Memory Enhancement and Cognitive Function
Jim English
The human brain is the most elegant —and
complex—structure ever devised. Comprising some ten billion
neurons and supportive cells, no other organized
structure—organic or silicon— can begin to match the sheer
complexity and processing power of the human brain. It regulates
virtually all life systems while simultaneously generating the
thoughts, dreams and feelings that define us and shape our
perception of reality. Every thought, concept, opinion, belief
and emotion arises from the untold millions of chemical and
electrical reactions that occur in the brain every second. And
to power all of this activity the brain places a huge demand on
the body’s energy reserves. Though it accounts for a mere two
percent of body’s weight, the brain greedily consumes more than
twenty percent of the body’s available energy in the form of
oxygen and glucose.
The Aging Brain
Time takes a terrible toll on the human brain. Many tissues,
such as the skin and liver cells, have the capacity to
regenerate, but this trait is not shared
by brain cells— once a brain cell is lost, it is gone forever.
By age seventy most people lose ten percent of their original
brain cells to the effects of “normal” aging. This continual
loss of brain cells is further aggravated by damage from other
age-related conditions, such as hypertension, arteriosclerosis
(hardening of the arteries), diabetes, and cerebrovascular
diseases (CVD) such as cerebrovascular insufficiency, strokes
and multi-infarct dementia (MID).
Dementia
Dementia is defined as the loss of cognitive or intellectual
functions. Unlike occasional forgetfulness, dementia is marked
by a profound impairment of memory as well as the loss of
additional, complex abilities required for problem-solving,
decision making, spatial orientation, and even the ability to
put simple words together to communicate. Dementia is a
permanent, progressive disease that mostly affects the elderly,
who, over time may lose the ability to function normally and
require round-the-clock care. It is estimated that up to 8
percent of all people over 65 suffer from some form of dementia,
and that the number of cases doubles with every additional five
years, leading to the estimate that anywhere from 20 percent to
50 percent of people in their 80s suffer from dementia. There
are close to fifty different causes of dementia, including
neurological disorders (Alzheimer’s disease), vascular disorders
(multi-infarct disease), inherited disorders (Huntington’s
disease), and infections (viruses such as HIV).
A common factor shared by all of these disorders is the
reduction in the flow of blood and oxygen to the brain. Reduced
blood flow, aside from starving brain cells of needed fuel, also
increases the production of free radicals that further damage
cell membranes and accelerate brain cell death. As the number of
lost brain cells grows—from the ravages of age or the
debilitating effects of degenerative diseases such as
Alzheimer’s—mental deterioration continues. Memories begin to
fade and the ability to form new thoughts and solve problems is
further reduced. Depression, incontinence, disorientation,
speech disturbances, tremor, muscle weakness, tinnitus (ringing
in the ears), and loss of both visual acuity and coordination
also increase as the conditions progress.
Alzheimer’s Disease
Alzheimer’s disease (also called “senile dementia of the
Alzheimer type”) is a chronic and progressive degenerative
neurological condition. Alzheimer’s currently afflicts over four
million people in the United States, and accounts for up to 60
percent of all cases of dementia. Alzheimer’s commonly appears
after age fifty, and from age sixty-five on, the risk of
developing the disease doubles with every additional five years
of age. As if these numbers weren’t bad enough, they are
expected to almost double in the coming
decades, placing a further drain on health care resources, and
leaving almost no family untouched.
While there is currently no cure for Alzheimer’s disease,
exciting new research shows that several nutrients may help to
halt the destructive progression of dementia and improve
cognitive function of patients suffering from Alzheimer’s and
other forms of dementia.
Hope for Aging Brains
While medical researchers and pharmaceutical companies race to
patent new (and profitable) treatments for Alzheimer’s and other
degenerative brain conditions, a number of existing nutritional
compounds have already been proven to safely support healthy
brain function while protecting and prolonging cognitive
ability. Supported by numerous double-blind controlled trials in
Europe and the US, these supplements can slow down the
age-related loss of higher-level cognitive functions that can
appear in healthy individuals as young as fifty years of age.
Huperzine
Alzheimer’s is characterized by the destruction of nerve cells
in key areas of the brain devoted to higher mental function.
Most noticeable is the loss of presynaptic cholinergic neurons
that results in a dramatic decrease in brain levels of
acetylcholine, a neurotransmitter involved in memory and
intracellular communication. Research has shown that levels of
acetylcholine are deficient in the brains of patients with
Alzheimer’s disease, and what little acetylcholine is produced
is quickly broken down by the enzyme, acetylcholinesterase (AchE),
contributing to the loss of memory and other cognitive
functions.
Huperzine is a nutritional supplement that readily crosses the
blood-brain barrier to prevent acetylcholinesterase (AchE) from
destroying acetylcholine. By inhibiting AChE and increasing
acetylcholine concentrations in the brain, Huperzine A has been
shown to be effective in alleviating some of the symptoms
associated with acetylcholine deficiencies.
Researchers have demonstrated that patients suffering from
Alzheimer’s and various other memory disorders gain significant
benefit from huperzine, both in terms of memory and life
quality. In one study, researchers found that 58 percent of
Alzheimer’s patients experience significant improvement in both
cognitive and memory function when given 200 mg of Huperzine per
day. Huperzine’s memory-enhancing properties suggest that it may
be an effective agent for improving memory and learning in
healthy humans as well. These findings suggest that Huperzine
not only protects from the effects of Alzheimer’s and senile
memory deficits, but also provides a unique and exciting
supplement for supporting memory in the healthy aging human as
well.
Vinpocetine
Vinpocetine is a powerful memory-enhancing nutrient that
facilitates cerebral metabolism by improving cerebral
microcirculation, stepping up brain cell ATP production, and
increasing utilization of glucose and oxygen. Vinpocetine also
selectively increases blood flow to the brain, particularly to
impaired areas, without affecting blood flow to the rest of the
body.
Because of its selective effects on improving cerebral
circulation, vinpocetine is often used for the treatment of
cerebral circulatory disorders such as memory problems, acute
stroke, aphasia (loss of the power of expression), apraxia
(inability to coordinate movements), motor disorders, dizziness
and other cerebrovestibular (inner-ear) problems, and headache.
In studies involving 882 patients with neurological disorders
ranging from stroke to cerebral insufficiency, vinpocetine was
found to confer significant improvements in 62 percent of the
patients. In one of the studies, cerebral insufficiency patients
were asked to memorize a list of ten words. Without vinpocetine
the subjects were able to memorize an average of six words.
After a month of treatment the average went up to ten words.
Reactive oxygen species (ROS) are believed to play a crucial
role in the neuronal damage occurring in ischemic injury
(stroke) and neurodegenerative disorders. In studies designed to
examine the antioxidant effects of vinpocetine to prevent the
formation of ROS and lipid peroxidation in brain synaptosomes,
researchers found that vinpocetine significantly decreased
oxidative stress and inhibited ROS formation up to 83 percent.
The researchers concluded that the antioxidant effects of
vinpocetine contributed to reducing neuronal damage in
pathological situations.
Pyroglutamate
Pyroglutamate (2-oxo-pyrrolidone carboxylic acid, or PCA) is an
amino acid found in vegetables, fruits, dairy products, and
meats. Pyroglutamate is also present in large amounts in the
human brain, cerebrospinal fluid, and blood.
Pyroglutamate is known to have a number of remarkable
cognitive-enhancing effects. After oral administration,
pyroglutamate passes into the brain through the blood-brain
barrier and stimulates cognitive functions. Pyroglutamate
improves memory and learning in rats, and has anti-anxiety
effects in rats.
Pyroglutamate has also been shown to be effective in
alcohol-induced memory deficits in humans and, more recently, in
people affected with multi-infarct dementia. In these patients,
the administration of pyroglutamate brought about a significant
increase of attention and an improvement on psychological tests
investigating short-term retrieval, long-term retrieval, and
long-term storage of memory. A statistically significant
improvement was observed also in the consolidation of memory.
In human subjects, pyroglutamate was compared with placebo in a
randomized double-blind trial for assessing its efficacy in
treating memory deficits in 40 aged subjects. Twenty subjects
were treated with pyroglutamate and 20 with placebo over a
period of 60 days. Memory functions were evaluated at baseline
and after 60 days of treatment by means of a test made up of six
memory tasks. The results show that pyroglutamate is effective
in improving verbal memory functions in subjects affected by
age-related memory decline.
Choline
Choline is a precursor to acetylcholine, a cholinergic
neurotransmitter that declines with advancing age. Individuals
predisposed to Alzheimer’s disease and other dementias, infants
and children, diabetics, and athletes (who often have reduced
plasma-choline levels after training or competition) may be at
increased risk of choline deficiency.
Choline has been shown to have considerable potential for
preserving the integrity of neuronal structures and in
preventing some of the alterations in the central nervous system
during aging. Choline supplementation appears to prevent the
age-induced decline of the dendritic network composed of neurons
that fire impulses to the cells. Choline increases the number of
dendritic spines in the cerebral cortex of old mice and improves
the animals’ learning performance.
Under conditions of increased demand for acetylcholine
production, excess choline availability becomes a limiting
factor for acetylcholine synthesis. When this additional,
exogenous choline supply is unavailable, cholinergic neurons are
able to use free choline taken from a choline “reservoir” to
continue the synthesis of acetylcholine. This process, termed “autocannabalism,”
can lead to a decrease in the quantity and quality of membrane
in these cells. Indeed, cholinergic neurons’ ability to use this
alternative source of choline appears to contribute to their
vulnerability in Alzheimer’s disease. Researchers believe
defects in choline-metabolism may play a central role in the
development of Alzheimer’s disease as defects in choline
transport exist in the cells of Alzheimer’s victims. Defects in
choline metabolism may also be influential in Down’s syndrome,
normal aging, Huntington’s disease, amyotropic lateral
sclerosis, the familial dysautonomias, and the post-polio
syndrome.
DMAE
DMAE (dimethylaminoethanol) is a nutrient found abundantly in
fish and in human brains. In the brain DMAE is converted into
choline, the precursor to acetylcholine. Because acetylcholine
conducts nerve impulses within the brain, the increased
acetylcholine synthesis seen after DMAE supplementation may
improve memory and learning skills, elevate mood, prevent memory
loss in elderly adults, and increase physical energy.
Studies suggest DMAE may work by inhibiting choline metabolism
in peripheral tissues, causing free choline to accumulate in the
blood, enter the brain and stimulate choline receptors. As the
imwww.e precursor to choline, DMAE assists in the building and
repair of cell membranes, particularly in the brain and central
nervous system.
Animal studies have demonstrated that DMAE stimulates brain
neurons and improves working memory performance. In one study,
rats treated with DMAE demonstrated
significant improvements in remembering how to negotiate a maze.
In another study, mice trained to negotiate a maze demonstrated
improved memory retention when
treated with DMAE.
DMAE’s ability to stimulate acetylcholine synthesis has led
researchers to explore its effects in senile dementia and
Alzheimer’s. In a promising study, 14 senile dementia patients
were treated with DMAE for four weeks. The dosage was gradually
increased to 600 mg, three times daily, during the first two
weeks, with no adverse effects. Although the patients
experienced no improvement in cognitive function or memory, ten
of the 14 patients experienced reduced depression, irritability
and anxiety and increased motivation and initiative.
Phenylalanine
Phenylalanine is an essential amino acid and vital precursor
used by the brain to produce dopamine, epinephrine and
norepinephrine, stimulatory neurotransmitters that regulate
mood, sex drive, memory, alertness, and learning.
L-phenylalanine is also converted, via a separate pathway, into
phenylethylamine (PEA), a mood-elevating compound that occurs
naturally in the brain.
Phenylalanine has been found useful for alleviating depression.
In one study forty depressed patients were treated with
L-phenylalanine daily for up to six months. Doses started at 500
milligrams and gradually built up to between 3 to 4 grams daily.
Patients also took 100 to 200 milligrams of vitamin B6 daily to
enhance neurotransmitter synthesis. Thirty-one patients (77
percent) reported positive benefits, and ten patients (25
percent) reported complete relief from symptoms of depression.
The principal investigators reported that those who responded
positively did so almost imwww.ely.
Ginkgo Biloba
A number of clinical studies have shown that Ginkgo biloba can
protect brain cells from damage caused by free radicals while
improving blood circulation and oxygen delivery, particularly
through the microcapillaries. In one study, researchers measured
a fifty-seven percent increase in blood flow through capillaries
within sixty minutes of giving Ginkgo to volunteers. A second
study by German scientists involved 60 patients diagnosed with
cerebral insufficiency and depression. Patients receiving Ginkgo
extract began to show marked improvement after only two weeks,
with a significant reduction of many of their symptoms.
In another clinical trial of 166 patients over the age of sixty,
researchers found that patients suffering from cerebral
insufficiency showed a significant improvement following three
months of treatment, confirming the efficacy of Ginkgo extract
in cerebral disorders due to aging.
Researchers have also found that Ginkgo can be especially
helpful when given to Alzheimer’s patients at the first sign of
symptoms. In one published study, German scientists gave a daily
dose of 120 mg of Ginkgo to twenty elderly patients exhibiting
various early symptoms of dementia. The results were dramatic,
and the patients receiving Ginkgo showed impressive improvements
on a variety of clinical tests, as compared to patients
receiving a placebo.
In one large study published in 1996, German researchers tested
Ginkgo extract on a group of 222 patients, aged fifty-five or
older, who were diagnosed with mild to moderate dementia caused
by either Alzheimer’s disease or multi-infarct dementia.
Patients were given either 240 milligrams of Ginkgo biloba
extract, twice a day before meals, or a placebo, for the
duration of the six-month long trial. At the conclusion of the
study the researchers reported that patients receiving Ginkgo
showed a remarkable overall improvement in their condition,
including a 300 percent increase in memory and attention as
compared to those receiving the placebo pills. The researchers
concluded their report by stating that, in cases of dementia,
Ginkgo extract could improve a patient’s quality of life while
preserving independence and postponing the need (and expense) of
full-time care.
Ginkgo Biloba and Multi-Infarct Dementia
The second most common cause of dementia in older people is
multi-infarct dementia (MID), a condition that accounts for
about fifteen percent of all cases of dementia.
Multi-infarct dementia usually affects people between the ages
of 60 and 75, and men are more likely to have multi-infarct
dementia than women. MID is typically caused by a series of
mini-strokes, also referred to as transient ischemic attacks (TIAs),
that can occur when an artery in the brain either becomes
blocked or ruptures. Strokes are generally caused by high blood
pressure, high blood cholesterol, diabetes, and heart disease.
Of these causes, the most important risk factor for
multi-infarct dementia is untreated high blood pressure. In
fact, it is extremely rare for a person to develop multi-infarct
dementia without also having high blood pressure.
While these mini-strokes may or may not be noticed at the time,
the effect on the brain is the same—brain cells become damaged
by a lack of oxygen and die. Over time a series of mini-strokes
can begin to destroy substantial portions of the brain that
control speech and visual processing.
As with Alzheimer’s disease, Ginkgo has been shown to help
patients suffering from MID by enhancing memory, alertness and
overall quality of life. Additionally, given the underlying
disorders that cause blood vessels to rupture, Ginkgo can also
benefit patients suffering from MID by restoring elasticity and
strength to stiff, weakened blood vessels.
Summary
Baby boomers and aging adults face a loss of cognitive powers
and impaired mental functions. Research supports the role of a
number of potent anti-aging therapies to slow brain aging and
preserve cognitive function. Rather than waiting for signs of an
irreversible decline in mental abilities or other, more serious
cognitive problems, it would be prudent to take steps to support
the brain’s ability to heal and self-repair. In short, we can
take steps now to slow age-dependent brain cell changes,
preserve vital functions, and maintain mental health and vigor.
Highly recommended
source of nutrients and supplements.
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References
1 Alzheimer’s Association, General Statistics and Demographics,
www.alz.org/hc/overview/stats.htm.
2. Watkins PB, Zimmerman HJ, Knapp MJ. Hepatotoxic effects of
tacrine administration in patients with Alzheimer’s disease.
JAMA 1994 Apr 6; 271:992-8
3. Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman
JL. Structure of acetylcholinesterase complexed with the
nootropic alkaloid, (-)-huperzine A. Nat Struct Biol 1997
Jan;4(1):57-63.)
4. Xu SS; Gao ZX; Weng Z; Du ZM; Xu WA; Yang JS; Zhang ML; Tong
ZH; Fang YS;Chai XS; et al, Efficacy of tablet huperzine-A on
memory’ cognition’ and behavior in Alzheimer’s disease. Chung
Kuo Yao Li, Hsueh Pao16:391-5, 1995.)
5. Santos MS, Duarte AI, Moreira PI, Oliveira CR Synaptosomal
response to oxidative stress: effect of vinpocetine. Free Radic
Res 2000 Jan;32(1):57-66
6. Haubrich DR, Gerber NH, Pflueger AB. Deanol affects choline
metabolism in peripheral tissues of mice. J Neurochem. 1981;
37(2):476-82.
7. Dean W, Morgenthaler J. Smart Drugs & Nutrients.
8. Kostopoulos GK, Phillis JW. The effects of
dimethylaminoethanol (deanol) on cerebral cortical neurons.
Psychopharmacol Commun. 1975; 1(3):339-47.
9. Levin ED, Rose JE, Abood L. Effects of nicotinic
dimethylaminoethyl esters on working memory performance of rats
in the radial-arm maze. Pharmacol Biochem Behav. 1995;
51(2-3):369-73.
10. Flood JF, Smith GE, Cherkin A. Memory retention:
potentiation of cholinergic drug combinations in mice. Neurobiol
Aging. 1983; 4(1):37-43.
11. Nagy I, Nagy K. On the role of cross-linking of cellular
proteins in aging. Mech Ageing Dev. 1980;14(1-2):245-51.
12. Marsh GR, Linnoila M. The effects of deanol on cognitive
performance and electrophysiology in elderly humans.
Psychopharmacology (Berl). 1979; 66(1):99-104.
13. Ferris SH, Sathananthan G, Gershon S, Clark C. Senile
dementia: treatment with deanol. J Am Geriatr Soc. 1977;
25(6):241-4.
14. Fisman M, Mersky H, Helmes E. Double-blind trial of
2-dimethylaminoethanol in Alzheimer’s disease. Am J Psychiatry.
1981; 138(7):970-2.
15. Lewis JA, Young R. Deanol and methylphenidate in minimal
brain dysfunction. Clin Pharmacol Ther. 1975; 17(5):534-40.
16. Pfeiffer C. Nutrition and Mental Illness: An Orthomolecular
Approach to Balancing Body Chemistry. Healing Arts Press.
17. Rimland B. Controversies in the treatment of autistic
children: vitamin and drug therapy. J Child Neurol. 1988; 3
Suppl:S68-72.
18. Cenni, A., et al. “Pharmacological Properties of a Nootropic
Agent of Endogenous Origin: D-Pyroglutamic Acid.” Journal of
Drug Development. 1988, 1, pp. 157-62.
19. Drago, F., Continella, G., Valerio, C., D’Agata, V., Astuto,
C., Spardaro, F., Scapagnini, U. “Effects of Pyroglutamic Acid
on Learning and Memory Processes of the Rat.” Acta Therapeutica.
1987, Vol. 13, pp. 587-94.
20. Filippo, V., Spignoli, G., Isidori, A. “Effects of Arginine
Pyroglutamate on Growth Hormone in Children.” Clinical Trials
Journal. 1987, Vol. 24, pp. 387-90.
21. Grioli, S. et al. “Pyroglutamic Acid Improves the Age
Associated Memory Impairment.” Fundamental and Clinical
Pharmacology. 1990, Vol. 4, pp. 169-73.
22. Moret, C., Briley, M. “The Forgotten Amino Acid
Pyroglutamate.” Trends in Pharmacological Sciences. 1988, Vol.
9, pp. 278-9.
23. Paoli, F., Spignoli, G., Pepeu, G. “Oxiracetam and D-Pyroglutamic
Acid Antagonize a Disruption of Passive Avoidance Behavior
Induced by the N-Methyl-Aspartate Receptor Antagonist
2-amino-5-phosphonovalerate.” Psychopharmacology. 1990, 100, pp.
130-1.
24. Spignoli, G., Magnani, M. Pepeu, G. “Pyroglutamic Acid
Antagonizes the Amnesic Effect and the Decrease in Brain
Acetylcholine Level Induced by Scopolamine.” Pharmacological
Research Communications. 1987, Vol. 10, pp. 901-7.
25. Sabelli HC. Clinical studies on the phenylethylamine
hypothesis of affective disorder: urine and blood phenylacetic
acid and phenylalanine dietary supplements. J Clin Psychiatry
1986;47:66-70.
26. Fischer E et al. Therapy of depression by phenylalanine.
Arzneimittelforsch 1975;25:132.
27. Heller B et al. Therapeutic action of D-phenylalanine in
Parkinson’s disease. Arzneimittelforsch 1976;26:577-579.
28. Budd K. Use of D-phenylalanine, an enkephalinase inhibitor,
in the treatment of intractable pain. Adv Pain Res Ther
1983;5:305-308.
29. Rai, GS, et al. A double-blind, placebo-controlled study of
Ginkgo biloba extract (“Tanakan”) in elderly outpatients with
mild to moderate memory impairment. Current Medical Research and
Opinion, 1991; 12:350-355.
30. Rapin, JR, et al. Local cerebral glucose consumption.
Effects of Ginkgo biloba extract. Presse-Medicale, 1986;
15:1494-1497.
31. Taillandier, J, et al. Ginkgo biloba extract in the
treatment of cerebral disorders due to ageing. Presse-Medicale,
1986; 15:1583-1587.
32. Vesper, J, Hansgen, K-D. Efficacy of Ginkgo biloba in 90
outpatients with cerebral insufficiency caused by old age.
Results of a placebo-controlled double-blind trial.
Phytomedicine, 1994; 1:9-16.
33. Vorberg, G. Ginkgo biloba extract (GBE): a long-term study
of chronic cerebral insufficiency in geriatric patients.
Clinical Trials Journal, 1985; 22:149-157.
34. Oberpichler, H, et al. Effects of Ginkgo biloba constituents
related to protection against brain damage caused by hypoxia.
Pharmacological Research and Communications, 1988; 20:349-368.
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