Major Adverse Cognitive Events (MACE-Cog): A New "MACE" Framework for Cognitive Outcomes in Cardiovascular Diseases and Stroke.

Ganesh A., Sujanthan S., Muir RT., Joundi RA., Hill MD., Quinn TJ., Menon B., Sajobi T., Rabin JS., Dainty KN., Barense MD., Lanctôt KL., Kennedy J., Kharbanda RK., Lee DS., Gaudio MFL., Fremes S., Masterson Creber RM., Smith EE., Swartz RH.

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.

DOI

10.1161/CIRCULATIONAHA.125.077180

Type

Journal article

Publication Date

2026-07-28T00:00:00+00:00

Volume

154

Pages

378 - 394

Total pages

16

Keywords

cardiovascular diseases, cognition, randomized controlled trial, stroke, Humans, Stroke, Cardiovascular Diseases, Cognition, Cognition Disorders, Cognitive Dysfunction

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