Belcher, Andrew
(2021)
Cognitive impairment in stroke and multiple sclerosis.
PhD thesis, University of Nottingham.
Abstract
Background: Due to the world’s ever-growing and ageing population, dementia and cognitive impairments are major global health and socioeconomic burdens. Stroke is a leading cause of acquired cognitive impairment and dementia. Multiple sclerosis (MS) although less common than stroke, also causes cognitive impairment and in rare cases overt dementia. The risk factors for cognitive decline are still not fully understood and there is currently no recommended intervention for preventing cognitive decline. Therefore, we must determine which risk factors are associated with cognitive impairment and which interventions can help to delay or prevent the onset of cognitive impairment, to reduce the number of people who suffer from cognitive decline.
Methods and results: The clinical and radiological predictors of post-stroke cognitive impairment (PSCI), following an ischaemic stroke (IS) or transient ischaemic attack (TIA) in previously independent adults, were investigated using data from the international multicentre randomised control trials, ENOS and TARDIS. Together (Chapter 3), this dataset of 4798 participants, is one of the largest international hospital-based studies of PSCI to date. The predictors of post-stroke cognitive decline in this cohort were older age, greater stroke severity (National Institute of Health Stroke Scale (NIHSS)), pre-stroke disability (modified Rankin Scale (mRS)), non-UK participants, history of atrial fibrillation, lower systolic blood pressure, and higher heart rate.
The clinical and radiological predictors of PSCI, following an intracerebral haemorrhage (ICH) in previously independent adults, were investigated using data from the international multicentre randomised control trial, TICH-2 (Chapter 4). This study involved 693 participants and is one of the largest cohorts of ICH survivors that focused on cognitive impairment. The predictors of long-term SCI were older age, non-Caucasian ethnicity, a greater level of deprivation (Index of Multiple Deprivations (IMD)), reduced level of consciousness (Glasgow coma scale (GCS)) and lobar ICH.
The effectiveness of intensive blood pressure and lipid-lowering on cognitive outcomes in patients with a recent stroke was investigated in the multicentre randomised trial, PODCAST (Chapter 5). Intensive BP and lipid-lowering did not alter cognition and did not have any long-lasting effects on cognition in participants approximately 5 years after stroke. Intensive lipid-lowering might still be partially effective at 33 months according to the global outcome and global cognition analysis.
The effectiveness of live hookworm infection on cognition in multiple sclerosis (MS) patients, as well as the clinical and radiological associations of cognitive function in MS patients, was investigated in the WIRMS trial (Chapter 6). We showed that there were no effects of hookworm infection on cognitive function, quality of life or fatigue over the 6 months of active treatment. We also showed there was no significant change in the cognition and functional outcomes over time in all participants and across both treatment groups. Worse cognitive function was associated with a greater number of T2 lesions and a poorer quality of life.
Discussion: The key predictors of cognitive impairment after IS and ICH were older age, a greater stroke severity, and non-UK/non-Caucasian ethnicity. Blood pressure and heart rate were identified as potential therapeutic targets for the prevention of cognitive decline after IS. An important predictor of cognitive decline after ICH was a greater level of social deprivation. Blood pressure and lipid interventions in stroke patients, and parasitic infection in MS patients, did not affect cognitive function, however, they are still feasible and require further study. A major limitation of cognition studies is the loss of participants to follow up due to disease severity therefore informant-based cognition questionnaires are essential. Future research should consider accounting for a participant’s level of education, ethnicity and other race-related factors, socioeconomic status, and should perform MRI scans and genetic analysis (AD biomarkers) where possible.
Conclusion: In conclusion, cognitive impairment due to stroke or multiple sclerosis is a socioeconomic burden that will continue to grow without further research into its risk factors and in turn potential interventions.
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