Alzheimer\'s Disease, Non-Alzheimer\'s Dementia, and Normal Age-Related Memory Loss

Most people over the age of 40 experience some ordinary age-related memory loss, technically known as Age-Related Cognitive Decline (ARCD) or Age-Associated Memory Impairment (AAMI). We dont know what causes this normal experience, and there is no conventional treatment available to treat it. As we shall see in this section, there are a few natural treatments that might be helpful.
Alzheimers disease is much more serious than ordinary forgetfulness. It leads to severe mental deterioration (dementia) in the elderly. It has been estimated that 30 to 50% of people over 85 years old suffer from this disease.
Microscopic examination shows that nerve cells in the thinking parts of the brain have died and disappeared, particularly cells that release a chemical called acetylcholine. However, we do not know exactly what causes Alzheimers disease.
Alzheimers begins with subtle symptoms, such as loss of memory for names and recent events. It progresses from difficulty learning new information, to a few eccentric behaviors, to depression, loss of spontaneity, and anxiety. Over the course of the disease, the individual gradually loses the ability to carry out the activities of everyday life. Disorientation, asking questions repeatedly, and an inability to recognize friends are characteristics of moderately severe Alzheimers. Eventually, virtually all mental functions fail.
Similar symptoms may be caused by conditions other than Alzheimers disease, such as multiple small strokes (called multi-infarct, or vascular dementia), alcoholism, and certain rarer causes. It is very important to begin with an examination to discover what is causing the symptoms of mental decline. Various easily treatable conditions, such as depression, can mimic the symptoms of dementia.
Once the diagnosis of Alzheimers or non-Alzheimers dementia has been made, treatment may begin with drugs such as Cognex or Aricept. These medications usually produce a modest improvement in mild to moderate Alzheimers disease by increasing the duration of action of acetylcholine. However, they can cause sometimes severe side effects due to the exaggeration of acetylcholines action in other parts of the body.

Treatments

Principal Proposed Treatments:
There are two natural treatments for Alzheimers disease with significant scientific evidence behind them: ginkgo and phosphatidylserine. Huperzine A and vinpocetine, while not technically natural substances, may also improve mental function. There is growing evidence that ginkgo and possibly phosphatidylserine might be helpful for normal age-related memory loss as well.
Acetyl-L-carnitine was once considered a promising option for improving mental function, but current evidence suggests that it does not work.
Ginkgo;
The most well-established herbal treatment for Alzheimers disease (and, indeed, one of the few herbs that probably deserves the description \\\"proven effective\\\") is the ancient herb Ginkgo biloba. Ginkgo, the oldest surviving species of tree, has been traced back 300 million years. Although it died out in Europe during the Ice Age, ginkgo survived in China, Japan, and other parts of East Asia. It has been cultivated extensively for both ceremonial and medical purposes, and some especially revered trees have been lovingly tended for over a 1,000 years. Asian herbalists used ginkgo seeds to treat asthma and other conditions.
In Europe, researchers focused on ginkgo leaf, using standardized extracts of it rather than the whole herb. By 1995, ginkgo leaf extract had become the most widely prescribed herb in Germany. Today, German family physicians generally favor it above all drug treatments for dementia.
Ginkgo may also be helpful for normal age-related memory loss, and improving mental function in younger people, but the supporting evidence is much weaker.
Alzheimer’s Disease and Non-Alzheimer’s Dementia;
According to a 1992 article published in Lancet, over 40 double-blind, controlled trials had at that time evaluated the benefits of ginkgo in treating various forms of dementia. Of these, eight were rated of good quality, involving a total of about 1,000 people and producing positive results in all but one study. The authors of the Lancet article felt that the evidence was strong enough to conclude that ginkgo extract is an effective treatment for this condition.
Most studies reported since 1992 have supported this conclusion, including a large US study published in the Journal of the American Medical Association. The US trial enrolled more than 300 individuals with Alzheimer’s disease or non-Alzheimer’s dementia. Participants were given either 40 mg of ginkgo biloba extract or placebo 3 times daily. The results showed significant (but far from dramatic) improvements in the treated group.
One fairly large study of ginkgo extract found no benefit. This 24-week, double-blind, placebo-controlled study of 214 individuals with either mild to moderate dementia or ordinary age-associated memory loss found no effect with ginkgo extract at a dose of 240 or 160 mg daily. However, this study has been sharply criticized for a number of serious flaws in its design.
Ordinary Age-Related Memory Loss;
Ginkgo has also been studied for milder forms of memory loss, such as the relatively slight decline in cognitive function that typically goes along with increased age. In six out of eight double-blind studies, use of ginkgo biloba extract significantly improved mental function compared to placebo.
For example, in a double-blind, placebo-controlled trial, 241 seniors complaining of mildly impaired memory were given either placebo or ginkgo for 24 weeks. The results showed that ginkgo produced modest improvements in certain types of memory.
Another double-blind, placebo-controlled trial examined the effects of ginkgo extract in 40 men and women (ages 55 to 86) who did not suffer from any mental impairment. Over a 6-week period, the results showed improvements in measurements of mental function.
Benefits were seen in four other trials as well, involving a total of about 135 individuals.
Set against these positive findings is the 24-week study mentioned above, which found no benefit in ordinary age-related memory loss. The reason for this negative outcome may be flaws in this trial’s design. However, another study failed to find benefit as well. This 6 week trial of 230 healthy individuals over age 60 found that 120 mg of ginkgo biloba extract daily produced no significant improvement in mental function.
Besides these negative trials, there is another weakness in the evidence. Those studies that did find benefits with ginkgo reported improvements in certain aspects of memory but not in others, and the pattern was not consistent between trials. This tends to decrease the confidence one can place in these apparently positive outcomes; if ginkgo is really working, its effects on memory should theoretically be more reproducible.
Improving Memory and Mental Function in Younger People;
Growing (but still highly preliminary) evidence suggests that ginkgo might improve memory and mental function in young people.
For example, a 30-day double-blind, placebo-controlled trial of 50 healthy men and women ranging in age from 18-40 years (average 30.4 years) evaluated the effects of 120mg of gingko extract daily. The results showed significant improvements in some measures of memory function.
Benefits were seen in two other small trials as well. However, a double-blind, placebo-controlled trial of 12 women aged 19 to 30 years failed to find benefit.
Another study looked at the effects of ginkgo combined with ginseng. This 3-month double-blind placebo-controlled trial evaluated various doses of the two herbs combined in 64 individuals complaining of neurasthenia (fatigue and tiredness). The highest dose worked the best. Participants given 200 mg of Panax ginseng and 120 mg of ginkgo daily showed improvements in memory and other aspects of mental function. Strangely, however, this effect appeared to be temporary. Several hours after the dose, memory and mental function actually worsened compared to those given placebo. Researchers speculate that there may be a \\\"payback\\\" for temporarily increased mental function caused by this combination treatment. However, more research is necessary to determine whether this hypothesis has any validity.
How Does Ginkgo Work?
In the past, scientists believed that dementia was caused by a reduced blood and oxygen supply to the brain. Because ginkgo appears to improve circulation (as described in the article on intermittent claudication), European physicians assumed that ginkgo was simply getting more blood to brain cells and thereby making them work better. However, advances in the understanding of age-related mental decline have led scientists to move away from this theory. Ginkgo is now believed to function by directly stimulating nerve cell activity and protecting nerve cells from further injury.
For more information, including dosage and safety issues, see the full ginkgo article.
Phosphatidylserine
Like ginkgo, the supplement phosphatidylserine (PS) is widely used in Europe to treat various forms of dementia as well as normal age-related memory loss. Phosphatidylserine is one of the many substances involved in the structure and maintenance of cell membranes. While it is tempting to speculate that phosphatidylserine works by strengthening nerve cells against damage, we really dont know how this supplement works.
Overall, the evidence for PS in dementia is quite encouraging. Double-blind studies involving a total of over 1,000 people suggest that phosphatidylserine (at least the older type made from a cows brain - see Phosphatidlyserine article for discussion) is an effective treatment for Alzheimers disease and other forms of dementia.
The largest of these studies followed 494 elderly subjects in northeastern Italy over a course of 6 months. All suffered from moderate to severe mental decline, as measured by standard tests. Treatment consisted of either 300 mg daily of PS or placebo. The group that took PS did significantly better in both behavior and mental function than the placebo group. Symptoms of depression also improved.
These results agree with those of numerous smaller double-blind studies involving a total of over 500 people with Alzheimers and other types of age-related dementia.
There is some evidence that PS can also help people with ordinary age-related memory loss. In one double-blind study that enrolled 149 individuals with memory loss but not dementia, phosphatidylserine provided significant benefits as compared with placebo. Individuals with the most severe memory loss showed the most improvement.
However, another double blind trial of 120 older individuals with memory complaints but not dementia found no benefits.126 This discrepancy may have to do with the type of phosphatidylserine used – the second trial used the more modern soy-derived form of the supplement.
For more information, including dosage and safety issues, see the full phosphatidylserine article.
Huperzine A
Huperzine A is an extremely potent chemical derived from a particular type of club moss (Huperzia serrata [Thumb] Trev.). Like caffeine and cocaine, huperzine A is a medicinally active, plant-derived chemical that belongs to the class known as alkaloids. It was first isolated in 1948 by Chinese scientists. This substance is really more a drug than an herb, but it is sold over the counter as a dietary supplement for memory loss and mental impairment.
Many experiments have found that huperzine A can improve memory skills in aged animals as well as in younger animals whose memories have been deliberately impaired.
According to three Chinese double-blind trials enrolling a total of more than 450 individuals, use of huperzine A can significantly improve symptoms of Alzheimer’s disease and other forms of dementia. One double-blind trial failed to find evidence of benefit, but it was relatively small.
Huperzine may also be helpful for improving memory in healthy individuals, although the evidence appears to be limited to one small, poorly designed trial.
Huperzine A inhibits the enzyme acetylcholinesterase. This enzyme breaks down acetylcholine, which seems to play an important role in mental function. When the enzyme that breaks it down is inhibited, acetylcholine levels in the brain tend to rise. Drugs that inhibit acetylcholinesterase (such as tacrine and donepezil) seem to improve memory and mental functioning in people with Alzheimers and other severe conditions. The research on huperzine A indicates that it works in much the same way.
The chemical action of huperzine A is very precise and specific. It \\\"fits\\\" into a niche on the enzyme where acetylcholine is supposed to attach. Because huperzine A is in the way, the enzyme cant grab and destroy acetylcholine. This mechanism has been demonstrated by considerable scientific work, including sophisticated computer modeling of the shape of the molecule.
Although it originally comes from a plant, huperzine A is highly purified in a laboratory and is just a single chemical. It is just not much like an herb. Herbs contain hundreds or thousands of chemicals. In this way, huperzine A resembles drugs such as digoxin, codeine, Sudafed, and vincristine (a chemotherapy drug), which are also highly purified chemicals taken from plants. If we wish to call huperzine A a natural treatment, we need to call these (and dozens of other standard drugs) natural as well.
For more information, including dosage and safety issues, see the full huperzine A article.
Vinpocetine
Vinpocetine is a chemical derived from vincamine, a constituent found in the leaves of common periwinkle (Vinca minor L.) as well as the seeds of various African plants. It is used as a treatment for memory loss and mental impairment.
Developed in Hungary over 20 years ago, vinpocetine is sold in Europe as a drug under the name Cavinton. In the United States it is available as a \\\"dietary supplement,\\\" although the substance probably doesnt fit that category by any rational definition. Vinpocetine doesnt exist to any significant extent in nature. Producing it requires significant chemical work performed in the laboratory.
Several studies indicate that vinpocetine can enhance memory and mental function in those with Alzheimers disease and related conditions.
For example, a 16-week double-blind placebo-controlled trial of 203 individuals with mild to moderate dementia found significant benefit in the treated group. Benefits have been seen in other studies as well.
It has been hypothesized that vinpocetine works by increasing blood flow to the brain and safeguarding brain cells against damage caused by lack of oxygen.
For more information, including dosage and safety issues, see the full vinpocetine article.
Acetyl-L-Carnitine
Carnitine is a vitamin-like substance that is often used for angina, congestive heart failure, and other heart conditions. A special form of carnitine, acetyl-L-carnitine has been extensively tested for the treatment of dementia: double- or single-blind studies involving a total of more than 1,400 people have been reported. However, while early studies found evidence of modest benefit, two large and well-designed studies failed to find acetyl-L-carnitine effective at all.
The first of these was a double-blind placebo-controlled trial that enrolled 431 participants for 1 year. Overall, acetyl-L-carnitine proved no better than placebo. However, because a close look at the data indicated that the supplement might help individuals who develop Alzheimers disease at an unusually young age, researchers performed a follow-up trial. This 1-year double-blind placebo-controlled trial evaluated acetyl-L-carnitine in 229 patients with early onset Alzheimers. Unfortunately, no benefits were seen here either.
For more information, including dosage and safety issues, see the full carnitine article.
Other Proposed Treatments: Ginseng may improve various aspects of mental function other than memory.
Mild vitamin B12 deficiency may impair mental function. Because such deficiency is relatively common in the elderly, B12 supplements may be appropriate.
Preliminary evidence suggests that vitamin E at the high dosage of 2,000 IU (dl-alpha-tocopherol) daily may slow the progression of Alzheimers disease. A physicians supervision is essential when taking this much vitamin E due to potential risks of bleeding complications. For other dosage and safety issues, see the full vitamin E article.
Preliminary double-blind trials suggest that the amino acid tyrosine may improve memory and mental function under conditions of sleep deprivation or other forms of stress.
An observational study suggests that regular use of vitamin E and vitamin C supplements might help prevent vascular dementia, but not Alzheimers disease. Another study suggests that a diet high in vegetables as well as vitamins E and C from food sources may help prevent Alzheimers disease and other forms of dementia.
DMAE inositol, magnesium, NADH, pregnenolone, vitamin B1, zinc, and bee pollen have also been suggested as treatments for Alzheimers disease. However, as yet there is no real scientific evidence to confirm or deny their effectiveness.
Some reports suggested that declining DHEA levels cause impaired mental function in the elderly. However, large studies have not found a connection between the two.
The related substances choline, phosphatidylcholine, and lecithin have been studied quite extensively in individuals with Alzheimers disease and other conditions involving the brain. The impetus for this research is the fact that an important neurotransmitter, acetylcholine, is made from choline. However, several studies, some of them double-blind, have not found any benefit from taking these supplements for Alzheimers disease.
Very preliminary evidence suggests that N-acetylcysteine might be helpful for slowing the progression of Alzheimers disease.
A double-blind, placebo-controlled trial of 76 individuals tested the potential memory-enhancing benefits of the herb brahmi (Bacopa monniera), but failed to find evidence of benefit.