Long-Term Dementia Risk in Parkinson Disease
Julia Gallagher, Caroline Gochanour, Chelsea Caspell‐Garcia, Roseanne D. Dobkin, Dag Aarsland, Roy N. Alcalay, Matthew J. Barrett, Lana M. Chahine, Alice Chen‐Plotkin, Christopher S. Coffey, Nabila Dahodwala, Jamie L. Eberling, Alberto J. Espay, James B. Leverenz, Irene Litvan, Eugenia Mamikonyan, James F. Morley, Irene Hegeman Richard, Liana S. Rosenthal, Andrew Siderowf, Tatyana Simuni, Michele K. York, Allison W. Willis, Sharon X. Xie, Daniel Weintraub, for the Parkinson's Progression Markers Initiative, for the Parkinson's Progression Markers Initiative, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana Chahine, Christopher S. Coffey, Kalpana Merchant, Kathleen L. Poston, Roseanne D. Dobkin, Tatiana Foroud, Brit Mollenhauer, Dan Weintraub, Ethan Brown, Karl Kieburtz, Duygu Tosun, Werner Poewe, Susan Bressman, Jan Hamer, Raymond James, Ekemini Riley, John Seibyl, Leslie M. Shaw, David G. Standaert, Sneha Mantri, Nabila Dahodwala, Michael A. Schwarzschild, Connie Marras, Hubert Fernandez, Ira Shoulson, Helen Rowbotham, Lucy Norcliffe‐Kaufmann, Paola Casalin, Claudia Trenkwalder, Todd Sherer, Sohini Chowdhury, Mark Frasier, Jamie L. Eberling, Katie Kopil, Alyssa O’Grady, James Gibaldi, Maggie Kuhl, L. Kirsch, Emily Flagg, Bridget McMahon, Craig Stanley, Kim Fabrizio, Dixie Ecklund, Trevis Huff, Richard M. Peters, Janel Fedler, Laura Heathers, Christopher Hobbick, Gena Antonopoulos, Chelsea Caspell‐Garcia, Michael C. Brumm, Arthur W. Toga, Karen Crawford, Andrew Singleton, Thomas J. Montine, Monica Korell, Ruth B. Schneider, Kelvin L. Chou, David Russell, Stewart A. Factor, Penelope Hogarth, Robert A. Hauser, Marie Saint‐Hilaire, David Shprecher, Kathrin Brockmann, Yen Tai, Paolo Barone, Stuart Isaacson
Abstract
BACKGROUND AND OBJECTIVES: It is widely cited that dementia occurs in up to 80% of patients with Parkinson disease (PD), but studies reporting such high rates were published over two decades ago, had relatively small samples, and had other limitations. We aimed to determine long-term dementia risk in PD using data from two large, ongoing, prospective, observational studies. METHODS: Participants from the Parkinson's Progression Markers Initiative (PPMI), a multisite international study, and a long-standing PD research cohort at the University of Pennsylvania (Penn), a single site study at a tertiary movement disorders center, were recruited. PPMI enrolled de novo, untreated PD participants and Penn a convenience cohort from a large clinical center. For PPMI, a cognitive battery is administered annually, and a site investigator makes a cognitive diagnosis. At Penn, a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Interval-censored survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using cognitive diagnosis of dementia as the primary end point and Montreal Cognitive Assessment (MoCA) score <21 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I cognition score ≥3 as secondary end points for PPMI. In addition, estimated dementia probability by PD disease duration was tabulated for each study and end point. RESULTS: For the PPMI cohort, 417 participants with PD (mean age 61.6 years, 65% male) were followed, with an estimated probability of dementia at year 10 disease duration of 9% (site investigator diagnosis), 15% (MoCA), or 12% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 participants with PD (mean age 69.3 years, 67% male) were followed, with 184 participants (47% of cohort) eventually diagnosed with dementia. The interval-censored curve for the Penn cohort had a median time to dementia of 15 years (95% CI 13-15); the estimated probability of dementia was 27% at 10 years of disease duration, 50% at 15 years, and 74% at 20 years. DISCUSSION: Results from two large, prospective studies suggest that dementia in PD occurs less frequently, or later in the disease course, than previous research studies have reported.