Treatment

Researchers are continually working to develop new drugs for AD and other types of dementia. Many researchers believe a vaccine that reduces the number of amyloid plaques in the brain might ultimately prove to be the most effective treatment for AD. In 2001, researchers began one clinical trial of a vaccine called AN-1792. The study was halted after a number of people developed inflammation of the brain and spinal cord. Despite these problems, one patient appeared to have reduced numbers of amyloid plaques in the brain. Other patients showed little or no cognitive decline during the course of the study, suggesting that the vaccine may slow or halt the disease. Researchers are now trying to find safer and more effective vaccines for AD.

Researchers are also investigating possible methods of gene therapy for AD. In one case, researchers used cells genetically engineered to produce nerve growth factor and transplanted them into monkeys' forebrains. The transplanted cells boosted the amount of nerve growth factors in the brain and seemed to prevent degeneration of acetylcholine-producing neurons in the animals. This suggests that gene therapy might help to reduce or delay symptoms of the disease. Researchers are now testing a similar therapy in a small number of patients. Other researchers have experimented with gene therapy that adds a gene called neprilysin in a mouse model that produces human beta amyloid. They found that increasing the level of neprilysin greatly reduced the amount of beta amyloid in the mice and halted the amyloid-related brain degeneration. They are now trying to determine whether neprilysin gene therapy can improve cognition in mice.

A clinical trial called the Vitamins to Slow Alzheimer's Disease (VITAL) study is testing whether high doses of three common B vitamins - folic acid, B12, and B6 - can reduce homocysteine levels and slow the rate of cognitive decline in AD.

Since many studies have found evidence of brain inflammation in AD, some researchers have proposed that drugs that control inflammation, such as NSAIDs, might prevent the disease or slow its progression. Studies in mice have suggested that these drugs can limit production of amyloid plaques in the brain. Early studies of these drugs in humans have shown promising results. However, a large NIH-funded clinical trial of two NSAIDS (naproxen and celecoxib) to prevent AD was stopped in late 2004 because of an increase in stroke and heart attack in people taking naproxen, and an unrelated study that linked celecoxib to an increased risk of heart attack.

Some studies have suggested that two drugs, pentoxifylline and propentofylline, may be useful in treating vascular dementia. Pentoxifylline improves blood flow, while propentofylline appears to interfere with some of the processes that cause cell death in the brain.

One study is testing the safety and effectiveness of donepezil (Aricept) for treating mild dementia in patients with Parkinson's dementia, while another is investigating whether skin patches with the drug selegiline can improve mental function in patients with cognitive problems related to HIV.

Glossary

acetylcholine - a neurotransmitter that is important for the formation of memories. Studies have shown that levels of acetylcholine are reduced in the brains of people with Alzheimer's disease.

Alzheimer's disease - the most common cause of dementia in people aged 65 and older. Nearly all brain functions, including memory, movement, language, judgment, behavior, and abstract thinking, are eventually affected.

amyloid plaques - unusual clumps of material found in the tissue between nerve cells. Amyloid plaques, which consist of a protein called beta amyloid along with degenerating bits of neurons and other cells, are a hallmark of Alzheimer's disease.

amyloid precursor protein - a normal brain protein that is a precursor for beta amyloid, the abnormal substance found in the characteristic amyloid plaques of Alzheimer's disease patients.

apolipoprotein E - a gene that has been linked to an increased risk of Alzheimer's disease. People with a variant form of the gene, called apoE epsilon 4, have about ten times the risk of developing Alzheimer's disease.

ataxia - a loss of muscle control.

atherosclerosis - a blood vessel disease characterized by the buildup of plaque, or deposits of fatty substances and other matter in the inner lining of an artery.

beta amyloid - a protein found in the characteristic clumps of tissue (called plaques) that appear in the brains of Alzheimer's patients.

Binswanger's disease - a rare form of dementia characterized by damage to small blood vessels in the white matter of the brain. This damage leads to brain lesions, loss of memory, disordered cognition, and mood changes.

CADASIL - a rare hereditary disorder which is linked to a type of vascular dementia. It stands for cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy.

cholinesterase inhibitors - drugs that slow the breakdown of the neurotransmitter acetylcholine.

cognitive training - a type of training in which patients practice tasks designed to improve mental performance. Examples include memory aids, such as mnemonics, and computerized recall devices.

computed tomographic (CT) scans - a type of brain scan that uses X-rays to detect brain structures.

cortical atrophy - degeneration of the brain's cortex (outer layer). Cortical atrophy is common in many forms of dementia and may be visible on a brain scan.

cortical dementia - a type of dementia in which the damage primarily occurs in the brain's cortex, or outer layer.

corticobasal degeneration - a progressive disorder characterized by nerve cell loss and atrophy in multiple areas of the brain.

Creutzfeldt-Jakob disease - a rare, degenerative, fatal brain disorder believed to be linked to an abnormal form of a protein called a prion.

dementia -a term for a collection of symptoms that significantly impair thinking and normal activities and relationships.

dementia pugilistica - a form of dementia caused by head trauma such as that experienced by boxers. It is also called chronic traumatic encephalopathy or Boxer's syndrome.

electroencephalogram (EEG) - a medical procedure that records patterns of electrical activity in the brain.

fatal familial insomnia - an inherited disease that affects a brain region called the thalamus, which is partially responsible for controlling sleep. The disease causes dementia and a progressive insomnia that eventually leads to a complete lack of sleep.

frontotemporal dementias - a group of dementias characterized by degeneration of nerve cells, especially those in the frontal and temporal lobes of the brain.

FTDP-17 - one of the frontotemporal dementias, linked to a mutation in the tau gene. It is much like other types of the frontotemporal dementias but often includes psychiatric symptoms such as delusions and hallucinations.

Gerstmann-Straussler-Scheinker disease - a rare, fatal hereditary disease that causes ataxia and progressive dementia.

HIV-associated dementia - a dementia that results from infection with the human immunodeficiency virus (HIV) that causes AIDS. It can cause widespread destruction of the brain's white matter.

Huntington's disease - a degenerative hereditary disorder caused by a faulty gene for a protein called huntington. The disease causes degeneration in many regions of the brain and spinal cord and patients eventually develop severe dementia.

Lewy body dementia - one of the most common types of progressive dementia, characterized by the presence of abnormal structures called Lewy bodies in the brain. In many ways the symptoms of this disease overlap with those of Alzheimer's disease.

magnetic resonance imaging (MRI) - a diagnostic imaging technique that uses magnetic fields and radio waves to produce detailed images of body structures.

mild cognitive impairment - a condition associated with impairments in understanding and memory not severe enough to be diagnosed as dementia, but more pronounced than those associated with normal aging.

Mini-Mental State Examination - a test used to assess cognitive skills in people with suspected dementia. The test examines orientation, memory, and attention, as well as the ability to name objects, follow verbal and written commands, write a sentence spontaneously, and copy a complex shape.

multi-infarct dementia - a type of vascular dementia caused by numerous small strokes in the brain.

myelin - a fatty substance that coats and insulates nerve cells.

neurofibrillary tangles - bundles of twisted filaments found within neurons, and a characteristic feature found in the brains of Alzheimer's patients. These tangles are largely made up of a protein called tau.

neurotransmitter - a type of chemical, such as acetylcholine, that transmits signals from one neuron to another. People with Alzheimer's disease have reduced supplies of acetylcholine.

organic brain syndrome - a term that refers to physical disorders (not psychiatric in origin) that impair mental functions.

Parkinson's dementia - a secondary dementia that sometimes occurs in people with advanced Parkinson's disease, which is primarily a movement disorder. Many Parkinson's patients have the characteristic amyloid plaques and neurofibrillary tangles found in Alzheimer's disease, but it is not yet clear if the diseases are linked.

Pick's disease - a type of frontotemporal dementia where certain nerve cells become abnormal and swollen before they die. The brains of people with Pick's disease have abnormal structures, called Pick bodies, inside the neurons. The symptoms are very similar to those of Alzheimer's diease.

plaques - unusual clumps of material found between the tissues of the brain in Alzheimer's disease. See also amyloid plaques.

post-traumatic dementia - a dementia brought on by a single traumatic brain injury. It is much like dementia pugilistica, but usually also includes long-term memory problems.

presenilin 1 and 2 - proteins produced by genes that influence susceptibility to early-onset Alzheimer's disease.

primary dementia - a dementia, such as Alzheimer's disease, that is not the result of another disease.

primary progressive aphasia - a type of frontotemporal dementia resulting in deficits in language functions. Many, but not all, people with this type of aphasia eventually develop symptoms of dementia.

progressive dementia - a dementia that gets worse over time, gradually interfering with more and more cognitive abilities.

secondary dementia - a dementia that occurs as a consequence of another disease or an injury.

senile dementia - an outdated term that reflects the formerly widespread belief that dementia was a normal part of aging. The word senile is derived from a Latin term that means, roughly, "old age. "

subcortical dementia - dementia that affects parts of the brain below the outer brain layer, or cortex.

substance-induced persisting dementia - dementia caused by abuse of substances such as alcohol and recreational drugs that persists even after the substance abuse has ended.

tau protein - a protein that helps the functioning of microtubules, which are part of the cell's structural support and help to deliver substances throughout the cell. In Alzheimer's disease, tau is changed in a way that causes it to twist into pairs of helical filaments that collect into tangles.

transmissible spongiform encephalopathies - part of a family of human and animal diseases in which brains become filled with holes resembling sponges when examined under a microscope. CJD is the most common of the known transmissible spongiform encephalopathies.

vascular dementia - a type of dementia caused by brain damage from cerebrovascular or cardiovascular problems - usually strokes. It accounts for up to 20 percent of all dementias.

Forgetfulness . . . It’s Not Always What You Think

Many older people worry about becoming more forgetful. They think forgetfulness is the first sign of Alzheimer’s disease (AD). In the past, memory loss and confusion were considered a normal part of aging. However, scientists now know that most people remain both alert and able as they age, although it may take them longer to remember things.

A lot of people experience memory lapses. Some memory problems are serious, and others are not. People who have serious changes in their memory, personality, and behavior may suffer from a form of brain disease called dementia. Dementia seriously affects a person’s ability to carry out daily activities. AD is one of many types of dementia.

The term dementia describes a group of symptoms that are caused by changes in brain function. Dementia symptoms may include:

asking the same questions repeatedly,

becoming lost in familiar places,

being unable to follow directions,

getting disoriented about time, people, and places, and

neglecting personal safety, hygiene, and nutrition.

People with dementia lose their abilities at different rates. Dementia is caused by many conditions. Some conditions that cause dementia can be reversed, and others cannot. Further, many different medical conditions may cause symptoms that seem like AD, but are not. Some of these medical conditions may be treatable. Reversible conditions can be caused by a high fever, dehydration, vitamin deficiency and poor nutrition, bad reactions to medicines, problems with the thyroid gland, or a minor head injury. Medical conditions like these can be serious and should be treated by a doctor as soon as possible.

Sometimes older people have emotional problems that can be mistaken for dementia. Feeling sad, lonely, worried, or bored may be more common for older people facing retirement or coping with the death of a spouse, relative, or friend. Adapting to these changes leaves some people feeling confused or forgetful. Emotional problems can be eased by supportive friends and family, or by professional help from a doctor or counselor.

The two most common forms of dementia in older people are AD and multi infarct dementia (sometimes called vascular dementia). These types of dementia are irreversible, which means they cannot be cured. In AD, nerve cell changes in certain parts of the brain result in the death of a large number of cells. Symptoms of AD begin slowly and become steadily worse. As the disease progresses, symptoms range from mild forgetfulness to serious impairments in thinking, judgment, and the ability to perform daily activities. Eventually, patients may need total care.

In multi infarct dementia, a series of strokes or changes in the brain’s blood supply may result in the death of brain tissue. The location in the brain where the strokes occur and the severity of the strokes determine the seriousness of the problem and the symptoms that arise. Symptoms usually begin abruptly and progress in a step-wise fashion with repeated strokes. At this time, there is no way to reverse damage that has already been caused by a stroke. However, treatment to prevent further strokes is very important.

Diagnosis

People who are worried about memory problems should see their doctor. If the doctor believes that the problem is serious, then a thorough physical, neurological, and psychiatric evaluation may be recommended. A complete medical examination for memory loss may include gathering information about the person’s medical history, including use of prescription and over the counter medicines, diet, past medical problems, and general health. Because a correct diagnosis depends on recalling these details accurately, the doctor also may ask a family member for information about the person.

Tests of blood and urine may be done to help the doctor find any problems. There are also tests of mental abilities (tests of memory, problem solving, counting, and language). A brain CT scan may assist the doctor in ruling out a curable disorder. A scan also may show signs of normal age related changes in the brain. It may be necessary to have another scan at a later date to see if there have been further changes in the brain.

Multi infarct dementia and AD can exist together, making it hard for the doctor to diagnose either one specifically. Scientists once thought that multi infarct dementia and other types of vascular dementia caused most cases of irreversible mental impairment. They now believe that most older people with irreversible dementia have Alzheimer’s disease.

Treatment

Even if the doctor diagnoses an irreversible form of dementia, much still can be done to treat the patient and help the family cope. A person with dementia should be under a doctor’s care, and may see a neurologist, psychiatrist, family doctor, internist, or geriatrician. The doctor can treat the patient’s physical and behavioral problems and answer the many questions that the person or family may have.

For some people in the early and middle stages of AD, the drugs tacrine (Cognex, which is still available but no longer actively marketed by the manufacturer), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne, formerly known as Reminyl) are prescribed to possibly delay the worsening of some of the disease’s symptoms. Another drug, memantine (Namenda), has been approved for treatment of moderate to severe AD. Doctors believe it is very important for people with multi infarct dementia to try to prevent further strokes by controlling high blood pressure, monitoring and treating high blood cholesterol and diabetes, and not smoking.

Many people with dementia need no medication for behavioral problems. But for some people, doctors may prescribe medications to reduce agitation, anxiety, depression, or sleeping problems. These troublesome behaviors are common in people with dementia. Careful use of doctor prescribed drugs may make some people with dementia more comfortable and make caring for them easier.

A healthy diet is important. Although no special diets or nutritional supplements have been found to prevent or reverse AD or multi infarct dementia, a balanced diet helps maintain overall good health. In cases of multi infarct dementia, improving the diet may play a role in preventing more strokes.

Family members and friends can assist people with dementia in continuing their daily routines, physical activities, and social contacts. People with dementia should be kept up-to-date about the details of their lives, such as the time of day, where they live, and what is happening at home or in the world. Memory aids may help in the day to day living of patients in the earlier stages of dementia. Some families find that a big calendar, a list of daily plans, notes about simple safety measures, and written directions describing how to use common household items are useful aids.

Advice for Today

Scientists are working to develop new drugs that someday may slow, reverse, or prevent the damage caused by AD and multi infarct dementia. In the meantime, people who have no dementia symptoms can try to keep their memory sharp.

Some suggestions include developing interests or hobbies and staying involved in activities that stimulate both the mind and body. Giving careful attention to physical fitness and exercise also may go a long way toward keeping a healthy state of mind. Limiting the use of alcoholic beverages is important, because heavy drinking over time can cause permanent brain damage.

Many people find it useful to plan tasks; make “things to do” lists; and use notes, calendars, and other memory aids. They also may remember things better by mentally connecting them to other meaningful things, such as a familiar name, song, or lines from a poem.

Stress, anxiety, or depression can make a person more forgetful. Forgetfulness caused by these emotions usually is temporary and goes away when the feelings fade. However, if these feelings last for a long period of time, getting help from a professional is important. Treatment may include counseling or medication, or a combination of both.

Some physical and mental changes occur with age in healthy people. However, much pain and suffering can be avoided if older people, their families, and their doctors recognize dementia as a disease, not part of normal aging.