High Plasma Cortisol Levels Associated with Global Cognition Deterioration

Healthy older people with high plasma cortisol levels show a significantly greater risk of the presence of beta-amyloid in the brain, in addition to greater declines in global cognition over 54 months, compared with those with low cortisol levels.

The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly measured according to plasma cortisol levels, and is linked to cognitive dysfunction, hippocampal atrophy and an increased risk for Alzheimer’s disease. However less is known of the role of cortisol levels in the prediction of cognitive decline or in moderating the effect of beta-amyloid in preclinical Alzheimer’s disease.


Scientists at the Florey Institute of Neuroscience and Mental Health (Melbourne, Australia) evaluated 401 cognitively normal adults enrolled in the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) who had undergone beta-amyloid neuroimaging at a single time point. The subjects also had comprehensive assessment of neuropsychological measures including global cognition, episodic memory and executive function at baseline, as well as follow-ups at 18, 36, and 54 months.

The team found that after 54 months higher plasma cortisol levels at baseline were associated with a 2.2 times greater risk of having beta-amyloid presence. The higher cortisol levels were also associated with increased declines in global cognition in general, and, compared with older adults with low cortisol and beta-amyloid deposits, those with high cortisol and beta-amyloid showed faster declines in various measures, with Cohen’s d values of 0.69 for episodic memory, 0.42 for global cognition, and 0.31 for attention. The effects were observed after adjusting for factors age, education, premorbid intelligence, Apolipoprotein E (APOE) and Brain-derived neurotrophic factor (BDNF) genotypes, subjective memory complaints, vascular risk factors, and depression and anxiety symptoms.

The authors concluded that in cognitively normal older adults, high plasma cortisol levels are associated with greater decline in global cognition, and accelerate the effect of beta-amyloid on decline in global cognition, episodic memory, and attention over at 54-month period. These results suggest that therapies targeted toward lowering plasma cortisol and beta-amyloid levels may help mitigate cognitive decline in the preclinical phase of Alzheimer’s disease. The study was presented at the Alzheimer’s Association International Conference, held July 22-28, 2016, in Toronto, ON, Canada.

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Florey Institute of Neuroscience and Mental Health