{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:41:33Z","timestamp":1790602893764,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T00:00:00Z","timestamp":1625788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Little is known about how frequently patients with a Unified Parkinson Disease Rating Scale part III (UPDRS-III) score of 3 or 4, including postural and action tremor, could be classified into early Parkinson's disease (PD).<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> To examine the prevalence of early PD in patients with subtle parkinsonian signs (rest tremor, postural tremor, and rigidity) without bradykinesia, having a UPDRS-III score of 3 or 4.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Parkinsonism was assessed using UPDRS-III based on both the United Kingdom PD Society Brain Bank criteria and the Movement Disorder Society PD criteria. Ninety patients with a UPDRS-III score of 3 or 4, including postural tremor, were evaluated by <jats:sup>123<\/jats:sup>I-FP-CIT SPECT (DaTscan), brain MRI, the Mini-Mental State Examination, and smell test. Some patients were additionally examined by <jats:sup>123<\/jats:sup>I-metaiodobenzylguanidine myocardial scintigraphy or <jats:sup>123<\/jats:sup>I-N-isopropyl-p-iodoamphetamine SPECT.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Seventy-five [mean age (standard deviation): 76.9 (8.1)] out of 90 patients (83.3%) showed abnormal findings on DaTscan imaging: 57 out of 75 (76.0%) showed a reduced specific binding ratio (SBR) accompanied by an egg shape pattern (<jats:italic>n<\/jats:italic> = 37, 49.3%) or a mixed type pattern (<jats:italic>n<\/jats:italic> = 14, 18.7%), both reduced SBR and increased asymmetry index (AI) with a normal shape (<jats:italic>n<\/jats:italic> = 4, 5.3%), and reduced SBR only (<jats:italic>n<\/jats:italic> = 2, 2.7%); 18 (24.0%) showed an egg shape pattern or a mixed type pattern without reduced SBR. In other words, 69 out of 75 patients (92.0%) showed either an egg shape or a mixed type pattern with or without reduced SBR. All patients were free of dementia, and their olfactory function was significantly impaired compared with controls (<jats:italic>n<\/jats:italic> = 141) on the odor-stick identification test for Japanese (<jats:italic>p<\/jats:italic> &amp;lt; 0.0001).<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> The prevalence of patients with subtle parkinsonian signs having a UPDRS-III score of 3 or 4, including postural tremor, is unexpectedly high in daily clinical practice, and most of these patients could be categorized into mild early-stage PD.<\/jats:p>","DOI":"10.3389\/fneur.2021.656679","type":"journal-article","created":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T10:21:54Z","timestamp":1625826114000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["High Prevalence of Early Parkinson's Disease in Patients With Subtle Parkinsonian Signs"],"prefix":"10.3389","volume":"12","author":[{"given":"Shoichi","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1136\/jnnp.51.6.745","article-title":"The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease","volume":"51","author":"Gibb","year":"1988","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson's disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov Disord."},{"key":"B3","first-page":"153","article-title":"Unified Parkinson's Disease Rating Scale","author":"Fahn","year":"1987","journal-title":"Recent Developments in Parkinson's Disease"},{"key":"B4","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1002\/mds.24985","article-title":"Defining at-risk populations for Parkinson's disease: lessons from ongoing studies","volume":"27","author":"Berg","year":"2012","journal-title":"Mov Disord."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1093\/brain\/aws093","article-title":"How does Parkinsonism start? Prodromal Parkinsonism motor changes in idiopathic REM sleep behavior disorder","volume":"135","author":"Postuma","year":"2012","journal-title":"Brain."},{"key":"B6","first-page":"CD011145","article-title":"Mini-mental state examination (MMSE) for the detection of dementia in clinically unevaluated people aged 65 and over in community and primary care populations","volume":"1","author":"Creavin","year":"2016","journal-title":"Cochrane Database Syst Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3233\/JAD-160119","article-title":"Mini-Mental State Examination in Elderly Chinese: A population-based normative study","volume":"53","author":"Li","year":"2016","journal-title":"J Alzheimers Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1002\/mds.26431","article-title":"MDS research criteria for prodromal Parkinson's disease","volume":"30","author":"Berg","year":"2015","journal-title":"Mov Disord."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1002\/mds.27802","article-title":"Update of the MDS research criteria for prodromal Parkinson's disease","volume":"34","author":"Heinzel","year":"2019","journal-title":"Mov Disord."},{"key":"B10","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1001\/jamaneurol.2017.0985","article-title":"Conversion to Parkinson disease in the PARS hyposmic and dopamine transporter-deficit prodromal cohort","volume":"74","author":"Jennings","year":"2017","journal-title":"JAMA Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"714","DOI":"10.2967\/jnumed.112.110106","article-title":"Value of semiquantitative analysis for clinical reporting of 123I-2-\u03b2-carbomethoxy-3\u03b2-(4-iodophenyl)-N-(3-fluoropropyl) nortropane SPECT studies","volume":"54","author":"S\u00f6derlund","year":"2013","journal-title":"J Nucl Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s00415-011-6163-1","article-title":"Visual assessment of dopaminergic degeneration pattern in 123I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease","volume":"259","author":"Kahraman","year":"2012","journal-title":"J Neurol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1007\/s00259-018-3976-5","article-title":"Japanese multicenter database of healthy controls for [123I]FP-CIT SPECT","volume":"45","author":"Matsuda","year":"2018","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.1007\/s00259-006-0155-x","article-title":"Quantification of [123I]FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio","volume":"33","author":"Tossici-Bolt","year":"2006","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00259-009-1202-1","article-title":"Validation of cardiac (123)I-MIBG scintigraphy in patients with Parkinson's disease who were diagnosed with dopamine PET","volume":"37","author":"Ishibashi","year":"2010","journal-title":"Eur J Nucl Med Mol Imaging."},{"key":"B16","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.parkreldis.2012.01.009","article-title":"123I-MIBG myocardial scintigraphy for differentiating Parkinson's disease from other neurodegenerative parkinsonism: a systematic review and meta-analysis","volume":"18","author":"Orimo","year":"2012","journal-title":"Parkinsonism Relat Disord."},{"key":"B17","doi-asserted-by":"publisher","first-page":"464","DOI":"10.4172\/2161-0460.1000464","article-title":"Synergistic effects of Alzheimer's disease and parkinsonism on olfactory impairment","volume":"9","author":"Sasaki","year":"2019","journal-title":"J Alzheimers Dis Parkinsonism."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.3174\/ajnr.A2935","article-title":"Automatic voxel-based morphometry of structural MRI by SPM8 plus diffeomorphic anatomic registration through exponentiated lie algebra improves the diagnosis of probable Alzheimer Disease","volume":"33","author":"Matsuda","year":"2012","journal-title":"Am J Neuroradiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1007\/s12149-013-0768-7","article-title":"Prediction of outcomes in MCI with 123I-IMP-CBF SPECT: a multicenter prospective cohort study","volume":"27","author":"Ito","year":"2013","journal-title":"Ann Nucl Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.sleep.2009.05.007","article-title":"The REM sleep behavior disorder screening questionnaire: validation study of a Japanese version","volume":"10","author":"Miyamoto","year":"2009","journal-title":"Sleep Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1002\/1531-8257(200005)15:3&lt;503::AID-MDS1013&gt;3.0.CO;2-V","article-title":"Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: The [123I]-FP-CIT study group","volume":"15","author":"Benamer","year":"2000","journal-title":"Mov Disord."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1212\/WNL.48.6.1578","article-title":"[11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson's disease: implications for the symptomatic threshold","volume":"48","author":"Guttman","year":"1997","journal-title":"Neurology."},{"key":"B23","doi-asserted-by":"publisher","first-page":"S43","DOI":"10.1002\/mds.10579","article-title":"Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it?","volume":"18","author":"Pirker","year":"2003","journal-title":"Mov Disord."},{"key":"B24","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1002\/1531-8257(200007)15:4&lt;692::AID-MDS1014&gt;3.0.CO;2-V","article-title":"Correlation of Parkinson's disease severity and duration with 123I-FP-CIT SPECT striatal uptake","volume":"15","author":"Benamer","year":"2000","journal-title":"Mov Disord."},{"key":"B25","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1590\/S0004-282X2012000900004","article-title":"Dopamine transporter imaging in clinically unclear cases of parkinsonism and the importance of scans without evidence of dopaminergic deficit (SWEDDs)","volume":"70","author":"Utiumi","year":"2012","journal-title":"Arq Neuropsiquiatr."},{"key":"B26","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.parkreldis.2021.01.005","article-title":"Toward subgroup-specific risk estimates: A meta-analysis of longitudinal studies on olfactory dysfunction and risk of Parkinson's disease","volume":"84","author":"Daalen","year":"2021","journal-title":"Parkinsonism Relat Disord."},{"key":"B27","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1002\/mdc3.13028","article-title":"Association between olfactory impairment and disease severity and duration in Parkinson's disease","volume":"7","author":"Sasaki","year":"2020","journal-title":"Mov Disord Clin Pract."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1212\/01.WNL.0000156157.97411.5E","article-title":"Association between mild parkinsonian signs and mild cognitive impairment in a community","volume":"12","author":"Louis","year":"2005","journal-title":"Neurology."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1212\/01.wnl.0000188878.81385.73","article-title":"Parkinsonian signs in subjects with mild cognitive impairment","volume":"27","author":"Boyle","year":"2005","journal-title":"Neurology."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1016\/j.jalz.2018.06.3054","article-title":"High prevalence of parkinsonism in patients with MCI or mild Alzheimer's disease","volume":"14","author":"Sasaki","year":"2018","journal-title":"Alzheimers Dement."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.656679\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,9]],"date-time":"2021-07-09T10:21:58Z","timestamp":1625826118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.656679\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":30,"alternative-id":["10.3389\/fneur.2021.656679"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.656679","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,9]]},"article-number":"656679"}}