Did you know stroke is the largest cause of disability in the UK and the fourth biggest killer? To mark Stroke Awareness Month, Dr Fatemeh Geranmayeh from the Department of Brain Sciences sheds light on her recent research looking at the recovery of cognitive functions after cerebrovascular disease and the ‘prediction problem.’
Stroke is a leading cause of death and disability worldwide. Given that stroke strikes every five minutes here in the UK, chances are that you personally know someone affected by stroke. Of the 1.3 million stroke survivors, three quarters have problems with cognition (that is problems with memory, thinking, language, problem solving, numbers or planning actions). A significant proportion (a third) develop dementia within five years. It’s not surprising therefore that vascular brain health is beginning to get the attention that it deserves in the field of dementia research.
The spectrum of post-stroke cognitive deficits is broad with significant negative impacts on therapy engagement, mental health, employment and societal costs. Consequently, diagnosis and treatment of cognitive impairment following stroke have been highlighted as priority by patients and national guidelines for stroke management.
From a research perspective, much effort has been put into understanding the ‘prediction problem’; that is which patients are likely to a) recover cognition, b) show cognitive deterioration requiring additional monitoring and care needs, and c) benefit most from personalised therapy.
Much of this work began with classic lesion-behaviour mapping – examinations of how specific brain lesions, typically resulting from injury or disease, correlate with particular behavioural deficits or changes – by the neuroscience giants of the 19th and early 20th century, such as those by Karl Wernicke, Paul Broca, Norman Geschwind and Wilder Penfield to name a few. More recently these cognitive functions, previously localised to a single lesion, are thought to be mediated via a more distributed network of brain regions. Therefore, the residual brain function after stroke is not only dictated by the stroke lesion anatomy, but also by the health of the rest of the brain. The latter is largely dictated by global brain aging, pre-existing neurodegenerative pathology or small vessel disease. Furthermore, post-stroke cognition is additionally affected by mood disorders which are themselves incredibly common after stroke (1/4 of patients have depression after stroke).
To address this gap, the Clinical Language and Cognition lab, led by Dr Fatemeh Geranmayeh, funded by the Medical Research Council, is conducting a large study of patients with stroke entitled the IC3 study (Imperial Comprehensive Cognitive assessment in Cerebrovascular disease). This is a longitudinal observational study, currently open to recruitment, with the aim of improving prediction of post-stroke cognitive outcomes using deep cognitive phenotyping – assessing and categorising participants based on their cognitive abilities, clinical characteristics and performance. (see ClinicalTrials.gov: NCT05885295). The overall aim is to improve prediction of stroke outcome by taking a holistic view using multimodal brain imaging (structural and functional brain imaging), and blood biomarkers of neuroaxonal injury – damage to the brain’s long connecting nerve fibers (axons), non-specific neurodegeneration as well as Alzheimer’s-specific pathology. The latter blood biomarkers have not been studied in patients with significant vascular disease burden, and in fact patients with stroke were largely excluded from the studies that confirmed the role of these blood biomarkers in Alzheimer’s disease. Therefore, there is a need to study them in patients with stroke.
As part of the IC3 study, we have been developing an online cognitive testing tool to allow reliable and cheap testing of cognition in patients after stroke. We have tested this in over six thousand older adults, and validated its use against commonly used clinical cognitive assessments in patients with stroke.
Despite the national recommendations for cognitive testing in patients with stroke, many patients with cognitive impairment remain undiagnosed, and untreated with significant impact on their life and that of their carers. This is largely due to cost and workforce pressures facing the NHS, with severe shortage of psychology services for stroke, currently at 10% of the required level, according to the latest national audits. Furthermore, in the absence of a gold-standard approach for identifying these deficits, clinicians often adopt an ad-hoc selection of cognitive tests which are largely insensitive to mild stroke-specific impairments.
We hope to develop the IC3 online cognitive testing tool further for use in the clinical setting. As a cost-effective, sensitive, and scalable tool for rapid cognitive phenotyping of patients with stroke and related vascular disorders, we hope that the IC3 will address significant unmet clinical benchmarks and research priorities. In the healthcare setting, it will deliver personalised testing and triaging of a wide range of disorders with vascular components, e.g. after stroke, allowing diversion of limited resources to therapy provision. In the research setting, it would facilitate drug/rehabilitation trial monitoring and large-scale mechanistic population-based studies as a standard cognitive outcome measure.