Major Adverse Cognitive Events (MACE-Cog): A New “MACE” Framework for Cognitive Outcomes in Cardiovascular Diseases and Stroke
Abstract
Cardiovascular diseases, particularly stroke, are leading causes of dementia. Several common cardiac interventions such as coronary artery bypass grafting and transcatheter aortic valve implantation are also associated with cognitive decline. However, cognitive outcomes continue to be poorly collected in clinical trials of cardiovascular diseases. In this article, we review the limitations of current approaches to cognitive assessment in cardiovascular disease studies. When assessed, there is wide variation in cognitive tasks used, and tasks have limited population-specific validation, are subject to floor and ceiling effects, and may suffer from sociocultural and linguistic biases. Many tasks are not available in multilingual formats and often rely on face-to-face testing with trained coordinators. All conventional cognitive outcomes in cardiovascular trials are associated with substantial incompletion, especially among older and more impaired individuals, the very people most important to capture. This nonrandom missingness generates survivor and attrition biases, an unacceptable situation for any trial outcome. Last, the meaning of measured cognitive outcomes is often unclear for patients, caregivers, clinicians, and regulators. To help address these limitations, we propose a new framework, major adverse cognitive events (MACE-Cog), to better capture cognitive outcomes in stroke and other cardiovascular populations. As an inclusive construct reflecting the multidimensional nature of cognitive decline, major adverse cognitive events do not rely solely on performance on cognitive testing but also consider inability to complete cognitive testing due to cognitive-behavioral factors, reported symptoms of cognitive decline, impairment in activities of daily living as a result of cognitive impairment, new clinical diagnoses of dementia, and care home admission. We hope that the proposed composite outcome and multiple use cases presented spark progress in cardiovascular research toward more inclusive approaches to the study of cognitive outcomes that move beyond the confines of cognitive tests alone.
Article Details
Authors (20)
Aravind Ganesh
Department of Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
Sajeevan Sujanthan
Institute of Medical Sciences, ON, Canada (S.S., R.T.M., R.H.S.)
Ryan T. Muir
Institute of Medical Sciences, ON, Canada (S.S., R.T.M., R.H.S.)
Raed A. Joundi
McMaster University, Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada
Michael D. Hill
Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary and Foothills Medical Centre, Calgary, AB, Canada
Terence J. Quinn
School of Cardiovascular and Metabolic Health, University of Glasgow, UK (T.J.Q.).
Bijoy Menon
Calgary Stroke Program, Departments of Clinical Neurosciences, Radiology, Medicine, and Community Health Sciences; Hotchkiss Brain Institute, Mathison Centre for Mental Health Research and Education, and O’Brien Institute for Public Health; University of Calgary Cumming School of Medicine, AB, Canada (A.G., M.D.H., B.M., T.S., E.E.S.)
Tolulope Sajobi
Calgary Stroke Program, Departments of Clinical Neurosciences, Radiology, Medicine, and Community Health Sciences; Hotchkiss Brain Institute, Mathison Centre for Mental Health Research and Education, and O’Brien Institute for Public Health; University of Calgary Cumming School of Medicine, AB, Canada (A.G., M.D.H., B.M., T.S., E.E.S.)
Jennifer S. Rabin
Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre (J.S.R., S.S., R.T.M., R.H.S.)
Katie N. Dainty
Morgan D. Barense
Department of Psychology, ON, Canada (M.D.B.)
Krista L. Lanctôt
Department of Psychiatry, Sunnybrook Health Sciences Centre, ON, Canada (K.L.L.)
James Kennedy
Acute Multidisciplinary Imaging and Interventional Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
Rajesh K. Kharbanda
Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Douglas S. Lee
Mario F.L. Gaudio
Weill Cornell Medicine, New York, NY (M.F.G.).
Stephen Fremes
Institute of Health Policy, Management and Evaluation, ON, Canada (K.N.D., S.F.)
Ruth M. Masterson Creber
Columbia University School of Nursing, Columbia University Irving Medical Center, New York, NY (R.M.M.C.).
Eric E. Smith
Richard H. Swartz
Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto