A memorable cup of tea ARUK 14th September 2016

Dr Ed Okello

Newcastle University - AFRD

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“WHAT IS THE POINT of a long life if you can’t remember it – and what is more tragic than losing your mind before you lose the use of your body?”

Holford 2005

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Current treatments for AD

No cure for AD: irreversible, progressive

brain disease

Treat symptoms

Slow progression

Prevent?

Alzheimer

disease

A ‘magic bullet’ for dementia?

ACh

degeneration

abnormal

amyloid

processing

plaques

and

tangles

inflammation

viral

exposure

free radical

damage

compromised

glucose

metabolism

brain

atrophy

nicotine

intake

alcohol

consumption

diet

socio-

economic

status

toxin

exposure

head

trauma

hormonal

status

ApoE

phenotype

ageing

RISK

FACTORS

DISEASE

PROCESSES

Quote from Thomas A. Edison (1847-1931): Inventor, Scientist and businessman

“The doctor of the future will

give no medication, but will

interest his patients in the care

of the human frame, diet and in

the cause and prevention of

disease.”

Alzheimer

disease

head

trauma

aluminium

exposure

ACh

degeneration

compromised

glucose

metabolism

ageing

ApoE

phenotype

nicotine

intake

socio-

economic

status

diet

alcohol

consumption

hormonal

status

inflammation

free radical

damage

abnormal

amyloid

processing

brain

atrophy

plaques

and

tangles

viral

exposure

Potential Natural products/nutritional targets

RISK

FACTORS

DISEASE

PROCESSES

PREVENTION TREATMENT?

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Plant derived drugs

• During the last 30 years- up to 50% of approved drugs are either directly or indirectly from natural products (food or none food sources) (Newman and Cragg, 2012 – J Nat Prod 75:311-335.

Medicinal Foods

• Research in to chemistry and biochemistry of bioactive compounds in food substances

• Their safety and efficacy

• Potential uses against a range of indications

*Tea – Camellia sinensis

• Tea most consumed beverage after

water

• UK 5th highest consumers of tea – ca

2.7 Kg/per capita

• Black Tea

• Green Tea

• Oolong Tea

• White Tea

• Purple Tea

• Herbal Teas ↑

• *1000’s of compounds in al teas

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O2-03-05 PROTECTIVE EFFECT OF JAPANESE GREEN TEA

AGAINST COGNITIVE IMPAIRMENT IN

THE ELDERLY, A TWO-YEAR FOLLOW-UP OBSERVATION

Tohru Hasegawa1, Edward Okello2, Tatsuo Yamada3;

1Saga Woman Junior College, Saga, Japan; 2University of Newcastle upon Tyne, Tyne,

United Kingdom; 3Fukuoka University, Medical School, Fukuoka, Japan

Background: Association between -

• Daily intake of polyphenols (Green tea)

• Cognitive Function (MMSE)

• Total plasma Homocysteine levels

Findings (published JAD – supplement 2005)

• ≤ 0.3 g/day tea polyphenol ↓ MMSE score

• ≥ 0.8 g/day or > no sig. change in MMSE

• ↑Thcy in cognitively impaired but ↓ with higher tea polyphenol intake

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Green tea consumption and cognitive function: a cross-sectional study

from the Tsurugaya project

Shinichi Kuriyama, et al., Amer J Clin Nutr 2006; 83:355-61

• Comprehensive Geriatric Assessment (CGA) conducted among elderly

Japanese, July and October 2002 (CGA – Physical, mental and social

functioning status):- Cross sectional data in 2002

• Subjects: 1003 Japanese subjects aged ≥70 y.

• Data: frequency of consumption of green tea, black or oolong tea, and

coffee and cognitive function.

• Mini-Mental State Examination with cut-offs of ≤ 28,≤ 26, and ≤ 24 and

calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment.

• Results: ORs decreased with frequency of green tea consumption ORs: 1 ≤

3 cups/week (reference) to 0.46 for 2 cups/day

• Conclusion: A higher consumption of green tea is associated with a lower

prevalence of cognitive impairment in humans.

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Tea consumption and cognitive impairment and decline in older

Chinese adults.

Tze-Pin Ng, et al., 2008. Am J Clin Nutr 88: 224 –31.

Study:

• Cross-sectional analysis of MMSE at baseline and 1-2 years later.

• 2501 participants aged ≥55 years (baseline) and longitudinal

analysis of data from 1438 cognitively intact participants of Chinese

adults (Singapore)

• Cognitive impairment was defined as an MMSE score ≤ 23 and

cognitive decline as a drop in MMSE score of ≥1 point.

Conclusion:

• Regular tea consumption was associated with lower risks of

cognitive impairment and decline independent of other risk factors.

• These effects were most evident for Black (fermented) and Oolong

(semi-fermented) teas, the predominant types in Singapore

• In contrast, no association between coffee intake and cognitive

status was found.

• Contrast with Green tea: genetic polymorphisms or chemistry?

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Scientific Evidence for

Biological activities of Tea

relevant to AD?

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Nutrition and Cognition

Research • We measure effects on

brain wave (electrical activities) using a simplified portable electroencephalograms (EEG).

• We measure effects on mood, anxiety, attention/ concentration and memory using an on-line battery of validated psychological/cognitive tests

EEG data acquisition

Nutritional Neuroscience

Volume 19, 2016 - Issue 5

Research article

• Effects of green and black tea consumption on brain wave

activities in healthy volunteers as measured by a simplified

Electroencephalogram (EEG): A feasibility study

Edward J. Okello et al.

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Unconscious Conscious

Delta (Δ) Theta (θ) Alpha(α) Beta (β)

0 – 4 Hz 4 – 8 Hz 8 – 12 Hz 12 – 30 Hz

Instinct Emotion Consciousness Thought

associated with deep

sleep, coma or

hypnosis

associated with

drowsiness,

meditation, feelings or

early sleeping states (

dreams)

Awareness of the body

and relaxation state/

calm feeling

alert, such as during

deep thinking and

concentration ( mental

activity)

EEG data after Green tea consumption

• Alpha and Theta

• Beta

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• 300 mg EGCG

• Theta (θ) ↑

• Alpha (α) ↑

• Beta (β) ↑

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GREEN TEA Camellia sinensis the ultimate NEUROPROTECTIVE?

• Antioxidant (Lee et al 2000)

• Anti-AChE (Okello et al 2004) and facilitates cholinergic transmission in vivo (Katayama et al 2002)

• Activates cell survival genes and PKC signalling [Mandel et al 2005].

• Neurite outgrowth enhanced [Reznichenko et al 2005]

• Anti amyloid -reduces abeta in models [ Rezai- Zadeh et al 2005, Lee SY et al 2005] , reduces toxicity a beta [ Levites Y et al 2003, chai YT et al 2001], inhibits beta secretase [Okello et al 2004]

• Proteasome inhibitor ( Arbiser et al, 2005; Wan et al, 2005 and 2004) -low doses of proteasome inhibitors improve proteasome function with anti alpha synuclein potential

active chemicals catechins eg (-)-epigallocatechin

not caffeine or theobromine

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CNS drugs from plants

(Perry et al…) • Arecoline Areca catechu (betel nut palm)

• Atropine Atropa belladonna

• Caffeine Coffea arabica

• Curcumin Curcuma longa

• Deserpide Rauvolfia canescens

• L-dopa Macuna

• Ephedrine Ephedra sinica

• Galantamine Galanthus

• Garlic Allium sativum

• Hyoscamine Hyoscyamus niger

• Kawain Kava kava

• Lobeline Lobelia inflata

• Morphine Papaver somniferum

• Physostigmine Physostigma venenosum

• Pilocarpine Pilocarpusjaborandi

• Reserpine Rauvolfia serpentina

• Scopolamine Datura/Scopolia

• Tetrahydrocannibinol Cannabis sativa

• Valapotriates Valerian officinalis

• Vasicine Vinca minor

• Yohimbe Pausinystalia yohimbe

Garlic

• Allicin

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B C 0.0375 0.075 0.15 0.3

“Alternative” medicines in the

management of dementia

• curcumin

– yellow pigment in turmeric (curry)

– anti-oxidant, anti-inflammatory, cholesterol

lowering

– reduces accumulation of amyloid in mice

brains

– in Phase II trials in US

CURCUMIN

Tentative evidence of better cognitive performance from curry consumption in non demented elderly Asians

Epidemiological study 1010 60-90 year olds

Frequent/ occasional curry consumers sig higher MMSEs cp non/ rare consumers

Curry consumption improves cognitive function in the elderly Ng et al. Am J Epidemiol. 2006;164:898-906

some reports lower prevalence AD

in India

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Nutritional interventions and

Dementia:

Back to the future for new leads

Thank you for listening

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