Cardiac Sympathetic Degeneration Correlates with Olfactory Function in Parkinson’s Disease Mutsumi Iijima, MD, PhD, 1 * Mikio Osawa, MD, PhD, 1 Mitsuru Momose, MD, PhD, 2 Tatsu Kobayakawa, PhD, 3 Sachiko Saito, PhD, 4 Makoto Iwata, MD, PhD, 1 and Shinichiro Uchiyama, MD, PhD 1 1 Department of Neurology, Tokyo Women’s Medical University, Tokyo, Japan 2 Department of Radiology, Tokyo Women’s Medical University, Tokyo, Japan 3 National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan 4 Saito Sachiko Taste and Smell Institute, Tsukuba, Japan Abstract: Autonomic and olfactory dysfunctions are consid- ered markers for preclinical diagnosis in Parkinson’s disease (PD), because pathological changes in these systems can start before motor symptoms develop. We investigated whether cardiac sympathetic function and olfactory function are asso- ciated in PD. Participants comprised 40 nondemented patients with idiopathic PD, and age-matched controls. Cardiac sym- pathetic function was evaluated by 123 I-metaiodobenzylgua- nidine (MIBG) uptake, in terms of the heart to mediastinum (H/M) ratio in both early and delayed images, and the wash- out rate (WR). Olfactory function was evaluated using the Odor Stick Identification Test for Japanese, which evaluates the detection of 12 odorants familiar to Japanese participants. Smell identification scores were significantly lower (P < 0.001) in patients with PD than in controls. Smell identifica- tion scores correlated positively with early (P < 0.05) and delayed H/M ratios (P < 0.01), and inversely with the WR (P < 0.005) especially in patients with early PD (below 5 years of the start of motor symptoms), whereas smell identifi- cation scores did not correlate with any parameters of MIBG in the advanced PD (above 5 years of the start of motor symptoms). There was no correlation between motor symp- tom scores and smell identification scores, H/M ratios, or WR. The results suggest that the cardiac sympathetic nervous system might degenerate in parallel with the olfactory system in patients with early PD, and that these two systems might degenerate at a different rate of speed in advanced PD. Ó 2010 Movement Disorder Society Key words: Parkinson’s disease; odor stick identification test; MIBG INTRODUCTION Olfactory and autonomic dysfunctions are nowadays recognized as nonmotor symptoms in patients with Parkinson’s disease (PD). These features are consid- ered diagnostic markers of preclinical PD 1–3 because pathological changes of the olfactory and autonomic systems begin before motor symptoms develop. 4 The sensitivity of olfactory disturbance as a marker of PD is 80–90%. 1,2,5 The proportion of patients with olfactory disturbance who develop PD is 7–10%. 6–11 Metaiodobenzylguanidine (MIBG) is a physiologic analog of norepinephrine, and iodone-123 ( 123 I) MIBG cardiac scintigraphy is a noninvasive tool for assessing myocardial sympathetic nerve terminals. 12 In patients with PD, cardiac uptake of MIBG decreases from the early stage of the disease 12,13 and correlates with the se- verity of hypokinesia and rigidity. 14,15,16 The sensitivity of MIBG cardiac scintigraphy in PD is 80–90%. 13,14,17–19 In this case-control study, we investigated whether there is an association between cardiac autonomic function and olfactory function in patients with PD. METHODS Participants Participants comprosed 40 patients with idiopathic PD (25 men and 15 women), ranging in age from 41 to 82 (mean 6 SD, 66.6 6 10.6) years, and 40 age- Potential conflict of interest: Nothing to report. *Correspondence to: Mutsumi Iijima, Department of Neurology, Tokyo Women’s Medical University School of Medicine, 8-1 Kawada-cho Shinjuku, Tokyo 162–8666, Japan E-mail: mutumi@nij.twmu.ac.jp Received 11 May 2009; Revised 31 August 2009; Accepted 11 December 2009 Published online 3 February 2010 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.23001 1143 Movement Disorders Vol. 25, No. 9, 2010, pp. 1143–1149 Ó 2010 Movement Disorder Society