Transcript A4 ADCS - Texas Alzheimer`s and Memory Disorders

Coconut oil to fish oil: update
on brain health and Alzheimer’s
prevention
Diana R. Kerwin, MD
Chief, Section of Geriatric Medicine
Director, Texas Alzheimer’s and Memory Disorders
Texas Health Presbyterian Hospital Dallas
Clinical Instructor, Department of Medicine-Education,
UT Southwestern
What Is Dementia?
• Dementia is a clinical
syndrome.
Dementia
• It may be defined as a
loss of cognitive functions
significant enough to
cause functional disability
in everyday life.
Primary
Progressive
Aphasia
Alzheimer’s disease
• It can be caused by
Alzheimer’s disease,
Frontotemporal dementia,
Vascular infarcts etc.
Vascular dementia
Lewy Body disease
Frontotemporal dementia
Do not replicate or redistribute this material without permission
Etc.
Dementia Risk
AGE is the most significant risk factor
Age 65 - 70:
1 in 50
Age 80+:
1 in 5
Memory Stages
Stage one:
ENCODING
Ability to learn new
information
Requires attention
Focus on important
and tune out
irrelevant info
Memory Stages
Stage two:
STORAGE
New info must be
stored in order to
remember later
Memory Stages
Stage three:
Retrieve
Finding the right
memory when you
want to
Pathology of Alzheimer’s
Disease
Tangles
Tau protein
Plaques
Beta-Amyloid Protein
Current clinical biomarkers
FDG-PET Biomarker-glucose metabolism
Development of Alzheimer Pharmacotherapy
Pre-1980
IDIOPATHIC
1980s
1990s
Neurochemical Deficit
CHOLINERGIC HYPOTHESIS
2000s
Systemic Deficiency
AMYLOID HYPOTHESIS
SYMPTOMATIC
TREATMENT
AChE
PRECURSORS,
ACh AGONISTS
ANTI-INFLAMMATORIES
NOOTROPICS
CHOLINESTERASE
INHIBITORS
HORMONE
REPLACEMENT
1993
Donepezil
1997
Protein Misfolding
Modified AMYLOID HYPOTHESIS
ORAL
ANTI-AMYLOID
AGENTS
IMMUNOTHERAPY
ANTI-OXIDANTS
(VITAMIN E)
NMDA
ANTAGONISTS
Tacrine
2010s
Rivastigmine
2000
Galantamine Memantine
2001
2003
RELKIN 2006
Pathway to Your Medicine Cabinet
PhRMA 2012 Annual Report
Interventional Therapies in Phase I and II
Clinical Trials Target Diverse Mechanisms
AADvac1
Tau
ABT-126
ABT-354
AC-1204
ACC-001 (vanutide
cridificar)
AFFITOPE-AD02/03
Anatabloc
Atomoxetine
AZD3293
AZD 3480
BAN2401
Bexarotene
BIIB037
CERE-110
Crenezumab (MABT5102A)
Curcumin
NGF
DBS-f (Deep brain stimulation
of the fornix)
Epothilone D (BMS-241027)
EVP-0962
EVP-6124 (MT-4666)
Exendin-4
Gantenerumab
Simvastatin
Insulin
Sodium oligo-mannurarate
Monoamine
Isotretinoin
Tetrahydrobiopterin
IVIg
Thalidomide
Insulin Transcranial magnetic
Ladostigil
stimulation (TMS)
L-arginine
VI-1121
Lipoic Acid
LY3002813
Mesenchymal stem cells
Minocycline
MSDC-0160
NIC5-15
Nicotinamide
Omega-3
PM-012
Resveratrol
RO4602522
Mitochondria
RPh201
R-Pramipexole
SAR228810
Saracatinib
Sargramostim
oxidase
(Sept. 24,
2013)
Therapeutic Agents in Phase III Clinical
Trials for Alzheimer’s Disease
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Gantenerumab
– Hoffman and La Roche
– Monoclonal antibody against betaamyloid
– DIAN-TU and preclinical AD
IVIg and Albumin
– Intravenous immunoglobulin
Lu AE58054
– Lundbeck and Otsuka
– An add-on agent Masitinib
MDX-8704
– Adamas Pharmaceuticals
– Memantine-donepezil combination
therapy
MK-8931
– Merck
– BACE inhibitor
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Pioglitazone
– Takeda
– PPAR-gamma activator
Solanezumab
– Eli Lilly
– Humanized antibody against
beta-amyloid
– Two studies: DIAN-TU and
mild Alzheimer’s disease
TRx0237
– TauRX
– Tau aggregation inhibitor
Possible Prevention of Alzheimer’s?
Overview
• Risk factors
• Prevention of dementia
• Alzheimer’s Disease Cooperative Studies
Group
– Fish oil (DHA study)
– Gingko biloba (GEM study)
– Vitamin E
– Exercise
– Coconut oil (active)
Exercise may alter risk of dementia
and improve cognitive function
Archives of Neurology 2001
• 4,600 cognitively normal Canadians 65 years or older followed for 5 years
• Physical activity measured from questionnaire
50% reduction!
1.2
Risk of Alzheimer's Disease
Risk of Cognitive Impairment
1.2
1.0
0.8
0.6
0.4
0.2
0.0
none
low
mod
Amount of Exercise
high
1.0
0.8
0.6
0.4
0.2
0.0
none
low
mod
Amount of Exercise
high
Background: why fish oil?
 Epidemiologic studies find a reduced risk of
Alzheimer’s disease in people consuming
increased amounts of fish in diet
• Kalmijn, et al, 1997 n=5386
• 18.5 grams fish/day-decreased risk of Alz. vs. <3 grams/day (p=0.005)
• Barberger-Gateau et al, 2002 n=1416
• fish consumption > 1x/week - reduced risk of dementia (p=0.009);
• Morris et al, 2003 n=815
• fish consumption > 1x/week - 60% risk reduction of developing AD (p=0.07);
• Of Omega-3 fatty acids, only DHA significant
• Schaefer, et al, 2003 n=1137, 10 years
• Fish consumption=3x/week-48% risk reduction for dementia; positive
association with plasma DHA
Fish oil and Alzheimer’s
• Fish contains omega 3 fatty acids, including
docosahexaenoic acid (DHA) and
eicosapentanoic acid (EPA), which are
thought to mediate health benefits of fish.
• DHA is abundant in the brain, whereas EPA
is virtually absent.
• Animal models have shown that DHA
modulates Alzheimer-like brain pathology.
Sources of dietary DHA
Although some DHA can be synthesized,
most of it comes from the diet
Dietary DHA determines tissue levels,
including brain levels
What is the best fish choice
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Sardines, anchovies
Atlantic salmon
Trout
Oysters are about the
same as 2 g fish oil
• Lowest:
– Tilapia, catfish, orange
roughy, cod, shrimp
Ginkgo biloba is among the most popular dietary
supplements for brain health. In 2007, Americans spent
$107 million on gingko supplements
Can gingko prevent dementia
• GEM Study completed by ADCS Group
2010
• 3069 community living persons >75yrs
• Gingko 120 mg twice a do or placebo
• 523 developed dementia during course of
study (16%placebo; 18% gingko)
• NO statistical difference in dementia
development between group
TEAM- VA AD Results
• Patients with mild to moderate AD,
• 2000 IU/d alpha tocopherol versus
placebo showed slower functional decline
and decreased caregiver burden
Coconut Oil and Ketones
What is the science.
• Ketone hypothesis: ketones provide an
alternative energy source to neurons, not
dependent on insulin presence
• Coconut oil contains medium chain
triglycerides (MCTs) form ketones
• May provide energy source to neurons
unable to take up glucose due to AD
The viral video: can the response
be replicated in a RCT?
Dose, side effects, efficacy
• A RCT is underway at University of South
Florida
• Currently most internet sites recommend 3
tablespoons/day
• Caveats: 115 calories per tablespoon
• GI side effects, diarrhea at high doses, ??
Effect on triglycerides, does this diminish
benefit
Late breaking study: resveratrol
Brain Health Diet
Nutrition
Dietary Recommendations:
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Foods rich in antioxidants
Green leafy vegetables
Cold water fish as protein and omega 3 FA source
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2-3 servings/week
Lean poultry 2-3/week
Nuts-walnuts, almonds peanuts
Legumes 3-4 servings/week
Vitamin E and C rich foods
– Almonds, kale, pumpkin seeds, parsley, papaya
– Healthy fats, no butter (sorry)
REMEMBER TO STAY HYDRATED
Which pharmacologic agents are
ineffective avoided?
• Ginkgo biloba
– Herbal supplement does not slow progression of
dementia and has not been shown to prevent it
– Risk of bleeding with aspirin
• Coconut oil
– Inadequate data, study underway
• Vitamin E possibly for treatment of AD
• B12 and folic acid-possibly beneficial, low risk
• Estrogen not for the treatment OR prevention
of dementia at this time.
Possible recommendations in
current practice
 Lifestyle factors that reduce risk
 Diet
• Omega-3, DHA, folic acid, Vitamin E, C
– Dietary sources BETTER than pill
– coconut oil, Axona
– Alternate “fuels” for the brain
 Exercise-Physical AND Cognitive
 Moderate exercise IMPROVES memory immediately and with a
sustained effect
 How much? 3 times a week, 30 minutes, moderate intensity
 Alcohol
• Moderate intake studies, red wine
– Resveratrol clinical trial beginning in ADCS
 Body Weight
 Higher body mass associated with increased risk
 Maintain ideal body weight
Optimize Memory
General Tips:
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Focus on diet and exercise
Incorporate more physical activity into every
day activities
Reduce distractions in the environment
Avoid multi-tasking; focus on one thing
Take your time
Ask for repetition (e.g., names)
Actively use all senses to
aid in detail of memory