Transcript Memory Enhancers

Dietary Supplements and Memory
Potential to increase memory
capabilities in the aging population
- Maria Skouroliakou, Ph.D., Clinical
Pharmacist, Lecturer of Harokopeio,
University of Athens, Director of TPN
Nutrition and Pharmacokinetics at IASO
Hospital, Greece
- Presentation created by: Tania Mitsinikos
Agenda
• Basic concepts of neural signaling and memory
• Memory and Age
• Memory Enhancers
– how they work
– studies on effectiveness
• Other areas that could have similar effects
• Which then work best?
Agenda
• Basic concepts of neural signaling and
memory
• Memory and Age
• Memory Enhancers
– how they work
– studies on effectiveness
• Other areas that could have similar effects
• Which then works best?
Structure of the Neuron
Types of Receptors
• Ionotropic receptor: allows various kinds of ions to
rapidly cross the cell membrane into the neuron
creating an electrical potential
• Metabotropic receptors promotes the release of
second messenger molecules and results in a
number of biological changes in the cell.
Neural Signals: How do they work?
• Neurotransmitter released
and upon binding to
ionotropic receptor, ions
flood into the post-synaptic
neuron, depolarizing the
membrane, and proliferate
the signal until it reaches its
target where a response is
initiated
…but this doesn’t create memory…
Neural Signals to Create Memory
• The neurotransmitter is
released, and binding to a
metabotropic receptor
produces a second
messenger which alters
neuronal functioning
• For example, activation of
protein kinases cause
prolonged changes in the
neuron like the activation of
certain genes and therefore
protein synthesis resulting in
formed memory
Agenda
• Basic concepts of neural signaling and
memory
• Memory and Age
• Memory Enhancers
– how they work
– studies on effectiveness
• Other areas that could have similar effects
• Which then works best?
Memory and Age: A gradual deterioration
• Normal Aging leads to degenerative
neural pathologies
• 3 main changes in the brain
– Neuronal changes (accumulation of
nonessential substance, loss of myelin, and
shrinkage)
– Connections between neurons altered
(reduced branching and reduced numbers,
hence interfere with neurotransmitter
availability)
– Change cerebrovascular system leading to
decreased blood flow and consequently
volume
Agenda
• Basic concepts of neural signaling and
memory
• Memory and Age
• Memory Enhancers
– how they work
– studies on effectiveness
• Other areas that could have similar effects
• What then works best?
Dietary supplements: Potential
Memory Enhancers
• Phosphatidylserine (PS)
• Choline
– Phosphatidylcholine
– Citicoline
• Piracetam
• Vinpocetine
• Acetyl-L-cartinine
• Antioxidants
– Vitamin E
– Vitamin C
Memory Enhancers: Theoretical Mechanisms
McDaniel, Mark A. et al. “Brain Specific Nutrients: A Memory Cure?” Nutrition 2003: 957-975
How these supplements work:
A closer look
Phosphatidylserine (PS)
• Naturally occurring
phospholipid taken in through
diet.
• Especially important in
phospholipid membranes of
neurons
– PS comprises a small percentage in
biological membranes, but that
small component may be critical in
the membrane potential of
neurons
• Purchased without prescription
Phosphatidylserine (PS): Mechanism
• Membrane and its
receptors are critical
for the neural signal to
reach its target but
with age, composition
changes, and
receptors are lost
• Rigidity of membrane
and message are not
proliferated
PS could reverse this, but how?
Phosphatidylserine (PS): Mechanism
• Protein kinase C (PKC) is essential in secondary
messaging in cell
• PS and Ca2+ ions activate PKC so the enzyme can be
functional
– PKC may then regulate neurotransmitters
Choline
• Acetylcholine (ACh) is an important
neurotransmitter and declines as individuals age,
which severely impairs memory
• Any source of choline could reverse ACh's declining
levels like:
– Phosphatidylcholine (PC) (main component lecithin)
– Citicoline
• Both can be purchased as nutritional supplements
and some foods have been enhanced by adding
lecithin
Choline: Mechanism
• Choline is essential for • The number of neurons
ACh production, so if it
diminishes due to age,so
is supplemented to diet,
the remaining neurons
ACh levels rise and
may function more
potentially increase
effectively with more
available ACh.
memory capabilities
Instead of gradual deterioration of neurons, choline
supplements have the capabilities to help stop the
destruction of neurons
Piracetam
• A nootropic drug, first
developed in 1967
• Sold as Nootropil and
Pirroxil and one of the
most widely know
cognitive enhancing drugs
• Not approved by Food
and Drug Administration
(FDA)
• Available in Europe and
Mexico
Piracetam: Mechanism
• Enhances metabolism, improves
neuronal efficiency, restores impaired
neurotransmitters
• Facilitates activity in several
neurotransmission systems
Piracetam: Mechanism
• May fight age related
decrease in the
number of N-methylD-aspartate
(ionotropic receptor)
and cholinergic
receptors on neuronal
membranes
Vinpocetine
• Nootropic supplement derived from
vincamine (extracted from periwinkle plant)
• Introduced into clinical practice 20 years
ago
• Used to treat patients with loss of cerebral
blood flow resulting in cerebral oxygen
deficits
Vinpocetine: Mechanism
• Increase blood flow • Improved blood flow
in brain and increased prevents damage and/or
transport and uptake
death to neurons and
of glucose to neurons
prevents memory loss
Could potentially increase ACh levels as well!
Acetyl-L-carnitine
• Amino acid
• Sold as “brain power”
supplements in health
food stores
• Promotes synthesis and
release of ACh
• Provides energy for
repair and maintenance
of neurons
Acetyl-L-carnitine: Mechanism
• Aids transport of substances across mitochondrial
membranes and therefore assisting energy production
•Increase PKC activity
•Increase levels of neurotrophins
•Neurotrophins guide differentiation and growth of nerves,
maintain adult neurons, and are critical in repair of damage
neurons.
Needed to produce structural changes that
are essential for permanent neurons
•Protection for CNS synapses
Antioxidants
• Aid in prevention of
oxidative damage
• Act as buffers
• Vitamin E and C are
antioxidants and have
capabilities of memory
enhancement
Antioxidants
• Brain more vulnerable to oxidative stress
due to immense amounts of O2 being
consumed
• Oxidative stress causes damage to
neurofilament proteins and induces death
• By increasing antioxidant levels, it may slow
down or stop the damaging effects of
oxidation on neurons
Agenda
• Basic concepts of neural signaling and
memory
• Memory and Age
• Memory Enhancers
– how they work
– studies on effectiveness
• Other areas that could have similar effects
• What then works best?
Memory Enhancers:
How effective are they?
This all sounds like it could overcome a
huge hurdle of declining memory as we
age, but do these supplements live up to
what they claim to fix?
Phosphatidylserine (PS): Studies
• Effects on patients with moderate cognitive
impairments:
– several double-blind, placebo-controlled
experiments in Italy (300 mg/day, 3 of 100 mg
for 8-24 weeks)
– Conducted memory tests, before, after and
during the study
– Consistently and significantly increased total
recall versus placebo but relatively modest
results.
Phosphatidylserine (PS): Studies
• Effects on normal aging adults (50-75 yrs)
with age related memory impairment
– double-blind, placebo-controlled,12 week study
– 5 mnemonic memory tests, administered every 3
weeks
– resulted in only moderate improvement based
on these tests (improvements during first 6
weeks but no improvement after)
Phosphatidylserine: Studies
• Details of study
– double-blind, placebo-controlled, 8-24 week
study
– 55-88 y with moderate cognitive decline as
determined through screening tests
– 300 mg/day, 3 doses of 100 mg or placebo
– Memory tests before, after and during treatment
•Short lists of words (5-15) were auditorily presented (1
word/sec) and auditorily recalled
Phosphatidylserine: Studies
• Results
– PS consistently improved total recall although
uniformly modest
•recall increases by 1-2 words total
•Placebo recall decreased by less than a word
– No other signs of improved memory except for
word recall
Choline: Studies
• Phosphatidylcholine (PC):
– Studied for treatment of Alzheimer’s disease
– Uniformly negative results
– No strong support that PC will prevent memory
deterioration for patients with probably
Alzheimer’s
– Positive preliminary in the improvement of
memory with memory problems due to aging
Choline: Studies
• Citicoline: Details of study
– double-blind, placebo-controlled of 42
days
•1000 mg/day treatment of 72 year olds
(avg.)
– Patients had dementia-related decline
rather than normal-age associated
memory impairment (as determined by
MMSE)
Choline: Studies
• Citicoline: Results
– Improved immediate and delayed prose recall
relative to base line
– Confirmed that choline levels increase
•Consistent with idea that changes in brain
metabolism related to acetylcholine levels and PC
underlies mnemonic benefits
Safety: Some patients complained of insomnia, stomach
distress, headache, rash, and cardiac anomalies
Piracetam: Studies
• Details of Study
– Initial double-blind, crossover study on patients with
probably Alzheimer’s disease
•4.8 g/day + lecithin for 3 months
•tested memory with multiple-recall-trial procedure with
same list of words
– No significant findings but in patients with
Alzheimer's type dementia the treatment with
Piracetem and lecithin may substantially improve
specific memory deficits
– Other follow up studies failed to show positive results
Vinpocetine: Studies
• Details of Study:
– 3 months in duration
•10 mg, 3 times a day for 1st 30
days
•15 mg/day for last 60 days
• older adults with brain
dysfunction (either circulatory
problems or mild to moderate
dementia-related brain disease
Vinpocetine: Studies
• Results:
– Showed improvement than placebo groups for
tests of measuring attention, concentration, and
memory. Size of improvement for reported
scores was noticeable.
– Increased scores on Mini-Mental Status
Questionnaire but placebo showed no
improvement
– No improvement in patients with Alzheimer’s
Disease
Acetyl-L-Carnitine
• Details of Study:
– Patients with probably Alzheimer’s
• Results:
– Showed less decline than placebo, but effects not
reversed but not significant difference
– In other large-scale, double-blind, placebocontrolled studies, there has been minimal or no
benefits of acetyl-L-carnitine with patients diagnosed
with probably Alzheimer’s
– Another study showed a slow down in cognitive
deterioration
Antioxidants: Studies
• Details of Study:
– Patients with brain pathology of moderate severity
• Vitamin E in 2000 IU/day for 2 years
• 85 patients with Alzheimer’s disease of moderate
severity
– Normal younger adults
• 17-27 year old college students
• 10 times the recommended daily dose (vitamins C
and E)
• Cognitive assessment at 3, 6, and 9 months
Antioxidants: Studies
• Results:
– Alzheimer’s disease patients:
•Vitamin E delayed time before required
institutionalization and loss of daily skills
•Overall slowed effects of mental illness in subjects
– Normal young adults
•No significant difference
Agenda
• Basic concepts of neural signaling and memory
• Memory and Age
• Memory Enhancers
– how they work
– studies on effectiveness
• Other areas that could have similar effects
• Which then work best?
What else could help?
• Docosahexaenoic Acid (DHA) is the principle
polyunsaturated fatty acid in the nervous
system.
– Its formation slows as we age and hence doesn’t
provide the necessary fatty acid to the neurons
– Studies have shown that deficits in this fatty acid
impairs neuronal functioning and hence cognitive
abilities by compromising neuronal structure.
– Enhancement through supplements of this fatty
acid has potential to reverse these cognitive
impairments
Agenda
• Basic concepts of neural signaling and
memory
• Memory and Age
• Memory Enhancers
– how they work
– studies on effectiveness
• Other areas that could have similar effects
• Which then works best?
Which then works best?
Which one do you think works best? Maybe a combination
or has one through these studies shown to be most effective?
Works Cited
Campbell, Neil A. et al. “Biology 6th Edition.” Menlo Park, CA:
Benjamin Cummings, 2003
Garrett, Reginald H. and Charles M. Grisham. “Biochemistry 3rd
Edition.” Belmont, CA: Thomson, 2005
McDaniel, Mark A. et al. “Brain Specific Nutrients: A Memory Cure?”
Nutrition 2003: 957-975
Watson, James D. et al. “Molecular Biology of the Gene 5th edition”.
Glenview, IL: Benjamin Cummings, 2004
Thank You!
QUESTIONS PLEASE