Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective

Fanny M Elahi; Suvarna Alladi; Sandra E Black; Jurgen A H R Claassen; Charles DeCarli; Timothy M Hughes; Justine Moonen; Nicholas M Pajewski; Brittani R Price; Claudia Satizabal; C Elizabeth Shaaban; Nárlon C B S Silva; Heather M Snyder; Lukas Sveikata; Jeff D Williamson; Frank J Wolters; Atticus H Hainsworth

doi:10.1016/j.xcrm.2023.101089

Clinical trials in vascular cognitive impairment following SPRINT-MIND: An international perspective

Cell Rep Med. 2023 Jun 20;4(6):101089. doi: 10.1016/j.xcrm.2023.101089.

Authors

Fanny M Elahi¹, Suvarna Alladi², Sandra E Black³, Jurgen A H R Claassen⁴, Charles DeCarli⁵, Timothy M Hughes⁶, Justine Moonen⁷, Nicholas M Pajewski⁸, Brittani R Price⁹, Claudia Satizabal¹⁰, C Elizabeth Shaaban¹¹, Nárlon C B S Silva¹², Heather M Snyder¹³, Lukas Sveikata¹⁴, Jeff D Williamson¹⁵, Frank J Wolters¹⁶, Atticus H Hainsworth¹⁷

Affiliations

¹ Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka 560030, India.
³ Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
⁴ Department of Geriatric Medicine and Donders Institute for Medical Neuroscience, Radboud University Medical Center, 6525 EN Nijmegen, the Netherlands.
⁵ Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA 95817, USA.
⁶ Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
⁷ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, the Netherlands.
⁸ Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC 27154, USA.
⁹ Life Molecular Imaging, GmbH, Boston, MA 01209, USA.
¹⁰ Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, Department of Population Health Sciences, UT Health San Antonio, San Antonio, TX 78229, USA.
¹¹ Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
¹² Djavad Mowafaghian Centre for Brain Health, Department of Physical Therapy, Faculty of Medicine, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
¹³ Alzheimer's Association, 225 N Michigan Avenue, Chicago, IL 60603, USA.
¹⁴ J.P. Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Division of Neurology, Department of Clinical Neurosciences, Geneva University Hospitals, 1205 Genève, Switzerland; Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
¹⁵ Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA; Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27154, USA.
¹⁶ Departments of Epidemiology and Radiology & Nuclear Medicine, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, the Netherlands.
¹⁷ Neurology, St George's University Hospitals NHS Foundation Trust, London SW17 0QT, UK; Molecular and Clinical Sciences Research Institute, St George's University of London, London SW17 0RE, UK. Electronic address: ahainsworth@sgul.ac.uk.

Abstract

A large interventional trial, the Systolic Blood Pressure Intervention Trial sub-study termed Memory and Cognition in Decreased Hypertension (SPRINT-MIND), found reduced risk of cognitive impairment in older adults with intensive, relative to standard, blood-pressure-lowering targets (systolic BP < 120 vs. <140 mm Hg). In this perspective, we discuss key questions and make recommendations for clinical practice and for clinical trials, following SPRINT-MIND. Future trials should embody cognitive endpoints appropriate to the participant group, ideally with adaptive designs that ensure robust answers for cognitive and cardiovascular endpoints. Reliable data from diverse populations, including the oldest-old (age > 80 years), will maximize external validity and global implementation of trial findings. New biomarkers will improve phenotyping to stratify patients to optimal treatments. Currently no antihypertensive drug class stands out for dementia risk reduction. Multi-domain interventions, incorporating lifestyle change (exercise, diet) alongside medications, may maximize global impact. Given the low cost and wide availability of antihypertensive drugs, intensive BP reduction may be a cost-effective means to reduce dementia risk in diverse, aging populations worldwide.

Keywords: aging; blood pressure; clinical trials; cognitive impairment; dementia; hypertension; prevention; vascular disease.

Publication types

Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Aged, 80 and over
Antihypertensive Agents / therapeutic use
Cognitive Dysfunction* / drug therapy
Dementia* / prevention & control
Humans
Hypertension* / drug therapy
Hypertension* / psychology
Internationality

Substances

Antihypertensive Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding