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CONFIDENTIAL Pg 1
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
1 2 31 2 3
Cortisol & Cognition in Amnestic-Mild Cognitive Impairment
CONFIDENTIAL Pg 2
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.
Pg 3
Acknowledgements
Triti NamiranianAngelina Polsinelli
Nicole D’SouzaDiana Smith
Preeyam Parikha
Morris Goldenberg Medical Research Endowment
Pg 4
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
Pg 9
Memory Tests
shoeviolettablegranitedaisybootchairstoneroseslipperwoodcouch
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
Google Image from superstock.comGoogle Image from superstock.comGoogle Image from inmagine.comGoogle Image from inmagine.com
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Cortisol level is elevated in MCI under test conditions
Error bars: 95% CIError bars: 95% CI
NCMCINCMCI
test test
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Challenge enhances episodic memory in controls and depresses it in MCI
Error bars: 95% CIError bars: 95% CI
NCMCINCMCI
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Negative impact of challenge also indicated in MCI for associative memory
Error bars: 95% CIError bars: 95% CI
NCMCINCMCI
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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.