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

详细信息    查看全文

• 作者：Robert H. Pietrzak^a ; ^b ; ¹ ; ^{robert.pietrzak@yale.edu} ; Simon M. Laws^c ; ^d ; ¹ ; Yen Ying Lim^e ; Sophie J. Bender^f ; Tenielle Porter^c ; ^d ; James Doecke^g ; David Ames^h ; ⁱ ; Christopher Fowler^e ; Colin L. Masters^e ; Lidija Milicic^c ; Stephanie Rainey-Smith^c ; Victor L. Villemagne^e ; ^j ; ^k ; Christopher C. Rowe^j ; ^k ; Ralph N. Martins^c ; ^j ; ¹ ; Paul Maruff^e ; ^l ; ^m ; ¹ ; for the Australian Imaging ; Biomarkers ; Lifestyle Research Group
• 关键词：Aging ; Amyloid ; Cognition ; Cortisol ; Epidemiology ; Memory
• 刊名：Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：2
• 期：1
• 页码：45-52
• 全文大小：258 K
• 卷排序：2

文摘

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.MethodsUsing 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.ResultsResults 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.ConclusionsIn 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.