Introducing the IC3 study - Deep cognitive phenotyping of patients with cerebrovascular disease in relation to novel plasma and MRI brain biomarkers

Abstract

Introduction: Cerebrovascular disease is a leading cause of death and disability worldwide. Identification and treatment of cognitive impairment following cerebrovascular disease (such as following stroke) remains a large unmet need. There is a growing need for in-depth scalable and cost-effective longitudinal assessment of cognitive function to better understand the range of factors that contribute to long-term cognitive outcomes after a vascular insult. To address this gap and to capitalise on the recent growth of telemedicine, we developed the IC3 online tool (Imperial College Comprehensive assessment for Cerebrovascular disease; https://ic3study.co.uk/) combined with MRI brain imaging and plasma biomarkers to identify novel multimodal predictors of recovery after stroke (Figure 1).Figure 1: Study Timeline. Methods: The IC3 platform is a web-based digital technology, designed to detect both domain-general and domain-specific cognitive deficits prevalent in cerebrovascular disease (Figure 2). Demographic, socio-economic, and neuropsychiatric information is collected alongside 22 short, computerised cognitive tests, with minimal input from a health professional, at 0-, 3-, 6-, and 12-months post- stroke. These are related to structural and functional brain MRI and plasma biomarkers (such as plasma brain-derived tau, neurofilament light, glial fibrillary acidic protein and amyloid entities). Results: We present IC3 assessment results from N>5000 older adults. We outline the cognitive performance of a modest sample of patients with stroke against a gender-, age- and education- matched control sample. Furthermore, we present an overview of our validation studies which examine the battery's specificity and sensitivity, and test-retest reliability. Finally, as the assessment has been designed to be self-administered remotely, we also present validation against face-to-face supervised delivery of the battery and discuss the effect of several technical confounds affecting a patient's performance (such as device type, operating system, and motoric impairments). Discussion: The IC3 tool is the first assessment to offer a an in-depth relatively unsupervised cognitive phenotyping of patients with cerebrovascular disease, facilitating scalable and cost-efficient longitudinal monitoring of cognition in this group. The assessment fares very well against various validation methods, making it an attractive tool for understanding the mechanisms of recovery in relation to novel brain and plasma biomarkers in a plethora of cerebrovascular disorders.