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Does Stress Worsen Cognitive Functions?

Does Stress Worsen Cognitive Functions?

Prolonged stress is often associated with health problems, such as heart disease, anxiety disorders, and sleep problems. A recent study published in Neurology reported that higher blood levels of the stress hormone cortisol are also associated with memory impairments and smaller brain volumes in young and middle-aged adults [1]. This relationship was especially pronounced in women compared to men.

These findings come from a large study of 2,231 men and women (average age, 48.5 years old) who were free of dementia. Their blood cortisol levels were measured, and then cognitive functions were evaluated, including memory, abstract reasoning, visual perception, attention, and executive function. Brain MRI imaging was also carried out in most of the participants (2,018 people) and total brain volume, brain volumes of different brain regions, and structural changes in the brain were assessed.

After adjusting for many variables, people with high blood cortisol levels (in the highest third) had smaller total cerebral brain volume compared to people who had average levels (in the middle third). Interestingly, this association was present in women but not among men, though the reason for this sex difference is unknown. Furthermore, compared to people with average cortisol levels, those with high cortisol levels had worse visual perception, memory, and global cognitive function. These associations between high cortisol levels and worse cognitive functions were found in both men and women.

These results are largely consistent with findings from previous studies, though most prior studies had focused on the relationship between cortisol levels and sizes of the hippocampus, a brain region important for memory functions [2][3]. The current study found that the associations between cortisol levels and brain structure are not specific to the hippocampus but occur throughout the brain.

While this study was strong in terms of its large size, extensive brain imaging data, and adjustment for potential variables that could confound the data, there were some limitations. Cortisol levels were measured only at a single time point so it is not known if this measure represents the individual's average cortisol level across time. Also, because this study was an observational study, it was not designed to prove that high cortisol levels cause brain shrinkage or cognitive decline. It is worth noting that there is a clinical trial currently underway that is testing whether a drug that inhibits the actions of cortisol can effectively treat people with mild Alzheimer's disease [4]. This study is scheduled to be completed in the summer of 2019.

If you have high stress levels, protect your brain by making changes to your lifestyle and learning ways to cope. The Centers for Disease Control and Prevention offers tips to reduce stress, such as eating healthy, exercising, and getting enough sleep.


  1. Echouffo-Tcheugui JB, Conner SC, Himali JJ et al. (2018) Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology 91, e1961-e1970.
  2. Knoops AJ, Gerritsen L, van der Graaf Y et al. (2010) Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study. Biol Psychiatry 67, 1191-1198.
  3. Lupien SJ, de Leon M, de Santi S et al. (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1, 69-73.
  4. Ruffles V (2016) A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu) (XanADu). ClinicalTrials.gov.

Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.

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