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Cognitive Sub-groups in ALS: Neuroanatomical Associations and Theory of Mind Impairments
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- Author / Creator
- Chenji, Sneha R.
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Amyotrophic Lateral Sclerosis (ALS) involves the progressive loss of upper and lower motor neurons. Frontotemporal lobar degeneration (FTLD) has been reported in a considerable proportion of patients, manifesting as cognitive and behavioural impairment in at least 25-50%, with 10-15% patients meeting criteria for co-morbid frontotemporal dementia (FTD). Executive function (EF) impairment is frequently reported while recent studies are identifying impairments in Theory of Mind (ability to decipher cognitive or emotional mental states of individuals).
The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) is emerging as an optimal screening tool to capture impairments and includes a test for ToM. Aim 1 of the thesis was to identify neuroanatomical associations using the ECAS. The study identified EF impairments in a sub-group of patients with ALS. Patients with impaired EF (ALS-exi) displayed a greater extent of frontotemporal white matter degeneration and focal grey matter atrophy, in line with proposed models of pathological spread of phosphorylated TAR DNA-binding protein of 43 kDa (pTDP-43) in ALS. Patients with normal EF (ALS-n) displayed changes in medial prefrontal cortex suggesting the possibility of structural changes in the absence of cognitive decline, or alternatively reflecting pathological changes in the presence of subtle cognitive changes that were not identified on the ECAS. Associations of neuroimaging metrics with EF revealed that extensive loss of white matter integrity contributed to lower EF performance.
Considering the emerging evidence of ToM impairments, aim 2 of the thesis was to identify associations between ToM and EF in ALS. The study revealed that ToM impairments were present in ALS, whereby patients displayed significantly reduced abilities to infer thoughts and emotions. ALS-exi patients performed worse than ALS-n patients, thus suggesting a link between EF and ToM performance.
To follow-up with the observed ToM impairments, aim 3 of the thesis was to identify structural and functional changes in brain regions associated with ToM deficits. ALS patients and healthy controls in this experiment were a sub-cohort of participants from the experiments for aim 1 and 2. A trend towards ToM impairments and mild atrophy in both grey matter and white matter was noted in ALS patients compared to controls. Functional changes in resting state networks were observed in ALS patients when compared to controls, however these did not reach thresholds for statistical significance. Both ToM and EF had mild associations with reduced grey matter density in the dorsolateral prefrontal cortex (dlPFC), suggesting that a shared neural substrate may be associated with the decline of both the domains.
In summary, the thesis provides evidence of frontotemporal degeneration in cognitive sub-groups identified using the ECAS. ToM impairments were identified in ALS patients and were associated with the degree of EF impairments. Mild associations of ToM and EF with grey matter density in the dlPFC suggests a shared neural substrate.
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- Graduation date
- Fall 2018
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.