CREB and Knockout Mice

A memory trace is solidified if there is a small gap in time between the pieces of information that need to be remembered. Using this technique, which is called spaced training, scientists engineered a fruit fly to have a photographic memory. In the same fruit fly species, they triggered a master gene called CREB, which has the ability to goad a number of other genes into action. In this manner, the fruit fly with a fabulous memory was born. Ideally, if we could stimulate CREB in the same way...

Alcohol Induced Brain Damage A Clinical Chameleon

Mary O'Brien illustrates that steady, moderate- to high-volume alcohol consumption can affect your memory. But why some people are more vulnerable than others remains a bit of a mystery. Genetic factors can play an important role people from a few Native American tribes are so genetically sensitive to alcohol that they can lose control and become violent after only one or two drinks. Clearly, psychological and social influences are also important. More puzzling is alcohol's range of effects...

Social Isolation Leads to Stress and Memory Loss

Loss of loved ones, loneliness, lack of things to do after retirement, and health problems can be major sources of stress, particularly in older people, who may lose hope. As we all know, severe depression is common following the profound trauma of bereavement. What is less well known is that memory loss occurs during the grieving process. In my own experience, I had poor concentration with memory lapses for several weeks after my father's death. I lost track of what people told me at work and...

Long Term Efficacy Data Are Lacking But Safety Data Do Exist

Although I have emphasized that we do not have data about any medications on long-term prevention of memory loss, we do have safety data on long-term use for many of these medications. The vitamins can be taken on a daily basis for years, and so can estrogen in women, provided there is gynecological monitoring. Aricept has been prescribed for several years of continuous usage without major adverse events in Alzheimer's patients, and selegiline has been taken by many Parkinson's patients...

Estrogen in Long Term Prevention of Memory Loss

Clinical anecdotes and observations about the power of estrogen have been supported by the results from systematic studies, especially of elderly women living at home. In a report from the Baltimore Longitudinal Study on Normal Aging, 472 menopausal and postmenopausal women were followed for sixteen years. Women on estrogen-replacement therapy were 50 percent less likely to develop dementia. Other studies of women living in the community have also shown that estrogen provides a protective...

Actions of Piracetam and Related Nootropics

In animal studies, they increase glucose metabolism in nerve cells. In other animal studies, piracetam increased the number of acetylcholine receptors and the amount of acetylcholine released into synapses. In the laboratory, nootropics can boost memory in animals and reverse memory loss induced by toxic drugs. Piracetam may improve communication between the right and left halves of the brain. Since this informational transfer and integration may be linked to creativity, many artists and...

Hydergine The First FDAApproved Antidementia Medication

Hydergine is derived from ergot alkaloids (present in rye fungus) that are also used in antimigraine medications. The drug company Sandoz (now part of Novartis) began to study hydergine after it learned that ergot alkaloids were used by nontraditional practitioners to lower a pregnant mother's blood pressure during childbirth. Sandoz's goal was to use hydergine to lower blood pressure and the risk of stroke this didn't pan out, but they did manage to get it approved as a treatment for dementia....

Physiologic Actions of Phosphatidylserine

Phosphatidylserine is present in the membrane that surrounds each cell, and it can alter the fluidity and functional state of these cell membranes. Stabilizing cell membranes may shield the nerve cell from injury and death. Phosphatidylserine indirectly increases the production and release of several neurotransmitters, including epinephrine, norepinephrine, serotonin, and dopamine. These neurotransmitters, especially norepinephrine and dopamine, are known to improve attention, concentration,...

Rivastigmine Exelon

Rivastigmine (Exelon) received FDA approval to treat Alzheimer's disease in May 2000, and it is a cholinesterase inhibitor that is very similar to donepezil (Aricept) in its clinical effects. Rivastigmine is given in doses of 3 to 12 mg daily but has to be taken twice (morning and evening), unlike the once-a-day dose for donepezil. Rivastigmine's common side effects include stomach upset, headache, and fatigue. More research is needed to find out if Exelon possesses any significant advantages...

Donepezil Aricept to Treat Alzheimers Disease

In the double-blind study that provided the basis for obtaining FDA approval, outpatients with mild to moderate Alzheimer's disease were randomized to receive 10 mg donepezil daily (157 patients), 5 mg donepezil daily (154 patients), and placebo (162 patients). Both the 5 mg and 10 mg donepezil groups showed an average 3 to 8 percent advantage over placebo on cognitive performance and global clinical improvement. The peak effect occurred after six weeks on medication, and by six months the...

The Rise and Fall of Tacrine Cognex

As the largely negative clinical trials with choline, lecithin, and acetyl-l-carnitine demonstrate, promemory effects in rats or mice are not easy to replicate in people. Improving cognition in the primitive rodent brain is a lot simpler than boosting it in the ultracomplex human brain. As a matter of fact, by the mid 1980s, research with a variety of cholinergic compounds lecithin, choline, phosphatidylcholine, acetyl-l-carnitine, and physostigmine had run into a dead end, despite the...

Properties of Acetyllcarnitine Alcar

Is found in muscle and helps get energy out of fat. Can repair damage in lymphocytes, a type of white blood cell that is essential for normal immune function. Boosts metabolism within nerve cells, and slows the loss of nerve growth factor that helps maintain the functioning of nerve cells in the hippocampus and frontal cortex. In fact, acetyl-l-carnitine raises the levels of nerve growth factor by 30 to 40 percent in the brains of rats. Prevents the loss of acetylcholinesterase, thereby...

Choline

Choline is directly converted into acetylcholine by combining with acetic acid, and you might think that choline should work quite well as a memory enhancer. Unfortunately, although animal studies show that choline heightens attention and helps to transfer information from short to long-term memory, the clinical data are inconsistent and unimpressive. Several placebo-controlled trials to treat Alzheimer's disease have met with failure. Similar efforts with choline have not worked in people with...

Different Ways to Boost Acetylcholine

Cholinesterase inhibitors are compounds that inhibit the action of this enzyme, acetylcholinesterase. Treatment with cholinesterase inhibitors indirectly raises the level of acetylcholine by preventing its breakdown, thereby leading to improved attention, mental arousal, learning, and memory. In fact, cholinesterase inhibitors have now reached the forefront of treatment in Alzheimer's disease, and memory loss more broadly. If you step back for a moment and think about the issue, this indirect...

Role of Acetylcholine in Cognition

Increase in acetylcholine leads to improved attention, mental arousal, and memory. From age forty to ninety, the nucleus basalis of Meynert gradually and progressively loses up to half its cholinergic nerve cells. This loss of cholinergic nerve cells causes a delay in the brain's ability to process information quickly and accurately, which is why aging leads to slower reactions as well as to mild memory loss. In Alzheimer's disease, the nucleus basalis is nearly wiped out within a few years...

Science in Evolution The Cholinergic Story

In 1976, Peter Davies, who was examining autopsied brains of patients with Alzheimer's disease, reported the death of nerve cells that normally produced the neurotransmitter acetylcholine. Around the same time, David Drachman showed that administering scopolamine, which is an antagonist of acetylcholine, to normal people could produce memory impairment and other cognitive deficits that mimicked Alzheimer's disease. These discoveries began the race to develop an effective medication that could...

Donepezil Aricept for Mild Memory Loss

There are more and more people like Diane Pozniak who are taking donepezil (Aricept) for memory loss. Some, like Diane, have very mild symptoms that fall beneath most clinicians' scanning radar, while others have more clear-cut symptoms that can be called mild to moderate memory loss without dementia. After all, if donepezil is successful in improving memory in a condition like Alzheimer's that is horrendously difficult to treat, why shouldn't it work as well, or even better, for milder forms...

Prescribing Off Label Is Common

Donepezil (Aricept) is approved by the FDA for Alzheimer's disease, and not for the treatment of mild memory loss. So what on earth was I doing prescribing this medication to Diane Pozniak, who had very mild memory loss by any definition, someone who clearly did not have any signs of dementia or Alzheimer's disease The answer to this seemingly loaded question is quite straightforward. Although the FDA labels the use of a medication only for a specific disease or diseases, all licensed...

Dianes Story

Diane Pozniak, a fifty-four-year-old divorced woman, worked during the day and took classes at night with the goal of obtaining a business degree and advancing her career and financial situation. She was not doing well in her classes and felt that it was because her memory was not good. She feared that these memory lapses would make it impossible for her to pass the required courses to complete her degree. On the other hand, she had no problems functioning at her day job as an administrative...

Choosing Antioxidants to Prevent Memory Loss

The brain needs the same nutrients and vitamins as the rest of the body it just needs a lot more of them. There is evidence supporting the use of antioxidants like vitamin E, and to a lesser extent vitamins A and C. One or more of these essential vitamins is a must in any program to prevent memory loss. One note of caution these antioxidants are true long-term prevention agents and not quick-fix therapies. You will not see any immediate effects on your memory, and may not observe any change for...

Vitamin C The Essential Acid

Vitamin C (ascorbic acid) is essential for the nervous system, and is concentrated a hundred times more in the cerebrospinal fluid compared to other body fluids. Vitamin C is a strong antioxidant. In earlier times, sailors on long voyages deprived of citrus fruits (vitamin C) developed scurvy, a condition causing decay of skin and teeth. Older people who stop eating vitamin C-rich citrus fruits and vegetables may develop memory loss and mild confusion. At the opposite end of the age spectrum,...

Vitamin A

Vitamin A is essential for normal functioning of the retina, and its deficiency causes night blindness, which used to be fairly common until the latter half of the twentieth century. Beta-carotene is converted by the body's natural enzymes into vitamin A, and eating beta-carotene-rich foods like carrots prevents vitamin A deficiency. Both beta-carotene and vitamin A are antioxidants and free-radical scavengers, and many people take them regularly as antiaging medications. However, unlike...

Selegilines Promemory Actions

Inhibition of the enzyme monoamine oxidase-B, which in turn leads to a reduction in the formation of toxic free radicals. Stimulation of superoxide dismutase, a powerful naturally occurring enzyme in the body that also destroys free radicals. This dual antioxidant action likely underlies selegiline's action in delaying functional decline in Alzheimer's disease. Giving selegiline to mice leads to a higher density of nerve fibers in the frontal cortex and hippocampus. Mice given selegiline at...

The Antioxidant Selegiline or Deprenyl

Jozsef Knoll, a Hungarian university professor, developed selegiline as an antidepressant medication in the 1950s. Its antidepressant action is related to its ability to inhibit the enzyme monoamine oxidase-B (MAO-B), thereby raising the brain level of monoamines, which function as neurotransmitters. These monoamines include dopamine, which is needed for normal muscle control, sex drive, cognition, and novelty seeking or adventurous behavior. Based on its actions on the brain's dopamine system,...

Take Vitamin E to Prevent Memory Loss

Vitamin E is present in high-fat (but luckily, low-saturated fat) foods like vegetable oils, germs, nuts, and seeds. It is impossible for you to get more than 200 IUs daily through diet alone. Since vitamin E-rich foods can only go so far, you should take 400 to 800 IUs of vitamin E daily as a promemory (and antiaging, more broadly) dose, with 1,200 units for those among you who are more adventurous. Higher doses of vitamin E can cause headache, raise blood pressure, and increase the risk of...

Vitamin E for Memory Loss

In the Introduction, I described the story of David Finestone, a forty-nine-year-old man whose memory loss for names was probably caused by a small stroke. His treatment regimen consisted of cutting down on saturated fats, eating more fresh fruits and vegetables, taking an aspirin a day for its anticoagulant effects to prevent further strokes, and ingesting a capsule of 800 IUs of vitamin E daily. At that time, the antioxidant and antiaging properties of vitamin E were well known, but there...

How Vitamin E Works

Vitamin E is a free-radical scavenger that destroys toxic free radicals like bad oxygen and hydrogen peroxide these antioxidant properties may benefit patients with Alzheimer's disease and protect against memory loss due to the aging process. The anticoagulant properties of vitamin E, which distinguish it from the other antioxidant vitamins A and C, may help protect against stroke. In laboratory experiments, exposing brain cells to vitamin E limits the number of cells damaged by glutamate, a...

Vitamin E

A few years ago, a visiting speaker at our weekly departmental presentation praised the virtues of vitamin E as a potential treatment for several neurologic and psychiatric disorders, and as a general antiaging therapy. At the end of his talk, Dr. Jack Gorman, one of my colleagues who likes to occupy the front row, rose to his full height of six feet three inches and asked the speaker how much vitamin E he took daily. The speaker turned the question around and asked Jack how much he took daily....

Alternative Medications Facts

Among the current alternative medications, only ginkgo biloba has established cognitive-enhancing properties, though its effect is small in magnitude. You should consider taking 120 mg daily of EGb 761 (ginkgo biloba) as one of the medications in your memory program. More solid clinical evidence about the promemory properties of ginseng, melatonin, and other alternative agents is needed before they can be recommended for regular use. Phosphatidylserine (PS) is sold in health food stores. Some...

Melatonin

Melatonin is a naturally occurring hormone that is formed mainly in the pineal gland. The pineal gland is the size of a small capsule and sits in the lower middle part of the brain. Descartes called the pineal gland the seat of the soul, but we now think of it merely as the source of melatonin, which regulates sleep and is involved in immune processes. Melatonin release from the pineal gland has a predictable twenty-four-hour cycle an increase in the evening is associated with drowsiness and...

Ginsengs Actions in the Brain

Ginseng seems to increase mental alertness and then maintain it in a relatively steady state, thereby smoothing out the ups and downs of the stress response. Pharmacologically, ginseng may stimulate the production of epinephrine, which helps to indirectly suppress stress-induced release of cortisol and related steroids that may damage hippocampal nerve cells. Ginseng seems to boost cholinergic neurotransmission in the brain. Given the link between loss of cholinergic nerve cells and memory...

Promemory Actions of Ginkgo

Leaf extracts improve the ability of mice to remember newly learned behavior. In animal studies, enhances recovery from injury to the frontal lobes. In animal studies, acts against the memory deficits associated with aging. In a few clinical studies, slows memory decline in dementia. In healthy young adults, speeds up reaction time in stimulus-response tests, improving alertness. Anticoagulant properties may protect against stroke (and hence indirectly against memory loss). Antioxidant effects...

Ginkgo Biloba

Ginkgo biloba is taken by millions of people. As with many other organic plant extracts, anecdotal health claims abound for ginkgo. Many people think of it as a general tonic and consider memory enhancement as a sidelight. Others call it a fad that they wouldn't touch with a pole of any size. But what are the facts What do we really know about ginkgo biloba Ginkgo contains many organic substances, which include flavonoids, terpenoids such as ginkgolides and bilobalide, and several acids. These...

The Major Alternative Systems of Medicine

Ayurveda is a complex system described in ancient Hindu religious and medical texts, detailing the use of literally hundreds of natural substances as medicines. Unani is a system of medicine developed centuries ago in Arabia and Persia, which later mingled with local influences in the Indian subcontinent. Its popularity has dwindled over time. Chinese medicines include a variety of plants and their extracts to treat both symptoms and diseases. Many of them are meant to promote health and block...

The Roots of Ayurveda

During my medical school years, I read some of the Ayurvedic texts, translated from Sanskrit into English, that described a wide range of therapies herbs and plant extracts, metals, and bloodletting for various maladies. The vedas, among which Ayurveda is only a small component, were both the Encyclopaedia Britannica and the Bible of ancient Indian civilization. They were rooted in religion but con tained a great deal of practical information and advice for everyday living. A number of...

Global Trade Practices

Many developing countries like India and china refuse to grant meaningful patent protection to drug companies because it is likely to raise the cost of prescription medications to levels far above the average person's ability to pay for them. Currently, the pharmaceutical industry in these and most developing countries consists mainly of chemical companies that copy and manufacture new medications developed by large multinational drug companies in the United States, Europe, and Japan. Only when...

BR16A Travails of a Promemory Ayurvedic Preparation

Chittaranjan Andrade, has studied an Ayurvedic preparation that now goes by its modern name, BR-16A. In controlled animal experiments, he showed that BR-16A improved learning and reversed short-term memory deficits in mice. But when he approached the four manufacturers of BR-16A in India, none of them were willing to fund further basic research to find out which of the twenty or more ingredients in the substance was responsible for improving memory. They also...

Alternative Remedies

For twenty-three years, my father suffered from Parkinson's disease, a chronic, disabling brain disorder to which he eventually succumbed. Muhammad Ali, Janet Reno, and Michael J. Fox are among the prominent people who suffer from this illness. Parkinson's disease is caused by a deficiency of the neurotransmitter dopamine. The most widely used western or allopathic treatment, Sinemet, is a combination of levodopa and carbidopa that works by increasing dopamine levels within the brain. This is...

Taking Medications to Improve Memory What to Ask Your Doctor

Why am I taking this particular medication How does this medication work on my memory How much improvement can I reasonably expect Does it interfere with any other medicines I am taking Is the medicine addictive in any way Can I drink alcohol while taking it Is there any risk in stopping it for a few days at a time Most studies of treatments for mild memory loss have evaluated people over a few months or at most a year or two. If there is a slight improvement in memory functioning, will this...

FDA Does Not Approve Medications to Prevent Age Related Memory Loss

The FDA does not recognize age-related memory loss to be an illness and is hence unwilling to approve any medication to prevent or treat this condition. This attitude has worked against research development efforts for both pharmaceutical agents and alternative remedies, because no company will invest tens of millions of dollars in clinical research on a compound or natural substance if at the end of this effort there is no hope of regulatory approval. This situation has led to most studies of...

Many Natural or Alternative Remedies Are Also Medicines

Robert's most striking feature was that he did not consider ginkgo, ginseng, saw palmetto, or melatonin to be medicines. And because these were natural substances that he obtained in a health food store, he was willing to spend a fair amount of money on them despite his financial difficulties. Many people do not count alternative remedies, or substances that occur naturally and are marketed for their health effects, as medicines. The reality is that many of these products do contain active...

Dont Take Any Medications Roberts Story

Robert Molson, a fifty-six-year-old man living in Greenwich Village, came to see me, stating that his memory had begun to decline, he was forgetting names more easily, and he was misplacing things more often. He was afraid he was getting Alzheimer's disease. He worked as a paralegal and hadn't yet run into problems at work, but he did point out that nothing short of a disastrous performance on his part would even be noticed in the New York City court system. He also had financial problems that...

Small Catch The Practice Effect

As discussed in the Preface, in evaluating treatments for memory loss, a unique factor absolutely mandates a placebo-controlled trial. This is called the practice effect. When you first try to complete neuropsychological tests, which include the tests of memory described in chapter 1, some parts seem difficult. The next time you do the same tests, you are likely to perform better, even on those tests that seemed hard to do the first time. This is the practice effect, which means that repeated...

Current Research Priorities

Making an early diagnosis and finding a treatment with robust effects are among the current research priorities in this field. If you already suffer from mild memory loss that continues to worsen even after you adopt the memory-enhancing strategies described in this book, I recommend physician consultation to make sure that you are not suffering from early dementia, whether it be Alzheimer's or a less common type. Medications That Prevent and Treat Memory

Frontotemporal Dementia

Frontal or frontotemporal dementia is a less common subtype. Earlier, all such cases were thought to have Pick's bodies, a specific type of microscopic abnormality, but many cases of frontotemporal dementia do not show this lesion. The clinical features overlap with those of Alzheimer's disease, but ''frontal lobe disinhibition signs are more prominent overeating, sleeping excessively, hypersexuality, motor agitation, and impulsive and unpredictable behavior. Following damage to the temporal...

Other Dementias

After Alzheimer's disease, the second most common form of dementia is vascular dementia, which is a direct result of multiple strokes destroying large portions of brain tissue (discussed in chapter 12). Diffuse Lewy body disease is a diagnosis that has gained in popularity in the 1990s. Lewy bodies are microscopic structures present in the brains of patients with Parkinson's disease. At least one-third of Alzheimer's patients also have clinical features of Parkinson's disease tremor, slow...

Potential Therapies

Caring for and treating patients with Alzheimer's disease costs over 100 billion annually in the United States alone. The introduction of FDA-approved cholinesterase inhibitors for treatment, and their potential utility in treating memory loss due to the aging process, has given rise to new hope that we are on the way to meaningful therapies for this terrible illness. There are suggestions that vitamin E, ginkgo biloba, estrogens, and anti-inflammatory agents may slow the progression of...

What If Memory Loss Persists after Depression Improves

In some people with both depression and memory loss, the memory deficit may not improve even after the depression is successfully treated. In such a situation, the memory loss that accompanies depression may be the first sign of Alzheimer's disease. We showed this in a community study of elderly subjects, where the presence of depression conferred a threefold increased risk of developing Alzheimer's disease during a follow-up period of up to five years. George Alexopoulos's research group at...

When Did Ronald Reagans Alzheimers Begin

During a deposition in 1990, President Ronald Reagan could not recall the name of the chairman of the Joint Chiefs of Staff. We now know that he went on to develop Alzheimer's disease. Did he already have the disease at that time, or perhaps even earlier While we will never know the answer definitively, his experience illustrates how Alzheimer's disease often starts. In Reagan's case it began with forgetting names, a common symptom of age-related memory loss. This is classic for Alzheimer's...

Evaluate Your Memory

A good storyteller is a person who has a good memory, and hopes other people haven't. Woody Allen once said that the brain was his second favorite organ. While the brain may indeed be the number two choice for many of us, it is by far our most important organ, and memory is one of its most critical functions. In this part of the book, you will learn how to assess your memory and determine whether it is normal or abnormal. You will also learn about the basic processes underlying memory formation...

The Memory Program

This comprehensive Memory Program has three major steps, each involving several components Step 1. Identifying and treating specific, reversible causes of memory loss Step 2. General measures to protect against memory loss that include a healthy diet, physical exercise, and memory training Step 3. Medication strategies to maintain and improve your memory. I will first describe the Memory Program in its entirety, and then individualize the program by focusing on subcategories of people, based on...

Your Future Memory Program

The long-standing defeatism about preventing and treating memory loss has now given way to a feeling of growing excitement that we will soon have the keys to the memory kingdom. But we have just scratched the surface, and new knowledge will eventually render obsolete our current repertoire of preventive and treatment strategies, including some of the components in the Memory Program. Several potential therapies for age-related memory loss are still in the development stage. These include a new...

Early Diagnostic Tests for Alzheimers Disease

After neurological and psychiatric evaluation, neuropsychological testing is essential. 2. Reduced ability to discriminate among smells odors . 3. Hippocampal and parahippocampal atrophy on MRI scan. 4. Temporoparietal blood flow and metabolism deficits on SPECT or PET. 5. Decreased A-Beta protein amyloid and increased tau protein levels in the cerebrospinal fluid. 6. Presence of apolipoprotein E e4 genotype. I will cover each of these in more detail. Neuropsychological Cognitive Testing...

Physostigmine

Studies with the cholinesterase inhibitor physostigmine in small numbers of Alzheimer's patients, some of which were conducted by my colleagues Drs. Yaakov Stern and Richard Mayeux, showed superior memory test performance compared to placebo. The size of the improvement was comparable to what would be shown years later with tacrine and donepezil, but physostigmine never succeeded in the same fashion for two main reasons the very short duration of action meant that pills needed to be given five...

Alzheimers Disease Memory Disorders Centers

These centers are funded by the National Institute of Aging part of the NIH and focus on research and clinical services for patients with Alzheimer's disease www.alzheimers.org , but in recent years they have expanded their efforts to patients with mild to moderate memory loss. If you suffer from mild to moderate memory loss, and wish to seek expert physician consultation, it is worth going to a center that is in your geographic region. The clinicians and researchers in these centers the name...

Biblography On Memory Loss

L., Grady, C. L., Pietrini, P., Brady, D. R., Mentis, M. J., Schapiro, M. B. Association of premorbid intellectual function with cerebral metabolism in Alzheimer's disease implications for the cognitive reserve hypothesis. American Journal of Psychiatry 154 165-172, 1997. Alexopoulos, G. S., Meyers, B. S., Young, R. C., Mattis, S., Kakuma, T. The course of geriatric depression with reversible dementia a controlled study. American Journal of Psychiatry 150 1693-1699,...

Lecithin

Lecithin is an essential ingredient of living cells. It prevents cholesterol accumulation in arteries, and helps prevent liver degeneration. Phosphatidylcholine is the active element in lecithin that works against memory loss. Phosphatidylcholine is broken down to choline, which the body then uses to synthesize Lecithin has a prolonged duration of action and needs to be taken only once or twice a day. Like choline, in more than a dozen controlled studies of Alzheimer's patients, lecithin's...

How Your Brain Remembersand Forgets

Memory Modulation Human Brain

Memory storage in the brain is not like a videotape that we can wind or unwind at will. New learning, old information, and the links between them are constantly formed and destroyed in a dynamic process. Memory can be classified into implicit and explicit categories. When you open your car door, turn on the ignition, and start driving, do you actually make a conscious effort to remember how to perform this sequence of actions Of course not. The memory of how to drive a car is already hardwired...