Neurofibrillary tangles

Definition

Dementia is a loss of mental ability severe enough to interfere with normal activities of daily living, lasting more than six months, not present since birth, and not associated with a loss or alteration of consciousness.

Description

Dementia is a group of symptoms caused by gradual death of brain cells. The loss of cognitive abilities that occurs with dementia leads to impairments in memory, reasoning, planning, and personality. While the overwhelming number of people with dementia are elderly, it is not an inevitable part of aging. Instead, dementia is caused by specific brain diseases. Alzheimer's disease is the most common cause, followed by vascular or multi-infarct dementia.

The prevalence of dementia has been difficult to determine, partly because of differences in definition among different studies, and partly because there is some normal decline in functional ability with age. Dementia affects 5-8% of all people between ages 65 and 74, and up to 20% of those between 75 and 84. Estimates for dementia in those 85 and over range from 30-47%. Between two and four million Americans have Alzheimer's disease; that number is expected to grow to as many as 14 million by the middle of the 21st century as the population as a whole ages.

The cost of dementia can be considerable. While most people with dementia are retired and do not suffer income losses from their disease, the cost of care is often enormous. Financial burdens include lost wages for family caregivers, medical supplies and drugs, and home modifications to ensure safety. Nursing home care may cost several thousand dollars a month or more. The psychological cost is not as easily quantifiable but can be even more profound. The person with dementia loses control of many of the essential features of his life and personality, and loved ones lose a family member even as they continue to cope with the burdens of increasing dependence and unpredictability.

Causes & symptoms

Causes

Dementia is usually caused by degeneration in the cerebral cortex, the part of the brain responsible for thoughts, memories, actions and personality. Death of brain cells in this region leads to the cognitive impairment which characterizes dementia.

The most common cause of dementia is Alzheimer's disease (AD), accounting for half to three quarters of all cases. The brain of a person with AD becomes clogged with two abnormal structures, called neurofibrillary tangles and senile plaques. Neurofibrillary tangles are twisted masses of protein fibers inside nerve cells, or neurons. Senile plaques are composed of parts of neurons surrounding a group of proteins called beta-amyloid deposits. Why these structures develop is unknown. Current research indicates possible roles for inflammation, blood flow restriction, and toxic molecular fragments known as free radicals. Several genes have been associated with higher incidences of AD, although the exact role of these genes is still unknown.

Vascular dementia is estimated to cause from 5-30% of all dementias. It occurs from decrease in blood flow to the brain, most commonly due to a series of small strokes (multi-infarct dementia). Other cerebrovascular causes include: vasculitis from syphilis, Lyme disease, or systemic lupus erythematosus; subdural hematoma; and subarachnoid hemorrhage. Because of the usually sudden nature of its cause, the symptoms of vascular dementia tend to begin more abruptly than those of Alzheimer's dementia. Symptoms may progress stepwise with the occurrence of new strokes. Unlike AD, the incidence of vascular dementia is lower after age 75.

Other conditions which may cause dementia include:

• AIDS
• Parkinson's disease
• Lewy body disease
• Pick's disease
• Huntington's disease
• Creutzfeldt-Jakob disease
• Brain tumor
• Hydrocephalus
• Head trauma
• Multiple sclerosis
• Prolonged abuse of alcohol or other drugs
• Vitamin deficiency: thiamin, niacin, or B₁₂
• Hypothyroidism
• Hypercalcemia.

Symptoms

Dementia is marked by a gradual impoverishment of thought and other mental activities. Losses eventually affect virtually every aspect of mental life. The slow progression of dementia is in contrast with delirium, which involves some of the same symptoms, but has a very rapid onset and fluctuating course with alteration in the level of consciousness. However, delirium may occur with dementia, especially since the person with dementia is more susceptible to the delirium-inducing effects of may types of drugs.

Symptomsinclude:

• Memory losses. Memory loss is usually the first symptom noticed. It may begin with misplacing valuables such as a wallet or car keys, then progress to forgetting appointments, where the car was left, and the route home, for instance. More profound losses follow, such as forgetting the names and faces of family members.
• Impaired abstraction and planning. The person with dementia may lose the ability to perform familiar tasks, to plan activities, and to draw simple conclusions from facts.
• Language and comprehension disturbances. The person may be unable to understand instructions, or follow the logic of moderately complex sentences. Later, he or she may not understand his or her own sentences, and have difficulty forming thoughts into words.
• Poor judgment. The person may not recognize the consequences of his or her actions or be able to evaluate the appropriateness of behavior. Behavior may become ribald, overly-friendly, or aggressive. Personal hygiene may be ignored.
• Impaired orientation ability. The person may not be able to identify the time of day, even from obvious visual clues; or may not recognize his or her location, even if familiar. This disability may stem partly from losses of memory and partly from impaired abstraction.
• Decreased attention and increased restlessness. This may cause the person with dementia to begin an activity and quickly lose interest, and to wander frequently. Wandering may cause significant safety problems, when combined with disorientation and memory losses. The person may begin to cook something on the stove, then become distracted and wander away while it is cooking.
• Personality changes and psychosis. The person may lose interest in once-pleasurable activities, and become more passive, depressed, or anxious. Delusions, suspicion, paranoia, and hallucinations may occur later in the disease. Sleep disturbances may occur, including insomnia and sleep interruptions.

Diagnosis

Since dementia usually progresses slowly, diagnosing it in its early stages can be difficult. Several office visits over several months or more may be needed. Diagnosis begins with a thorough physical exam and complete medical history, usually including comments from family members or caregivers. A family history of either Alzheimer's disease or cerebrovascular disease may provide clues to the cause of symptoms. Simple tests of mental function, including word recall, object naming, and number-symbol matching, are used to track changes in the person's cognitive ability.

Depression is common in the elderly and can be mistaken for dementia; therefore, ruling out depression is an important part of the diagnosis. Distinguishing dementia from the mild normal cognitive decline of advanced age is also critical. The medical history includes a complete listing of drugs being taken, since a number of drugs can cause dementia-like symptoms.

Determining the cause of dementia may require a variety of medical tests, chosen to match the most likely etiology. Cerebrovascular disease, hydrocephalus, and tumors may be diagnosed with x-rays, CT or MRI scans, and vascular imaging studies. Blood tests may reveal nutritional deficiencies or hormone imbalances.

Treatment

Treatment of dementia begins with treatment of the underlying disease, where possible. The underlying causes of nutritional, hormonal, tumor-caused and drug-related dementias may be reversible to some extent. Treatment for stroke-related dementia begins by minimizing the risk of further strokes, through smoking cessation, aspirin therapy, and treatment of hypertension, for instance. There are no therapies which can reverse the progression of Alzheimer's disease. Aspirin, estrogen, vitamin E, and selegiline are currently being evaluated for their ability to slow the rate of progression.

Care for a person with dementia can be difficult and complex. The patient must learn to cope with functional and cognitive limitations, while family members or other caregivers assume increasing responsibility for the person's physical needs. In progressive dementias such as Alzheimer's disease, the person may ultimately become completely dependent. Education of the patient and family early on in the disease progression can help them anticipate and plan for inevitable changes.

Symptoms of dementia may be treated with a combination of psychotherapy, environmental modifications, and medication. Drug therapy can be complicated by forgetfulness, especially if the prescribed drug must be taken several times daily.

Behavioral approaches may be used to reduce the frequency or severity of problem behaviors, such as aggression or socially inappropriate conduct. Problem behavior may be a reaction to frustration or overstimulation; understanding and modifying the situations which trigger it can be effective. Strategies may include breaking down complex tasks, such as dressing or feeding, into simpler steps, or reducing the amount of activity in the environment to avoid confusion and agitation. Pleasurable activities, such as crafts, games, and music, can provide therapeutic stimulation and improve mood.

Modifying the environment can increase safety and comfort while decreasing agitation. Home modifications for safety include removal or lock-up of hazards such as sharp knives, dangerous chemicals, and tools. Child-proof latches or Dutch doors may be used to limit access as well. Lowering the hot water temperature to 120°F (48.9°C) or less reduces the risk of scalding. Bed rails and bathroom safety rails can be important safety measures, as well. Confusion may be reduced with simpler decorative schemes and presence of familiar objects. Covering or disguising doors (with a mural, for example) may reduce the tendency to wander. Positioning the bed in view of the bathroom can decrease incontinence.

Two drugs, tacrine (Cognex) and donepezil (Aricept), are commonly prescribed for Alzheimer's disease. These drugs inhibit the breakdown of acetylcholine in the brain, prolonging its ability to conduct chemical messages between brain cells. They provide temporary improvement in cognitive functions for about 40% of patients with mild-to-moderate AD. Hydergine is sometimes prescribed as well, though it is of questionable benefit for most patients.

Psychotic symptoms, including paranoia, delusions, and hallucinations, may be treated with antipsychotic drugs, such as haloperidol, chlorpromazine, risperidone, and clozapine. Side effects of these drugs can be significant. Antianxiety drugs such as Valium may improve behavioral symptoms, especially agitation and anxiety, although BuSpar has fewer side effects. The anticonvulsant carbamazepine is also sometimes prescribed for agitation. Depression is treated with antidepressants, usually beginning with selective serotonin reuptake inhibitors (SSRIs) such as Prozac or Paxil, followed by monoamine oxidase inhibitors or tricyclic antidepressants. Electroconvulsive therapy may be appropriate for some patients with severe depression who are unresponsive to drug therapy. In general, medications should be administered very cautiously to demented patients, in the lowest possible effective doses, to minimize side effects. Supervision of taking medications is generally required.

Long-term institutional care may be needed for the person with dementia, as profound cognitive losses often precede death by a number of years. Early planning for the financial burden of nursing home care is critical. Useful information about financial planning for long-term care is available through the Alzheimer's Association.

Family members or others caring for a person with dementia are often subject to extreme stress, and may develop feelings of anger, resentment, guilt, and hopelessness, in addition to the sorrow they feel for their loved one and for themselves. Depression is an extremely common consequence of being a full-time caregiver for a person with dementia. Support groups can be an important way to deal with the stress of caregiving. The location and contact numbers for caregiver support groups are available from the Alzheimer's Association; they may also be available through a local social service agency or the patient's physician. Medical treatment for depression may be an important adjunct to group support.

Alternative treatment

Several drugs are currently being tested for their ability to slow the progress of Alzheimer's disease. These include acetyl-l-carnitine, which acts on the cellular energy structures known as mitochondria; propentofylline, which may aid circulation; milameline, which acts similarly to tacrine and donezepil; and ginkgo extract.

Ginkgo extract, derived from the leaves of the Ginkgo biloba tree, interferes with a circulatory protein called platelet activating factor. It also increases circulation and oxygenation to the brain. Ginkgo extract has been used for many years in China and is widely prescribed in Europe for treatment of circulatory problems. A 1997 study of patients with dementia seemed to show that gingko extract could improve their symptoms, though the study was criticized for certain flaws in its method.

Prognosis

The prognosis for dementia depends on the underlying disease. On average, people with Alzheimer's disease live eight years past their diagnosis, with a range from one to twenty years. Vascular dementia is usually progressive, with death from stroke, infection, or heart disease.

Prevention

There is no known way to prevent Alzheimer's disease, although several of the drugs under investigation may reduce its risk or slow its progression. The risk of developing multi-infarct dementia may be reduced by reducing the risk of stroke.

Key Terms

Donepezil

A drug commonly prescribed for Alzheimer's disease which provides temporary improvement in cognitive functions for some patients with mild-to-moderate forms of the disease.

Ginkgo extract

Made from the leaves of the tree, this extract, used in other countries to treat circulatory problems, may improve the symptoms of patients with dementia.

Neurofibrillary tangles

Abnormal structures, composed of twisted masses of protein fibers within nerve cells, found in the brains of persons with Alzheimer's disease.

Senile plaques

Abnormal structures, composed of parts of nerve cells surrounding protein deposits, found in the brains of persons with Alzheimer's disease.

Tacrine

A drug commonly prescribed for Alzheimer's disease which provides temporary improvement in cognitive functions for some patients with mild-to-moderate forms of the disease.

Further Reading

For Your Information

Books

• Jacques, Alan. Understanding Dementia. New York: Churchill Livingstone, 1992.
• Mace, Nancy L. and Peter V. Rabins. The 36-Hour Day. Baltimore, MD: John Hopkins University Press, 1995.

  Organizations

• Alzheimer's Association. 919 North Michigan Ave., Suite 1000, Chicago, IL 60611. 800-272-3900 (TDD: 312-335-8882). http://www.alz.org/.

Gale Encyclopedia of Medicine. Gale Research, 1999.