Plasma cortisol, brain amyloid-β, and cognitive decline in preclinical Alzheimer’s disease: A 6-year prospective cohort study
Robert H. Pietrzak
Simon Laws, Edith Cowan UniversityFollow
Yen Ying Lim
Sophie J. Bender
Tenielle Porter, Edith Cowan UniversityFollow
Colin L. Masters
Lidija Milicic, Edith Cowan UniversityFollow
Stephanie Rainey-Smith, Edith Cowan UniversityFollow
Victor L. Villemagne
Christopher C. Rowe
Ralph Martins, Edith Cowan UniversityFollow
Australian Imaging, Biomarkers and Lifestyle Research Group
Simon Laws Orcid: https://orcid.org/0000-0002-4355-7082 Ralph Martins Orcid: https://orcid.org/0000-0002-4828-9363
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Aging, Amyloid, Cognition, Cortisol, Epidemiology, Memory
Centre of Excellence for Alzheimer’s Disease Research and Care
National Health and Medical Research Council
NHMRC Number : 1009292
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.
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 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.
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.