Objective To evaluate the evolution of cognitive impairment in relation to cerebrospinal fluid (CSF) profiles of amyloid-β (Aβ), total-Tau and phosphorylated-Tau in Parkinson’s disease (PD).
Methods Prospective, longitudinal, observational study up to 10 years with follow-up every 2 years. We assessed CSF profiles in 415 patients with sporadic PD (median age 66; 63% men) and 142 healthy controls (median age 62; 43% men).
Results Patients with PD with low CSF Aβ1–42 levels at baseline were more often cognitively impaired than patients with intermediate and high Aβ1–42 levels. Sixty-seven per cent of the patients with low Aβ1–42 levels at baseline and normal cognition developed cognitive impairment during follow-up, compared with 41% and 37% of patients having intermediate and high CSF Aβ1–42 levels. Kaplan-Meier survival curves and Cox regression revealed that patients with low CSF Aβ1–42 levels at baseline developed cognitive impairment more frequently and earlier during follow-up.
Conclusion We conclude that in patients with sporadic PD, low levels of Aβ1–42 are associated with a higher risk of developing cognitive impairment earlier in the disease process at least in a subgroup of patients.
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Contributors KB, DB, TG and WM designed the study. IW, BR, GM, MZ, FB, ES, CD, CS, DB, WM and KB collected data. ES performed the immunoassays for CSF measurements. SL performed the statistical analysis and drafted the manuscript. All authors were involved in interpretation of the data and critical revision of the manuscript. All authors gave their final approval.
Competing interests DB has served on scientific advisory boards for Novartis, UCB/ SCHWARZ PHARMA, Lundbeck, Prexton Therapeutics and GE Healthcare; and has received research support from Michael J Fox Foundation, Janssen Pharmaceutica N.V. German Parkinson’s Disease Association (dPV), BMWi, BMBF, Parkinson Fonds Deutschland gGmbH, UCB Pharma GmbH, TEVA Pharma GmbH, EU, Novartis Pharma GmbH and Lundbeck. KB has received research support from the University of Tuebingen (Clinician Scientist), the German Society of Parkinson’s Disease (dpv), the Michael J Fox Foundation (MJFF) and BMBF (the Federal Ministry of Education and Research FKZ 01EK1606D), travel grants from the Movement Disorders Society and speaker honoraria from Lundbeck, Zambon, UCB and Abbvie. TG serves on the editorial boards of Parkinsonism & Related Disorders, Movement Disorders and Journal of Neurology; holds a patent re: KASPP (LRRK2) Gene, its Production and Use for the Detection and Treatment of Neurodegenerative Diseases; serves as a consultant for Cephalon, Inc. and Merck Serono; serves on speaker’s bureaus of Novartis, Merck Serono, SCHWARZ PHARMA, Boehringer Ingelheim and Valeant Pharmaceuticals International; and receives research support from Novartis, the European Union, BMBF (the Federal Ministry of Education and Research) and Helmholtz Association. OH has consultant relationships with GE Healthcare, Hoffmann-La Roche and Eli Lilly and received funding from the European Research Council, Swedish Research Council and the Michael J Fox Foundation. GM is supported by an Edmond J Safra Fellowship in Movement Disorders from the Michael J Fox Foundation. WM received and receives funding from the European Union, the Michael J Fox Foundation, Robert Bosch Foundation, Neuroalliance, Lundbeck and Janssen, and holds part of a patent for the assessment of dyskinesias (German patent office, 102015220741.2). He received speaker honoraria from GlaxoSmithKline, Abbvie, UCB, Licher MT and Rölke Pharma, and was invited to Advisory Boards of Market Access & Pricing Strategy GmbH and Abbvie. HZ is one of the founders of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. SL, IW, BR, MZ, FB, ES, CD and CS have nothing to disclose.
Patient consent Obtained.
Ethics approval The study was approved by the Ethics Committee of the Faculty of Medicine at the University of Tuebingen (199/2011BO1).
Provenance and peer review Not commissioned; externally peer reviewed.