Causes of memory impairment
| May 1, 2008
In-Depth Report
Causes of memory impairment
Although mild age-related memory loss is considered normal, more severe memory impairment is not. Many people assume that memory loss is exclusively caused by either aging or Alzheimer's disease. In truth, a wide range of causes, including medical disorders, medications, and even lifestyle factors can contribute to memory loss. Several health problems are now known to cause memory loss and increase the risk of dementia. Some, such as hypertension, become more common with age and, together with age-related changes in the brain, help explain why you might become more forgetful as you age. And the capacity of your memory also depends, in part, on the genes you inherit. Fortunately, memory loss caused by illness or lifestyle factors can often be prevented or treated.
Figure 5: Risk of Alzheimer's disease with age
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Neurological disorders
When neurons are damaged or cannot function effectively, memory impairment and cognitive decline can occur. Following are some examples of conditions that prevent neurons from functioning normally, causing a variety of mental impairments, including memory loss.
Mild cognitive impairment
The distinction between normal age-related cognitive decline and abnormal cognitive dysfunction has blurred as researchers have focused on a particular group of older people: those who have cognitive problems that are above and beyond those seen in normal aging, but who do not have dementia. These people have mild cognitive impairment (MCI) — the loss of memory or some other mental function that is more persistent and severe than is seen in normal aging but does not meet the criteria for a diagnosis of dementia. MCI has two major subtypes: amnestic (when memory is impaired) and nonamnestic (when other types of cognitive functioning are affected).
Normal memory loss also differs from amnestic MCI with regard to the kind of information you forget. With normal memory loss, you tend to forget things that aren't terribly important to you — the name of a casual acquaintance, for example, or an appointment to have your teeth cleaned. With MCI, you may forget important information, such as the names of close friends or the birthdays of family members.
When taking memory tests, people with the amnestic type of MCI have more trouble remembering the details of pictures they've seen or paragraphs they've read just a few minutes earlier. Their memory difficulty is comparable to that of someone with very mild Alzheimer's disease. But on tests that measure other mental functions, such as their ability to keep the details of routine activities straight, people with MCI perform as well as healthy people and much better than people with Alzheimer's. People with nonamnestic MCI may have trouble in other cognitive areas, such as language or navigation.
Studies show that the risk of developing Alzheimer's disease is much higher for people with mild cognitive impairment than for people with normal age-related memory loss. Based on a range of studies, the progression from MCI to Alzheimer's disease among elderly individuals ranges from 8% to 16% a year. In contrast, the rate of new Alzheimer's cases among the general population is 1% to 3% a year. One study showed that the cumulative rate of dementia in people with MCI may be as high as 80% at the end of six years. However, it may take as long as eight years for MCI to progress into full dementia.
Researchers continue to study the link between MCI and Alzheimer's disease. A crucial question is whether treating MCI with certain medications can prevent future progression to dementia. A study by the National Institute on Aging found that people with MCI who took donepezil (Aricept) progressed to dementia more slowly than similar people who took a placebo.
Symptoms of memory-related mild cognitive impairmentSubjective memory complaint, preferably backed up by another person such as a family member Memory impairment (for age and education) as determined by testing Essentially normal general cognitive function No difficulties carrying out activities of daily living No dementia |
Dementia
Dementia isn't a disease per se. Instead, it's a descriptive term for a host of symptoms that can be caused by a number of disorders that can affect the brain. Although memory loss is a common symptom, memory loss by itself does not signify dementia. With dementia, people lose their cognitive abilities to the extent that they are unable to carry out normal activities and relationships. They may also experience personality and behavior changes such as agitation and delusions. According to a 2007 report, one in seven people ages 71 and older has dementia. Following are short summaries of the different forms.
Alzheimer's disease. Alzheimer's disease is far and away the leading cause of dementia, accounting for 60% to 80% of all dementia cases in elderly people. Although it is extremely rare before age 60, Alzheimer's, like dementia in general, becomes much more common with age (see Figure 5). The disease involves a substantial loss of neurons along with the appearance of abnormal structures in the brain called "plaques" and "tangles," particularly in regions of the brain associated with memory. Eventually, these abnormalities and the loss of neurons extend into other areas of the cortex.
The vast majority of people who develop Alzheimer's disease with symptoms commencing after age 65 have no family history or known genetic predisposition. But in a small number of cases where symptoms begin earlier in life, the disease has a strong familial basis (see "Genes").
Vascular dementia. The second leading cause of dementia, vascular dementia refers to cognitive impairment that stems from damage to blood vessels that feed the brain (see Figure 6). These vessels may become narrowed or blocked. Many factors, including high blood pressure and high cholesterol, may contribute to this damage (see "Cardiovascular disease and its risk factors").
Figure 6: What happens during an ischemic stroke
Ischemia refers to an insufficient supply of blood to an organ. Most strokes — more than 80% — are so-called ischemic strokes, which are caused by blockage to an artery in the brain. About 60% are caused by emboli, blood clots that travel to the brain after forming elsewhere, typically in the heart or aorta. |
Brain cells, like tissues elsewhere in the body, need a constant supply of oxygen to live; they get this oxygen from the blood. When blood flow is interrupted during a stroke, some brain cells may die. Sometimes, dementia symptoms occur suddenly, immediately after a stroke. But even "silent" strokes, or transient ischemic attacks — those that cause few or no obvious persisting symptoms — can lead to dementia. A large study published in The New England Journal of Medicine in 2003 found that people who had suffered "silent" strokes were more than twice as likely to develop dementia within an average of three and a half years compared with people who had not had strokes. People who had experienced this type of stroke also exhibited a sharper decline in memory test performance as well as in overall intellectual functioning. This effect might be explained by the fact that these smaller strokes often occur in the brain's white matter, which contains the "wiring" that allows communication between brain regions.
Other types of dementia. Several less common brain disorders may also lead to dementia:
Frontotemporal dementia (FTD). Formerly called Pick's disease, this rare group of diseases causes the frontal and temporal lobes of the brain to shrink. It is often confused with Alzheimer's disease because the symptoms (behavior and personality changes) can be similar. However, people with one type of FTD typically experience language problems in the early stage of the illness, which usually develops between ages 35 and 75. In the other major variant of FTD, individuals tend to exhibit changes in personality and behavior. Up to half of those with FTD have a family history of dementia, suggesting the illness has a genetic component.
Dementia with Lewy bodies (DLB). This progressive form of dementia stems from a buildup of bits of protein called Lewy bodies in the nuclei of brain cells that control memory and motor control. Over 50% of people with Parkinson's disease develop Parkinson's disease dementia, which is a form of Lewy body dementia. The similarities between Alzheimer's disease and dementia with Lewy bodies can make diagnosis difficult. Symptoms such as cognitive decline, memory loss, language difficulties, mood changes, and disorientation are characteristic of both diseases. Dementia with Lewy bodies can be treated with some of the drugs used to treat Alzheimer's disease, such as donepezil. However, levodopa, the mainstay of treatment of motor control symptoms in Parkinson's disease, does not alleviate cognitive symptoms in this dementia syndrome.
Cerebral amyloid angiopathy (CAA). Abnormal deposits of amyloid protein in the brain are the hallmark of Alzheimer's disease. When this protein accumulates in the brain's small and medium-sized blood vessels, it can cause the vessel walls to break down. Blood can then leak into the surrounding tissue, causing a brain hemorrhage. Cerebral amyloid angiopathy is often associated with Alzheimer's disease but can also occur sporadically or in individuals who have a family history of the disorder. Like Alzheimer's, CAA most often occurs in elderly people, with risk of the condition increasing with age.
Recognizing dementiaAlthough people in the earliest stages of dementia often sense that something is wrong, the illness eventually deprives them of the insight necessary to understand their problems. So it's usually up to a family member or friend to recognize the symptoms. If you suspect that someone you know has dementia, arrange for a medical evaluation. Many forms of dementia are not reversible, but early detection provides an opportunity to minimize other medical conditions that may compound the dementia, and it allows family members more time to come to terms with the illness and to plan for long-term care. There are several medications approved for the treatment of dementia that can bring about moderate, temporary improvement in memory and other elements of cognitive function (see "Medications for memory impairment"). |
Head trauma
A blow to the head that is strong enough to cause a concussion — a brief alteration of consciousness — can also impair memory. The blow can damage brain cells, or it can stretch or tear the axons, the fine filament "tails" of the neurons that compose the white matter of the brain and spinal cord. Most people who suffer mild concussions recover their memories and other mental functions completely within a few hours or days.
More severe head trauma, such as an injury sustained in a high-speed collision, frequently destroys brain tissue and injures nerve fibers throughout the brain. This type of damage is permanent. People who sustain multiple injuries from concussion — prizefighters, for example — are prone to later development of dementia and other brain disorders. There is also a growing awareness of reduced cognitive function caused by other sports activities that involve impact to the head, such as football, soccer, and ice hockey. Many professional organizations, universities, and secondary schools in the United States have put into place concussion prevention and management guidelines.
Other neurological disorders
Among the many illnesses that interfere with brain activities — including memory — are Parkinson's disease, multiple sclerosis, epilepsy, brain tumors, Lyme disease that affects the brain and nervous system, Huntington's disease, Creutzfeldt-Jakob disease, and late-stage AIDS.
Amnesia: Memory loss caused by injury or traumaAmnesia is the inability to form new memories or, in some cases, to remember existing ones. Amnesia occurs when key structures of the brain — such as the hippocampus, which is essential for consolidating memories — don't function properly. The malfunction can be caused by some types of stroke, concussive injury, chronic alcoholism, disruption of oxygen supply, or certain kinds of infections such as viral encephalitis. Amnesia is also a common side effect of electroconvulsive therapy used to treat major depression, although the effect is typically temporary. People with amnesia don't forget everything, and they retain their general level of intelligence. They have a normal attention span and can form short-term memories lasting perhaps a few minutes. Their procedural memory — which covers well-established skills such as driving a car or brushing teeth — remains intact, because retention of these skills doesn't depend on the hippocampus. The breakdown occurs with acquiring new long-term declarative memories, which often depend on the hippocampus. People with anterograde amnesia are unable to form new long-term memories after the moment of an accident or the onset of illness. People with retrograde amnesia have difficulty retrieving previously learned information, memories that had been acquired before the onset of the condition that caused the amnesia. The duration of amnesia depends on the cause. If the disruption of brain function is temporary (as in a blow to the head that causes a minor concussion), most of the lost memory will be restored, although memories formed just before and soon after the injury occurred are usually lost forever. There is also a rare condition called transient global amnesia (TGA). TGA refers to a brief period of time (usually hours) during which a person is able to engage in normal behavior but after which she or he does not remember the events that occurred during that period. TGA is not related to later development of a more serious memory disorder such as Alzheimer's disease, although the actual cause of the condition is unknown. Emotionally or physically stressful events such as intense physical activity, sudden immersion in hot or cold water, sexual intercourse, or medical procedures can trigger an episode. Some experts suspect that TGA is related to a temporary loss of blood flow to areas of the brain involved in memory formation. However, imaging studies of the region during the time frame after the event when vascular changes are most likely to appear do not support this theory. TGA appears to be more frequent in people who get migraines. Certain drugs and medications can also produce TGA-like episodes. |
Genes
Dozens of studies — involving more than 10,000 pairs of twins — have shown that genetic differences account for about half of the variation in people's mental abilities. Your genetic makeup also affects the degree to which you experience age-related memory loss and your risk for conditions that can impair memory, such as high blood pressure and Alzheimer's disease. If your parents or older siblings have memory loss, you are at higher risk than others who do not have this problem in their families.
Scientists have identified a common genetic variant that impairs memory. Normally, the gene directs the production of a chemical called brain-derived neurotropic factor, which travels to the synapses and regulates memory. However, the gene's so-called met variant, which is inherited by one-third of all people, encodes for a variant of this chemical. The result is that the chemical doesn't reach the synapses effectively. In one study, people who inherited one or two copies of the met variant did not do nearly as well on a memory test as people who inherited two normal copies of the gene. The brains of these people also appeared to function differently: functional MRI images revealed that people with this gene variant had a different pattern of activity in the hippocampus than did other people.
Genetic factors are clearly relevant for families with a history of early-onset Alzheimer's. This rare form of the illness, which accounts for less than 1% of all Alzheimer's disease cases, typically appears before age 50. It is caused by abnormalities in three genes, all of which increase the production of beta-amyloid, which is deposited in the plaques found in Alzheimer's.
However, one form (or allele) of a gene that directs the manufacture of a protein called apolipoprotein E (Apo E) has been linked to the more common late-onset Alzheimer's disease. In particular, inheriting the APOE4 gene variation increases your chances of getting the disorder when you are older.
In 2007, researchers uncovered another gene that appears to contribute to Alzheimer's-related brain changes. Their study, described in Nature Genetics , linked variations in a gene known as SORL1 to the formation of amyloid plaques in the brain. Using blood samples from 6,000 people in North America, Europe, and Asia, scientists isolated the SORL1 variation by looking at the genetic profiles of families in which two or more members have Alzheimer's disease. When they compared blood samples of people with and without Alzheimer's, researchers found that the people with the disease had less than half the level of SORL1 protein as did non-affected individuals.
Lessons from the Nun StudyIn 1986, a young epidemiologist named David Snowdon engaged a community of 678 retired Catholic sisters in Minnesota in his research on healthy aging. This marked the beginning of an ongoing research project known as the Nun Study, which has yielded groundbreaking insights into the hows and whys of Alzheimer's disease. The unprecedented wealth of information available about the sisters' personal and medical histories, combined with the relative uniformity of their lifestyles, allowed researchers to tease out the medical and social factors that put an individual at risk for developing dementia. One of the most significant findings has been the understanding of how cardiovascular factors interact with Alzheimer's disease pathology. The women in the study who seemed to fare the best cognitively were those whose brains showed little evidence of stroke, even if they had brain damage consistent with moderate to advanced Alzheimer's. From this, researchers conclude that a healthy brain has reserve capacity it can draw on to maintain normal functions even when Alzheimer's disease is present. On the other hand, when the brain is compromised by cardiovascular disease, dementia symptoms appear at an earlier stage (see "Cognitive reserve: Engage your brain"). |
Cardiovascular disease and its risk factors
Physicians now know that what's bad for the heart is also bad for the brain. Conditions that have been linked with heart disease — high blood pressure, high cholesterol, and diabetes — have also been linked to memory problems. More and more, researchers are strengthening the link between injuries to the brain tissue caused by "silent" strokes and the manifestation of clinical symptoms of Alzheimer's disease (see "Lessons from the Nun Study").
Hypertension
Adults with high blood pressure (hypertension) are more prone to memory impairment than people with normal blood pressure. Moreover, people with hypertension experience memory loss that is more severe than that suffered by individuals who don't have hypertension. These differences hold true regardless of age.
A 2007 study in Archives of Neurology reconfirmed this phenomenon. Researchers followed 918 elderly people with no signs of cognitive impairment at the start of the study. After an average of about five years, over a third of those with high blood pressure had developed MCI.
Preliminary research has even documented visual evidence of the effects of hypertension on the brain. Using a technology called arterial spin-labeled magnetic resonance imaging, researchers compared the level of cerebral blood flow in people with hypertension, MCI, and Alzheimer's disease to that of people who did not have these conditions. The images revealed that those with high blood pressure and those with Alzheimer's disease both had marked decreases in blood flow to the brain. Although not as severely limited, the group with MCI also showed trends in this direction. People with both Alzheimer's and hypertension showed the most severely limited brain circulation.
Hypertension appears to impair memory by damaging the brain's white matter. Changes in white matter occur to some degree in virtually everyone over age 60 and contribute to normal age-related memory loss. But damage to white matter is especially prevalent among people with hypertension, according to a 2004 report in the American Journal of Hypertension . In this study, 60 people with untreated hypertension had the most extensive white-matter abnormalities and performed worst on tests of memory, learning, and other mental functions.
Physicians believe that controlling blood pressure may help preserve memory and other aspects of cognitive function well into old age. But be aware that one class of hypertension drugs, the beta blockers, can temporarily impair memory (see "Medications"). If you experience memory impairment while taking a beta blocker, replacing the drug with a different blood pressure medicine may restore memory function to normal within several days.
High cholesterol
In contrast to hypertension, which can cause memory problems fairly quickly after it develops, high cholesterol appears to increase the risk for mild cognitive impairment and Alzheimer's disease many years down the road. People with high cholesterol have a higher than average incidence of these two conditions. It's not clear how high cholesterol might lead to memory loss, or whether the crucial factor is excessive LDL (the "bad" cholesterol) or insufficient HDL (the "good" cholesterol).
Some studies suggest that people who are treated with statins, a class of cholesterol-lowering medications, reap the additional benefit of decreasing their risk of Alzheimer's disease and mild cognitive impairment. Other studies suggest that statins can help treat dementia (see "Statins"). However, anecdotal reports linking statin use to memory loss appeared in The Wall Street Journal and other media outlets in early 2008, raising concerns that these drugs might be less benign to the brain than once believed. Although controlled studies have not documented this effect, further research on the effect of statins on cognition and mood are under way.
Cholesterol and triglyceride levels |
|
Total cholesterol level |
Category |
Less than 200 mg/dL |
Desirable |
200−239 mg/dL |
Borderline high |
240 mg/dL and above |
High |
LDL cholesterol level |
Category |
Less than 100 mg/dL |
Optimal (70 mg/dL for high-risk group) |
100−129 mg/dL |
Near optimal/above optimal |
130−159 mg/dL |
Borderline high |
160−189 mg/dL |
High |
190 mg/dL and above |
Very high |
HDL cholesterol level |
Category |
Less than 40 mg/dL |
Low (increased risk) |
60 mg/dL and above |
High (heart-protective) |
Triglyceride level |
Category |
Less than 150 mg/dL |
Normal |
150−199 mg/dL |
Borderline high |
200−499 mg/dL |
High |
500 mg/dL and above |
Very high |
Adapted from the Third Report of the National Cholesterol Education Program of the National Heart, Lung, and Blood Institute . |
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Coronary artery bypass surgery
Both memory loss and diminished ability to concentrate are prevalent among people who have had coronary artery bypass surgery to treat blocked arteries. An often-cited study found that about half of the people who underwent bypass surgery experienced memory impairment and cognitive decline immediately afterward. And six months later, about one in four people continued to have cognitive impairment.
Why does this happen? During traditional bypass surgery, patients are hooked up to a heart-lung machine, which temporarily takes over the function of both organs. But blood can collect atherosclerotic particles while passing through the heart-lung machine and then deposit them in the brain, causing memory-impairing damage (see Figure 7).
Some people may be able to avoid this risk by undergoing a less invasive innovation in coronary artery bypass surgery called off-pump bypass or beating-heart surgery. In this procedure, the operating team doesn't place you on a heart-lung machine. Instead, the surgeon uses special equipment to hold the heart steady, enabling surgeons to operate on it while it continues beating. These days, about 20% of bypass surgeries are performed off-pump.
On the other hand, the problem may not be the surgery. Some research has suggested that some of the biological processes involved in coronary artery disease also contribute to Alzheimer's disease and other types of dementia — raising the possibility that it is the underlying disease, and not bypass surgery, that contributes to cognitive problems.
Figure 7: How bypass surgery can cause brain damage
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Diabetes
Several large studies document links between diabetes and cognitive decline. A review of the research suggests that diabetes confers a 50% to 100% increased risk of Alzheimer's disease and overall dementia. The mechanisms behind the higher risk of dementia associated with diabetes are not entirely clear. Damage to the small blood vessels in the brain from high blood sugar, the hallmark of the disease, is one factor. In addition, high blood sugar depresses the function of the hippocampus. Middle-aged and elderly people with high blood sugar are likely to have a smaller hippocampus than younger adults, according to a report in Proceedings of the National Academy of Sciences .
The role of insulin, the hormone that transports sugar from the blood into the body's cells — including cells in the brain — is also being examined. In a study that looked at the brain tissue of people who had died in various stages of Alzheimer's disease, people with the most advanced stage of dementia had as little as one-fifth as many insulin receptors in their brains, indicating that the cells were not processing sugar efficiently.
In another study reported in Archives of Neurology in 2005, even moderately high insulin levels increased biochemical markers for inflammation, which is thought to promote Alzheimer's disease. For the study, in which researchers raised insulin levels of 16 adults ages 55 to 81, elevated insulin also led to an increase in blood levels of beta-amyloid, the sticky substance that degrades brain function in Alzheimer's.
Current investigations are studying whether a class of oral diabetes drugs called thiazolidinediones (TZDs) can lower the risk of Alzheimer's disease in people with elevated blood sugar. In one study of over 140,000 veterans, the number of new cases of Alzheimer's was lower among veterans who were taking TZDs compared to those taking other diabetes drugs.
Depression
The relationship between depression and memory loss is complex. Depression can be a cause as well as an effect of memory dysfunction. Severe, ongoing, and untreated depression can make people forgetful by interfering with their ability to concentrate and process information. This is particularly true in the elderly. In fact, doctors coined the term "depressive pseudo-dementia" to describe elderly patients with severe memory impairment based on depression. Once their depression is treated, memory returns to baseline.
Research suggests that long-term depression may result in a loss of neurons in structures within the limbic system of the brain, including the hippocampus and amygdala. For example, one imaging study found that these structures were smaller in women with a history of recurrent major depression than in people who had not experienced depression. In the same study, women with a history of depression did not perform as well as other women on tests of verbal memory.
Depression might also increase the risk of Alzheimer's disease. In a 2006 study published in Archives of General Psychiatry , researchers examined the brains of 95 people who had died of Alzheimer's. In the individuals who had a lifetime history of major depression — about half the study subjects — there were significantly more Alzheimer's-related plaques and tangles in the brain. The people with a history of depression also underwent a faster cognitive decline during the course of the disease.
Although depression can be a symptom of early Alzheimer's disease, there are key differences in the memory loss experienced by people suffering from depression alone and people experiencing depression in conjunction with Alzheimer's. In people with depression alone, cognitive function usually fluctuates with mood. When mood improves — usually in response to treatment with medication, psychotherapy, or both — cognitive function generally improves as well. By contrast, someone with Alzheimer's disease will continue to have impaired cognitive functioning even when the depression lifts.
Hearing loss
It makes sense: if you have trouble hearing something, you're bound to have trouble remembering it. One study found that adults with mild to moderate hearing loss remembered fewer of the items from a list of 15 spoken words than did adults with good hearing. The researchers concluded that the extra effort involved in trying to hear the words diverted brain resources from acquisition and consolidation of memory. Hearing loss is a remarkably common but highly treatable problem, particularly in the elderly. Periodic hearing tests should be part of routine medical care.
Hormones
Many naturally occurring hormones can affect memory and overall cognitive function. A good deal of research has been done on memory and three of these hormones: estrogen, testosterone, and thyroid hormone.
Estrogen
Many women experience trouble with memory during menopause, when their levels of estrogen fall sharply. However, stress or other psychological issues, sleep disturbance due to hot flashes, or a combination of factors could also be to blame.
Some studies suggest that estrogen protects neurons, which might explain a connection with memory. If that's true, hormone supplements should protect against age-related memory difficulties. In fact, research has revealed the opposite (see "Estrogen therapy and memory").
Testosterone
Men with high levels of testosterone have better visual and verbal memories than men with low levels. Still, the value of testosterone supplementation in older men is controversial. One early study found that testosterone supplements led to improvements in working memory in men, but a 2007 study of healthy older men found no such benefit. Testosterone supplements have drawbacks — they can increase the risk of some kinds of cancer and may also raise the risk for stroke and for vascular dementia. Nevertheless, some experts think testosterone may have therapeutic value in the treatment of Alzheimer's disease.
Thyroid
The thyroid gland secretes hormones that control metabolism, the rate at which the body burns energy. When the thyroid doesn't function properly, it can release too much or too little of these hormones, making the metabolism run too fast or too slow. Either problem can interfere with learning and memory. Hyperthyroidism, which causes an abnormally fast metabolism, can make people feel confused. Hypothyroidism, which causes an abnormally slow metabolism, can make people feel sluggish, sleepy, and depressed. Research on animals shows that changes in the levels of thyroid hormone cause physiological changes in the hippocampus. Research also shows that when thyroid problems are treated, people's memory problems diminish.
Medications
Many prescription and over-the-counter medicines can impair memory (see "Medications and memory loss"). Antihistamines and tranquilizers cause drowsiness or interfere in other ways with the ability to maintain attention. Anticholinergic agents, such as those used to treat bladder dysfunction, affect the activity of certain neurotransmitters in the brain that are crucial to memory. The tricyclic class of antidepressants also has anticholinergic side effects that can impair memory and other elements of cognitive function. Other medicines that can cause memory loss include insulin for diabetes, narcotic painkillers such as meperidine (Demerol), beta blockers for hypertension, cimetidine (Tagamet) for ulcers, amantadine (Symmetrel) for Parkinson's disease, sleeping pills, benzodiazepines for anxiety, eye drops for glaucoma, and chemotherapy for cancer.
As people age, they are more likely to experience side effects from medications for two reasons. First, older people tend to take more medications because they generally have more health problems. The more medications people take, the greater the chance of an adverse reaction to a single drug or interactions among drugs. Second, because metabolism slows with age, medications linger longer in the body.
If you are experiencing memory problems and suspect that one or more of your medications is responsible, make a list of all your medications and talk with your doctor. Don't stop taking a medicine until you have consulted your doctor. If you and your doctor pinpoint a medication that may be causing your memory problems, you may be able to stop taking the drug and see whether your memory improves. Alternately, your doctor may be able to replace a troublesome medication with a different drug that does not interfere with your memory or cognitive abilities. It may take up to several weeks for any improvement to occur.
Medications and memory lossCommon prescription drugs in the following categories may cause memory loss as a side effect. Sleep medications Tranquilizers/anxiety medications Painkillers Antihypertensives Heartburn medications Antidepressants Antiepileptics Antipsychotics Parkinson's disease medications Anticholinergics |
Lifestyle factors
The way you live, what you eat and drink, and how you treat your body can also affect memory.
Alcohol use
Excessive alcohol use increases the risk for memory loss and dementia. People with alcoholism have difficulty performing short-term memory tasks, such as memorizing lists. A small group of scientists has voiced the opinion that the gradual memory decline often seen after years of heavy drinking may not be the direct result of alcoholism as is currently assumed. They contend that brain pathologies, such as the plaques and tangles seen in Alzheimer's disease, may be the real root of the dementia. However, the evidence for this point of view is not yet established, and the majority of researchers continue to view excessive alcohol use as a potentially harmful toxic condition.
Another type of memory loss associated with alcohol use is called Korsakoff's syndrome, in which severe amnesia comes on suddenly and dramatically as a result of long-term vitamin B1 (thiamine) deficiency combined with the toxic effects of alcohol on the brain. The memory loss of Korsakoff's syndrome is usually permanent, but other alcohol-related memory problems may be reversible if the person sharply cuts down on drinking and maintains optimal nutrition.
Moderate drinking, on the other hand, may actually reduce the risk of dementia. In a 2003 study in The Journal of the American Medical Association , people over age 65 who took up to one drink a day had roughly half the risk of Alzheimer's disease compared with people who didn't drink. Heavier drinkers, however, had a 22% higher risk than did the nondrinkers. A 2007 study in The Journal of Neuroscience looked at the effects of moderate and heavy drinking on cognitive function in rats. Researchers added alcohol to the animals' water supply to simulate moderate (about two drinks a day) or heavy alcohol use. At the end of eight weeks, the rats who had been given moderate levels of alcohol performed better on cognitive tests than did either the heavy-drinking rats or the teetotalers.
Clearly, many questions remain about the relationship between alcohol and memory. Experts caution that even though research is mounting in support of the biological benefits of alcohol on memory, it's still better to forgo alcohol altogether than to over-imbibe.
Vitamin B basicsOnce thought to be a single entity, the vitamin B complex actually includes eight distinct substances. Among the best known (and important) are folic acid, or folate (vitamin B9 ), and vitamins B6 and B12 . They often coexist and are found in many foods, including whole-grain cereals, rice, nuts, milk, eggs, meats, liver, fish, fruits, and leafy green vegetables. The recommended daily intake for adults is 400 micrograms (mcg) of folic acid, 1.3 to 1.7 milligrams (mg) of vitamin B6 , and 2.4 mcg of vitamin B12 . Recommended intake levels are slightly higher for women who are pregnant or breast-feeding. |
Diet
For years, scientists have believed that diet might influence the risk of age-related memory loss as well as dementia. Fat and cholesterol were considered possible risk factors, and several antioxidants and other nutrients were considered potentially protective. Studies have confirmed some dietary links and cast doubt on others.
B vitamins. People with deficiencies in any of the B vitamins (see "Vitamin B basics") are more likely to develop memory loss and dementia. The B vitamins seem to have two beneficial effects on memory.
First, vitamin B12 supports neuron health by helping to make and preserve myelin, the protective sheath that surrounds the axon. A deficiency of this vitamin sometimes occurs in older people and can be caused by dietary factors or an inability of the intestine to absorb vitamin B12 . A lack of vitamin B12 can lead to permanent neuronal damage, including memory loss. People who drink heavily are at sharply increased risk. B12 deficiency can be detected with a blood test and is usually treatable with vitamin supplementation. In cases caused by malabsorption, it may not help to take vitamin B12 supplements orally because the vitamin won't be absorbed sufficiently during digestion. Instead, people with this deficiency can be treated with monthly injections of the vitamin.
B vitamins may also support memory by helping to moderate homocysteine, an amino acid in the blood that, in high levels, is considered a significant risk factor for cardiovascular disease and dementia, including Alzheimer's disease. The B vitamins break down homocysteine in the blood. Deficiencies of these vitamins are associated with elevated homocysteine levels. There is no officially designated "normal" level for homocysteine, but research suggests that readings below 12 micromoles per liter (mmol/L) are desirable. A 2002 study in The New England Journal of Medicine reported that each 5-mmol/L increase in homocysteine raised the risk for Alzheimer's by 40%. In addition, a study in Annals of Neurology in 2003 found that people whose homocysteine levels were higher than 15 mmol/L had three times the risk of cognitive decline over a three-year period as people with lower levels.
Getting the recommended amounts of the B vitamins, either through diet or supplements, can lower homocysteine and improve cognitive function. Several epidemiological studies showed that blood concentrations of vitamins B6 and B12 and folate affect people's performance on tests of memory and abstract thinking. One study found that older men with higher levels of B6 , B12 , and folate in their blood and in their diets did better on a test designed to measure spatial thinking. In another, investigators collected blood test results for 816 older people. After about four years, 112 of them had developed dementia, including 70 diagnosed with Alzheimer's disease. The stored blood samples revealed that people who started with higher concentrations of folate were less likely to have suffered cognitive decline.
While keeping homocysteine low seems to help prevent cognitive decline, including memory loss, it is still unknown whether taking B vitamins can restore lost memory function. It is also unclear whether taking supplements above the recommended levels can offer additional protection against memory loss, but one study suggests the possibility. The study, reported by Dutch researchers at the 2005 International Conference on Prevention of Dementia, included 818 healthy people ages 50 to 75. It found that those who took high doses of folic acid — around 800 micrograms (mcg) — had less age-related memory loss over the course of three years than did people in a comparable group who took a placebo. Their scores on memory tests were comparable to those of people five years younger.
Vitamin E. Despite early hope that large amounts of vitamin E might slow the progress of Alzheimer's disease, research has produced mixed results. In a study of about 770 people with MCI, those who took 2,000 IU per day of vitamin E fared no better than those who took a placebo in preventing the progression to Alzheimer's. However, study participants who took vitamin E supplements were able to avoid being institutionalized longer than those who did not. Also, there's some evidence that getting enough of this vitamin in food may offer some help. One report that followed about 800 men and women who were at least 65 and free of Alzheimer's disease at the start of the study found that those who obtained the most vitamin E from food were far less likely to develop Alzheimer's compared with those who consumed the least. It's possible, though, that other nutrients in the foods played a role. Around the same time, a similar study reported that high dietary intake of vitamin E (and, to a lesser extent, vitamin C) lowered the risk of developing Alzheimer's disease.
Fats. With regard to fats, it's not the amount of overall fat you eat but the type of fat that may increase your risk of Alzheimer's disease. A 2003 study in Archives of Neurology found that consuming large amounts of saturated fats (found primarily in meat and dairy products) and trans fats (found mostly in processed foods with partially hydrogenated oils) increased the risk of Alzheimer's, whereas eating large amounts of unsaturated fats — including most vegetable oils and fish oils — decreased risk. The role of omega-3 fatty acids (found in cold-water fish such as mackerel and salmon) has attracted considerable interest. In particular, data from the Framingham Heart Study revealed that people with initially higher blood levels of the omega-3 fatty acid docosahexaenoic acid (DHA) had lower rates of dementia over a period of nine years.
Intellectual stimulation
Over time, people who don't challenge their minds exhibit a greater degree of memory decline compared with people who remain mentally active. The landmark MacArthur Foundation Study on Successful Aging found that education level was the strongest predictor of mental capacity as people aged. A 2005 study in the Journal of Gerontology: Psychological Sciences reported that people who held jobs that involved complex work, such as speaking to, instructing, or negotiating with others, had a lower risk of dementia than people whose jobs were less intellectually demanding.
Most experts think it's not the years of formal education or the type of occupation per se that benefits memory. Instead, a lifelong habit of learning and engaging in mentally challenging activities seems to keep the brain in shape.
Scientists believe that intellectual enrichment and learning stimulate the brain to make more connections, increasing the density of synapses. As a result, the "educated brain" may possess greater reserves of cognitive ability — a deeper well, so to speak — and be able to sustain more neuronal loss. Researchers refer to this enhancement of skills or abilities as cognitive reserve (see "Cognitive reserve: Engage your brain").
Level of physical activity
Insufficient physical exercise also increases the likelihood of memory impairment as people age. The MacArthur study researchers were surprised to find that sedentary people had greater memory declines compared with people who were physically active on a regular basis. The active people didn't necessarily work out at a gym, but they did engage in more routine physical activity such as climbing the stairs at home or taking walks in the neighborhood.
A Swedish study of 1,500 people ages 65 to 79, published in The Lancet Neurology in 2005, found that those who participated in a physical activity at least twice a week were only 40% as likely to develop Alzheimer's disease and half as likely to develop any form of dementia compared with sedentary people (see "Exercise").
Stress
Several studies link stress to memory loss. The key here is not the minor stresses of daily life, like deadline pressures or petty arguments, but rather an ongoing sense of extreme anxiety. Such severe stress may impair a person's memory. Some people — for example, veterans of wars or others who experience profoundly traumatic events — may develop post-traumatic stress disorder (see "Post-traumatic stress disorder").
Through animal research, scientists have discovered that neurons in the hippocampus are damaged by cortisol, a hormone released during stressful "fight or flight" situations. One study implicated cortisol in memory dysfunction in humans as well. In the study, a group of healthy adults received daily low-dose treatments of cortisol over the course of four consecutive days — about the amount that would be released under everyday stress. Another group received high doses over the same period of time. All participants took a test in which they listened to stories and then had to remember details about them immediately and 30 minutes later. People who had received the higher cortisol dose remembered less, both immediately and later, than people receiving the lower dose.
The memory dysfunction induced by this four-day experiment was reversible; once the cortisol wore off, the participants' memories returned to normal. No one knows how many days, weeks, months, or years of high-level stress it takes to cause irreversible memory impairment. What we do know is that a stressful event will cause some people to react more intensely than others, and it is the resulting long-term stress reaction that does the damage. To that extent, people may be able to control the harm that stress does to the memory by trying to modify their exposure and responses to stressful life events.
Post-traumatic stress disorderExtreme psychological trauma sometimes leads to post-traumatic stress disorder (PTSD), a condition in which intrusive memories of the traumatic event recur persistently and cause the individual to experience episodes of sustained, severe anxiety. Prolonged or frequently elevated levels of the stress hormone cortisol (as seen in PTSD) can harm brain structures vital to memory. Brain imaging studies reveal that the hippocampus may sustain damage or shrink in people with PTSD. Prompt, effective treatment can reverse the memory problems caused by PTSD. Treatment typically entails a combination of medication and psychotherapy. However, if cortisol damages the hippocampus and other brain structures, the resulting memory difficulties will persist. Scientists are now looking at ways to use medication to blunt painful memories at the time of the traumatic event, thereby preventing PTSD from developing in the first place. The high level of cortisol present in the body during a traumatic event has the effect of fortifying the emotions surrounding the memories of the incident. However, taking the beta-blocker drug propranolol (most commonly used to control high blood pressure) immediately after an emotionally disturbing event disrupts the release of adrenaline-related hormones, thereby undermining the formation of a traumatic memory. In a 2003 study in France, doctors in the emergency departments of two hospitals offered propranolol to victims of auto accidents or physical assaults who did not have serious physical injuries. The participants took the drug in the emergency room and continued with lesser doses for periods of two to three weeks afterward. At a two-month follow-up, these people had fewer symptoms of PTSD than did a similar group who didn't receive medication. Although this was a small pilot study, the results raise interesting questions about the ability to alter the process of forming troubling memories. On the one hand, nipping PTSD in the bud could spare potential sufferers the pain of dealing with the condition down the road. However, the use of drugs to alter emotion and memory formation raises significant ethical and legal questions that have yet to be answered. |
Sleep
People who don't sleep well at night tend to be more forgetful than people who sleep soundly. A good night's sleep is essential for consolidating memories. Although people vary in their need for sleep, six hours may be the minimum that you need to ensure adequate daytime alertness and memory function (see "Sleep and memory").
Sleep may aid memory in another way as well — by decreasing levels of stress hormones. Stress hormones decline during the first few hours of sleep, which experts believe may free up the hippocampus to consolidate memories.
With age, people become more prone to sleep disorders. The most common sleep disorder is insomnia, which is difficulty falling asleep or staying asleep. Unfortunately, many medicines used in the treatment of insomnia can also impair memory and general cognitive function, and it's best to avoid long-term use of sleep-inducing medications. Lifestyle changes are often helpful (see "Get a good night's sleep").
Another common disorder is obstructive sleep apnea, in which interrupted breathing can cause sleep to be fragmented by hundreds of "mini-awakenings" each night.
Sleep and memoryWhy does sleep make a difference? One theory suggests that changes in brain activity during two phases of sleep — slow-wave sleep and rapid eye movement (REM) sleep — are important for memory consolidation. Research with rodents showed that during slow-wave sleep, the pattern of activity in the hippocampus was very similar to the pattern that appeared earlier when the animals were engaged in learning something. This finding suggests that during slow-wave sleep, the hippocampus "replays" the recently acquired information to strengthen the neuronal patterns that were activated during the acquisition phase. This replaying of the learning scenario is the key component of the consolidation process. An interesting study in the March 2007 Science elaborates on this theory. Research participants played a memory game called Concentration, in which they were asked to recall the locations of like cards. Each time a person matched a pair of cards correctly, he or she was exposed to the scent of roses. Later that night, the rose fragrance was reintroduced during slow-wave sleep for half of the participants. The next morning, these individuals demonstrated a greater ability to match the locations of previously learned pairs over the subjects who did not receive sleep-time exposure to the scent. These results can be explained, the researchers say, by the fact that the rose scent activated the hippocampus and provided contextual information that aided in the consolidation of the memory and completing the learning task. Research has also revealed that important changes take place in the brain during REM sleep, which is the time when dreaming occurs. In particular, there is increased activity in the cortex during dreams. Some scientists now think that dreaming is one of the ways in which the brain strengthens the neuronal pathways that encode memories. |
Smoking
Smokers have a greater degree of age-related memory loss and other memory problems than nonsmokers. Research shows that they're less adept at recalling names and faces. A 2003 British study reported that the verbal memory function of people ages 43 to 53 was weaker in the smokers than in the nonsmokers. A 2004 study published in Neurology tracked the memory of 9,209 people ages 65 and older annually for several years by giving them the Mini-Mental State Examination, a standard test of cognitive functions. Nearly everyone's score dropped during this period, but the decline was five times greater for smokers than for people who never smoked. These conclusions were confirmed in a 2007 meta-analysis of 19 studies involving a total of more than 26,000 participants. Smokers showed a greater yearly decline in cognitive scores compared with nonsmokers. In addition, current smokers exhibited a higher risk of Alzheimer's disease than did former smokers.
Substance abuse
People who use certain illicit drugs are likely to have problems with memory and related cognitive functions — not only while they are under the influence, but also for weeks after the drugs' immediate effects wear off.
A 2006 study in Neurology found that people who used marijuana heavily for 10 or more years had substantially higher rates of memory impairment than did shorter-term heavy users or nonusers. Long-term users also scored significantly lower than the published norms on the verbal learning tests used in the study. Marijuana's active chemical, THC, causes its psychoactive effect by attaching to receptors in brain regions vital for memory formation, including the hippocampus, amygdala, and cerebral cortex.
Memory impairment is also a side effect of habitual cocaine use. Cocaine users score lower than nonusers on tests of working memory and recall of long-term memories. Deficits are apparent on tests of verbal memory, even after users have abstained from cocaine for 45 days.
One of the worst things you can do to your memory is to use illicit drugs. It is unclear how much of the memory impairment can be restored by quitting, but at the very least, quitting can prevent further damage.
Toxic exposure
Lead, mercury, and other chemicals present in homes and workplaces can cause memory loss and poor concentration. Lead poisoning can result from drinking contaminated tap water and breathing in lead dust generated by the deterioration of lead paint in homes built before 1978, when it was outlawed. Carbon monoxide fumes leak from malfunctioning household furnaces and are spewed from automobile exhaust systems. Mercury and other toxic substances are found in some paints, dyes, and inks used in artwork. Still other sources of toxic exposure are pesticides used in home gardens and farms, darkroom chemicals, and chemicals used in metalwork and woodwork.
Review Date: 2008-05-01
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