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

Article type: Research Article

Authors: Tene, Oren^{a; b} | Hallevi, Hen^{a; b} | Korczyn, Amos D.^b | Shopin, Ludmila^a | Molad, Jeremy^a | Kirschbaum, Clemens^c | Bornstein, Natan M.^{b; d} | Shenhar-Tsarfaty, Shani^a | Kliper, Efrat^a | Auriel, Eitan^e | Usher, Sali^a | Stalder, Tobias^{c; f} | Ben Assayag, Einor^{a; b; *}

Affiliations: [a] Department of Neurology and Psychiatry, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel | [b] Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel | [c] Department of Psychology, TU Dresden, Germany | [d] Brain Center, Shaare Zedek Medical Center, Jerusalem, Israel | [e] Carmel Medical Center, Haifa, Israel | [f] Department of Clinical Psychology, University Siegen, Germany

Correspondence: [*] Correspondence to: Einor Ben Assayag, PhD, Department of Neurology, Tel-Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel. Tel.: +972 3 6947868; Fax: +972 3 6972189; E-mail: einorba@tlvmc.gov.il.

Abstract: Background and Objective:Previous studies suggest that excessive cortisol levels after stroke are associated with cognitive dysfunction. However, limited data exist regarding associations between post-stroke cortisol levels, brain abnormalities, genetic factors, and cognitive outcome. We sought to study these issues in a longitudinal stroke survivors cohort. Methods:Data from 182 cognitively intact ischemic stroke patients from the TABASCO study were available. Saliva cortisol levels (bedtime and post-awakening) and cognitive assessments were obtained on admission, and 6, 12, and 24 months thereafter. During hospitalization, patients underwent 3T MRI scans and APOE genotyping. Results:Higher bedtime cortisol levels immediately post-stroke were associated with larger neurological deficits (p < 0.001), brain atrophy (p = 0.025), worse white matter integrity (p = 0.003), and worse cognitive results up to 24 months post-stroke. These findings remained significant when adjusted for age, gender, education, smoking, stroke severity, apolipoprotein E4 (ApoE4) status, and body mass index. ApoE4 negatively modified the relation between cortisol and memory. As a group, participants who presented with high admission bedtime cortisol levels continued to present relatively elevated bedtime levels across all examined time-points, and this group had inferior memory and executive functioning scores compared to the lower cortisol group 24 months post-stroke (p = 0.05, p = 0.035, respectively). Post-awakening cortisol levels were not associated with neuroimaging findings or cognitive scores. Conclusions:High bedtime salivary cortisol levels post-stroke may provide information about dysregulation of diurnal HPA-axis activity under acute challenge conditions, and predict worse cognitive outcome. ApoE4 genotype might modify this association. These findings call for specific stress management interventions in stroke survivors.

Keywords: ApoE4, brain atrophy, cognitive impairment, HPA axis, salivary cortisol, stroke

DOI: 10.3233/JAD-180486

Journal: Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1365-1375, 2018