Objective: The objective of this study was to clarify the relationship between autonomic and non-autonomic non-motor symptoms in patients with Parkinson’s disease (PD). Methods: Sixty-five PD patients were included in this study (27 men and 38 women; aged 68.5 ± 10.0; Hoehn and Yahr (HY) stage 2.6 ± 1.1). The autonomic symptoms were evaluated by the Japanese version of the Scales for outcomes in PD autonomic (SCOPA-AUT) questionnaire. The patients were assessed with the mini-mental state examination (MMSE), PD sleep evaluation scale-2 (PDSS-2), Epworth sleepiness scale (ESS) and Beck’s depression inventory II (BDI-II). The Non-Motor Symptom Scale (NMSS) total scores and subscores of non-autonomic non-motor symptom domains (sleep/fatigue, mood/cognition, perceptual problems/hallucination, and attention/memory) were evaluated. A dopamine transporter (DAT) scan, metaiodobenzylguanidine (MIBG) myocardial scintigraphy, and card type olfactory identification test (open essence [OE, Wako]) were performed. Results: The SCOPA-AUT total score was positively correlated with the disease duration, HY stage, levodopa equivalent dose, PDSS-2, ESS, BDI-II and non-autonomic NMSS and inversely correlated with the MMSE. The high-SCOPA-AUT group (≥9) had lower MMSE scores and higher PDSS-2, ESS, BDI-II and non-motor NMSS scores than the low-SCOPA-AUT group (< 9). The DAT scan, MIBG uptake and OE score did not differ between the groups. In a stepwise linear regression analysis, which excluded possibly overlapping items among the scales, the subtotals of PDSS-2 items, except for item 8 (nocturia), (p < 0.0001) and non-autonomic NMSS domains (p = 0.00040) were significant predictors of the total SCOPA-AUT score. Conclusion: Our study shows significant correlations among autonomic symptoms, PD-related sleep problems and non-autonomic non-motor symptoms in PD patients.

Schapira AHV, Chaudhuri KR, Jenner P: Non-motor features of Parkinson disease. Nat Rev Neurosci 2017; 18: 435–450.
Barone P, Antonini A, Colosimo C, Marconi R, Morgante L, Avarello TP, Bottacchi E, Cannas A, Ceravolo G, Ceravolo R, Cicarelli G, Gaglio RM, Giglia RM, Iemolo F, Manfredi M, Meco G, Nicoletti A, Pederzoli M, Petrone A, Pisani A, Pontieri FE, Quatrale R, Ramat S, Scala R, Volpe G, Zappulla S, Bentivoglio AR, Stocchi F, Trianni G, Dotto PD; PRIAMO study group: The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord 2009; 24: 1641–1649.
Micieli G, Tosi P, Marcheselli S, Cavallini A: Autonomic dysfunction in Parkinson’s disease. Neurol Sci 2003; 24(suppl 1):S32–S34.
Verbaan D, Marinus J, Visser M, van Rooden SM, Stiggelbout AM, van Hilten JJ: Patient-reported autonomic symptoms in Parkinson disease. Neurology 2007; 69: 333–341.
Chaudhuri KR, Naidu Y: Early Parkinson’s disease and non-motor issues. J Neurol 2008; 255(suppl 5): 33–38.
Merola A, Romagnolo A, Rosso M, Suri R, Berndt Z, Maule S, Lopiano L, Espay AJ: Autonomic dysfunction in Parkinson’s disease: a prospective cohort study. Mov Disord 2018; 33: 391–397.
Merola A, Romagnolo A, Rosso M, Lopez-Castellanos JR, Wissel BD, Larkin S, Bernardini A, Zibetti M, Maule S, Lopiano L, Espay AJ: Orthostatic hypotension in Parkinson’s disease: does it matter if asymptomatic? Parkinsonism Relat Disord 2016; 33: 65–71.
Maeda T, Shimo Y, Chiu SW, Yamaguchi T, Kashihara K, Tsuboi Y, Nomoto M, Hattori N, Watanabe H, Saiki H; J-FIRST Group: Clinical manifestations of nonmotor symptoms in 1021 Japanese Parkinson’s disease patients from 35 medical centers. Parkinsonism Relat Disord 2017; 38: 54–60.
Visser M, Marinus J, Stiggelbout AM, Van Hilten JJ: Assessment of autonomic dysfunction in Parkinson’s disease: the SCOPA-AUT. Mov Disord 2004; 19: 1306–1312.
Matsushima M, Yabe I, Hirotani M, Kano T, Sasaki H: Reliability of the Japanese version of the scales for outcomes in Parkinson’s disease-autonomic questionnaire. Clin Neurol Neurosurg 2014; 124: 182–184.
Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G: MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 2015; 30: 1591–1601.
Kashihara K, Kondo T, Mizuno Y, Kikuchi S, Kuno S, Hasegawa K, Hattori N, Mochizuki H, Mori H, Murata M, Nomoto M, Takahashi R, Takeda A, Tsuboi Y, Ugawa Y, Yamanmoto M, Yokochi F, Yoshii F, Stebbins GT, Tilley BC, Luo S, Wang L, LaPelle NR, Goetz CG; MDS-UPDRS Japanese Validation Study Group: Official Japanese Version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale: validation against the original English version. Mov Disord Clin Pract 2014; 1: 200–212.
Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE: Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 2010; 25: 2649–2653.
Suzuki K, Miyamoto M, Miyamoto T, Tatsumoto M, Watanabe Y, Suzuki S, Iwanami M, Sada T, Kadowaki T, Numao A, Trenkwalder C, Hirata K: Nocturnal disturbances and restlessness in Parkinson’s disease: using the Japanese version of the Parkinson’s disease sleep scale-2. J Neurol Sci 2012; 318: 76–81.
Takegami M, Suzukamo Y, Wakita T, Noguchi H, Chin K, Kadotani H, Inoue Y, Oka Y, Nakamura T, Green J, Johns MW, Fukuhara S: Development of a Japanese version of the Epworth Sleepiness Scale (JESS) based on item response theory. Sleep Med 2009; 10: 556–565.
Miyamoto T, Miyamoto M, Iwanami M, Kobayashi M, Nakamura M, Inoue Y, Ando C, Hirata K: The REM sleep behavior disorder screening questionnaire: validation study of a Japanese version. Sleep Med 2009; 10: 1151–1154.
Chaudhuri KR, Martinez-Martin P, Brown RG, Sethi K, Stocchi F, Odin P, Ondo W, Abe K, Macphee G, Macmahon D, Barone P, Rabey M, Forbes A, Breen K, Tluk S, Naidu Y, Olanow W, Williams AJ, Thomas S, Rye D, Tsuboi Y, Hand A, Schapira AH: The metric properties of a novel non-motor symptoms scale for Parkinson’s disease: results from an international pilot study. Mov Disord 2007; 22: 1901–1911.
Beck AT, Steer RA, Brown GK: The Beck Depression Inventory Second Edition. Boston Houghton Mifflin, 1996.
Nakajima K, Matsumoto N, Kasai T, Matsuo S, Kiso K, Okuda K: Normal values and standardization of parameters in nuclear cardiology: Japanese society of nuclear medicine working group database. Ann Nucl Med 2016; 30: 188–199.
Yoshii F, Ryo M, Baba Y, Koide T, Hashimoto J: Combined use of dopamine transporter imaging (DAT-SPECT) and 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy for diagnosing Parkinson’s disease. J Neurol Sci 2017; 375: 80–85.
Saito S, Ayabe-Kanamura S, Takashima Y, Gotow N, Naito N, Nozawa T, Mise M, Deguchi Y, Kobayakawa T: Development of a smell identification test using a novel stick-type odor presentation kit. Chem Senses 2006; 31: 379–391.
Watanabe Y, Suzuki K, Miyamoto T, Miyamoto M, Numao A, Fujita H, Uchiyama T, Kadowaki T, Matsubara T, Hirata K: A card-type odor identification test for Japanese patients with Parkinson’s disease and related disorders. Intern Med 2017; 56: 2871–2878.
Martinez-Martin P, Rodriguez-Blazquez C, Abe K, Bhattacharyya KB, Bloem BR, Carod-Artal FJ, Prakash R, Esselink RA, Falup-Pecurariu C, Gallardo M, Mir P, Naidu Y, Nicoletti A, Sethi K, Tsuboi Y, van Hilten JJ, Visser M, Zappia M, Chaudhuri KR: International study on the psychometric attributes of the non-motor symptoms scale in Parkinson disease. Neurology 2009; 73: 1584–1591.
Sellami L, Kacem I, Nasri A, Djebara MB, Sidhom Y, Gargouri A, Gouider R: Evaluation of an Arabic version of the non-motor symptoms scale in Parkinson’s disease. Neurol Sci 2016; 37: 963–968.
Arnao V, Cinturino A, Valentino F, Perini V, Mastrilli S, Bellavia G, Savettieri G, Realmuto S, D’Amelio M: In patient’s with Parkinson disease, autonomic symptoms are frequent and associated with other non-motor symptoms. Clin Auton Res 2015; 25: 301–307.
Kim JS, Park HE, Oh YS, Lee SH, Park JW, Son BC, Lee KS: Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder. J Neurol Sci 2016; 362: 59–63.
Nomura T, Inoue Y, Hogl B, Uemura Y, Kitayama M, Abe T, Miyoshi H, Nakashima K: Relationship between (123)I-MIBG scintigrams and REM sleep behavior disorder in Parkinson’s disease. Parkinsonism Relat Disord 2010; 16: 683–685.
Wakabayashi K, Takahashi H: Neuropathology of autonomic nervous system in Parkinson’s disease. Eur Neurol 1997; 38(suppl 2): 2–7.
Jellinger KA: Synuclein deposition and non-motor symptoms in Parkinson disease. J Neurol Sci 2011; 310: 107–111.
Titova N, Chaudhuri KR: Nonmotor Parkinson’s and future directions. Int Rev Neurobiol 2017; 134: 1493–1505.
Leclair-Visonneau L, Magy L, Volteau C, Clairembault T, Le Dily S, Preterre C, Peyre A, Damier P, Neunlist M, Pereon Y, Derkinderen P: Heterogeneous pattern of autonomic dysfunction in Parkinson’s disease. J Neurol 2018; 265: 933–941.
Dayan E, Sklerov M, Browner N: Disrupted hypothalamic functional connectivity in patients with PD and autonomic dysfunction. Neurology 2018; 90:e2051–e2058.
Pyatigorskaya N, Mongin M, Valabregue R, Yahia-Cherif L, Ewenczyk C, Poupon C, Debellemaniere E, Vidailhet M, Arnulf I, Lehericy S: Medulla oblongata damage and cardiac autonomic dysfunction in Parkinson disease. Neurology 2016; 87: 2540–2545.
Marras C, Chaudhuri KR: Nonmotor features of Parkinson’s disease subtypes. Mov Disord 2016; 31: 1095–1102.
van der Heeden JF, Marinus J, Martinez-Martin P, Rodriguez-Blazquez C, Geraedts VJ, van Hilten JJ: Postural instability and gait are associated with severity and prognosis of Parkinson disease. Neurology 2016; 86: 2243–2250.
Suzuki K, Okuma Y, Uchiyama T, Miyamoto M, Sakakibara R, Shimo Y, Hattori N, Kuwabara S, Yamamoto T, Kaji Y, Hirano S, Kadowaki T, Hirata K; Kanto NMPD investigators: Impact of sleep-related symptoms on clinical motor subtypes and disability in Parkinson’s disease: a multicentre cross-sectional study. J Neurol Neurosurg Psychiatry 2017; 88: 953–959.
Fereshtehnejad SM, Romenets SR, Anang JB, Latreille V, Gagnon JF, Postuma RB: New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol 2015; 72: 863–873.
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