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

https://doi.org/10.1016/j.bpsc.2016.08.006Get rights and content

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.

Section snippets

Methods And Materials

CN older adults (n = 416) enrolled in the AIBL study (30) underwent Aβ neuroimaging and provided a blood sample to assess plasma cortisol levels. Selection into the full AIBL cohort was controlled to ensure 1) a wide age distribution from 60 years through to 100 years and 2) enrollment of approximately 50% of individuals with subjective memory complaints. Exclusion criteria for the CN older adult cohort were diagnosis of schizophrenia, depression (score ≥6 on the Geriatric Depression Scale

Results

Of the 416 CN older adults who completed the baseline assessment, 402 (96.6%), 389 (93.5%), 379 (91.1%), and 347 (83.4%) completed 18-, 36-, 54-, and 72-month follow-ups, respectively. Table 1 shows characteristics of the full sample and the sample stratified according to cortisol and Aβ status at the baseline assessment. Compared with the low-cortisol/Aβ− and high-cortisol/Aβ− groups, the low-cortisol/Aβ+ and high-cortisol/Aβ+ groups were older and more likely to be APOE ε4 allele carriers. No

Discussion

Results of this study supported our hypothesis that Aβ+ would be associated with greater cognitive decline, and that high plasma cortisol levels would moderate cognitive decline related to Aβ+, such that Aβ+ CN older adults with high plasma cortisol levels would have greater rates of decline in cognitive function compared with Aβ+ CN older adults with low plasma cortisol levels. By convention (41), the combined effect of high cortisol level and Aβ+ was moderate in magnitude for episodic memory

Acknowledgments And Disclosures

The Australian Imaging, Biomarkers and Lifestyle (AIBL) study was supported in part by the study partners (Commonwealth Scientific Industrial and Research Organization, Edith Cowan University, Mental Health Research institute, National Ageing Research Institute, Austin Health, CogState Ltd.). The study also was supported by the National Health and Medical Research Council (NHMRC) and the Dementia Collaborative Research Centres program; the Science and Industry Endowment Fund; Cooperative

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