Mild Parkinsonian Signs in the Elderly – Is There an Association with PD? Crossectional Findings in 992 Individuals Stefanie Lerche 1,2 *, Markus Hobert 1,2 , Kathrin Brockmann 1,2 , Isabel Wurster 1,2 , Alexandra Gaenslen 1,2 , Sandra Hasmann 1,2 , Gerhard W. Eschweiler 3 , Walter Maetzler 1,2 , Daniela Berg 1,2 1 Center of Neurology, Department of Neurodegeneration and Hertie-Institute for Clinical Brain Research, University of Tu ¨ bingen, Tu ¨ bingen, Germany, 2 German Center for Neurodegenerative Diseases, University of Tu ¨ bingen, Tu ¨ bingen, Germany, 3 Geriatric Center and Department of Psychiatry and Psychotherapy, University Hospital of Tu ¨ bingen, Tu ¨ bingen, Germany Abstract Background: Mild parkinsonian signs (MPS) are common in the elderly population, and have been associated with vascular diseases, mild cognitive impairment and dementia; however their relation to Parkinson’s disease (PD) is unclear. Hypothesizing that individuals with MPS may reflect a pre-stage of PD, i.e. a stage in which the nigrostriatal system is already affected although to a milder degree than at the time of PD diagnosis, aim of this study was to evaluate the similarities between MPS and PD. Methods: The TREND study is a prospective cross-sectional cohort study in individuals .50 years with biennial assessments designed to identify markers for an earlier diagnosis of Parkinson’s and Alzheimer’s disease. For this substudy 992 individuals were included for analyses (892 controls, 73 MPS individuals, 27 PD patients). Parameters defining risk of PD (sex, age, positive family history), prodromal markers (hyposmia, REM sleep behavior disorder, depression and autonomic failure) as well as quantitative fine motor, axial motor and cognitive parameters were compared between the three cohorts. Results: As expected, PD patients differed from controls with regard to 12 of 15 of the assessed parameters. MPS individuals differed significantly from controls in 12 of the PD-associated parameters, but differed from PD only in 5 parameters. Conclusion: This study shows that individuals with MPS share many prodromal and clinical markers of PD with PD patients, implying that either a common dynamic process or similar constitutional factors occur in MPS individuals and PD patients. Citation: Lerche S, Hobert M, Brockmann K, Wurster I, Gaenslen A, et al. (2014) Mild Parkinsonian Signs in the Elderly – Is There an Association with PD? Crossectional Findings in 992 Individuals. PLoS ONE 9(3): e92878. doi:10.1371/journal.pone.0092878 Editor: Patrick Lewis, UCL Institute of Neurology, United Kingdom Received November 11, 2013; Accepted February 27, 2014; Published March 27, 2014 Copyright: ß 2014 Lerche et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This analysis of the TREND study was financially supported by a grant of UCB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: Dr. Lerche, Mr. Hobert, Ms. Wurster, Dr. Gaenslen and Ms. Hasmann reports no disclosures. Dr. Brockmann has received honoraria for lectures from the Deutsche Gesellschaft fu ¨ r klinische Neurophysiologie (DGKN) as well as travel grants from GlaxoSmithKline, UCB and the Movement Disorders Society. Prof. Maetzler has received speaker honoraria from GlaxoSmithKline, and receives research support from the European Union and the Robert Bosch Foundation. Prof. Eschweiler has received grants for Phase II and phase III study in alzheimer disorders from AC Immune and Janssen Alzheimer Immunotherapy Research. Prof. Berg has received Advisory Boards from UCB SchwarzPharma, Novartis, Merz; Honoraria from UCB SchwarzPharma, GSK, TEVA, Lundbeck; Grants from Michael J Fox Foundation, BmBF, Janssen Pharmaceutica, TEVA Pharma GmbH, Bo ¨ hringer, dPV (German Parkinson’s disease association), Abbott and Center of Integrative Neurosciences. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: Stefanie.lerche@uni-tuebingen.de Introduction Parkinson’s disease (PD) is characterized by the cardinal motor features resting tremor, rigidity and bradykinesia. However, each symptom individually as well as in combination is also highly prevalent in elderly people who do not meet the criteria for Parkinson’s disease (PD) [1] or other neurodegenerative diseases [2–7]. Therefore they are referred to as mild parkinsonian signs (MPS). MPS are associated with depression [8], hyposmia [9], slight cognitive impairment [10] and dementia [11]. Moreover, in individuals with MPS they are claimed to be a predictor for mortality [12]. These symptoms are also known to occur as ‘‘prodromal markers’’ in Parkinson’s disease [13–15]. Up to now it is not entirely clear whether individuals with MPS progress to a distinct neurological disease entity and if so, whether they develop primarily PD, Alzheimer’s Disease (AD), vascular parkinsonian syndromes or vascular dementia [16,17]. To solve this issue, there are several studies focusing on the association of MPS with the future development of dementia [3,5,7], but little is known about the association with PD. If MPS, at least in a subgroup of individuals, reflect a pre-stage of PD it must be a stage in which the nigrostriatal system is already affected – i.e. an early motor stage. Thus, assuming that the neurodegenerative process in most PD patients indeed affects the central nervous system in an ascending way, as first hypothesized by Braak et al. [18], individuals with MPS should have a similar prodromal phase as PLOS ONE | www.plosone.org 1 March 2014 | Volume 9 | Issue 3 | e92878