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Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Jan;2(1):45-52. doi: 10.1016/j.bpsc.2016.08.006. Epub 2016 Sep 7.

Plasma Cortisol, Brain Amyloid-β, and Cognitive Decline in Preclinical Alzheimer's Disease: A 6-Year Prospective Cohort Study.

Author information

1
U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Electronic address: robert.pietrzak@yale.edu.
2
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia; Co-operative Research Centre for Mental Health.
3
The Florey Institute, The University of Melbourne, Parkville, Victoria.
4
School of Health Sciences, University of Notre Dame Australia, Fremantle, Western Australia.
5
The Commonwealth Scientific and Industrial Research Organization, Canberra.
6
Academic Unit for Psychiatry of Old Age, St. Vincent's Health, Department of Psychiatry, The University of Melbourne, Kew; National Ageing Research Institute, Parkville, Victoria.
7
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia.
8
The Florey Institute, The University of Melbourne, Parkville, Victoria; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia; Department of Nuclear Medicine and Centre for PET, Austin Health.
9
Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia; Department of Nuclear Medicine and Centre for PET, Austin Health.
10
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, Western Australia; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia.
11
The Florey Institute, The University of Melbourne, Parkville, Victoria; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg; Cogstate Ltd., Melbourne, Victoria, Australia.

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:

Aging; Amyloid; Cognition; Cortisol; Epidemiology; Memory

PMID:
29560886
DOI:
10.1016/j.bpsc.2016.08.006
[Indexed for MEDLINE]

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