Motor, cognitive, and functional declines contribute to a single progressive factor in early HD

Authors: Scott Schobel, Giuseppe Palermo, Peggy Auinger, Jeffrey D. Long, Shiyang Ma, Omar Khwaja, Dylan Trundell, Merit Cudkowicz, Steven M. Hersch, Cristina Sampaio, E. Ray Dorsey, Blair R. Leavitt, Karl Kieburtz, Jeffrey Sevigny, Douglas R. Langbehn, Sarah J. Tabrizi, For the TRACK-HD, COHORT, CARE-HD, and 2CARE Huntington Study Group Investigators, TRACK-HD, COHORT, CARE-HD, and 2CARE Huntington Study Group Investigators, John Adams, Mandar Jog, Christopher Hyson, Sarah Furtado, Andrew P. Duker, Melissa J. Armstrong, Christian Lachner, Hubert H. Fernandez, Michael S. Okun, David Shprecher, Michael S. Cartwright, Clement T. Loy, Joohi Jiminez-Shahed, B. Robottom, Gregory Suter, Theresa HM Moore, Jane Forsyth, Andrea Hurt, Joann Belden, Katie Price, Diane Erickson, Breanna Nickels, Misty M. Thompson, Linda Cole, Julie Megens, Emilija Makaji, Sara-Lynn Masse, Keith Malarick, Louisa Mook, Susan Maya, Alex Bender, Jessica Meyer, Puja Turakhia, Katherine Harwood, Kathryn Duderstadt, S. Lenarz, Judy Hamerlinck, Patricia Edern, Charlyne Hickey, Ashley Owens, Clare Gibbons, Carolyn Steele Gray, Jean A. Jaglin, Kimberly Janko, Holly Lawrence, B. Estes, Brigid Hayward, Allison E. Johnson, Amit Gode, Giselle Huet, Beverly Romero-Kersh, K. Wernette, Elizabeth Sullivan, Jamie Guyot, Julie Konkle, Christine J. O’Neill, Pamela King, Amanda Martin, John Bautista, Nicole Mans, Jane Griffith, Erica Surles, Sharon Halton, Alicia Palao, Nathalie Padron, Kolleen Elliott, Lynn Elizabeth Oelke, London Butterfield, Peggy Perry-Trice, Sarah Wyne, Carol Pantella, Lorelei Tainsh, Elaine Sperin, Sharon Evans, Maureen Gartner, Amy Duffy, Pamela Kristof, Lisa Niles, Steven Rainone, Angie Wernle, Ronda Clouse, Michelle Cines, Kelly Dustin, Maura Deeley, Stacy Merritt, Heather Ferreri, Alison McMurray, Alanna Sheinberg, Marsha Hughes-Gay, Kori A. LaDonna, Erin Chung, Jennifer Y. Lee, Rachel Goldstein, Lindsay Esposito, Nicholas Scoglio, Matthew J. Grana, Carol Zimmerman, Lucia M. Blasucci, William Thayer, Jennifer Hawkins, J. Koch, Victoria Hunt, Jessica Bargoil, Ingrid U. Scott, Terry Tempkin, Linda Stewart, Emily Hayes, Donna Galea, Beatriz Belmar, Kylie Richardson, Christine Hunter, Ernesto Jiménez, Monica Quesada, Wendy Levy, Anita Blenke, Lisa Gauger, Joanna Stoner, Mary Lou Klimek, Barbara Sommerfeld, Mary Eglow, Katy Regan, Erin Neefus, Marie Malikowski, Teri Radam, Marci Zomok, Margaret C. Lannon, Rhonda Agramonte, Johanna M Hartlein, Constance Nickerson, Samantha M. Gibson, Erin Hastings Monari, Camille Swartz, Anne Smith-Bova, Randi Jones, Catherine L. Wielinski, Shanthi Graham, D. Psych, Jillian McMillan M Clin Neuropsych, Walter J. Koroshetz, Michael McDermott, M. Flint Beal, J. Timothy Greenamyre, Christopher A. Ross, Ira Shoulson, Merit Cudkowicz, Paul Sexton, C. Skeuse, Diana Rosas, Bruce G. Jenkins, Adam Rosenblatt, M. Sherr, Steven J. Hersch, Janet Cellar, Mark Guttman, Corey Brown, Peter G. Como, Frederick J. Marshall, Joy A. deMarcaida, Carol Zimmerman, Karen Marder, Carol Moskowitz, Carlos Polanco, Jeffry Beltre, Kathleen M. Shannon, Jean A. Jaglin, F. Niederman, Tetsuo Ashizawa, Christine Hunter, Christine Hunter, Robert A. Hauser, A. Walker, L. Gauger, Michael Hahn, H. Delgado, Ted M. Dawson, Eric Siemers, Lauren Seeberger, Colleen Dingmann, Richard Dubinsky, Carolyn Steele Gray, William J. Weiner, D. Rodriguez–Batemen, Roger L. Albin, K. Wernette, Mark Harrison, Elke Rost‐Ruffner, Jane S. Paulsen, R.L. Rodnitzky, Jon Dobson, Lynn Vining, Oksana Suchowersky, Carol Pantella, Marie Saint‐Hilaire, Jeremy D. Furtado, W. R. Wayne Martin, Marguerite Wieler, Francis O. Walker, Victoria Hunt, Lynn A. Raymond, E. Almqvist, Aaron Rubin, Bryan Blair, Kenneth Marek, K. Caplan, Daryll Baker, Alicia Brocht, Cindy Casaceli, Constance Orme, Alice Rudolph, L. Rumfola, Giovanni Schifitto, Aileen Shinaman, K. Sulimowicz, Arthur Watts, S. Eapen, L. Zhang, Pierre N. Tariot, Stanley Fahn, Wendy A. Hall, William C. Koller, Jay M. Gorell, Robert F. Woolson, Ira Shoulson, James F. Gusella, Tatiana Foroud, Daniël P. van Kammen, Frederick J. Marshall, Charlyne Hickey, Karen Marder, Steven J. Frucht, Carol Moskowitz, Ronda Clouse PaulaWasserman, Lisa M. Muratori, Elan D. Louis, Kathleen M. Shannon, Jeana Jaglin, Joseph Jankovic, Alicia Palao, Madaline B. Harrison, Robert J. Davis, Susan Dietrich, Carlos Singer, Monica Quesada, Steven J. Hersch, Diana Rosas, Kaloyan S. Tanev, Keith Malarick, Robert McInnis, Juan Sanchez‐Ramos, Sandra K. Kostyk, Nick Doucette, Jane S. Paulsen, Ergun Uc, Robert L. Rodnitzky, Anne Leserman, Stacie Vik, Joel S. Perlmutter, Samer D. Tabbal, Amy P. Schmidt, Stacey K. Barton, Christopher R. Ross, Ray Dorsey, Frederick C. Nucifora, Richard Dubinsky, Hilary Dubinsky, Janice Broyles, Oksana Suchowersky, Mary Lou Klimek, Randi Jones, Claudia Testa, Elaine Sperin, Claudia Testa, Dana Jennings, Donald S. Higgins, Eric Molho, John Adams, Samuel Frank, Marie Saint‐Hilaire, Melissa Diggin, Sarah Furtado, FrancisWalker Christine O'Neill, Kimberly A. Quaid, Melissa Wesson, S. Elizabeth Zauber, Mark S. LeDoux, Lynn A. Raymond, Blair R. Leavitt, Joji Decolongon, Susan Perlman, Jody Corey‐Bloom, Guerry M. Peavy, Rajeev Kumar, Vicki Segro, Diane Erickson, Elizabeth McCusker, Jane Griffith, Clement T. Loy, Vicki Wheelock, Terry Tempkin, Amanda Martin, Martha Nance, Un Jung Kang, William Mallonee, Greg Suter, Fred Revilla, Carolyn Drazinic, Mary Jane Fitzpatrick, Kevin Duff, B.L. Scott, B. Robottom, Edmond Chiu, Olga Yastrubetskaya, Andrew Churchyard, Timothy John Greenamyre, N. Lucarelli, Pinky Agarwal, Irina Antonijevic, Jeanen DeLaRosa, Peter K. Panegyres, Allison Coleman, David Oakes, Christopher Beck, Suzanne Robertson, Dustina Holt, Ken Eaton, Patricia Lindsay, Lisa M. Deuel, Marcy E. MacDonald, Tatiana Foroud, Ray Dorsey, Joseph Giuliano, Louise Vetter, Oksana Suchowersky, Christopher Beck, David Oakes, Sarah J. Tabrizi, Alexandra Dürr, Blair R. Leavitt, RA Roos, Beth Borowsky, G. Bernhard Landwehrmeyer, Chris Frost, Hans J. Johnson, Douglas R. Langbehn, David Craufurd, Ralf Feilmann, Julie C. Stout, A Campbell, Michelle Campbell, Izelle Labuschagne, C Milchman, Canada A Coleman, R Dar Santos, Joji Decolongon, Aaron Sturrock, France C Jauff ret, Damián Justo, Stéphane Lehéricy, Cécilia Marelli, K Nigaud, Romain Valabrègue, Germany N Bechtel, Stefan Bohlen, Netherlands S J A van den Bogaard, E M Dumas, Jeroen van der Grond, Ellen P. Hart, UK N Arran, John J. Callaghan, Cheryl Stopford, David M. Cash, Helen Crawford, Nick C. Fox, Nicola Z. Hobbs, Nayana Lahiri, Ian B. Malone, Joy Read, Miranda J. Say, D. Whitehead, Edward J. Wild, Rob Jones, USA E Axelson, Sarah Queller, C. M. Campbell - Neurology 2017 cited by 155

OBJECTIVE: To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials. METHODS: We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up. RESULTS: The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy. CONCLUSIONS: Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures.