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Alzheimer’s Disease InternationalMarch 29, 2011

Kelly J. Murphy1,2, Angela K. Troyer1 & Liisa A.M. Galea3Kelly J. Murphy1,2, Angela K. Troyer1 & Liisa A.M. Galea3

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Cortisol & Cognition in Amnestic-Mild Cognitive Impairment

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Conflict of Interest Disclosure

Kelly Murphy, Ph.D.Angela Troyer, Ph.D.

Liisa Galea, Ph.D.

Has no real or apparent

conflicts of interest to report.

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Acknowledgements

Triti NamiranianAngelina Polsinelli

Nicole D’SouzaDiana Smith

Preeyam Parikha

Morris Goldenberg Medical Research Endowment

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Cortisol & Cognition

• Inverted U shaped function between cortisol levels (a main stress hormone) and memory performance

• Prolonged exposure to stress hormones results in decreased memory ability and hippocampal volume

Google Image from nwlink.comGoogle Image from nwlink.com

For Review See: Lupien et al., Psychoneuroendocrinology 2005:30;225-242

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Cortisol

• Elevated basal levels in moderate to severe level of disease

• No clear relationship between memory performance and cortisol level

•For update see: Gil-Bea et al., (2010) J Alzheimer’s Disease 22;829-838

• No difference in basal levels (increased awakening levels?)

• Negative correlation between memory performance and cortisol level (inconsistent across tasks). •Wolf et al., (2002) Psychoneuroendocrinology 27:777-789•Souza-Talarico et al., (2010) J Alzheimer’s Disease 19:839-848

Alzheimer’s DiseaseAlzheimer’s Disease MCIMCI

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Study Questions

• Is there a change in cortisol response to challenge in MCI?

• Will sampling saliva on the same day as testing produce a more reliable association between cortisol and memory in MCI?

• Will a stressor influence memory behaviour differently in MCI?

We attempted to answer these questions by sampling salivary cortisol both basally and across two test sessions. On the second test session we exogenously manipulated cortisol level with the application of a psychosocial stressor.

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Participant Group Demographics

Control

(n=14)

aMCI

(n=14)

Cohen’s d

Age (yrs) 75.3 (8.7) 74.6 (8.0) 0.08

Female: Male ratio 7:7 5:9

Education (yrs) 14.4 (3.5) 14.9 (3.0) 0.15

MMSE* 29.0 (1.0) 27.7 (1.9) 0.89

Vocabulary SS 14.3 (2.5) 13.3 (2.6) 0.40

HADS – Depression 2.6 (2.3) 2.6 (2.3) 0

HADS - Anxiety 5.1 (3.8) 5.6 (2.5) 0.16

Mean scores with standard deviations in parentheses; *group differences p < .05.

aMCI classification based after Petersen (2004) Journal of Internal Medicine 256:183-194.,

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Basal Cortisol Circadian Fluctuations(no group differences)

Error bars: 95% CIError bars: 95% CI

NCMCINCMCI

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Memory Tests

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shoeviolettablegranitedaisybootchairstoneroseslipperwoodcouch

Episodic MemoryWord List Learning

Episodic MemoryWord List Learning

Associative Memory Face-Name

Associative Memory Face-Name

Spatial Working MemorySpatial Working Memory

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Cortisol sampling during test sessions

Trier Social Stress Test (Kirshbaum et al., (1993) Neuropsychobiology 28:76-81)

1. Anticipation period 2. Test period

Session 2 • 10:10 a.m. • (Anticipation) 10:30 a.m. (Test)• 11:00 a.m. (30 min after challenge)• ~11:30 a.m. (~60 min later).

Psychosocial challenge – Session 2

Session 1 • 10:10 a.m. • ~11:45 a.m.

public speaking & mental arithmeticin front of an audiencepublic speaking & mental arithmeticin front of an audience

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Cortisol level is elevated in MCI under test conditions

Error bars: 95% CIError bars: 95% CI

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test test

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Challenge enhances episodic memory in controls and depresses it in MCI

Error bars: 95% CIError bars: 95% CI

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Negative impact of challenge also indicated in MCI for associative memory

Error bars: 95% CIError bars: 95% CI

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Summary of Findings

Cortisol• No differences in basal cortisol level (including awakening)• MCI show greater increase in cortisol level from psychosocial

stressor compared to controls

Cognition• Memory behavior can benefit from the immediate effects of a

challenge in controls, but not in MCI.

Cortisol Level & Cognitive Performance Level• Inconsistent findings across tasks suggestive of an inverse

relationship between memory performance and cortisol level in MCI.