Alzheimer Disease

Alzheimer Disease

Causes

The ultimate cause of this disease is unknown. Various causes have been suggested, including a defective gene, an infection, the body making proteins in the wrong way (especially the protein amyloid), and exposure to poisons or items in your environment that cause changes in your nerve cells.
Whatever the ultimate cause, Alzheimer disease results in the widespread loss of nerve cells.

• A connection with certain chemical messengers (substances needed to help messages travel through the brain) seems to be present.
• The nerve cells that die often contain the chemical messenger called acetylcholine.
• Lowered levels of this key enzyme (choline acetyltransferase) needed to form this chemical messenger have been found in brains of people with Alzheimer disease.
• Various attempts to treat the disease with medicines that increase brain levels of acetylcholine, however, have been unsuccessful.

• Low levels of other chemical messengers in the brain (such as serotonin and norepinephrine) may also play a role.

Although most cases are spontaneous, 5%-10% of cases run in families.

• Defects in a particular chromosome are linked with the disease in some cases.
• This chromosome is the location of the amyloid protein gene, as well as the chromosome involved in Down syndrome (trisomy 21). Almost all people with Down syndrome also have Alzheimer disease by age 40 years

Symptoms

Through years of study, various features have been noted in people with Alzheimer disease.

• Outward changes
• As nerve cells die, affected areas of the brain wither and become smaller.
• The areas of the brain most affected are the areas that control numerous functions including memory, logical thinking, and personality.
• Other areas of the brain may also be affected and show withering.
• As these areas become smaller, the cavities within the brain containing fluid (ventricles) become enlarged.

• Microscopic changes

• Certain microscopic structures in nerve cells (called neurofibrillary tangles) were noted by German psychiatrist Alois Alzheimer (1864-1915), who first described this disorder that eventually was named after him. Other microscopic changes have also been found in brains of patients with this disease, but their role in causing symptoms is unknown.
• Symptoms
• Progression of the disease is slow and gradual. Alzheimer disease may go unrecognized for years.
• Symptoms eventually interfere with job performance and relations with friends, family, and coworkers.
• Loss of recent memory is usually seen early in the disease.
• Problems with language, calculation, abstract thinking, judgment, and the ability to plan and make decisions occur later in the disease.
• Depression, anxiety, personality changes, and odd or unpredictable quirks of behavior may be seen.
• Delusions and hallucinations are common in the late stages of the disease

When to Seek Medical Care

You or your family should call a doctor when it becomes evident that you can no longer safely function on your own. Often, family members are overwhelmed caring for people with Alzheimer disease. Permanent nursing home placement is required. Routine visits to your doctor should continue.
Any sudden worsening of your mental state may point to an underlying infection, stroke, or heart problem that may be treated to improve your overall functioning. Often, you can no longer communicate your symptoms effectively. Alzheimer disease primarily affects elderly people who may have other underlying medical conditions. Fever, mental status changes, chest pain, or problems breathing usually require a trip to the emergency department.

Exams and Tests

No single test (other than abnormal findings on autopsy) can be used to diagnose Alzheimer disease.
Features that strongly suggest Alzheimer disease may include the following:

• The condition begins in persons aged 40-90 years.
• No disturbance usually occurs in level of consciousness or "wakefulness."
• You may have problems in at least 2 areas of thinking, with progressive worsening of memory and other functions. Language is often affected early, with difficulty naming objects and finding the right word, followed by problems speaking in a manner that makes any sense. This may be followed by total lack of speech in the end stages.
• Visual or spatial oddities are common. Problems recognizing and interpreting your environment through your senses of sight, smell, touch, and taste may be found, as well as difficulty performing skilled movements.
• Mood disturbances are common in early stages, where depression may be seen in 15%-20% of people with Alzheimer disease.
• Delusional thinking and behavioral problems (such as accusing a loved one of stealing or crying for no reason) are seen in about half of people at some point in the disease process.

A thorough history and physical examination usually suggest the diagnosis in a person with progressive cognitive impairment.

Formal diagnosis requires that dementia (mental impairment) be established in these ways:

• A clinical examination is performed.
• Formal mental status tests may be given. Mini-Mental State Examination and Blessed Dementia Scale are examples. These tests are standardized paper tests in which you answer questions that test your ability to think and remember.
• Tests are performed by a neurologist or neuropsychologist (doctors and psychologists who specialize in disorders of the nervous system).

First, your doctor (or the specialist) looks at other treatable causes of altered mental status and reversible dementias.

• Often, they perform a CT scan of the brain, especially for people whose symptoms have just started, whose symptoms are not straightforward, whose symptoms have progressed quickly, who have a history of head trauma, or who have had other tests that suggest another cause of the symptoms.
• Other laboratory tests may be used to screen for other treatable causes of mental status changes.

Other problems that your doctor will look for and that may be causing the symptoms may include the following:

• Chronic subdural hematoma - A collection of blood between the brain and the skull that compresses the underlying brain
• Slowly growing frontal cancers
• Hydrocephalus - A problem with the normal flow of brain fluid in and around the brain and spinal cord (often called water in the brain)
• Metabolic problems - Liver disease, low vitamin B-12 levels, and low thyroid hormone levels
• Side effects of medications - Especially sleep aids, antidepressants, antihistamines, and antipsychotic and antianxiety drugs
• Depression and other mental illnesses
• Infection - Such as late-stage syphilis or Creutzfeldt-Jakob disease
• Delirium - A state of reversible waxing and waning of consciousness (this can be caused by poisons, brain disease associated with liver problems, infections, or alcohol withdrawal)
• Other dementias - Such as Pick disease, multi-infarction dementia, Huntington disease, and Parkinson disease

Treatment

Self-Care at Home

Home care should focus on helping you perform the daily activities of life. This may include helping with the monthly bills, assistance in getting dressed, or preparing meals. Some amount of assistance is usually required within months to years of the diagnosis, but it is always necessary for the safety of someone in the later stages of the disease.
Home providers must watch closely for sudden changes in mental state that might signal other illnesses that may be harder to recognize because of the presence of Alzheimer disease.

Medications

Alzheimer disease is progressive, which means that persons with the disease get worse over time. Unfortunately, no curative treatment is currently available.  Some medications, however, can temporarily improve symptoms and functioning for some people, although they do not prevent progression of the basic disease process

Approved drugs
Tacrine (Cognex), donepezil (Aricept), galanthamine (Reminyl), and rivastigmine (Exelon) are approved by the US Food and Drug Administration (FDA) for use in Alzheimer disease. To date, these are the only drugs formally approved for such use. They work by delaying the breakdown of acetylcholine, a brain chemical needed for nerve cells to communicate. Currently, donepezil, galanthamine, and rivastigmine are used significantly more than tacrine because of a lower incidence of side effects.
These drugs can have small but noticeable effects, depending on the stage of disease, differences in the way the drugs act in different people, and other factors. At least temporarily, many people taking these drugs experience improvements in their thinking abilities and are less likely to demonstrate common symptoms of advanced Alzheimer disease, such as wandering, agitation, and socially inappropriate behaviors. None of these drugs prevents a patient with Alzheimer disease from getting worse over time.
In general, tacrine, donepezil, galanthamine, and rivastigmine have the same side effects, the most frequent of which include nausea, vomiting, diarrhea, muscle cramps, headaches, dizziness, fainting, appetite loss, and skin reddening. These effects can be lessened if the drugs are started at low doses then slowly increased until the desired maintenance dose is reached.
No current evidence supports using more than one of the approved drugs at a time. Any of these drugs can gradually become less effective, and their side effects can become intolerable. In such cases, one of the other drugs may be tried to see if it works better.
Once a patient is started on tacrine, donepezil, galanthamine, or rivastigmine, he or she should stay on the drug (or one of the others). Completely stopping medication may quickly cause severe worsening of a patient’s ability to think and behave properly, which may not be reversed by restarting the drug.
Other drugs
Over the short term, other medicines can somewhat relieve Alzheimer disease symptoms like anxiety, agitation, depression, and psychotic or inappropriate behavior, but they do not prevent patients from slowly getting worse.
These drugs include anxiolytics for anxiety and agitation, neuroleptics for unusual and/or troublesome behavior, and antidepressants or mood stabilizers for mood disorders and specific problems like spells of anger or rage.
No specific drugs or dosages address the wide range of problems that patients with Alzheimer disease experience. Many doctors prefer medications like haloperidol (Haldol), risperidone (Risperdal), olanzapine (Zyprexa), and, more recently, quetiapine (Seroquel). In general, such agents should be used as seldom as possible and at the lowest effective doses. This will help minimize side effects in frail, elderly patients.
Physostigmine (Eserine, Isopto) may modestly improve functioning in some patients with Alzheimer disease. Nicotine, given in the form of a nicotine patch, may also provide temporary improvement.
New drugs
In Germany, memantine (Axura) has long been used to treat Alzheimer disease. Although this drug’s effects may be slight, an FDA advisory panel recently decided that it provides some benefit to people who have moderate-to-severe symptoms and is safe enough to try. (Whether memantine works in early stages of Alzheimer disease is not known.) The FDA usually follows its panels’ recommendations, and memantine may be approved for use in the United States in the near future.
Instead of delaying the breakdown of acetylcholine, as with tacrine, donepezil, galanthamine, and rivastigmine, memantine blocks surplus amounts of a brain chemical called glutamate. This chemical can injure or destroy nerve cells. Tacrine, donepezil, galanthamine, and rivastigmine are used for the early stages of Alzheimer disease, while memantine is used for the later, typically more severe stages. The approval of memantine could for the first time allow doctors to prescribe combination drug therapies for the treatment of Alzheimer disease, which might bring better results. One study found the combination of memantine and donepezil to be more helpful than donepezil alone.
Memantine does not appear to be a “miracle drug,” but it does seem to help slow the worsening of Alzheimer symptoms, allowing patients to continue normal daily living activities (for example, going to the bathroom by themselves) for a few months longer. Some patients have reported improved memory and thinking skills, but for most, memantine just slows the progression of the disease.

Next Steps

Follow-up

Follow up with your doctor for yearly medical exams. Rapid progression of symptoms may require more frequent follow-up and early referral to an assisted living or full nursing care facility.

Prevention

No measures prevent onset or progression of Alzheimer disease.

Outlook

Alzheimer disease is progressive, leading to death on average 5-12 years from the time of diagnosis. The disease, however, can progress rapidly (1-year survival), or slowly (15-year survival).

About 10-20% of progressive cognitive impairments have been classified as reversible on the basis that these are caused with potentially treatable conditions. Treatment of people with reversible dementia, however, usually results in only slight, temporary improvement of thinking. A return to normal mental function is rare, and most treated people eventually develop progressive deterioration with Alzheimer disease.

Synonyms and Keywords

senile dementia, degenerative disorders, progressive dementia, Alzheimer's disease

Authors and Editors

Author: Jeffrey A Gunter, MD, Staff Physician, Department of Surgery, Division of Emergency Medicine, Denver Health Medical Center.

Coauthor(s): Erik Barton, MD, MS, Associate Director, Assistant Professor, Department of Surgery, Division of Emergency Medicine, University of Utah Health Sciences Center.

Editors: Scott H Plantz, MD, FAAEM, Research Director, Assistant Professor, Department of Emergency Medicine, Mount Sinai School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; Anthony Anker, MD, Private Consultant

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