- Title
- Investigation of cognition after stroke a translational approach
- Creator
- Chow, Wei Zhen
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2020
- Description
- Higher Doctorate - Doctor of Philosophy (PhD)
- Description
- Stroke survivors often report worse cognitive function post-stroke, that can extend for months or years. Cognitive impairment reduces long-term quality of life in stroke survivors, increases the risk of developing dementia and affects participation in stroke rehabilitation programs. At present, no approved pharmacological therapy or rehabilitation program exists that can help improve cognitive function after stroke. Current understanding of factors that affect recovery of cognitive function after stroke is limited. This has hindered the development and evaluation of novel therapies and interventions in clinical research. These limitations include (i) understanding the impact of chronic stress and resilience on cognitive function after stroke, (ii) identifying which specific cognitive domains are more important to, or strongly associated with, long-term stroke recovery and quality of life (QOL), and (iii) the lack of similar testing methods to evaluate cognitive function after stroke in preclinical (animal) studies and clinical research. As such, there remains no proven therapy to improve cognitive function in stroke survivors. This thesis therefore aimed to address these major research gaps by investigating cognition post-stroke in both clinical and pre-clinical studies using a translational approach in the chronic recovery phase. In the cross-sectional clinical trial (Stress in people recovering from stroke), the role of chronic stress and resilience in determining stroke recovery was investigated. Perceived stress and resilience were assessed in stroke survivors and a control group who had no previous history of stroke, using the Perceived Stress scale (PSS) and Brief Resilience scale (BRS) while stroke recovery was assessed using the Stroke Impact Scale (SIS). Stroke survivors reported higher perceived stress and lower resilience compared to controls. In stroke survivors, both perceived stress and resilience were associated with worse stroke recovery, specifically in mood, memory and communication dimensions. Since stress and resilience are known modifiers of stress, these results suggest developing stress minimising or resilience-building strategies may represent future potential therapies for improving cognitive function during stroke recovery. In the same cohort of stroke survivors, the relationship between cognitive function and long-term QOL was explored. Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and self-reported health-related quality of life (HRQOL) was assessed using the SIS. Compared to controls, stroke survivors demonstrated worse cognitive performance in the visuospatial paired-associates learning (PAL), reaction time and executive function tasks. These were associated with worse stroke outcomes, especially in the memory and communication dimensions. These results suggest that specific cognitive domains may play important roles in determining long-term recovery after stroke. Future studies could investigate further whether cognitive rehabilitation programs that target these domains are effective to improve functional outcomes in stroke survivors. In order to help improve the translational value of cognitive assessment post-stroke, a comparable touchscreen-based PAL test was used to assess associative learning (in separate experiments) in both stroke survivors and a mouse model of stroke in the chronic recovery phase. The results of this study demonstrated a similar form of cognitive impairment in both stroke survivors and mice. This study represents the first alignment of cognitive assessments using touchscreen platforms in both humans and animal models following stroke. These findings represent the first step towards bridging the translational gap in stroke research, expanding the potential for clinically relevant research to be conducted in pre-clinical models to further investigate neural mechanisms and cognitive outcomes during stroke recovery. The potential for growth hormone therapy to improve cognitive function and induce neural repair mechanisms after stroke was explored in an experimental stroke model. Growth hormone was administered subcutaneously for 28 days, staring 48 hours post-induction of experimental stroke. Cognitive performance was assessed using the rodent touchscreen PAL test. In rodents treated with growth hormone therapy, cognitive performance was improved compared to a control (sham) group. Analysis of brain tissue revealed this therapy stimulated brain repair processes post-stroke, resulting in reduced tissue loss in the peri-infarct and increased expression of neurotrophic factors, neural plasticity and vascular remodelling markers. These findings provide compelling novel pre-clinical evidence to support the efficacy of growth hormone therapy for improving cognition post-stroke, paving the way for future clinical trials that evaluate the effects of growth hormone therapy on cognitive outcomes in stroke survivors. In conclusion, this thesis has produced several novel findings that have improved our current understanding of cognitive function in both stroke survivors and animal models in the chronic recovery phase. Cognitive impairment is an important concern for stroke survivors as it can persist for years and decreases long-term QOL. These findings suggest it may be possible to improve stroke recovery and QOL by modifying stress and resilience levels to help in the adjustment to life after stroke. Further, the pre-clinical evidence demonstrating that growth hormone improves cognitive function after stroke may lead to the development of a new pharmacological option for cognitive impairment after stroke. The evidence supporting the use of touchscreen platforms for assessment of cognition in humans and animal models of stroke may help accelerate the translation of stroke research from the bench to bedside, bridging the translational gap between humans and animal models.
- Subject
- stroke; cognition; translational; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1428349
- Identifier
- uon:38621
- Rights
- Copyright 2020 Wei Zhen Chow
- Language
- eng
- Full Text
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| Thumbnail | File | Description | Size | Format | |||
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| View Details Download | ATTACHMENT01 | Thesis | 29 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 444 KB | Adobe Acrobat PDF | View Details Download |