses find that showering with their afflicted mate can solve the problem for a while. Establishing a daily and familiar routine can be helpful.

Often patients with AD lose their sense of color and design and will put on odd or mismatched clothing. It is important to maintain a sense of humor and perspective and to learn which battles are worth fighting and which ones are best abandoned. Caregivers can pick a selection of outfits and allow the patient to select a favorite. Try to choose clothes that are easy to put on and take off.

Weight loss and the gradual inability to swallow are two major related problems in late-stage AD and are associated with an increased risk for death. As AD progresses, patients may change their food preferences or find some kinds of foods more difficult to eat. Try different foods and be sure to allow enough time for the patient to eat. Limit distractions around mealtimes. Because choking is a danger, you should learn how to administer the Heimlich maneuver. Dehydration can also become a problem. It is important to encourage fluid intake equal to 8 cups of water daily. Coffee and tea are mild diuretics that may deplete fluid.

Patients at any stage of dementia, including mild, are at high risk for unsafe driving. Typical AD symptoms, such as difficulty remembering and navigating locations, poor judgment, and slow decision making, all pose dangers for driving. A history of recent citations, crashes, or aggressive or reckless driving are specific warning signs. As soon as AD is diagnosed, the patient should be prevented from driving. This includes hiding car keys.

Wandering is a common problem. As memory problems worsen, patients may become easily confused, disoriented, and lost. The following precautions are recommended:

Incontinence (loss of control of bowel or urine function) is one of the main reasons why many caregivers decide to seek nursing home placement. When the patient first shows signs of incontinence, the doctor should make sure that it is not caused by an infection. Urinary incontinence may be controlled for some time by trying to monitor times of liquid intake, feeding, and urinating. Once a schedule has been established, the caregiver may be able to anticipate incontinent episodes and get the patient to the toilet before they occur.

Urinary tract infections (UTIs) are a common cause of urinary incontinence. UTIs can also cause behavioral changes, and worsen aggression and confusion symptoms. Antibiotics are used to treat UTIs.

As the disease progresses to later stages, patients become immobile, literally forgetting how to move. Eventually, they become almost entirely wheelchair-bound or bedridden. Bedsores can be a major problem. Sheets must be kept clean, dry, and free of food. The patient's skin should be washed frequently, gently blotted thoroughly dry, and moisturizers applied. Try to move the patient every few hours and keep their feet raised with pillows or pads. Manipulation exercises can help keep legs and arms flexible.

Caregiving for a loved one with AD is undoubtedly stressful. Most patients with AD are cared for at home by family members, who often lack adequate support, finances, or training for this difficult job.

It is important for caregivers to recognize and take care of their own physical and emotional needs. Depression, exhaustion, guilt, and anger can lead to caregiver burnout as well as poor health.

Seek out support from family, friends, and professional associations. Such support includes individual and family counseling, support groups, and stress management and problem-solving techniques.

Resources

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Review Date: 10/24/2016
Reviewed By: Amit M. Shelat, DO, FACP, Attending Neurologist and Assistant Professor of Clinical Neurology, SUNY Stony Brook, School of Medicine, Stony Brook, NY. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.
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