Sex differences in cortisol and memory following acute social stress in amnestic mild cognitive impairment

ABSTRACT

Objective

Older adults with amnestic mild cognitive impairment (aMCI) develop Alzheimer’s type dementia approximately 10 times faster annually than the normal population. Adrenal hormones are associated with aging and cognition. We investigated the relationship between acute stress, cortisol, and memory function in aMCI with an exploratory analysis of sex.

Method

Salivary cortisol was sampled diurnally and during two test sessions, one session with the Trier Social Stress Test (TSST), to explore differences in the relationship between cortisol and memory function in age-normal cognition (NA) and aMCI. Participants with aMCI (n = 6 women, 9 men; mean age = 75) or similarly aged NA (n = 9 women, 7 men, mean age = 75) were given tests of episodic, associative, and spatial working memory with a psychosocial stressor (TSST) in the second session.

Results

The aMCI group performed worse on the memory tests than NA as expected, and males with aMCI had elevated cortisol levels on test days. Immediate episodic memory was enhanced by social stress in NA but not in the aMCI group, indicating that stress-induced alterations in memory are different in individuals with aMCI. High cortisol was associated with impaired performance on episodic memory in aMCI males only. Cortisol in Session 1 moderated the relationship with spatial working memory, whereby higher cortisol was associated with worse performance in NA, but better spatial working memory in aMCI. In addition, effects of aMCI on perceived anxiety in response to stress exposure were moderated by stress-induced cortisol in a sex-specific manner.

Conclusions

We show effects of aMCI on Test Session cortisol levels and effects on perceived anxiety, and stress-induced impairments in memory in males with aMCI in our exploratory sample. Future studies should explore sex as a biological variable as our findings suggest that effects at the confluence of aMCI and stress can be obfuscated without sex as a consideration.

KEYWORDS:

• Diurnal
• psychosocial stressor
• men
• women
• aMCI
• Trier Social Stress Test; episodic memory; older adults; associative memory; spatial memory; gender

Acknowledgments

We gratefully acknowledge the participants for generously volunteering their time and effort. We thank Triti Namiranian, Angelina Polsinelli, Nicole D’Souza, Diana Smith, Preeyam Parikha, and Tallinn Splinter for assistance with data collection and management and Elizabeth Perez for editorial assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by grants from the Canadian Institutes of Health Research [CIHR-IA #131486 to LAMG, KJM, and AKT], the Dawn Shaw Alzheimer's Research Award (LAMG), and by the Morris Goldenberg Medical Research Endowment (to KJM). The funders had no role in the study design, collection, analyses or interpretation of the data