Abstract
Background
Hypothalamic-pituitary-adrenal axis dysregulation, which is typically assessed by
measuring cortisol levels, is associated with cognitive dysfunction, hippocampal atrophy,
and increased risk for mild cognitive impairment and Alzheimer’s disease (AD). However,
little is known about the role of hypothalamic-pituitary-adrenal axis dysregulation
in moderating the effect of high levels of amyloid-β (Aβ+) on cognitive decline in
the preclinical phase of AD, which is often protracted, and thus offers opportunities
for prevention and early intervention.
Methods
Using data from a 6-year multicenter prospective cohort study, we evaluated the relation
between Aβ level, plasma cortisol level, and cognitive decline in 416 cognitively
normal older adults.
Results
Results revealed that Aβ+ older adults experienced faster decline than Aβ− older adults
in all cognitive domains (Cohen’s d at 6-year assessment = 0.37–0.65). They further indicated a significant interaction
between Aβ and cortisol levels for global cognition (d = 0.32), episodic memory (d = 0.50), and executive function (d = 0.59) scores, with Aβ+ older adults with high cortisol levels having significantly
faster decline in these domains compared with Aβ+ older adults with low cortisol levels.
These effects were independent of age, sex, APOE genotype, anxiety symptoms, and radiotracer type.
Conclusions
In cognitively healthy older adults, Aβ+ is associated with greater cognitive decline
and high plasma cortisol levels may accelerate the effect of Aβ+ on decline in global
cognition, episodic memory, and executive function. These results suggest that therapies
targeted toward lowering plasma cortisol and Aβ levels may be helpful in mitigating
cognitive decline in the preclinical phase of AD.
Keywords
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Article info
Publication history
Published online: September 07, 2016
Accepted:
August 29,
2016
Received in revised form:
August 17,
2016
Received:
July 29,
2016
Identification
Copyright
Published by Elsevier Inc. on behalf of Society of Biological Psychiatry
