Evaluation of ATN PD Framework and Biofluid Markers to Predict Cognitive Decline in Early Parkinson Disease.

Autor: Cousins KAQ; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Irwin DJ; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Tropea TF; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Rhodes E; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Phillips J; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Chen-Plotkin AS; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Brumm MC; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Coffey CS; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Kang JH; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Simuni T; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Foroud TM; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Toga AW; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Tanner CM; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Kieburtz KD; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Mollenhauer B; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Galasko D; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Hutten S; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Weintraub D; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Siderowf AD; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Marek K; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Poston KL; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia., Shaw LM; From the Department of Neurology (K.A.Q.C., D.J.I., T.F.T., E.R., J.P., A.S.C.-P., D.W.), University of Pennsylvania, Philadelphia; Department of Biostatistics (M.C.B., C.S.C.), College of Public Health, University of Iowa, Iowa City; Department of Pharmacology and Clinical Pharmacology (J.H.K.), Inha University, Incheon, South Korea; Feinberg School of Medicine (T.S.), Northwestern University, Chicago, IL; Department of Medical and Molecular Genetics (T.M.F.), Indiana University, Indianapolis; Laboratory of Neuro Imaging (A.W.T.), University of Southern California, Los Angeles; Department of Neurology (C.M.T.), Weill Institute for Neurosciences, University of California San Francisco; Department of Neurology (K.D.K.), University of Rochester Medical Center, NY; Department of Neurology (B.M.), University Medical Center, Göttingen, Paracelsus-Elena-Klinik, Germany; Department of Neurology (D.G.), University of California San Diego; The Michael J. Fox Foundation (S.H.), New York, NY; Department of Psychiatry (D.W.), School of Medicine at the University of Pennsylvania; Michael J. Crescenz VA Medical Center (D.W.), Parkinson's Disease Research, Education, and Clinical Center; Department of Neurology (A.D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Institute for Neurodegenerative Disorders (K.M.), New Haven, CT; Department of Neurology (K.L.P.), Stanford University, Palo Alto, CA; and Department of Pathology and Laboratory Medicine (L.M.S.), University of Pennsylvania, Philadelphia.
Jazyk: angličtina
Zdroj: Neurology [Neurology] 2024 Feb; Vol. 102 (4), pp. e208033. Date of Electronic Publication: 2024 Feb 02.
DOI: 10.1212/WNL.0000000000208033
Abstrakt: Background and Objectives: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers-β-amyloid 1-42 (Aβ 42 ), phosphorylated tau 181 (p-tau 181 ), and total tau (t-tau)-in PD is poorly understood and may be distinct from clinical AD. Moreover, it is unclear whether CSF p-tau 181 and serum neurofilament light (NfL) have added prognostic utility in PD, when combined with CSF Aβ 42 . First, we describe longitudinal trajectories of biofluid markers in PD. Second, we modified the AD β-amyloid/tau/neurodegeneration (ATN) framework for application in PD (ATN PD ) using CSF Aβ 42 (A), p-tau 181 (T), and serum NfL (N) and tested ATN PD prediction of longitudinal cognitive decline in PD.
Methods: Participants were selected from the Parkinson's Progression Markers Initiative cohort, clinically diagnosed with sporadic PD or as controls, and followed up annually for 5 years. Linear mixed-effects models (LMEMs) tested the interaction of diagnosis with longitudinal trajectories of analytes (log transformed, false discovery rate [FDR] corrected). In patients with PD, LMEMs tested how baseline ATN PD status (AD [A+T+N±] vs not) predicted clinical outcomes, including Montreal Cognitive Assessment (MoCA; rank transformed, FDR corrected).
Results: Participants were 364 patients with PD and 168 controls, with comparable baseline mean (±SD) age (patients with PD = 62 ± 10 years; controls = 61 ± 11 years]; Mann-Whitney Wilcoxon: p = 0.4) and sex distribution (patients with PD = 231 male individuals [63%]; controls = 107 male individuals [64%]; χ 2 : p = 1). Patients with PD had overall lower CSF p-tau 181 (β = -0.16, 95% CI -0.23 to -0.092, p = 2.2e-05) and t-tau than controls (β = -0.13, 95% CI -0.19 to -0.065, p = 4e-04), but not Aβ 42 ( p = 0.061) or NfL ( p = 0.32). Over time, patients with PD had greater increases in serum NfL than controls (β = 0.035, 95% CI 0.022 to 0.048, p = 9.8e-07); slopes of patients with PD did not differ from those of controls for CSF Aβ 42 ( p = 0.18), p-tau 181 ( p = 1), or t-tau ( p = 0.96). Using ATN PD , PD classified as A+T+N± (n = 32; 9%) had worse cognitive decline on global MoCA (β = -73, 95% CI -110 to -37, p = 0.00077) than all other ATN PD statuses including A+ alone (A+T-N-; n = 75; 21%).
Discussion: In patients with early PD, CSF p-tau 181 and t-tau were low compared with those in controls and did not increase over 5 years of follow-up. Our study shows that classification using modified ATN PD (incorporating CSF Aβ 42 , CSF p-tau 181 , and serum NfL) can identify biologically relevant subgroups of PD to improve prediction of cognitive decline in early PD.
Databáze: MEDLINE