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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. 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. Alzheimer's disease 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 Alzheimer's disease, 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 Alzheimer's disease and multi-infarct dementia (sometimes called vascular dementia). These types of dementia are irreversible, which means they cannot be cured. In Alzheimer's disease, nerve cell changes in certain parts of the brain result in the death of a large number of cells. Symptoms of Alzheimer's disease 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 small strokes or changes in the brain's blood supply may result in the death of brain tissue. The location in the brain where the small strokes occur determines the seriousness of the problem and the symptoms that arise. Symptoms that begin suddenly may be a sign of this kind of dementia. People with multi infarct dementia are likely to show signs of improvement or remain stable for long periods of time, then quickly develop new symptoms if more strokes occur. In many people with multi-infarct dementia, high blood pressure is to blame. One of the most important reasons for controlling high blood pressure is to prevent strokes.
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.
Alzheimer's disease and multi-infarct dementia 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.
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 Alzheimer's disease, the drugs tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) are prescribed to possibly delay the worsening of some of the disease's symptoms. 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 Alzheimer's disease 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 very useful aids.
Advice for Today
Scientists are working to develop new drugs that someday may slow, reverse, or prevent the damage caused by Alzheimer's disease 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.
The Alzheimer’s Association is a nonprofit organization offering information and support services to people with Alzheimer’s disease and their families. For more information, contact:
Alzheimer’s Association
919 Michigan Avenue, Suite 1100
Chicago, IL 60611-1676
e-mail: [email protected]
The Alzheimer's Disease Education and Referral (ADEAR) Center is a service of the National Institute on Aging, part of the Federal Government’s National Institutes of Health. The Center provides information to health professionals, Alzheimer’s disease patients and their families, and the public. For more information contact:
ADEAR Center
PO Box 8250
Silver Spring, MD 20907 8250
e-mail: [email protected]
Families often need information about community resources, such as home care, adult day care, respite programs, and nursing homes. This information usually is available from State and Area Agencies on Aging. For help in finding the appropriate agency in your area, call the Eldercare Locator, toll-free at 1-800-677-1116 or visit
National Institute on Aging
U.S. Department of Health and Human Services
Public Health Service
National Institutes of Health

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Human Gene Affects Memory
NIH scientists have shown that a common gene variant influences memory for events in humans by altering a growth factor in the brain's memory hub. On average, people with a particular version of the gene that codes for brain derived neurotrophic factor (BDNF) performed worse on tests of episodic memory — tasks like recalling what happened yesterday. They also showed differences in activation of the hippocampus, a brain area known to mediate memory, and signs of decreased neuronal health and interconnections. These effects are likely traceable to limited movement and secretion of BDNF within cells, according to the study, which reveals how a gene affects the normal range of human memory, and confirms that BDNF affects human hippocampal function much as it does animals'.
Michael Egan, M.D., Daniel Weinberger, M.D., National Institute of Mental Health (NIMH), Bai Lu, Ph.D., National Institute of Child Health and Human Development (NICHD) and colleagues, report on their discovery in the January 24 issue of Cell.
Long known to be critical for the growth and survival of neurons, BDNF has also recently been shown to play a key role in memory and hippocampal function in animals. To find out if it works similarly in humans, the researchers explored the consequences of a tiny variance in the human BDNF gene, where its molecular makeup differs slightly across individuals. People inherit two copies of the BDNF gene — one from each parent — in either of two versions. Slightly more than a third inherit at least one copy of a version nicknamed "met," which the researchers have now linked to poorer memory. It's called "met" because its chemical sequence contains the amino acid methionine in a location where the more common version, "val," contains valine.
"We are finding that this one amino acid substitution exerts a substantial influence on human memory, presumably because of its effects on the biology of the hippocampus," said Weinberger.
Despite its negative effect on memory, the "met" version's survival in the human genome suggests that it "may confer some compensatory advantage in other biological processes," note the researchers. Although they found that it does not confer increased susceptibility to schizophrenia, they suggest that the "met" variant might contribute to risk for — or increase functional impairment in — other disorders involving hippocampal dysfunction, such as Alzheimer's disease or mood disorders.
Drawing on participants in the NIMH intramural sibling study of schizophrenia, Egan and colleagues first assessed their hippocampal function and related it to their BDNF gene types.
Among 641 normal controls, schizophrenia patients, and their unaffected siblings, those who had inherited two copies of the "met" variant scored significantly lower than their matched peers on tests of verbal episodic (event) memory. Most notably, normal controls with two copies of "met" scored 40 percent on delayed recall, compared to 70 percent for those with two copies of "val." BDNF gene type had no significant effect on tests of other types of memory, such as semantic or working memory.
The researchers then measured brain activity in two separate groups of healthy subjects while they were performing a working memory task that normally turns off hippocampus activity. Functional magnetic resonance imaging (fMRI) scans revealed that those with one copy of "met" showed a pattern of activation along the sides of the hippocampus, in contrast to lack of activation among those with two copies of "val."
Next, an MRI scanner was used to measure levels of a marker inside neurons indicating the cell's health and abundance of synapses — tiny junctions through which neurons communicate with each other. Again, subjects with one copy of "met" had lower levels of the marker, N-acetyl-aspartate (NAA), than matched individuals with two copies of "val." Analysis showed that NAA levels dropped as the number of inherited "met" variants increased, suggesting a possible "dose effect."
Unlike other growth factors, hippocampal BDNF is secreted, in part, in response to neuronal activity, making it a likely candidate for a key role in synaptic plasticity, learning and memory. To explore possible mechanisms underlying the observed "met"- related memory effect, the researchers examined the distribution, processing and secretion of the BDNF proteins expressed by the two different gene variants within hippocampal cells. When they tagged the gene variants with green fluorescent protein and introduced them into cultured neurons, they discovered that "val" BDNF spreads throughout the cell and into the branch-like dendrites that form synapses, while "met" BDNF mostly clumps inside the cell body without being transported to the synapses. To regulate memory function, BDNF must be secreted near the synapses.
"We were surprised to see that 'met' BDNF secretion can't be properly regulated by neural activity," said Lu.
The observed memory decrements are likely traceable to the failure of "met" BDNF to reach the synapses, as well as its inability to secrete in response to neuronal activity, say the researchers.
"Our study provides direct in vivo data that the molecular mechanisms related to activity dependent BDNF secretion and signaling, such as synaptic plasticity, may underlie humans' greatly expanded verbally-mediated memory system, just as it does for more rudimentary forms of memory in animals," said Egan.
In following-up their leads, the researchers are searching for a possible BDNF connection with the memory problems and hippocampal changes of Alzheimer's disease, depression and normal aging.

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