Cardiac Stress Test Is Normal in Pre-motor Parkinson’s Disease Gilad Yahalom, MD, 1,8*† Elad Maor, MD, PhD, 2,7† Sharon Hassin-Baer, MD, 1,8 Shlomo Segev, MD, 3 Yechezkel Sidi, MD, 4,8 and Shaye Kivity, MD 4,5,6,7,8 1 The Parkinson Disease and Movement Disorders Clinic, Department of Neurology and Sagol Neuroscience Center 2 The Olga and Lev Leviev Heart Center 3 Institute for Medical Screening 4 Department of Medicine C 5 Department of Medicine A 6 Center for Autoimmune Diseases, Sheba Medical Center 7 The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Tel Hashomer, Israel 8 Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel ABSTRACT: Cardiac sympathetic denervation is an early nonmotor feature of Parkinson’s disease (PD). The aim of the current study was to trace evidence for cardiac dysfunction abnormalities in the premotor phase of PD. We retrospectively reviewed treadmill ergometric tests of a large cohort (n 5 16,841) between 2000 and 2012, that attended the Executive Screening Survey (ESS) at Sheba Medical Center. Heart rate and blood pressure profiles as well as exercise capacity were compared between subjects who later developed PD and age- and sex-matched subjects (ratio 1:2) who did not. We identi- fied 28 subjects (24 males) who developed PD at follow- up. The PD group was older than the group of subjects who did not develop PD on first ergometric test (64.82 6 8.82 vs. 48.91 6 10.60 years, P < 0.001). The time between the first ergometric test and motor symptoms onset was 4.64 6 2.86 years. Patients who later devel- oped PD had lower maximal heart rate (P < 0.001) and lower heart rate reserve than healthy controls (P < 0.001); however, compared with age- and sex-matched subjects, subjects who developed PD had similar exercise capacity and heart rate profile during rest, exercise, and recovery, even 1 year before diagnosis. In this study, we did not detect significant signs of sympathetic dysfunction during the premotor phase of PD. V C 2014 International Parkinson and Movement Disorder Society Key Words: ergometric; exercise stress test; Parkin- son’s disease; premotor; preclinical Parkinson’s disease (PD) is a common neurodegener- ative disease, mainly of the elderly. Some nonmotor symptoms, predating the motor phase and diagnosis of PD by many years, commonly occur, including sensory and autonomic phenomena. 1 Over the last few years, some clinical, laboratory, and imaging procedures have been developed for diagnostic purposes, some- times enabling early detection of PD in the premotor phase. These procedures include the detection of sleep abnormalities, neurobehavioral symptoms, and olfac- tory dysfunction. 2 This will hopefully pave the way for major advances in disease-modifying therapies. One nonmotor feature that was found to be associated with PD is cardiac sympathetic denervation, 3,4 as dem- onstrated by the metaiodobenzyl-guanidine (MIBG) cardiac scan. The role of the MIBG-cardiac scan in preclinical PD has not yet been determined. A single case report has been published of decreased sympa- thetic innervation demonstrated by a 6-[ 18 F]fluorodop- amine cardiac positron emission tomography scan performed 4 years before the appearance of initial motor symptoms of PD. 5 In another study, positive immunostaining for alpha-synuclein aggregates, in biopsy specimens of autonomic plexuses obtained ------------------------------------------------------------ *Correspondence to: Gilad Yahalom, The Parkinson Disease and Move- ment Disorders Clinic, Department of Neurology, the Chaim Sheba Medi- cal Center, Ramat-Gan, Israel, E-mail: gyahalom@gmail.com Funding agencies: None. Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online ver- sion of this article. † Both authors contributed equally to this article. Received: 2 September 2013; Revised: 9 May 2014; Accepted: 28 May 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25943 RESEARCH ARTICLE Movement Disorders, Vol. 00, No. 00, 2014 1