Rethinking Alzheimer’s Disease through Nutritional Medicine · Rethinking Alzheimer’s disease through Nutritional Medicine Lisa Mosconi, PhD, CHC Assistant Professor of Psychiatry,

Rethinking Alzheimer’s disease through Nutritional Medicine Lisa Mosconi, PhD, CHC Assistant Professor of Psychiatry, New York University School of Medicine Director, Nutrition & Brain Fitness Lab, New York University School of Medicine Certified Health Coach & Integrative Nutritionist

MIT/CIA reThinkFood conference St. Helena, CA, Nov. 7-9, 2014

THE GOOD NEWS: WE LIVE LONGER

US life expectancy at Time of Birth

THE NOT SO GOOD NEWS: LONGER ≠ HEALTHIER

Increased life expectancy does not mean quality of life. Increased risk for age-related neuro-degenerative disease like Alzheimer’s, the most common form of dementia. Alzheimer’s causes deficits in memory, judgment, language, thinking, and activities of daily living.

THE ALZHEIMER’S EPIDEMIC Unprecedented scale. By 2050, over 13MM Alzheimer’s patients in the USA alone. No treatment. “Symptomatic” drugs have limited effectiveness with lots of side effects, while some disease-modifying drugs are in the pipeline.

THE ALZHEIMER’S OF 2050 IS STARTING TODAY The Alzheimer’s of 2050 is in the room right now. Alzheimer’s is not a disease of old age.

ALZHEIMER’S BEGINS LONG BEFORE SYMPTOMS OCCUR C

ogni

tive

func

tion

Alzheimer’s unfolds over a 20-40 year period prior to clinical symptoms. Genetic, lifestyle and environmental factors damage the brain when we are still young. Long prevention timeline.

Genes Lifestyle Environment

ALZHEIMER'S IS LARGELY A PREVENTABLE ILLNESS

The best way to stop Alzheimer’s is to strike before it takes place, before irreversible brain changes.

While there is no “silver bullet” to predict who will get Alzheimer’s, we can identify people with increased risk.

WHAT PRODUCES RISKS FOR ALZHEIMER’S?

1. Genetics (risks that can’t be modified) Determinant genes (very rare, <1%), family history,

susceptibility genes.

2. Medical illnesses (risks that can be modified) Diabetes, cardiovascular disease, toxin exposures,

infections, metabolic problems.

3. Lifestyle (risks that can be eliminated) Lack of exercise, smoking, too much alcohol, some drugs,

lack of social interactions, and poor diet.

HOW MUCH DO LIFESTYLE AND DIET MATTER?

1%

30%

69%

Determinant genesRisk genesLifestyle (diet, fitness, etc)

8,970,000

130,000

3,900,000

Of the 13MM AD patients of 2050: 130,000 we can’t do much for. 3,900,000 might be helped. 8,970,000 people don’t need to get sick at all.

GENES LOAD THE GUN BUT LIFESTYLE PULLS THE TRIGGER.

RETHINKING ALZHEIMER’S IS RETHINKING FOOD

• Food is important for the brain

• Food is important for brain aging

WE ARE WHAT WE EAT

Core principle of modern nutrition.

The nutritional content of what we eat determines the composition of our cell membranes, bone marrow, blood, hormones.

Food is the foundation upon which our body and our brain are built.

Anthelme Brillat-Savarin, French Chef & Gastronomist, 1826

FOOD FROM OUTSIDE = TISSUE INSIDE

Amino acids Structure

Vitamins & Fibers Immunity

Essential fats Healthy heart

Bad fats & Sugar Fat

FOOD IS TYPICALLY ASSOCIATED WITH THE WAY WE LOOK.

BUT FOOD CHANGES OUR BRAINS, AND THE WAY WE THINK.

THE BRAIN REALLY NEEDS FOOD

The most delicate organ of our body

The most metabolically expensive (20% of total calories)

The fattiest organ (60% saturated fats, PUFA, cholesterol)

Limited “energy storage capacity” (no fat storage system)

Relies entirely on food for energy, nourishment and functionality through constant and uninterrupted blood supply of nutrients.

NEUROTRANSMISSION

The brain is made up of 100 billion neurons which communicate to one another via neurotransmitters

The proper amount of neurotransmitter and receptors are needed for the brain to work well

Most neurotransmitter problems involve inefficient absorption, metabolism or storage of key nutrients

FOUR MAJOR NEUROTRANSMITTERS

ACETYLCHOLINE (2-acetoxy-N,N,N-trimethylethanaminium) Memory, cognition, plasticity, reward

SEROTONIN (5-Hydroxytryptamine, 5-HT) Mood, appetite, sleep

DOPAMINE (3,4-dihydroxyphenethylamin) Reward motivated behavior, motor control

GABA (γ-aminobutyric acid) Inhibition, muscle tone

FOUR MAJOR NEUROTRANSMITTERS

ACETYLCHOLINE (2-acetoxy-N,N,N-trimethylethanaminium) Memory, cognition, plasticity, reward

SEROTONIN (5-Hydroxytryptamine, 5-HT) Mood, appetite, sleep

DOPAMINE (3,4-dihydroxyphenethylamin) Reward motivated behavior, motor control

GABA (γ-aminobutyric acid) Inhibition, muscle tone

1. ACETYLCHOLINE

Neurotransmitter synthesized through acetylation of Choline with Acetyl coenzyme A (CoA). Choline is a water-soluble essential nutrient that is not synthesized by the brain. 10% comes from the liver. The rest comes from food.

3 eggs

CHOLINE: RECOMMENDED DIETARY ALLOWANCE (RDA) Women (425 mg/day) and Men (550 mg/day)

3 quarts milk (3 l.)

3 lbs. broccoli (1.5 kg)

1 lbs. chicken (0.5 kg)

2 tbsp soy lecithin (15 g)

2. SEROTONIN

Neurotransmitter biochemically derived from L-tryptophan. L-tryptophan is an essential amino acid. 100% comes from food.

½ egg white

Hypothetically: 500 mg/day + high Trp/Protein ratio

4 oz. turkey (150 g)

1.1 lbs. cacao (500 g)

0.2 lbs. soy beans

TRYPTOPHAN: NO RECOMMENDED DIETARY ALLOWANCE (RDA)

0.4 lbs. seeds

Core principle of Post-Modern Nutrition

WE ARE WHAT WE EAT WE WILL BE WHAT WE EAT

FOOD IS INFORMATION Your DNA is not your destiny. There is a big difference between your genotype (DNA sequence) and your phenotype (molecular outcome).

Changes in gene expression occur in the absence of DNA changes. Genes in any given cell can be turned on or turned off. Dietary nutrients are a major source of epigenetic changes. Food changes the way our DNA works.

THE BRAIN NEEDS (THE RIGHT) FOODS

For structure (cell integrity, support and energy) For function (synthesis of neurotransmitters) For protection (silencing of bad genes) For sustenance (activation of good genes) For livelihood (ensuring individual needs are met)

FOOD SUPPORTS BRAIN AGING AND CAN PREVENT ALZHEIMER’S DISEASE.

DIET IS RELATED TO MEMORY Healthy dietary patterns have been associated with reduced risk of memory loss and Alzheimer’s.

There is a great need to identify foods and nutrients that promote healthy brain aging and minimize risk of memory loss.

Essential for people of any age.

MEDITERRANEAN DIET One of the healthiest dietary patterns. Reduced risk of cardiovascular disease, cancer, dementia, and mortality rates. Mediterranean diet pattern includes:

• Lots of fruits, vegetables, grains, legumes, nuts and seeds • Some dairy products, fish, poultry, eggs • Little red meat • No processed foods • Olive oil main fat source • 1-2 glasses of wine with meals • Food is not consumed in isolation, walking or watching TV!

Lower adherence to the Mediterranean diet is associated with:

• Higher risk of dementia

• Higher risk of cerebrovascular burden

• Increased brain atrophy (10-25% smaller brains)

MEDITERRANEAN DIET & ALZHEIMER’S

Mediterranean diet 52 y/o woman CDR=0, MMSE=29E=29

MEDITERRANEAN DIET & RISK OF ALZHEIMER’S

Mosconi et al JPAD 2014 Matthews et al Adv Mol Imaging 2014

American diet 50 y/o woman CDR=0, MMSE= 28

DIET vs. NUTRITION

Diet: patterns of foods eaten, which contain nutrients

Nutrition: the components of the foods which one may absorb

Berries = flavonoids (anthocyanins) anti-allergic, anti-inflammatory, anti-oxidant, anti-microbial, anti-viral,

anti-cancer, anti-diarrheal

NUTRIENTS THAT SUPPORT BRAIN AGING

Mosconi et al. Br Med J 2014; Berti et al. J Nutr Health Aging 2014; Mosconi & McHugh Curr Report Nutr 2014

Fats: ω-3 : ω-6 polyunsaturated fats (PUFA) Monounsaturated fats (MUFA) Vitamins: Carotenoids (α- and β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin) Vitamin E (β- γ- and δ-tocopherol) B vitamins (folate and B12) Vitamin D Minerals & salts: Copper Selenium Zinc Dietary fibers Water

NUTRIENTS THAT IMPAIR MEMORY Fats: Trans-saturated fats Saturated fats Cholesterol Minerals & salts: Sodium

Mosconi et al. Br Med J 2014; Berti et al. J Nutr Health Aging 2014; Mosconi & McHugh Curr Report Nutr 2014

Smith et al PLoS One 2010; Douaud et al PNAS 2013

CLINICAL TRIALS – B vitamins Patients with mild cognitive impairments were treated with high dose supplementation of B vitamins (folic acid, vitamin B12, vitamin B6) for 24 months.

As compared to placebo, treated patients showed lower rates of brain atrophy on MRI.

B vitamins help reduce brain damage during aging, and possibly reduce risk of Alzheimer’s disease.

Food is essential for healthy brain aging. Food is information and speaks to our genes. Food is medicine. Alzheimer’s disease and memory loss are largely preventable by making healthy lifestyle choices. reThink Food for prevention of disease. Eat right for your brain!

No disclosures. Financial support: NIH/NIA grants AG035137, AG13616, AG032554, The Alzheimer’s Association, Funds from NYULMC

Nutrition & Brain Fitness Lab Lisa Mosconi Valentina Berti Michelle Davies Pauline McHugh John Murray Crystal Quinn Isabella Varsavsky Schantel Williams

New York University Shankar Vallhabhajosula David Mozley (Moze) Stanley Goldsmith Simon Morim

Weill Cornell Med Center

ACKNOWLEDGMENTS

Center for Brain Health Mony J. de Leon Lidia Glodzik Yi Li Ricardo Osorio Liz Pirraglia Nicole Spector Wai Tsui

ADCC James E. Galvin BODyLab Antonio Convit

Dawn C. Matthews Ana Lukic Randy Andrews

ADM Diagnostics

Alberto Pupi Valentina Berti

University of Florence

NEUROTRANSMISSION

The brain is made up of 100 billion neurons which communicate to one another via neurotransmitters

The proper amount of neurotransmitter and receptors are needed for the brain to work well

Most neurotransmitter problems involve inefficient absorption, metabolism or storage of key nutrients