Chronic stress is a contributing factor to cognitive aging, and genetic factors may amplify its role in cognitive dysfunction. Acute ischemic stroke, a well-known risk factor for dementia and cognitive decline is associated with elevated levels of cortisol, the primary stress hormone. In a newly published prospective study, Tel Aviv Medical Center researchers led by Dr. Einor Ben Assayag evaluated whether higher cortisol levels at bedtime and post-awakening are associated with long-term brain alterations and changes in cognitive performance [NeuroTrax], and whether APOE genotype modifies these associations in stroke patients.

Participants were 182 cognitively intact ischemic stroke and transient ischemic attack (TIA) survivors from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study. Salivary cortisol levels (bedtime and post-awakening) were measured and computerized cognitive assessment [NeuroTrax] completed on admission and after 6, 12, and 24 months. During hospitalization, participants received 3T MRI scans and APOE genotyping. Higher bedtime cortisol levels immediately post-stroke were associated with larger neurological deficits as well as poorer white matter integrity and cognitive function (executive function, attention, and overall) up to 24 months post-stroke. These findings remained significant after adjustment for age, gender, education, smoking, stroke severity, apolipoprotein E4 (ApoE4) status, and body mass index. The deleterious effect of high bedtime cortisol on memory was more pronounced for carriers of the ApoE4 genotype. Participants with high admission bedtime cortisol levels continued to have relatively elevated bedtime levels across all examined timepoints, and this group had poorer memory and executive function scores compared with the lower cortisol group at 24 months post-stroke. Post-awakening cortisol levels were not associated with neuroimaging findings or cognitive performance.

In summary, high bedtime salivary cortisol level may predict worse cognitive outcome in stroke survivors up to 2 years after the event, and this association may be modified by ApoE4 genotype. To mitigate these effects, the authors recommend stress management interventions in these patients. Of note, the authors cite “use of an extensive and validated computerized cognitive tool battery of multi-domain cognitive tests” [NeuroTrax] as a study strength.

Citation:
Tene, O., Hallevi, H., Korczyn, A.D., Shopin, L., Molad, J., Kirschbaum, C., Bornstein, N.M., Shenhar-Tsarfaty, S., Kliper, E., Auriel, E., Usher, S., Stalder, T., and Ben Assayag, E. (2018). The price of stress: High bedtime salivary cortisol levels are associated with brain atrophy and cognitive decline in stroke survivors. Results from the TABASCO prospective cohort study. Journal of Alzheimer‘s Disease, 65, 1365–1375. PMID: 30149451