@article{211e6f739a4449cc863fb9c1b8197e2a,
title = "Predicting Parkinson's disease trajectory using clinical and neuroimaging baseline measures",
abstract = "Introduction: Predictive biomarkers of Parkinson's Disease progression are needed to expedite neuroprotective treatment development and facilitate prognoses for patients. This work uses measures derived from resting-state functional magnetic resonance imaging, including regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF), to predict an individual's current and future severity over up to 4 years and to elucidate the most prognostic brain regions. Methods: ReHo and fALFF are measured for 82 Parkinson's Disease subjects and used to train machine learning predictors of baseline clinical and future severity at 1 year, 2 years, and 4 years follow-up as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Predictive performance is measured with nested cross-validation, validated on an external dataset, and again validated through leave-one-site-out cross-validation. Important predictive features are identified. Results: The models explain up to 30.4% of the variance in current MDS-UPDRS scores, 55.8% of the variance in year 1 scores, and 47.1% of the variance in year 2 scores (p < 0.0001). For distinguishing high and low-severity individuals at each timepoint (MDS-UPDRS score above or below the median, respectively), the models achieve positive predictive values up to 79% and negative predictive values up to 80%. Higher ReHo and fALFF in several regions, including components of the default motor network, predicted lower severity across current and future timepoints. Conclusion: These results identify an accurate prognostic neuroimaging biomarker which may be used to better inform enrollment in trials of neuroprotective treatments and enable physicians to counsel their patients.",
keywords = "Functional MRI, Machine learning, Neuroimaging, Parkinson's disease, Prognosis",
author = "Nguyen, {Kevin P.} and Vyom Raval and Alex Treacher and Cooper Mellema and Yu, {Fang Frank} and Pinho, {Marco C.} and Rathan Subramaniam and Dewey, {Richard B.} and Montillo, {Albert A.}",
note = "Funding Information: PPMI-–a public-private partnership-–is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbvie, Allergan, Avid Radiopharmaceuticals, Biogen, Biolegend, Bristol-Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. Funding Information: Additional data and biospecimens used in preparation of this manuscript were obtained from the Parkinson's Disease Biomarkers Program (PDBP) Consortium, supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health . Investigators include: Roger Albin, Roy Alcalay, Alberto Ascherio, Thomas Beach, Sarah Berman, Bradley Boeve, F. DuBois Bowman, Shu Chen, Alice Chen-Plotkin, William Dauer, Ted Dawson, Paula Desplats, Richard Dewey, Ray Dorsey, Jori Fleisher, Kirk Frey, Douglas Galasko, James Galvin, Dwight German, Lawrence Honig, Xuemei Huang, David Irwin, Kejal Kantarci, Anumantha Kanthasamy, Daniel Kaufer, James Leverenz, Carol Lippa, Irene Litvan, Oscar Lopez, Jian Ma, Lara Mangravite, Karen Marder, Laurie Orzelius, Vladislav Petyuk, Judith Potashkin, Liana Rosenthal, Rachel Saunders-Pullman, Clemens Scherzer, Michael Schwarzschild, Tanya Simuni, Andrew Singleton, David Standaert, Debby Tsuang, David Vaillancourt, David Walt, Andrew West, Cyrus Zabetian, Jing Zhang, and Wenquan Zou. The PDBP Investigators have not participated in reviewing the data analysis or content of the manuscript. Funding Information: Dr. Montillo was supported by NIH NIA R01AG059288, NIH NCI U01 CA207091, the King Foundation, the Lyda Hill Foundation, and the UT Southwestern Lyda Hill Department of Bioinformatics. Dr. Dewey reports personal fees (consulting) from Amneal, Acorda, Supernus, Teva, Adamas, US WorldMeds, Acadia, and Lundbeck, unrelated to the submitted work. Unrelated to this work, Dr. Pinho is a consultant for ABC Medical Education and Dr. Dewey is a consultant for Supernus, Acorda and Amneal Pharmaceuticals.PPMI-?a public-private partnership-?is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including Abbvie, Allergan, Avid Radiopharmaceuticals, Biogen, Biolegend, Bristol-Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, and Voyager Therapeutics. Additional data and biospecimens used in preparation of this manuscript were obtained from the Parkinson's Disease Biomarkers Program (PDBP) Consortium, supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. Investigators include: Roger Albin, Roy Alcalay, Alberto Ascherio, Thomas Beach, Sarah Berman, Bradley Boeve, F. DuBois Bowman, Shu Chen, Alice Chen-Plotkin, William Dauer, Ted Dawson, Paula Desplats, Richard Dewey, Ray Dorsey, Jori Fleisher, Kirk Frey, Douglas Galasko, James Galvin, Dwight German, Lawrence Honig, Xuemei Huang, David Irwin, Kejal Kantarci, Anumantha Kanthasamy, Daniel Kaufer, James Leverenz, Carol Lippa, Irene Litvan, Oscar Lopez, Jian Ma, Lara Mangravite, Karen Marder, Laurie Orzelius, Vladislav Petyuk, Judith Potashkin, Liana Rosenthal, Rachel Saunders-Pullman, Clemens Scherzer, Michael Schwarzschild, Tanya Simuni, Andrew Singleton, David Standaert, Debby Tsuang, David Vaillancourt, David Walt, Andrew West, Cyrus Zabetian, Jing Zhang, and Wenquan Zou. The PDBP Investigators have not participated in reviewing the data analysis or content of the manuscript. Special thanks to Padraig O'Suilleabhain and Umar Yazdani for providing additional feedback during the writing of this manuscript. Funding Information: Dr. Montillo was supported by NIH NIA R01AG059288 , NIH NCI U01 CA207091 , the King Foundation , the Lyda Hill Foundation , and the UT Southwestern Lyda Hill Department of Bioinformatics . Dr. Dewey reports personal fees (consulting) from Amneal, Acorda, Supernus, Teva, Adamas, US WorldMeds, Acadia, and Lundbeck, unrelated to the submitted work. Unrelated to this work, Dr. Pinho is a consultant for ABC Medical Education and Dr. Dewey is a consultant for Supernus, Acorda and Amneal Pharmaceuticals. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd",
year = "2021",
month = apr,
doi = "10.1016/j.parkreldis.2021.02.026",
language = "English (US)",
volume = "85",
pages = "44--51",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",
}