Coconut oil to fish oil: update on brain health and Alzheimer’s

prevention

Diana R. Kerwin, MDChief, 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.

• It may be defined as a loss of cognitive functions significant enough to cause functional disability in everyday life.

• It can be caused by Alzheimer’s disease, Frontotemporal dementia, Vascular infarcts etc.

Alzheimer’s disease

Vascular dementia

Frontotemporal dementia

Lewy Body disease

Primary Progressive Aphasia

Etc.

Dementia

Do not replicate or redistribute this material without permission

Dementia Risk

AGE is the most significant risk factor

Age 65 - 70: 1 in 50

Age 80+: 1 in 5

Memory Stages

Widely

distribut

ed network

Ability to learn new information

Requires attention

Focus on important and tune out irrelevant info

Stage one:

ENCODING

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 youwant to

Pathology of Alzheimer’s Disease

PlaquesBeta-Amyloid Protein

Tangles

Tau protein

Current clinical biomarkers

FDG-PET Biomarker-glucose metabolism

Development of Alzheimer Pharmacotherapy

1993 1997 2000 2001

Rivastigmine

Pre-1980 1980s 2000s 2010s

NOOTROPICS

IMMUNOTHERAPY

CHOLINESTERASE INHIBITORS

1990s

ANTI-OXIDANTS

(VITAMIN E)

ANTI-INFLAMMATORIES ORAL

ANTI-AMYLOID AGENTS

AChE PRECURSORS,ACh AGONISTS

Memantine

2003

NMDA ANTAGONISTS

HORMONE REPLACEMENT

DonepezilTacrine

RELKIN 2006

Galantamine

SYMPTOMATIC TREATMENT

Neurochemical Deficit CHOLINERGIC HYPOTHESIS

IDIOPATHIC Systemic Deficiency AMYLOID HYPOTHESIS

Protein Misfolding Modified AMYLOID HYPOTHESIS

Pathway to Your Medicine Cabinet

PhRMA 2012 Annual Report

Interventional Therapies in Phase I and II Clinical Trials Target Diverse Mechanisms

AADvac1

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

DBS-f (Deep brain stimulation of the fornix)

Epothilone D (BMS-241027)

EVP-0962

EVP-6124 (MT-4666)

Exendin-4

Gantenerumab

Insulin

Isotretinoin

IVIg

Ladostigil

L-arginine

Lipoic Acid

LY3002813

Mesenchymal stem cells

Minocycline

MSDC-0160

NIC5-15

Nicotinamide

Omega-3

PM-012

Resveratrol

RO4602522

RPh201

R-Pramipexole

SAR228810

Saracatinib

Sargramostim

Simvastatin

Sodium oligo-mannurarate

Tetrahydrobiopterin

Thalidomide

Transcranial magnetic stimulation (TMS)

VI-1121

(Sept. 24, 2013)

Tau

NGF

Insulin

Mitochondria

Monoamine oxidase

Therapeutic Agents in Phase III Clinical Trials for Alzheimer’s Disease• Gantenerumab

– Hoffman and La Roche– Monoclonal antibody against beta-

amyloid– 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

• 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!

Amount of Exercise

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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

• 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:

• Foods rich in antioxidants• Green leafy vegetables• Cold water fish as protein and omega 3 FA source

– 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

• 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.

Which pharmacologic agents are ineffective avoided?

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

• 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

General Tips: