Andrew ScholeyCentre for Human Psychopharmacology

Swinburne UniversityMelbourne, Australia

Food Industry Forum 29/08/11

andrew@scholeylab.com

FOODS FOR MOODS AND MINDS

www.scholeylab.com

fMRI, MEG

psychopharmacologyCurrent studies include ‘ARCLI’:large (N > 600) 12-month 4-arm intervention trial in elderly- cognition- brain mapping- biomarkers- genotyping

Optimal mental performance

MENTAL

ABILITY

MENTAL PERFORMANCE

optimizing cognitive performance

Normal AChtransmission Action of Cholinesterase Cholinesterase Inhibitors

A ‘magic bullet’ for dementia?

AChdegeneration

young

healthy old

AlzheimersAlzheimerdisease

Alzheimerdisease

A „magic bullet‟ for dementia?

AChdegeneration

abnormalamyloid

processingplaques

andtangles

inflammation

viralexposure

free radicaldamage compromised

glucosemetabolism brain

atrophynicotineintake

alcoholconsumption

diet

socio-economic

status

toxinexposure

headtrauma

hormonalstatus

ApoEgenotype

ageing RISK FACTORS

DISEASEPROCESSES

Alzheimerdisease

headtrauma

AChdegeneration

compromisedglucose

metabolism

ageing

nicotineintake

socio-economic

status

diet

alcoholconsumption

hormonalstatus

inflammation

free radicaldamage

abnormalamyloid

processing

brainatrophy

plaquesand

tangles

viralexposure

PREVENTIONTREATMENT?

attention workingmemory

secondarymemory

executive function

mood

a simple model of cognition

Top down strategy: capturing behavioural effects in humans

• Focus on „safe‟ treatments/interventions thought to improve mood and/or cognition from– history/tradition– anecdote– market

comprehensivebehavioural screen

‘proof of concept’

theory-driven/mechanistic studies

PLANT EXTRACTS• Ginkgo biloba• Panax ginseng*• Ginseng quinquefolius*• Ginkgo-ginseng combination• Melissa officinalis*• Salvia officinalis*• Salvia lavandulaefolia*• Valerian• Guaraná*• Ginkgo-phosphatidylserine*• Cocoa polyphenols*• Bacopa monnieri*• Pycnogenol*• Enzogenol*• EGCG

OTHERS• oxygen*• glucose• aromatherapy oils• caffeine • theanine• water• chewing gum*• alcohol [low dose]• DHA• multivitamins

*first controlled human study [11/14]

full-blown clinicaltrials

e.g. Salvia (sage)

• Historical use (Ayurvedic, Chinese, European) – "It is singularly good for the head and brain and

quickeneth the nerves and memory” (John Gerard, 1597)– “Sage will retard that rapid progress of decay that

treads upon our heels so fast in latter years of life, will preserve faculties and memory, more valuable to the rational mind than life itself” (John Hill 1756)

• Laboratory studies– +ve effects on memory in young adults– +ve effects on memory (and attention) in the elderly– +ve mood effects– +ve „everyday‟ memory performance– cholinesterase inhibition

Salvia extracts cholinergic activity and cognition

Tildesley et al (2003; 2005):Improved 2° memory

Kennedy et al (2004):Improved attention(no 2° memory measure)

Scholey et al (2008):Improved 2° memory & attention (elderly)

Kennedy et al (2011):Improved 2° memory

sage extract

muscarinicreceptors

nicotinicreceptors

cholinesterase

acetylcholine

muscarinicreceptors

nicotinicreceptors

cholinesterase

S. lavandulaefolia oil

S. lavandulaefolia oil

S. officinalis ethanol extract

S. officinalis leaf

PLACEBO167 mg 333 mg 666 mg 1332 mg

1hr 2.5hr 4hr 6hr-80

-60

-40

-20

0

20

*******

***********

SECONDARY MEMORY

CH

AN

GE

FR

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BA

SE

LIN

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1hr 2.5hr 4hr 6hr-3-2-10123

ACCURACY OF ATTENTION

******* *

exposureAlzheimerdisease

Salvia properties

AChdegeneration

abnormalamyloid

processingplaques

andtangles

inflammation

viralexposure

free radicaldamage

compromisedmetabolism

brainatrophy

nicotineintake

alcoholconsumption

diet

socio-economic

status

toxinexposure

headtrauma

hormonalstatus

ApoEphenotype

ageing RISK FACTORS

DISEASEPROCESSES

Alzheimerdisease

headtrauma

AChdegeneration

ageing ApoEphenotype

nicotineintake

socio-economic

status

alcoholconsumption

inflammation

free radicaldamage

abnormalamyloid

processing

brainatrophy

plaquesand

tangles

PREVENTIONTREATMENT?

Letenneur L et al. (2007) Am J Epidemiol;165:1364–1371

Flavonoid intake and cognitive decline in men aged 65–70 years

intake quartiles

Cocoa flavanols

Cognitive Demand Battery

• [2 min] Computerised Serial Threes– repeated subtraction of 3 from random

starting number between 800 and 999– e.g. 984-981-978-975……

• [2 min] Computerised Serial Sevens

• [5 min] RVIP– Detect target string

(3 odd/3 even) amongst rapid digit presentation

• [1 min] Mental fatigue rating

74

21

95

67

74

21

95

67

Cognitive Demand Battery

PERFORMANCE

MENTAL FATIGUE

INTE

RVE

NTI

ON -glucose

-caffeine, -herbals/supplements-guaraná-vits-chewing gum-PUFAs-cocoa flavanols (this study)

TIME

Mental Fatigue

mm

CH

AN

GE

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E-20

-10

0

10

20Control

High cocoa dose

Num

ber

Serial 3s

-8

-4

0

4

8****** *

********** ***

*** * *****

BETTER

WORSE

Results.

Coincides with-peak serum flavanol-peak FMD-peak cerebral blood flowLow cocoa dose

**

*****

***

****

Num

ber

7s Errors

*

******

0

1

2

3

410 20 30 40 50 6010 20 30 40 50 60 MINS

BETTER

WORSE

BETTER

WORSE

Scholey A et al (2010) J Psychopharm 24, 1505–1514.

Melissa officinalis [Lemon Balm]

• Appears in „Historia Plantarum‟ [approximately 300 BC] and the „Materia Medica‟ [approximately 50-80 BC]

• e.g. Paracelsus [16th Century] indication for “all complaints supposed to proceed from a disordered state of the nervous system”.

• e.g. Culpepper [1616-1654] “It causeth the Mind and Heart to becom merry….

and driveth away al troublesom cares and thoughts out of the mind arising from Melancholly…takes away grief, sorrow and care, instead of which it produceth joy and mirth”

laboratory studies confirm positive mood/anti-stress effects

multi-tasking framework

300mg 600mg

**

300mg 600mg

*

300mg 600mgplacebo

ALERT

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placebo

CALM

placebo

CONTENT

-10

0

10

20

-10

0

10

20

-10

0

10

20

20 min

2563

Mathematicalprocessing

Visualmonitoring

Auditory monitoring

Memorysearch

25632563

Mathematicalprocessing

Visualmonitoring

Auditory monitoring

Memorysearch

25632563

Mathematicalprocessing

Visualmonitoring

Auditory monitoring

Memorysearch

25632563

Mathematicalprocessing

Visualmonitoring

Auditory monitoring

Memorysearch

follow-up study confirms results and suggests effects

may emerge after 5 days

Summary and issues

• complex dose-time-task interactions• Acute/chronic effects can be dissociated• what about combinations?

– e.g. sage + melissa + bacopa + ginseng +?• mechanisms?

– full receptor/enzyme screening– co-monitoring physiological activity/biomarkers– In vivo receptor blocking studies

• refinement– sometimes better effects from less „refined‟ products?

• standardisation– GMP– GLC/MRI fingerprinting

• standardisation• standardisation

oxidativestress

glycaemiccontrol

ANSactivity

neurocognitivefunction

inflammationbloodflow

cardiovascularfunction

cardiovascularfunction

cardiovascularfunction

oxidativestress

oxidativestress

glycaemiccontrol

glycaemiccontrol

geneticsgeneticsgeneticsageage

ANSactivity

ANS/HPAactivity

insulinresistance

insulinresistance

insulinresistance

neurocognitive

inflammationinflammation

SAMactivity

psychologicalstress

psychologicalstress

psychologicalstress

Neuro-transmitter

Human Psychopharmacology capabilities

• cognitive testing• mood assessment• brain imaging

– EEG– fMRI– MEG– TMS

• biomarkers– cardiovascular

• field testing– internet– mobile phones

Key collaboratorsKevin Croft (UWA) Stephen Myers (Southern Cross)Denis Chang (UWS) Peter Howe (UniSA) Frank Rosenfedlt (Alfred Hospital)

DirectorsAndrew Scholey Con Stough

Head of Aging StudiesAndrew Pipingas [ageing]

Clinical Trials Co-ordinatorTinette Goh

Post-docsLauren Owen [glucose/nutrition]David Camfield [imaging]Jerome Sarris [psychiatry/naturopathy]Talitha Best [saccharides]Luke Downey [drugs/nutrition]

Research NurseRosamund McIllaith

PhDsAnastasia Oussokhova [glucoreg herbs]Christina Kure [heart and brain health] Vanessa Bilog [anti-oxidants]Helen MacPherson [anti-oxidants]Liz Harris [vitamins]Renee Rowsell [vitamins]Chris Neale [bacopa, neuroimaging]Rita Brien [oxytocin]Naomi Perry [phytoestrogens]Isabelle Bauer [fish oils]Rachel Gold [fish oils] Michaela Pascoe [fish oils]Matt Pase [heart-brain axis] James Kean [ADHD]Sarah Benson [alcohol/caffeine] Karen Nolidin [genetic determinants]

RAsAmy Gibbs Rebecca King Justine LomasKaren Savage Erin Fogg Robyn CockerellKatrina Rushworth Kate Cox David WhiteElizabeth Nelson Zahra Wahid

Centre for Human Psychopharmacology