Poster No:
1123
Submission Type:
Abstract Submission
Authors:
Annelies van't Westeinde1, Olle Kämpe1, Sophie Bensing1, Svetlana Lajic1
Institutions:
1Karolinska Institute, Stockholm, Stockholm's Län
First Author:
Co-Author(s):
Olle Kämpe
Karolinska Institute
Stockholm, Stockholm's Län
Introduction:
Individuals with autoimmune Addison's disease (AAD) lack production of adrenal hormones and therefore need to take daily oral replacement for cortisol and aldosterone (Husebye, Pearce et al. 2021). This replacement in its current form is sub-optimal, and frequently results in supra- and infra-physiological cortisol levels that might negatively affect the brain and cognitive functioning. Research has begun mapping the effects of having AAD on cognition, neuro-structure and neuro-function, in an effort to understand if the brain needs to be better protected in this patient group (Schultebraucks, Wingenfeld et al. 2015, Russell, Kalafatakis et al. 2023). Our group has found some indication of reduced total brain volume and changes in resting-state connectivity in individuals with AAD (Van't Westeinde, Padilla et al. 2022, Van't Westeinde, Padilla et al. 2023). Most notably, women with AAD report to be mentally fatigued, which impairs their daily functioning (van't Westeinde, Ström et al. 2022). The present study aims to further our understanding of brain function in AAD by investigating brain activity during verbal and visuo-spatial working memory in a cohort of young adults with AAD, compared to healthy controls. In addition, we investigate the modulating role of mental fatigue.
Methods:
All participants (56 with AAD (33 females) and 62 controls (39 females), aged 19-43 years), underwent MRI scanning of the brain while performing a visuo-spatial and verbal working memory task. FSL was used to compare task-related BOLD-signal between patients and controls, for the encoding and decoding phases of both tasks. In addition, we estimated the temporal standard deviation of the BOLD-signal in certain regions of interest where a significant group difference or interaction was found. Estimates of working memory performance included reaction time, variability in reaction time (coefficient of variation) and accuracy. Self-reported mental fatigue in the two days prior to testing was estimated with the multidimensional fatigue inventory (MFI), which was used in an analysis testing if the relationship between fatigue and brain activity during the task differed between patients and controls.
Results:
No difference in mean accuracy, reaction time or brain activity during the working memory tasks were found between the groups, and there were no interactions with sex. Patients did have more variable reaction times during the control conditions of both tasks. In addition, a differential association between mental fatigue and brain activity during the visuo-spatial task was found in a cluster in the right occipital pole (80 voxels, peak MNI 32, -94, -6), and three in the cerebellum, specifically a cluster covering Vermis VI; Left V and Bilateral VI, (117 voxels, peak MNI -4, -68, -10), a cluster in Right I-IV (67 voxels, peak MNI 8, -50, -20) and a cluster in Right Crus I (67 voxels, peak MNI 40, -82, -30), where patients with more mental fatigue had stronger activity in these clusters. Stronger activity in the right occipital pole was associated with slower reaction times in patients, and a greater temporal standard deviation in the bilateral cerebellum region VI was associated with more mental fatigue in patients, but not controls.
Conclusions:
These findings suggest that while patients perform at the same level as controls on this specific task, mental fatigue is affecting their brain activity, in particular in the cerebellum and primary visual areas. Our findings suggest that the cerebellum is involved in fatigue and performance regulation in patients with AAD, which is in line with a recent study showing the involvement of cerebellar excitability in fatigue regulation (7). Future studies are needed to better understand fatigue in patients with AAD, how to improve this and how to best protect their brains on the long term. In particular, the development of a pump to deliver cortisol might help improve brain function in AAD and should be further investigated (3).
Learning and Memory:
Working Memory 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Keywords:
Cerebellum
1|2Indicates the priority used for review
Provide references using author date format
Casamento-Moran, A. (2023). "Cerebellar Excitability Regulates Physical Fatigue Perception." J Neurosci 43(17): 3094-3106.
Husebye, E. S. (2021). "Adrenal insufficiency." Lancet 397(10274): 613-629.
Russell, G. (2023). "Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial." J Intern Med.
Schultebraucks, K. (2015). "Cognitive function in patients with primary adrenal insufficiency (Addison's disease)." Psychoneuroendocrinology 55: 1-7.
Van't Westeinde, A. (2023). "Increased resting-state functional connectivity in patients with autoimmune Addison's disease." J Clin Endocrinol Metab.
Van't Westeinde, A. (2022). "Brain structure in autoimmune Addison's disease." Cereb Cortex.
van't Westeinde, A. (2022). "Young adult Swedish patients with autoimmune Addison's disease report difficulties with executive functions in daily life despite overall good cognitive performance." Psychoneuroendocrinology. 140: 105714.