Abstract
Parkinsonian disorders are a heterogeneous group of incurable neurodegenerative diseases that significantly reduce quality of life and constitute a substantial economic burden. Nuclear imaging (NI) and magnetic resonance imaging (MRI) have played and continue to play a key role in research aimed at understanding and monitoring these disorders. MRI is cheaper, more accessible, nonirradiating, and better at measuring biological structures and hemodynamics than NI. NI, on the other hand, can track molecular processes, which may be crucial for the development of efficient diseasemodifying therapies. Given the strengths and weaknesses of NI and MRI, how can they best be applied to Parkinsonism research going forward? This review aims to examine the effectiveness of NI and MRI in three areas of Parkinsonism research (differential diagnosis, prodromal disease identification, and disease monitoring) to highlight where they can be most impactful. Based on the available literature, MRI can assist with differential diagnosis, prodromal disease identification, and disease monitoring as well as NI. However, more work is needed, to confirm the value of MRI for monitoring prodromal disease and predicting phenoconversion. Although NI can complement or be a substitute for MRI in all the areas covered in this review, we believe that its most meaningful impact will emerge once reliable Parkinsonian proteinopathy tracers become available. Future work in tracer development and high-field imaging will continue to influence the landscape for NI and MRI.
Keywords: Parkinson’s disease, magnetic resonance imaging, nuclear imaging, cerebral blood flow, MSA, corticobasal degeneration.
[http://dx.doi.org/10.1016/S0140-6736(21)00218-X] [PMID: 33848468]
[http://dx.doi.org/10.1111/j.1365-2990.2011.01234.x] [PMID: 22074330]
[http://dx.doi.org/10.1097/WCO.0b013e32833be924] [PMID: 20610990]
[http://dx.doi.org/10.1093/jnen/61.11.935] [PMID: 12430710]
[http://dx.doi.org/10.1093/brain/114.5.2283] [PMID: 1933245]
[http://dx.doi.org/10.1093/jnen/60.4.393] [PMID: 11305875]
[http://dx.doi.org/10.1093/brain/awh303] [PMID: 15509623]
[http://dx.doi.org/10.1093/brain/awt192] [PMID: 23884810]
[http://dx.doi.org/10.1093/brain/122.8.1449] [PMID: 10430831]
[http://dx.doi.org/10.1212/WNL.0000000000003512] [PMID: 27940650]
[http://dx.doi.org/10.3389/fneur.2020.572976] [PMID: 33178113]
[http://dx.doi.org/10.1007/s00702-013-1133-7] [PMID: 24337696]
[http://dx.doi.org/10.1093/brain/awh488] [PMID: 15788542]
[http://dx.doi.org/10.1016/S2468-2667(20)30190-0] [PMID: 33007212]
[http://dx.doi.org/10.1001/jamaneurol.2013.3579] [PMID: 24042491]
[http://dx.doi.org/10.1007/s00702-017-1686-y] [PMID: 28150045]
[http://dx.doi.org/10.1002/mds.22966] [PMID: 20108378]
[http://dx.doi.org/10.1212/WNL.49.5.1284] [PMID: 9371909]
[http://dx.doi.org/10.1016/S1474-4422(04)00936-6] [PMID: 15556806]
[http://dx.doi.org/10.1002/mds.21839] [PMID: 18044727]
[http://dx.doi.org/10.3389/fneur.2021.736784] [PMID: 34650511]
[http://dx.doi.org/10.1136/jnnp.64.2.184] [PMID: 9489528]
[http://dx.doi.org/10.1212/WNL.0000000000002638] [PMID: 27037234]
[http://dx.doi.org/10.1002/mds.22340] [PMID: 19025984]
[http://dx.doi.org/10.1002/mds.20255] [PMID: 15452868]
[http://dx.doi.org/10.1093/brain/awm032] [PMID: 17405767]
[http://dx.doi.org/10.1002/mds.28470] [PMID: 33513292]
[http://dx.doi.org/10.1016/j.parkreldis.2020.08.021] [PMID: 32947108]
[http://dx.doi.org/10.3389/fneur.2020.00665] [PMID: 32765399]
[http://dx.doi.org/10.1002/mdc3.12673] [PMID: 30637278]
[http://dx.doi.org/10.1007/s11910-018-0894-7] [PMID: 30280267]
[http://dx.doi.org/10.1002/mds.26968] [PMID: 28370449]
[http://dx.doi.org/10.1001/jamaneurol.2021.1312] [PMID: 34459865]
[http://dx.doi.org/10.1146/annurev-bioeng-071114-040723] [PMID: 26643024]
[http://dx.doi.org/10.3174/ajnr.A1175] [PMID: 18583408]
[http://dx.doi.org/10.1212/01.wnl.0000324625.00404.15] [PMID: 18725592]
[http://dx.doi.org/10.1002/mds.26987] [PMID: 28467028]
[http://dx.doi.org/10.1002/mds.26424] [PMID: 26474316]
[http://dx.doi.org/10.1212/WNL.0b013e31827f0fd1] [PMID: 23359374]
[http://dx.doi.org/10.1136/jnnp.55.3.181] [PMID: 1564476]
[http://dx.doi.org/10.1016/j.parkreldis.2014.04.019] [PMID: 24816002]
[http://dx.doi.org/10.1212/WNL.0000000000001807] [PMID: 26138942]
[http://dx.doi.org/10.1212/WNL.0000000000002350] [PMID: 26764028]
[http://dx.doi.org/10.1212/WNL.0000000000000641] [PMID: 24975862]
[http://dx.doi.org/10.1016/j.neuroimage.2005.03.012] [PMID: 15955501]
[http://dx.doi.org/10.2967/jnumed.116.186403] [PMID: 28912150]
[http://dx.doi.org/10.1080/01616412.2017.1312211] [PMID: 28378615]
[http://dx.doi.org/10.1212/WNL.0b013e31826c1b0a] [PMID: 22914831]
[http://dx.doi.org/10.1007/s00234-012-1132-7] [PMID: 23314836]
[http://dx.doi.org/10.1111/ene.13269] [PMID: 28244178]
[http://dx.doi.org/10.1016/S1474-4422(10)70002-8] [PMID: 20061183]
[http://dx.doi.org/10.2967/jnumed.115.161992] [PMID: 26449840]
[http://dx.doi.org/10.1016/bs.irn.2018.08.006] [PMID: 30409259]
[http://dx.doi.org/10.1007/s00429-010-0246-0] [PMID: 20361208]
[http://dx.doi.org/10.1016/j.jocn.2020.05.005] [PMID: 32389545]
[http://dx.doi.org/10.1016/j.jns.2013.09.005] [PMID: 24075472]
[http://dx.doi.org/10.1007/s00259-006-0344-7] [PMID: 17245531]
[http://dx.doi.org/10.1002/mds.23915] [PMID: 21830234]
[http://dx.doi.org/10.1016/j.jns.2019.116627] [PMID: 31865188]
[http://dx.doi.org/10.1097/MD.0000000000016603] [PMID: 31348305]
[http://dx.doi.org/10.1148/radiol.2453061703] [PMID: 17991785]
[http://dx.doi.org/10.1016/j.parkreldis.2021.05.002] [PMID: 34000497]
[http://dx.doi.org/10.1002/mds.28007] [PMID: 32092195]
[http://dx.doi.org/10.1016/j.parkreldis.2017.10.020] [PMID: 29126761]
[http://dx.doi.org/10.1002/mds.23529] [PMID: 21287599]
[http://dx.doi.org/10.3174/ajnr.A5618] [PMID: 29622555]
[http://dx.doi.org/10.1002/mds.28060] [PMID: 32357259]
[http://dx.doi.org/10.1002/mds.28364] [PMID: 33151015]
[http://dx.doi.org/10.1016/j.parkreldis.2018.07.016] [PMID: 30068492]
[http://dx.doi.org/10.1002/mds.27621] [PMID: 30759325]
[http://dx.doi.org/10.1002/mds.28348] [PMID: 33137232]
[http://dx.doi.org/10.1016/j.neuroimage.2006.05.044] [PMID: 16854598]
[http://dx.doi.org/10.1002/mrm.22055] [PMID: 19623619]
[http://dx.doi.org/10.1002/hbm.24760] [PMID: 31403737]
[http://dx.doi.org/10.1093/brain/awr307] [PMID: 22171354]
[http://dx.doi.org/10.1007/s00429-019-02017-1] [PMID: 31894407]
[http://dx.doi.org/10.1093/brain/awv361] [PMID: 26705348]
[http://dx.doi.org/10.1016/S2589-7500(19)30105-0] [PMID: 32259098]
[http://dx.doi.org/10.1093/brain/awx146] [PMID: 28899020]
[http://dx.doi.org/10.3174/ajnr.A5545] [PMID: 29419398]
[http://dx.doi.org/10.1002/mds.27100] [PMID: 28714593]
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.10.029] [PMID: 25467638]
[http://dx.doi.org/10.1093/brain/awv136] [PMID: 25981960]
[http://dx.doi.org/10.1016/j.parkreldis.2019.01.007] [PMID: 30639168]
[http://dx.doi.org/10.1093/brain/awab039] [PMID: 33880500]
[http://dx.doi.org/10.1016/j.nicl.2022.103022] [PMID: 35489192]
[http://dx.doi.org/10.1002/mds.28886] [PMID: 34936139]
[http://dx.doi.org/10.1016/j.parkreldis.2010.05.006] [PMID: 20573537]
[http://dx.doi.org/10.3174/ajnr.A1615] [PMID: 19589886]
[http://dx.doi.org/10.1093/brain/awn195] [PMID: 18819991]
[http://dx.doi.org/10.1016/j.parkreldis.2014.01.023] [PMID: 24656943]
[http://dx.doi.org/10.1002/mds.22193] [PMID: 18973249]
[http://dx.doi.org/10.1172/JCI200319010] [PMID: 12840051]
[http://dx.doi.org/10.1016/j.nicl.2019.101720] [PMID: 30785051]
[http://dx.doi.org/10.1016/j.nicl.2019.102112] [PMID: 31821953]
[http://dx.doi.org/10.1016/j.nicl.2017.09.008] [PMID: 28951832]
[http://dx.doi.org/10.3389/fneur.2017.00248] [PMID: 28634465]
[http://dx.doi.org/10.1016/j.parkreldis.2017.03.008] [PMID: 28318985]
[http://dx.doi.org/10.1007/s11910-014-0448-6] [PMID: 24744021]
[http://dx.doi.org/10.1016/j.parkreldis.2018.01.012] [PMID: 29352721]
[http://dx.doi.org/10.3389/fnagi.2017.00266] [PMID: 28848423]
[http://dx.doi.org/10.1002/hbm.23260] [PMID: 27207613]
[http://dx.doi.org/10.1016/j.ynirp.2021.100026]
[http://dx.doi.org/10.1038/sj.jcbfm.9600358] [PMID: 16804550]
[http://dx.doi.org/10.1212/WNL.0000000000002985] [PMID: 27421545]
[http://dx.doi.org/10.1002/hbm.23213] [PMID: 27089850]
[http://dx.doi.org/10.1002/hbm.22694] [PMID: 25413603]
[http://dx.doi.org/10.1002/mds.21933] [PMID: 18186116]
[PMID: 22966219]
[http://dx.doi.org/10.3171/2019.9.FOCUS19567] [PMID: 31786550]
[http://dx.doi.org/10.1093/brain/awq377] [PMID: 21310726]
[http://dx.doi.org/10.1186/s12880-020-00479-y] [PMID: 32660445]
[http://dx.doi.org/10.3389/fnagi.2021.687649] [PMID: 34413766]
[http://dx.doi.org/10.1016/j.parkreldis.2020.02.009] [PMID: 32109737]
[http://dx.doi.org/10.3389/fnins.2019.00777] [PMID: 31417345]
[http://dx.doi.org/10.1016/j.neuroimage.2011.10.033] [PMID: 22032942]
[http://dx.doi.org/10.3389/fneur.2020.00562] [PMID: 32655485]
[http://dx.doi.org/10.1080/01616412.2021.1954842] [PMID: 34313185]
[http://dx.doi.org/10.1177/0271678X19874643] [PMID: 31500521]
[http://dx.doi.org/10.1002/mds.27224] [PMID: 29119634]
[http://dx.doi.org/10.1523/JNEUROSCI.3634-15.2016] [PMID: 27170132]
[http://dx.doi.org/10.1002/ana.22361] [PMID: 21387372]
[http://dx.doi.org/10.1016/j.parkreldis.2016.03.015] [PMID: 27039056]
[http://dx.doi.org/10.5334/tohm.166] [PMID: 24116345]
[http://dx.doi.org/10.4103/neuroindia.NI_880_16] [PMID: 28879902]
[http://dx.doi.org/10.3389/fneur.2020.00540] [PMID: 32754107]
[http://dx.doi.org/10.1002/mds.25844] [PMID: 24619848]
[http://dx.doi.org/10.1016/j.parkreldis.2018.09.011] [PMID: 30224266]
[http://dx.doi.org/10.1136/jnnp-2015-311890] [PMID: 26848171]
[http://dx.doi.org/10.2147/nedt.2007.3.1.145] [PMID: 19300544]
[http://dx.doi.org/10.1002/mds.24996] [PMID: 22508280]
[http://dx.doi.org/10.1001/archneur.63.4.584] [PMID: 16606773]
[http://dx.doi.org/10.1016/j.nicl.2017.04.011] [PMID: 28529878]
[http://dx.doi.org/10.1101/cshperspect.a008888] [PMID: 22315721]
[http://dx.doi.org/10.1016/S1474-4422(08)70117-0] [PMID: 18539534]
[http://dx.doi.org/10.1212/WNL.0000000000001708] [PMID: 26062626]
[http://dx.doi.org/10.1002/mds.23965] [PMID: 21954089]
[http://dx.doi.org/10.1002/mds.27802] [PMID: 31412427]
[http://dx.doi.org/10.1016/j.nbd.2020.104996] [PMID: 32599063]
[http://dx.doi.org/10.1016/j.smrv.2018.09.008] [PMID: 30503716]
[http://dx.doi.org/10.1093/brain/awz030] [PMID: 30789229]
[http://dx.doi.org/10.1016/j.sleep.2012.10.015] [PMID: 23474058]
[http://dx.doi.org/10.1093/brain/awaa365] [PMID: 33348363]
[http://dx.doi.org/10.1002/ana.25026] [PMID: 28833467]
[http://dx.doi.org/10.1212/WNL.0000000000009246] [PMID: 32161031]
[http://dx.doi.org/10.1016/S1474-4422(11)70152-1] [PMID: 21802993]
[http://dx.doi.org/10.1016/S1474-4422(10)70216-7] [PMID: 20846908]
[http://dx.doi.org/10.1016/j.neurobiolaging.2015.08.025] [PMID: 26410306]
[http://dx.doi.org/10.1093/brain/123.6.1155] [PMID: 10825354]
[http://dx.doi.org/10.1212/WNL.0000000000003838] [PMID: 28330956]
[http://dx.doi.org/10.1002/mds.27094] [PMID: 28734065]
[http://dx.doi.org/10.1148/radiol.2017162486] [PMID: 29232183]
[http://dx.doi.org/10.3389/fneur.2019.00802] [PMID: 31404164]
[http://dx.doi.org/10.1212/WNL.0000000000010942] [PMID: 32989104]
[http://dx.doi.org/10.1016/S1474-4422(17)30173-4] [PMID: 28684245]
[http://dx.doi.org/10.1212/WNL.55.9.1410] [PMID: 11087796]
[http://dx.doi.org/10.1016/S1474-4422(18)30162-5] [PMID: 29866443]
[http://dx.doi.org/10.1093/brain/awab191] [PMID: 33978742]
[http://dx.doi.org/10.1212/WNL.0000000000000130] [PMID: 24453082]
[http://dx.doi.org/10.1212/WNL.0000000000012228] [PMID: 34011571]
[http://dx.doi.org/10.1093/brain/awu290] [PMID: 25338949]
[http://dx.doi.org/10.1002/mds.28260] [PMID: 32909650]
[http://dx.doi.org/10.1111/j.1468-1331.2010.03283.x] [PMID: 21143707]
[http://dx.doi.org/10.1212/01.wnl.0000242879.39415.49] [PMID: 17101893]
[http://dx.doi.org/10.1111/ggi.12068] [PMID: 23586530]
[http://dx.doi.org/10.1046/j.1440-1819.2002.00961.x] [PMID: 12047600]
[http://dx.doi.org/10.1002/mds.23721] [PMID: 21542022]
[http://dx.doi.org/10.1002/mds.25034] [PMID: 22791632]
[http://dx.doi.org/10.1212/WNL.0b013e318278b658] [PMID: 23115214]
[http://dx.doi.org/10.1016/S1474-4422(14)70117-6] [PMID: 25231526]
[http://dx.doi.org/10.1007/s00702-012-0894-8] [PMID: 22941506]
[http://dx.doi.org/10.1002/nbm.3546] [PMID: 27240118]
[http://dx.doi.org/10.1259/bjr.20181016] [PMID: 30933548]
[http://dx.doi.org/10.1002/jmri.26161] [PMID: 29897645]
[http://dx.doi.org/10.1148/radiol.10100495] [PMID: 20843991]
[http://dx.doi.org/10.1016/j.neuroimage.2014.11.010] [PMID: 25462797]
[http://dx.doi.org/10.1016/j.neuroimage.2020.117216] [PMID: 32745677]
[http://dx.doi.org/10.3389/fneur.2020.00366] [PMID: 32547468]
[http://dx.doi.org/10.3389/fneur.2019.00074] [PMID: 30809185]
[http://dx.doi.org/10.1002/ana.24646] [PMID: 27016314]
[http://dx.doi.org/10.1002/mds.27929] [PMID: 31846123]
[http://dx.doi.org/10.1093/sleep/zsab131] [PMID: 34015127]
[http://dx.doi.org/10.1016/j.parkreldis.2014.03.023] [PMID: 24731528]
[http://dx.doi.org/10.1093/sleep/zsx149] [PMID: 28958075]
[http://dx.doi.org/10.1038/s41531-018-0047-3] [PMID: 29644335]
[http://dx.doi.org/10.1007/s12640-009-9140-z] [PMID: 19957214]
[http://dx.doi.org/10.1016/S0014-5793(01)03269-0] [PMID: 11801257]
[http://dx.doi.org/10.1073/pnas.0403495101] [PMID: 15210960]
[http://dx.doi.org/10.1016/j.parkreldis.2014.04.005] [PMID: 24768616]
[http://dx.doi.org/10.1093/brain/awaa216] [PMID: 32856056]
[http://dx.doi.org/10.1007/s00234-013-1171-8] [PMID: 23525598]
[http://dx.doi.org/10.1016/j.neulet.2013.02.012] [PMID: 23428505]
[http://dx.doi.org/10.3174/ajnr.A5702] [PMID: 29954816]
[http://dx.doi.org/10.1007/s00234-013-1199-9] [PMID: 23673875]
[http://dx.doi.org/10.1093/brain/aww006] [PMID: 26920675]
[http://dx.doi.org/10.1016/j.sleep.2013.02.004] [PMID: 23790501]
[http://dx.doi.org/10.1007/s10072-019-04014-y] [PMID: 31392640]
[http://dx.doi.org/10.1002/ana.22245] [PMID: 21387382]
[http://dx.doi.org/10.1093/sleep/33.6.767] [PMID: 20550017]
[http://dx.doi.org/10.1093/sleep/zsaa199] [PMID: 32974664]
[http://dx.doi.org/10.1016/j.parkreldis.2010.08.014] [PMID: 20846895]
[http://dx.doi.org/10.1016/j.parkreldis.2011.08.023] [PMID: 21924943]
[http://dx.doi.org/10.1002/mds.25820] [PMID: 24676967]
[http://dx.doi.org/10.1093/cercor/bhx137] [PMID: 28591814]
[http://dx.doi.org/10.1212/WNL.0000000000005523] [PMID: 29669906]
[http://dx.doi.org/10.3389/fneur.2019.00312] [PMID: 31024418]
[http://dx.doi.org/10.1111/jsr.13136] [PMID: 32608031]
[PMID: 32540338]
[http://dx.doi.org/10.1038/s41531-019-0079-3] [PMID: 31069252]
[http://dx.doi.org/10.1016/j.nicl.2020.102421] [PMID: 32957013]
[http://dx.doi.org/10.1016/j.nicl.2019.102138] [PMID: 31911344]
[http://dx.doi.org/10.5665/sleep.3222] [PMID: 24293763]
[http://dx.doi.org/10.1093/brain/aww124] [PMID: 27297241]
[http://dx.doi.org/10.1016/j.sleep.2020.01.010] [PMID: 32135454]
[http://dx.doi.org/10.1016/j.parkreldis.2020.08.003] [PMID: 32858487]
[http://dx.doi.org/10.1007/s10072-019-04118-5] [PMID: 31792718]
[http://dx.doi.org/10.1002/mds.22484] [PMID: 19260097]
[http://dx.doi.org/10.1093/brain/awr233] [PMID: 22075521]
[http://dx.doi.org/10.1155/2013/143532] [PMID: 24163811]
[http://dx.doi.org/10.1212/WNL.57.11.2089] [PMID: 11739831]
[http://dx.doi.org/10.1002/mds.1265] [PMID: 11835438]
[http://dx.doi.org/10.1007/s00259-012-2100-5] [PMID: 22460689]
[http://dx.doi.org/10.3233/JPD-191710] [PMID: 31707374]
[PMID: 15471835]
[http://dx.doi.org/10.1002/mds.27361] [PMID: 29572948]
[http://dx.doi.org/10.1093/brain/awm086] [PMID: 17470495]
[http://dx.doi.org/10.1056/NEJMoa033447] [PMID: 15590952]
[http://dx.doi.org/10.3233/JPD-181471] [PMID: 30400107]
[http://dx.doi.org/10.1093/brain/awm328] [PMID: 18178568]
[http://dx.doi.org/10.1038/sj.clpt.6100386] [PMID: 17898702]
[http://dx.doi.org/10.3390/ph14090847] [PMID: 34577548]
[http://dx.doi.org/10.1038/s41467-019-13564-w] [PMID: 31797870]
[http://dx.doi.org/10.1007/s00401-020-02157-3] [PMID: 32356200]
[http://dx.doi.org/10.1007/s00259-020-05133-x] [PMID: 33369690]
[http://dx.doi.org/10.1016/j.bbagen.2015.05.021] [PMID: 26028294]
[http://dx.doi.org/10.1002/mds.27562] [PMID: 30452793]
[http://dx.doi.org/10.1053/j.semnuclmed.2020.12.003] [PMID: 33431202]
[http://dx.doi.org/10.1002/mds.27546] [PMID: 30468693]
[http://dx.doi.org/10.1186/s40478-016-0315-6] [PMID: 27296779]
[http://dx.doi.org/10.1007/s40336-018-0290-y] [PMID: 30148121]
[http://dx.doi.org/10.1007/s00429-017-1507-y] [PMID: 28884232]
[http://dx.doi.org/10.1093/brain/aww098] [PMID: 27190023]
[http://dx.doi.org/10.1016/0896-6273(92)90117-V] [PMID: 1530909]
[http://dx.doi.org/10.1007/BF00296367] [PMID: 1831952]
[PMID: 7992852]
[http://dx.doi.org/10.1093/brain/aww339] [PMID: 28087578]
[http://dx.doi.org/10.1002/mds.28531] [PMID: 33751655]
[http://dx.doi.org/10.1016/j.neulet.2016.09.011] [PMID: 27619539]
[PMID: 34724257]
[http://dx.doi.org/10.1093/brain/awaa252] [PMID: 32947614]
[http://dx.doi.org/10.1016/j.nicl.2017.02.012] [PMID: 28275542]
[http://dx.doi.org/10.1016/j.parkreldis.2018.01.001] [PMID: 29336906]
[http://dx.doi.org/10.1016/j.parkreldis.2013.10.002] [PMID: 24239142]
[http://dx.doi.org/10.1371/journal.pone.0157218] [PMID: 27310132]
[http://dx.doi.org/10.1093/brain/awu036] [PMID: 24613932]
[http://dx.doi.org/10.1093/brain/awv211] [PMID: 26173861]
[http://dx.doi.org/10.1002/mds.25240] [PMID: 23124622]
[http://dx.doi.org/10.1038/s41467-017-02416-0] [PMID: 29295991]
[http://dx.doi.org/10.1016/j.parkreldis.2017.05.005] [PMID: 28522171]
[http://dx.doi.org/10.1212/WNL.0000000000002492] [PMID: 26888982]
[http://dx.doi.org/10.1212/WNL.0000000000003305] [PMID: 27742814]
[http://dx.doi.org/10.1371/journal.pone.0041873] [PMID: 22848644]
[http://dx.doi.org/10.1136/jnnp-2017-317443] [PMID: 29348302]
[http://dx.doi.org/10.1093/brain/awl021] [PMID: 16455792]
[http://dx.doi.org/10.1002/mds.23318] [PMID: 20623690]
[http://dx.doi.org/10.1016/j.parkreldis.2020.01.019] [PMID: 32036297]
[http://dx.doi.org/10.1016/j.parkreldis.2017.05.002] [PMID: 28487107]