CAFFEINE AND COGNITION: THE SHORT AND THE LONG TERM

Caffeine and cognition: The short and the long term (or Experimental Psychology to Epidemiology) Peter Rogers School of Experimental Psychology

Outline • Plan • Caffeine consumption and physiological effects • Acute alerting, anxiogenic and performance effects – Non-consumers vs consumers

• Tea, coffee and cognitive decline

Acknowledgements • Colleagues – – – –

Sue Heatherley Henk Smit Emma Mullings Jess Smith

• Funders

Humankind’s favourite drug

Around 6 billion caffeinecontaining drinks are consumed worldwide every day Coffee ranks second only to oil in terms of monetary value traded worldwide Caffeine (1,3,7-trimethylxanthine)

Tea

Maté

Cola

Cocoa

Coffee

Guarana

Physiological actions of caffeine • Caffeine acts at cell surface receptors widely distributed throughout the body – It is a non-selective adenosine A1 and A2A receptor antagonist

• Adenosine modulates neural activity – Activation of adenosine postsynaptic receptors by endogenous adenosine slows neural activity – Caffeine prevents activation of adenosine receptors by adenosine, thus removing this brake on neural activity

Physiological actions of caffeine • Caffeine has significant CNS, cardiovascular, cerebrovascular, renal, gastrointestinal, and metabolic effects • Exposure to caffeine leads to changes in adenosine signalling that oppose the effects of caffeine (tolerance)

Metabolism of caffeine • Peak blood level 30-60 minutes after ingestion in a drink • Elimination half life of 3-7 hours

– Faster in smokers and slower during pregnancy

>80%

James (1991) Caffeine and health. London: Academic Press

Hollingworth, H. L. (1912) The influence of caffein on mental and motor efficiency. Archives of Psychology, 22, 1-166. • n=16, 6 female, 19-39 years

• Varied levels of habitual caffeine consumption – Abstainer=2, Occasional=3, Moderate=2, Regular=8

• Attended laboratory (six-room apartment) for 40 days up to 12 hours each day • Various studies (n=1 to 5 per group) – Caffeine swallowed in a capsule in doses between 1 and 6 grains (65-390 mg) – Placebo capsule contained ‘sugar of milk’ (lactose)

• Tests of motor and mental performance included – Hand steadiness, Tapping, Coordination – Choice reaction time, Number cancellation, Calculation, Naming opposites, Colour naming, Typewriting

Effects of caffeine on tapping performance and hand steadiness Tapping (time taken to make 400 taps)

Hand steadiness (number of contacts)

1.15

5.5 Ratio of post to pre- treatment performance (mean ± SE)

Ratio of post to pre- treatment performance (mean ± SE)

Treatment, p =0.013 1.1 1.05 1 0.95 0.9

4.5

3.5

2.5

1.5

0.5

0.85 0

65

130

195

Caffeine (mg)

260

390

0

65-130

195-260

390

Caffeine (mg)

Hollingworth (1912) Archives of Psychology 22, 1-166

“The widespread consumption of caffeinic beverages. . . . seems to be justified by the results of this experiment.” Hollingworth, 1912 (p 165-166)

Test schedule for typical caffeine experiment Pre-treatment tasks (baseline)

Caffeine or Placebo

Wait (30 minutes)

Post-treatment tasks

Effects of caffeine on performance of tasks requiring sustained attention Rapid number search task

Mean SRT, ms

520

500

*

* *

480

Mean number of hits (max = 8)

Simple reaction time task 5.5

*

*

12.5

25

* *

5

4.5

4

3.5

460 0

12.5

25

50

100

0

50

100

Caffeine (mg)

Caffeine (mg)

* p<0.05, versus placebo

Adapted from Smit & Rogers (2000) Psychopharmacology, 152, 167-173

Effects of caffeine on performance of tasks requiring sustained attention Moderate caffeine consumers, overnight caffeine deprived Rapid number search task

Mean SRT, ms

520

500

*

* *

480

Mean number of hits (max = 8)

Simple reaction time task 5.5

*

*

12.5

25

* *

5

4.5

4

3.5

460 0

12.5

25

50

100

0

50

100

Caffeine (mg)

Caffeine (mg)

* p<0.05, versus placebo

Adapted from Smit & Rogers (2000) Psychopharmacology, 152, 167-173

Caffeine withdrawal symptoms?

Psychostimulant effects of caffeine: net benefit or withdrawal reversal? • Withdrawal reversal hypothesis – Acute (e.g., overnight) caffeine withdrawal lowers alertness and degrades mental performance – Caffeine restores alertness and mental performance to, but not above, baseline (normal) levels

– Withdrawal reversal (negatively) reinforces liking for the caffeine-containing vehicle For example, James and Rogers (2005) Psychopharmacology, 182, 1-8

Psychostimulant effects of caffeine: net benefit or withdrawal reversal? • Caffeine consumers versus ‘non-consumers’ – Compare the effects of caffeine in people who consume caffeine frequently with those in people who usually do not consume caffeine

Effects of caffeine on alertness* in coffee drinkers Coffee drinkers overnight caffeine deprived

Mean mood cluster score (max=3)

Drinkers 2 1.5 1 0.5 0 0

30

60

90

120

Time (mins) 0

150 mg

300 mg

* Alert, Attentive, Observant, Able to concentrate

Goldstein, Kaizer & Whitby (1969) Clinical Pharmacology and Therapeutics, 10, 489-497

Effects of caffeine on alertness* in coffee drinkers and abstainers Coffee drinkers overnight caffeine deprived Abstainers Mean mood cluster score (max=3)


Drinkers 2 1.5 1 0.5 0 0

30

60

90

120

2 1.5 1 0.5 0 0

30

Time (mins) 0

150 mg

60

90

120

Time (mins) 300 mg

0

150 mg

300 mg

* Alert, Attentive, Observant, Able to concentrate


Psychostimulant effects of caffeine: net benefit or withdrawal reversal? • Effects of caffeine in people who do not usually consume caffeine (‘non-consumers’) – But this is a self-selected group

Effects of caffeine on jitteriness* in coffee drinkers and abstainers Coffee drinkers overnight caffeine deprived Abstainers Mean mood cluster score (max=3)


Drinkers 2 1.5 1 0.5 0 0

30

60

90

120

2 1.5 1 0.5 0 0

30

Time (mins) 0

150 mg

60

90

120

Time (mins) 300 mg

0

150 mg

300 mg

* Jittery, Nervous, Shaky


Peak change from baseline in anxiety (mean ±SE)

Effects of caffeine on self-reported anxiety for the three genotypic groups at the rs5751876 adenosine A2a receptor gene polymorphism locus Non/low caffeine consumers Caffeine vs placebo p<0.05

4 3 2 1 0 -1 -2 C/C

C/T

T/T

Genotype group

Note: rs5751876 = 1976T>C

Placebo

Caffeine: 150 mg

Alsene, Deckert, Sand & de Wit (2003) Neuropsychopharmacology, 28, 1694-1702

Association between A2a receptor gene polymorphisms and caffeine-induced anxiety Alsene et al (2003) Neurpsychopharmacology, 28, 1694-1702 Childs et al (2008) Neuropsychopharmacology, 33, 2791-2800

• Variation in the gene that codes for the adenosine A2a receptor predicts caffeine-induced anxiety – studies tested only non/low-caffeine consumers

• Perhaps susceptibility to caffeine-induced anxiety causes avoidance of coffee, tea, etc Cornelis et al. (2007) American Journal of Clinical Nutrition, 86, 240-44

Caffeine-induced anxiety as a function of ADORA2A rs5751876 genotype group Mean ± SE anxiety (0-8 pt scale)

2

**

1.5

1

0.5

0 CC

CT

TT

Genotype group Caffeine (100 mg)

Placebo

Rogers et al. (2010) Neuropsychopharmacology, 35, 1973-1983

ADORA2A rs5751876 genotype group distribution in caffeine consumers and non-consumers

CC & CT

TT

182 (84%)

35 (16%)

132 (81.5%)

30 (18.5%)

Consumers

Non-consumers

Chi-square = 0.37, P = .54

Rogers et al. (2010) Neuropsychopharmacology, 35, 1973-1983

Mean ± SE caffeine intake (mg/d)

Sources of caffeine intake in caffeine consumers* as a function of ADORA2A rs5751876 genotype group 300 250

200

P<.05

150 100 50 0 Coffee

Tea

Other

CC&CT

TT

Total

* ≥40 mg caffeine per day Rogers et al. (2010) Neuropsychopharmacology, 35, 1973-1983

Caffeine-induced anxiety as a function of ADORA2A rs5751876 genotype group and consumer status CC and CT

2.5 Mean ± SE anxiety (0-8 point scale)

Mean ± SE anxiety (0-8 point scale)

2.5 2 1.5 1 0.5 0 NL

MH

Consumer status group Caffeine (100+150 mg)

Placebo

TT

2 1.5 1 0.5 0 NL

MH


Placebo

Effect of genotype P<.01 Effect of Consumer status P<.01 Rogers et al. (2010) Neuropsychopharmacology, 35, 1973-1983

Caffeine-induced anxiety as a function of ADORA2A rs5751876 genotype group and consumer status CC and CT

2.5 Mean ± SE anxiety (0-8 point scale)

Mean ± SE anxiety (0-8 point scale)

2.5 2 1.5 1 0.5 0 NL

MH


Placebo

TT

2 1.5 1 0.5 0 NL

MH


Placebo

Effect of genotype P<.01 Effect of Consumer status P<.01 Rogers et al. (2010) Neuropsychopharmacology, 35, 1973-1983

Anxiety effect does not deter caffeine consumption Rogers et al. (2010) Neuropsychopharmacology, 35, 1973-1983

• Anxiety-susceptible individuals (rs5751876 TT genotype) no less likely to be caffeine non-consumers – and they drank more coffee!

• Regular consumption leads to reduced anxiety effect (tolerance) • Even in non-consumers ‘anxiety’ effect is rarely severe (and perhaps even pleasant)

Back to withdrawal reversal • Effects of caffeine in acutely (overnight) withdrawn versus long-term withdrawn caffeine consumers

Morning drowsiness in caffeine consumers and non-consumers *

Mean ± SE drowsiness rating, mm (0 to 100 mm scale)

50

40

30 20

10

0 1.5 hours

13 hours

7days

Caffeine consumers: time since last caffeine

Nonconsumers

* p<0.05, versus 1.5 hours, 7 days and non-consumers Richardson, Rogers, Elliman & O’Dell (1995) Pharmacology Biochemistry and Behaviour 52, 313-320

Alerting effects of caffeine in consumers and non-consumers

– Acute (e.g., overnight) caffeine withdrawal lowers alertness and degrades mental performance – Caffeine restores alertness and mental performance to, but not above, baseline (normal) levels


• Withdrawal reversal hypothesis (consumers)

Drinkers 2 1.5 1 0.5 0 0

30

60

90

120

Time (mins) 0

150 mg

300 mg

• But why doesn’t caffeine increase alertness in non-consumers? – Might expect improvement initially, then tolerance with repeated consumption


Abstainers 2 1.5 1 0.5 0 0

30

60

90

120

Time (mins) 0

150 mg

300 mg

Alert, Attentive, Observant, Able to concentrate

Effects of caffeine on sleepiness, anxiety and mental alertness in caffeine consumers and non-consumers

Sleepiness: 'I feel sleepy / drowsy / half awake'

Anxiety/Jitteriness: I feel anxious / tense / nervous / on edge and I feel jittery / shaky.

Mental alertness: 'I feel mentally alert / attentive / able to concentrate / observant'

Rogers et al. (2012) Psychopharmacology 226, 229-40















Rogers et al. (2012) Psychopharmacology, DOI 10.1007/s00213-012-2889-4

How the effects of caffeine on sleepiness and anxiety might combine to influence mental alertness (and mental performance) Anxiety/ Jitteriness

Sleepiness

Mental alertness

Non-low consumer, after caffeine

↓

+

Medium-high consumer, caffeine withdrawn

↑

+ →

=

Medium-high consumer, after caffeine

→

+ →

= →

1.5 1 0.5 0 60

90

120



2

30

150 mg

↓

→ normal level ↑ increased ↓ decreased

2 1.5

Alert, Attentive, Observant, Able to concentrate

1 0.5 0 0

30

Time (mins) 0

= →

Abstainers

Drinkers

0

↑

60

90

120

Time (mins) 300 mg

0

150 mg

300 mg

Not smarter: No benefit for mental alertness and (therefore) no benefit for cognitive performance


Rogers et al. (2012) Psychopharmacology, DOI 10.1007/s00213-012-2889-4

But faster: caffeine enhances motor performance



Relationship between habitual coffee and tea consumption and cognitive performance Choice reaction time

Incidental verbal memory 6.9 Adjusted mean # of words recalled

Adjusted mean reaction time, ms

690

670

650

6.7

6.5

6.3

630 None

1-2

3-4

5-6

Usual number of cups per day Coffee

Tea

7+

None

1-2

3-4

5-6

7+

Usual number of cups per day Coffee

Tea

Data are from the Health and Lifestyle Survey of British adults, n=7087 Relationship between ‘caffeine’ consumption and task performance, p<0.0001* *Controlling for: demographic variables (age, sex, SES, etc), general health, and tobacco, alcohol and tranquilliser use.

Jarvis (1993) Psychopharmacology, 110, 45-52

Relationship between habitual caffeine consumption and cognitive performance as a function of age Caffeine and performance association for each age group Caffeine X age interaction

16-34 years

35-54 years

54+ years

n=2243

n=2637

n=2207

Simple reaction time

ns

ns

ns

p<0.001

Choice reaction time

ns -7 ms

p<0.05

p<0.05 -32 ms

p<0.001

ns +0.04 items

ns

p<0.01 +0.52 items

p<0.001

ns

p<0.05

p<0.05

ns

Incidental verbal memory Visuo-spatial reasoning

Jarvis (1993) Psychopharmacology, 110, 45-52

Effects of caffeine on performance of a simple reaction time task in young and older adults Moderate to high caffeine consumers, overnight caffeine deprived

Caffeine effect, p<0.001

Mean ± SE reaction time

400 380 360 340 320

Young adults

Older adults

20-35 years

55-84 years

Placebo

Caffeine:1 mg/kg

Caffeine:2 mg/kg

Adapted from Rogers and Dernoncourt (1998) Pharmacology Biochemistry and Behavior 59, 1039-1045

Lack effect of caffeine on memory performance in young and older adults

Mean ± SE number of words correctly recalled (max =20)

Moderate to high caffeine consumers, overnight caffeine deprived Age effect, p<0.001

10 8 6 4 2 0 Young adults

Older adults

20-35 years

55-84 years

Placebo

Caffeine:1 mg/kg

Caffeine:2 mg/kg

Adapted from Rogers and Dernoncourt (1998) Pharmacology Biochemistry and Behavior 59, 1039-1045

How tea and coffee may help to protect against cognitive decline • Neuroprotective role of adenosine during brain ischaemia • Polyphenols and other compounds in tea and coffee may protect against vascular disease – effects on blood cholesterol, blood coagulation and inflammatory processes, vasorelaxant effects

Neuroprotective actions of adenosine in brain ischaemia

ischaemia

cell death

Rudolphi et al. (1992) Trends in Pharmacological Sciences, 13, 439-445

Actually a balance of bad good effects? • Caffeine increases blood pressure – this ought to increase risk of cardiovascular disease and stroke, and contribute to greater risk cognitive decline later in life James (2004) Psychosomatic Medicine 6, 63-71

• Cafestol in coffee (conc varies with brewing method) increases LDL cholesterol • Presumably these bad effects are outweighed by – beneficial vascular and other effects of polyphenols, etc (tea and coffee) – possible sensitisation of the neuroprotective action of adenosine by caffeine consumption

• Note – Theanine (tea) reduces blood pressure Rogers et al (2008) Psychopharmacology 195, 560-577

– Coffee consumption (caf and decaf) associated with reduced risk of type-2 diabetes – Sugared cola consumption (caf and decaf) associated with increased risk of type-2 diabetes Bhupathiraju et al (2013) American Journal of Clinical Nutrition 97, 155-66

– Coffee consumption associated with reduced risk of hypertension – Sugared and ‘diet’ cola consumption associated with increased risk of hypertension Winkelmayer et al (2005) JAMA 294, 2330-5 Rogers & Smith (2011) In Benton (ed) Lifetime nutritional influences on cognition, behaviour and psychiatric illness.

Caffeine summary • Widely consumed; various physiological and behavioural effects • Is caffeine a cognitive enhancer? Day to day, the frequent caffeine consumer probably does not benefit from caffeine consumption – due to tolerance to the alerting effect of caffeine – though significant adverse effects of withdrawal are normally avoided by the typical daily pattern of caffeine intake – tolerance also develops to the small anxiogenic effect of caffeine

• Physical performance – enhanced motor speed and endurance – decreased hand steadiness

• Frequent caffeine consumers are caffeine dependent, but addiction potential of caffeine is low • Tea and coffee protect against cognitive decline – role of caffeine and other compounds?

CAFFEINE AND COGNITION: THE SHORT AND THE LONG TERM

Recommend Documents