Association of Intensive vs Standard Blood Pressure Control With Magnetic Resonance Imaging Biomarkers of Alzheimer Disease
Authors: Ilya M. Nasrallah, Sarah A. Gaussoin, Raymond Pomponio, Sudipto Dolui, Guray Erus, Clinton B. Wright, Lenore J. Launer, John A. Detre, David A. Wolk, Christos Davatzikos, Jeff D. Williamson, Nicholas M. Pajewski, R. Nick Bryan, Paul Whelton, Karen C. Johnson, Joni Snyder, Diane Bild, Denise Bonds, Nakela Cook, Jeffrey Cutler, Lawrence Fine, Peter Kaufmann, Paul Kimmel, Lenore Launer, Claudia Moy, William Riley, Laurie Ryan, Eser Tolunay, Song Yang, David Reboussin, Jeff D. Williamson, Walter T. Ambrosius, William Applegate, Greg Evans, Capri Foy, Barry I. Freedman, Dalane Kitzman, Mary Lyles, Nicholas M. Pajewski, Steve Rapp, Scott Rushing, Neel Shah, Kaycee M. Sink, Mara Vitolins, Lynne Wagenknecht, Valerie Wilson, Letitia Perdue, Nancy Woolard, Tim Craven, Katelyn Garcia, Sarah Gaussoin, Laura Lovato, Jill Newman, James Lovato, Lingyi Lu, Chris McLouth, Greg Russell, Bobby Amoroso, Patty Davis, Jason Griffin, Darrin Harris, Mark King, Kathy Lane, Wes Roberson, Debbie Steinberg, Donna Ashford, Phyllis Babcock, Dana Chamberlain, Vickie Christensen, Loretta Cloud, Christy Collins, Delilah Cook, Katherine Currie, Debbie Felton, Stacy Harpe, Marjorie Howard, Michelle Lewis, Pamela Nance, Nicole Puccinelli-Ortega, Laurie Russell, Jennifer Walker, Brenda Craven, Candace Goode, Margie Troxler, Janet Davis, Sarah Hutchens, Anthony A. Killeen, Anna M. Lukkari, Robert Ringer, Brandi Dillard, Norbert Archibeque, Stuart Warren, Mike Sather, James Pontzer, Zach Taylor, Elsayed Z. Soliman, Zhu-Ming Zhang, Yabing Li, Chuck Campbell, Susan Hensley, Julie Hu, Lisa Keasler, Mary Barr, Tonya Taylor, R. Nick Bryan, Christos Davatzikos, Ilya Nasrallah, Lisa Desiderio, Mark Elliott, Ari Borthakur, Harsha Battapady, Guray Erus, Alex Smith, Ze Wang, Jimit Doshi, Jackson T. Wright Jr., Mahboob Rahman, Alan J. Lerner, Carolyn H. Still, Alan Wiggers, Sara Zamanian, Alberta Bee, Renee Dancie, George Thomas, Martin Schreiber, Jr., Sankar Dass Navaneethan, John Hickner, Michael Lioudis, Michelle Lard, Susan Marczewski, Jennifer Maraschky, Martha Colman, Andrea Aaby, Stacey Payne, Melanie Ramos, Carol Horner, Paul E. Drawz, Pratibha P. Raghavendra, Scott Ober, Ronda Mourad, Muralidhar Pallaki, Peter Russo, Paul Fantauzzo, Lisa Tucker, Bill Schwing, John R. Sedor, Edward J. Horwitz, Jeffrey R. Schellling, John F. O’Toole, Lisa Humbert, Wendy Tutolo, Suzanne White, Alishea Gay, Walter Clark, Jr, Robin Hughes, Mirela Dobre, Monique Williams, Udayan Bhatt, Lee Hebert, Anil Agarwal, Melissa Brown Murphy, Nicole Ford, Cynthia Stratton, Jody Baxter, Alicia A. Lykins, Alison McKinley Neal, Leena Hirmath, Osei Kwame, Kyaw Soe, William F. Miser, Colleen Sagrilla, Jan Johnston, Amber Anaya, Ashley Mintos, Angel A. Howell, Kelly Rogers, Sara Taylor, Donald Ebersbacher, Lucy Long, Beth Bednarchik, Adrian Schnall, Jonathan Smith, Lori Peysha, Lisa Leach, Megan Tribout, Carla Harwell, Pinkie Ellington, Mary Ann Banerji, Pranav Ghody, Melissa Vahided Rambaud, Raymond Townsend, Debbie Cohen, Yonghong Huan, Mark Duckworth, Virginia Ford, Juliet Leshner, Ann Davison, Sarah Vander Veen, Crystal A. Gadegbeku, Avi Gillespie, Anuradha Paranjee, Sandra Amoroso, Zoe Pfeffer, Sally B. Quinn, Jiang He, Jing Chen, Eva Lustigova, Erin Malone, Marie Krousel-Wood, Richard Deichmann, Patricia Ronney, Susan Muery, Donnalee Trapani, Michael Rocco, David Goff, Carlos Rodriguez, Laura Coker, Amret Hawfield, Joseph Yeboah, Lenore Crago, John Summerson, Anita Hege, Matt Diamond, Laura Mulloy, Marcela Hodges, Michelle Collins, Charlene Weathers, Heather Anderson, Emily Stone, Walida Walker, Andrew McWilliams, Michael Dulin, Lindsay Kuhn, Susan Standridge, Lindsay Lowe, Kelly Everett, Kelry Preston, Susan Norton, Silena Gaines, Ali A. Rizvi, Andrew W. Sides, Diamond Herbert, Matthew M. Hix, Melanie Whitmire, Brittany Arnold, Philip Hutchinson, Joseph Espiritu, Mark Feinglos, Eugene Kovalik, Georgianne Gedon-Lipscomb, Kathryn Evans, Connie Thacker, Ronna Zimmer, Mary Furst, MaryAnn Mason, James Powell, Paul Bolin, Junhong Zhang, Mary Pinion, Gail Davis, Winifred Bryant, Presley Phelps, Connie Garris-Sutton, Beatrice Atkinson, Gabriele Contreras, Maritza Suarez, Ivonne Schulman, Don Koggan, Jackie Vassallo, Gloria Peruyera, Sheri Whittington, Cassandra Bethea, Laura Gilliam, Carolyn Pedley, Geraldine Zurek, Miriam Baird, Charles Herring, Mary Martha Smoak, Julie Williams, Samantha Rogers, Lindsay Gordon, Erin Kennedy, Beverly Belle, Jessica McCorkle-Doomy, Jonathan Adams, Ramon Lopez, Juris Jamavs, Frederic Rahbari-Oskoui, Arlene Chapman, Allen Dollar, Olubunmi Williams, Yoosun Han, William Haley, Peter Fitzpatrick, Joseph Blackshear, Brian Shapiro, Anna Harrell, Arta Palaj, Katelyn Henderson, Ashley Johnson, Heath Gonzalez, Jermaine Robinson, Leonardo Tamariz, Dhurga Krishnamoorthy, Rody Barakat, Jennifer Denizard, Frank Greenway, Ron Monce, Timothy Church, Chelsea Hendrick, Aimee Yoches, Leighanne Sones, Markee Baltazar, Priscilla Pemu, Connie Jones, Derrick Akpalu, Alfred K. Cheung, Srinivasan Beddhu, Gordon Chelune, Jeffrey Childs, Lisa Gren, Anne Randall, Laura Dember, Denise Soares, Jerry Yee, Kausik Umanath, Naima Ogletree, Schwana Thaxton, Karen Camapana, Dayna Sheldon, Krista MacArthur, J. Brent Muhlestein, Nathan Allred, Brian Clements, RItesh Dhar, Kent Meredith, Viet Le, Edward Miner, James Orford, Erik R. Riessen, Becca Ballantyne, Ben Chisum, Kevin Johnson, Dixie Peeler, Glenn Chertow, Manju Tamura, Tara Chang, Kevin Erickson, Jenny Shen, Randall S. Stafford, Gregory Zaharchuk, Margareth Del Cid, Michelle Dentinger, Jennifer Sabino, Rukmani Sahay, Ekaterina Telminova, Daniel E. Weiner, Mark Sarnak, Lily Chan, Amanda Civiletto, Alyson Heath, Amy Kantor, Priyanka Jain, Bethany Kirkpatrick, Andrew Well, Barry Yuen, Michel Choncol, Beverly Farmer, Heather Farmer, Carol Greenwald, Mikaela Malaczewski, James Lash, Anna Porter, Ana Ricardo, Robert T. Rosman, Janet Cohan, Nieves Lopez-Barrera, Daniel Meslar, Patricia Meslar, Margaret Conroy, Mark Unruh, Rachel Hess, Manisha Jhamb, Holly Thomas, Pam Fazio, Elle Klixbull, Melissa Komlos-Weimer, LeeAnne Mandich, Tina Vita, Robert Toto, Peter Van Buren, Julia Inrig, Martha Cruz, Tammy Lightfoot, Nancy Wang, Lori Webster, Kalani Rapheal, Barry Stults, Tahir Zaman, Debra Simmons, Tooran Lavasani, Rebecca Filipowicz, Guo Wei, Gracie Mary Miller, Jenice Harerra, Jeff Christensen, Ajay Giri, Xiaorui Chen, Natalie Anderton, Arianna Jensen, Julia Lewis, Anna Burgner, Jamie P. Dwyer, Gerald Schulman, Terri Herrud, Ewanda Leavell, Tiffany McCray, Edwina McNeil Simaan, Munmum Puodel, Malia Reed, Mohammed Sika, Delia Woods, Janice L. Zirkenback, Dominic S. Raj, Scott Cohen, Samir Patel, Manuel Velasquez, Roshni S. Bastian, Maria Wing, Akshay Roy-Chaudhury, Thomas Depner, Lorien Dalyrymple, George Kaysen, Susan Anderson, John Nord, Ajay GIri, Joachim H. Ix, Leonard Goldenstein, Cynthia M. Miracle, Nketi Forbang, Maja Mircic, Brenda Thomas, Tiffany Tran, Anjay Rastogi, Mihae Kim, Mohamad Rashid, Bianca Lizarraga, Amy Hocza, Kristine Sarmosyan, Jason Norris, Tushar Sharma, Amanda Chjoy, Eric Bernard, Eleanore Cabrera, Christina Lopez, Susana Nunez, Joseph Riad, Suzanne Schweitzer, Siran Sirop, Sarah Thomas, Lauren Wada, Holly Kramer, Vinod Bansal, Corliss E. Taylor, Mark S. Segal, Karen L. Hall, Amir Kazory, Lesa Gilbert, Linda Owens, Danielle Poulton, Elaine Whidden, Jocelyn Wiggins, Caroline Blaum, Linda Nyquist, Lillian Min, Tanya Gure, Ruth Lewis, Jennifer Mawby, Eileen Robinson, Suzanne Oparil, Cora E. Lewis, Virginia Bradley, David Calhoun, Stephen Glasser, Kim Jenkins, Tom Ramsey, Nauman Qureshi, Karen Ferguson, Sumrah Haider, Mandy James, Christy Jones, Kim Renfroe, April Seay, Carrie Weigart, Denyse Thornley-Brown, Dana Rizik, Bari Cotoon, Meredith Fitz-Gerald, Tiffany Grimes, Carolyn Johnson, Sara Kennedy, Chanel Mason, Lesa Rosato-Burson, Robin Willingham, Eric Judd, Tonya Breaux-Shropshire, Felice Cook, Julia Medina, Lama Ghazi, Hemal Bhatt, James Lewis, Roman Brantley, John Brouilette, Jeffrey Glaze, Stephanie Hall, Nancy Hiott, David Tharpe, Spencer Boddy, Catherine Mack, Catherine Womack, Keiko Asao, Beate Griffin, Carol Hendrix, Karen Johnson, Lisa Jones, Chelsea Towers, Henry Punzi, Kathy Cassidy, Kristin Schumacher, Carmen Irizarry, Ilma Colon, Pedro Colon-Ortiz, Pedro J. Colon-Hernandez, Orlando J. Carrasquillo-Navarro, Merari Carrasquillo, Nivea Vasquez, Miguel Sosa-Padilla, Alex Cintron-Pinero, Mayra Ayala, Olga Pacheco, Catalina Rivera, Irma Sotomayor-Gonzalez, Jamie Claudio, Jose Lazaro, Migdalia Arce, Lourdes Heres, Alba Perez, Jose Tavarez-Valle, Ferlinda Arocho, Mercedes Torres, Melvaliz Vazquez, Gerard P. Aurigemma, Rebecca TakisSmith, Julie Andrieni, Noelle Bodkin, Kiran Chaudhary, Paula Hu, John Kostis, Nora Cosgrove, Denise Bankowski, Monica Boleyn, Laurie Casazza, Victoria Giresi, Tosha Patel, Erin Squindo, Yan Wu, Zeb Henson, Marion Wofford, Jessica Lowery, Deborah Minor, Kimberley Harkins, Alexander Auchus, Michael Flessner, Cathy Adair, Jordan Asher, Debbie Loope, Rita Cobb, Reiner Venegas, Thomas Bigger, Natalie Bello, Shunichi Homma, Daniel Donovan, Carlos Lopez-Jimenez, Amilcar Tirado, Asqual Gataneh, Rocky Tang, Sabrina Durant, Matthew Maurer, Sergio Teruya, Stephen Helmke, Julissa Alvarez, Ruth Campbell, Roberto Pisoni, Rachel Sturdivant, Deborah Brooks, Caroline Counts, Vickie Hunt, Lori Spillers, Donald Brautigam, Timothy Kitchen, Timothy Gorman, Jessica Sayers, Sarah Button, June Chiarot, Rosemary Fischer, Melissa Lyon, Maria Resnick, Nicole Hodges, Jennifer Ferreira, William Cushman, Barry Wall, Linda Nichols, Robert Burns, Jennifer Martindale-Adams, Dan Berlowitz, Elizabeth Clark, Sandy Walsh, Terry Geraci, Carol Huff, Linda Shaw, Karen Servilla, Darlene Vigil, Terry Barrett, Mary Ellen Sweeney, Rebecca Johnson, Susan McConnell, Khadijeh Shahid Salles, Francoise Watson, Cheryl Schenk, Laura Whittington, Maxine Maher, Jonathan Williams, Stephen Swartz, Paul Conlin, George Alexis, Rebecca Lamkin, Patti Underwood, Helen Gomes, Clive Rosendorff, Stephen Atlas, Saadat Khan, Waddy Gonzalez, Samih Barcham, Lawrence Kwon, Matar Matar, Anwar Adhami, Jan Basile, Joseph John, Deborah Ham, Hadi Baig, Mohammed Saklayen, Jason Yap, Helen Neff, Carol Miller, Ling Zheng-Phelan, Saib Gappy, Shiva Rau, Arathi Raman, Vicki Berchou, Elizabeth Jones, Erin Olgren, Cynthia Marbury, Michael Yudd, Sithiporn Sastrasinh, Jennine Michaud, Jessica Fiore, Marianne Kutza, Ronald Shorr, Rattana Mount, Helen Dunn, Susan Stinson, Jessica Hunter, Addison Taylor, Jeffery Bates, Catherine Anderson, Kent Kirchner, Jodi Stubbs, Ardell Hinton, Anita Spencer, Santosh Sharma, Thomas Wiegmann, Smita Mehta, Michelle Krause, Kate Dishongh, Richard Childress, Geeta Gyamlani, Atossa Niakan, Cathy Thompson, Janelle Moody, Carolyn Gresham, Jeffrey Whittle, Gary Barnas, Dawn Wolfgram, Heidi Cortese, Jonette Johnson, Christianne Roumie, Adriana Hung, Jennifer Wharton, Kurt Niesner, Lois Katz, Elizabeth Richardson, George Brock, Joanne Holland, Troy Dixon, Athena Zias, Christine Spiller, Penelope Baker, James Felicetta, Shakaib Rehman, Kelli Bingham, Suzanne Watnick, David Cohen, Jessica Weiss, Tera Johnston, Stephen Giddings, Hala Yamout, Andrew Klein, Caroline Rowe, Kristin Vargo, Kristi Waidmann, Vasilios Papademetriou, Jean Pierre Elkhoury, Barbara Gregory, Susan Amodeo, Mary Bloom, Dalia Goldfarb-Waysman, Richard Treger, Mehran Kashefi, Christina Huang, Karen Knibloe, Areef Ishani, Yelena Slinin, Christine Olney, Jacqueline Rust, Paolo Fanti, Christopher Dyer, Shweta Bansal, Monica Dunnam, Lih-Lan Hu, Perla Zarate-Abbott
Journal: JAMA Neurology (2021)

Meta-analyses of randomized clinical trials have indicated that improved hypertension control reduces the risk for cognitive impairment and dementia. However, it is unclear to what extent pathways reflective of Alzheimer disease (AD) pathology are affected by hypertension control.To evaluate the association of intensive blood pressure control on AD-related brain biomarkers.This is a substudy of the Systolic Blood Pressure Intervention Trial (SPRINT MIND), a multicenter randomized clinical trial that compared the efficacy of 2 different blood pressure-lowering strategies. Potential participants (n = 1267) 50 years or older with hypertension and without a history of diabetes or stroke were approached for a brain magnetic resonance imaging (MRI) study. Of these, 205 participants were deemed ineligible and 269 did not agree to participate; 673 and 454 participants completed brain MRI at baseline and at 4-year follow-up, respectively; the final follow-up date was July 1, 2016. Analysis began September 2019 and ended November 2020.Participants were randomized to either a systolic blood pressure goal of less than 120 mm Hg (intensive treatment: n = 356) or less than 140 mm Hg (standard treatment: n = 317).Changes in hippocampal volume, measures of AD regional atrophy, posterior cingulate cerebral blood flow, and mean fractional anisotropy in the cingulum bundle.Among 673 recruited patients who had baseline MRI (mean [SD] age, 67.3 [8.2] years; 271 women [40.3%]), 454 completed the follow-up MRI at a median (interquartile range) of 3.98 (3.7-4.1) years after randomization. In the intensive treatment group, mean hippocampal volume decreased from 7.45 cm3 to 7.39 cm3 (difference, -0.06 cm3; 95% CI, -0.08 to -0.04) vs a decrease from 7.48 cm3 to 7.46 cm3 (difference, -0.02 cm3; 95% CI, -0.05 to -0.003) in the standard treatment group (between-group difference in change, -0.033 cm3; 95% CI, -0.062 to -0.003; P = .03). There were no significant treatment group differences for measures of AD regional atrophy, cerebral blood flow, or mean fractional anisotropy.Intensive treatment was associated with a small but statistically significant greater decrease in hippocampal volume compared with standard treatment, consistent with the observation that intensive treatment is associated with greater decreases in total brain volume. However, intensive treatment was not associated with changes in any of the other MRI biomarkers of AD compared with standard treatment.ClinicalTrials.gov Identifier: NCT01206062.