Distinct FP-CIT PET patterns of Alzheimer’s disease with parkinsonism and dementia with Lewy bodies



Little is known regarding the clinical relevance or neurobiology of subtle motor disturbance in Alzheimer’s disease (AD). This study aims to investigate the patterns of striatal 18F-FP-CIT uptake in patients with AD-related cognitive impairment (ADCI) with mild parkinsonism.


We recruited 29 consecutive patients with ADCI with mild parkinsonism. All patients underwent 18F-FP-CIT PET scans and dopamine transporter (DAT) availability in striatal subregions (anterior/posterior caudate, anterior/posterior putamen, ventral putamen, ventral striatum) was quantified. Additionally, 32 patients with dementia with Lewy bodies (DLB) and 21 healthy controls were included to perform inter-group comparative analyses of the striatal DAT availability. The discriminatory power of striatal DAT availability to differentiate ADCI from DLB was assessed using receiver operating characteristics (ROC) analyses. The Spearman’s correlation coefficient was calculated to assess the relationship between motor severity and DAT availability in striatal subregions.


Patients with ADCI with mild parkinsonism exhibited decreased DAT availability in the caudate that was intermediate between healthy controls and patients with DLB. The DAT availability in other striatal subregions, including the posterior putamen, did not differ between the ADCI with parkinsonism and healthy control groups. The ROC analysis showed that DAT availability of all striatal subregions, especially the whole striatum, had a fair discriminatory power. Parkinsonian motor severity did not correlate with the striatal DAT availability in ADCI with parkinsonism.


The present study demonstrated that patients with ADCI with mild parkinsonism had distinct DAT scan patterns and suggests that parkinsonism is associated with the extranigral source of pathology.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    Horvath J, Burkhard PR, Herrmann FR, Bouras C, Kovari E. Neuropathology of parkinsonism in patients with pure Alzheimer’s disease. J Alzheimers Dis. 2014;39(1):115–20. https://doi.org/10.3233/jad-131289.

    Article  PubMed  Google Scholar 

  2. 2.

    Molsa PK, Marttila RJ, Rinne UK. Extrapyramidal signs in Alzheimer’s disease. Neurology. 1984;34(8):1114–6.

    CAS  Article  Google Scholar 

  3. 3.

    Scarmeas N, Hadjigeorgiou GM, Papadimitriou A, Dubois B, Sarazin M, Brandt J, et al. Motor signs during the course of Alzheimer disease. Neurology. 2004;63(6):975–82.

    CAS  Article  Google Scholar 

  4. 4.

    Portet F, Scarmeas N, Cosentino S, Helzner EP, Stern Y. Extrapyramidal signs before and after diagnosis of incident Alzheimer disease in a prospective population study. Arch Neurol. 2009;66(9):1120–6. https://doi.org/10.1001/archneurol.2009.196.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Stern Y, Albert M, Brandt J, Jacobs DM, Tang MX, Marder K, et al. Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer’s disease: prospective analyses from the predictors study. Neurology. 1994;44(12):2300–7.

    CAS  Article  Google Scholar 

  6. 6.

    Reinikainen KJ, Paljarvi L, Halonen T, Malminen O, Kosma VM, Laakso M, et al. Dopaminergic system and monoamine oxidase-B activity in Alzheimer’s disease. Neurobiol Aging. 1988;9(3):245–52.

    CAS  Article  Google Scholar 

  7. 7.

    de la Monte SM, Wells SE, Hedley-Whyte T, Growdon JH. Neuropathological distinction between Parkinson’s dementia and Parkinson’s plus Alzheimer’s disease. Ann Neurol. 1989;26(3):309–20. https://doi.org/10.1002/ana.410260302.

    Article  PubMed  Google Scholar 

  8. 8.

    Burns JM, Galvin JE, Roe CM, Morris JC, McKeel DW. The pathology of the substantia nigra in Alzheimer disease with extrapyramidal signs. Neurology. 2005;64(8):1397–403. https://doi.org/10.1212/01.wnl.0000158423.05224.7f.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Morris JC, Drazner M, Fulling K, Grant EA, Goldring J. Clinical and pathological aspects of parkinsonism in Alzheimer’s disease. A role for extranigral factors? Arch Neurol. 1989;46(6):651–7.

    CAS  Article  Google Scholar 

  10. 10.

    Braak H, Braak E. Alzheimer’s disease: striatal amyloid deposits and neurofibrillary changes. J Neuropathol Exp Neurol. 1990;49(3):215–24.

    CAS  Article  Google Scholar 

  11. 11.

    Murray AM, Weihmueller FB, Marshall JF, Hurtig HI, Gottleib GL, Joyce JN. Damage to dopamine systems differs between Parkinson’s disease and Alzheimer’s disease with parkinsonism. Ann Neurol. 1995;37(3):300–12. https://doi.org/10.1002/ana.410370306.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Schauer TH, Lochner M, Kovacs GG. Nigral tau pathology and striatal amyloid-beta deposition does not correlate with striatal dopamine deficit in Alzheimer’s disease. J Neural Transm (Vienna). 2012;119(12):1545–9. https://doi.org/10.1007/s00702-012-0832-9.

    CAS  Article  Google Scholar 

  13. 13.

    Rinne JO, Sahlberg N, Ruottinen H, Nagren K, Lehikoinen P. Striatal uptake of the dopamine reuptake ligand [11C]beta-CFT is reduced in Alzheimer’s disease assessed by positron emission tomography. Neurology. 1998;50(1):152–6.

    CAS  Article  Google Scholar 

  14. 14.

    Ceravolo R, Volterrani D, Gambaccini G, Bernardini S, Rossi C, Logi C, et al. Presynaptic nigro-striatal function in a group of Alzheimer’s disease patients with parkinsonism: evidence from a dopamine transporter imaging study. J Neural Transm (Vienna). 2004;111(8):1065–73. https://doi.org/10.1007/s00702-004-0140-0.

    CAS  Article  Google Scholar 

  15. 15.

    McKeith I, O’Brien J, Walker Z, Tatsch K, Booij J, Darcourt J, et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 2007;6(4):305–13. https://doi.org/10.1016/s1474-4422(07)70057-1.

    Article  PubMed  Google Scholar 

  16. 16.

    Yoo HS, Jeon S, Chung SJ, Yun M, Lee PH, Sohn YH, et al. Olfactory dysfunction in Alzheimer’s disease- and Lewy body-related cognitive impairment. Alzheimers Dement. 2018. https://doi.org/10.1016/j.jalz.2018.05.010.

  17. 17.

    Landau SM, Harvey D, Madison CM, Koeppe RA, Reiman EM, Foster NL, et al. Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging. 2011;32(7):1207–18. https://doi.org/10.1016/j.neurobiolaging.2009.07.002.

    Article  PubMed  Google Scholar 

  18. 18.

    Mistur R, Mosconi L, Santi SD, Guzman M, Li Y, Tsui W, et al. Current challenges for the early detection of Alzheimer’s disease: brain imaging and CSF studies. J Clin Neurol. 2009;5(4):153–66. https://doi.org/10.3988/jcn.2009.5.4.153.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Buchman AS, Wilson RS, Shulman JM, Leurgans SE, Schneider JA, Bennett DA. Parkinsonism in older adults and its association with adverse health outcomes and neuropathology. J Gerontol A Biol Sci Med Sci. 2016;71(4):549–56. https://doi.org/10.1093/gerona/glv153.

    Article  PubMed  Google Scholar 

  20. 20.

    Buchman AS, Leurgans SE, Yu L, Wilson RS, Lim AS, James BD, et al. Incident parkinsonism in older adults without Parkinson disease. Neurology. 2016;87(10):1036–44. https://doi.org/10.1212/wnl.0000000000003059.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Chu Y, Buchman AS, Olanow CW, Kordower JH. Do subjects with minimal motor features have prodromal Parkinson disease? Ann Neurol. 2018;83(3):562–74. https://doi.org/10.1002/ana.25179.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium. Neurology. 2017;89(1):88–100. https://doi.org/10.1212/wnl.0000000000004058.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Blanc F, Colloby SJ, Cretin B, de Sousa PL, Demuynck C, O’Brien JT, et al. Grey matter atrophy in prodromal stage of dementia with Lewy bodies and Alzheimer’s disease. Alzheimers Res Ther. 2016;8:31. https://doi.org/10.1186/s13195-016-0198-6.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55(3):181–4.

    CAS  Article  Google Scholar 

  25. 25.

    Chung SJ, Yoo HS, Moon H, Oh JS, Kim JS, Park YH, et al. Early-onset drug-induced parkinsonism after exposure to offenders implies nigrostriatal dopaminergic dysfunction. J Neurol Neurosurg Psychiatry. 2018;89(2):169–74. https://doi.org/10.1136/jnnp-2017-315873.

    Article  PubMed  Google Scholar 

  26. 26.

    Noh Y, Lee Y, Seo SW, Jeong JH, Choi SH, Back JH, et al. A new classification system for ischemia using a combination of deep and periventricular white matter hyperintensities. J Stroke Cerebrovasc Dis. 2014;23(4):636–42. https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.06.002.

    Article  PubMed  Google Scholar 

  27. 27.

    Ahn HJ, Chin J, Park A, Lee BH, Suh MK, Seo SW, et al. Seoul neuropsychological screening battery-dementia version (SNSB-D): a useful tool for assessing and monitoring cognitive impairments in dementia patients. J Korean Med Sci. 2010;25(7):1071–6. https://doi.org/10.3346/jkms.2010.25.7.1071.

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Brooks DJ, Ibanez V, Sawle GV, Quinn N, Lees AJ, Mathias CJ, et al. Differing patterns of striatal 18F-dopa uptake in Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Ann Neurol. 1990;28(4):547–55. https://doi.org/10.1002/ana.410280412.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Gibb WR, Mountjoy CQ, Mann DM, Lees AJ. The substantia nigra and ventral tegmental area in Alzheimer’s disease and Down’s syndrome. J Neurol Neurosurg Psychiatry. 1989;52(2):193–200.

    CAS  Article  Google Scholar 

  30. 30.

    Liu Y, Stern Y, Chun MR, Jacobs DM, Yau P, Goldman JE. Pathological correlates of extrapyramidal signs in Alzheimer’s disease. Ann Neurol. 1997;41(3):368–74. https://doi.org/10.1002/ana.410410312.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Joyce JN, Smutzer G, Whitty CJ, Myers A, Bannon MJ. Differential modification of dopamine transporter and tyrosine hydroxylase mRNAs in midbrain of subjects with Parkinson’s, Alzheimer’s with parkinsonism, and Alzheimer’s disease. Mov Disord. 1997;12(6):885–97. https://doi.org/10.1002/mds.870120609.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Wolf DS, Gearing M, Snowdon DA, Mori H, Markesbery WR, Mirra SS. Progression of regional neuropathology in Alzheimer disease and normal elderly: findings from the Nun study. Alzheimer Dis Assoc Disord. 1999;13(4):226–31.

    CAS  Article  Google Scholar 

  33. 33.

    Almeida OP, Burton EJ, McKeith I, Gholkar A, Burn D, O’Brien JT. MRI study of caudate nucleus volume in Parkinson’s disease with and without dementia with Lewy bodies and Alzheimer’s disease. Dement Geriatr Cogn Disord. 2003;16(2):57–63. https://doi.org/10.1159/000070676.

    Article  PubMed  Google Scholar 

  34. 34.

    Molina V, Lubeiro A, Blanco J, Blanco JA, Rodriguez M, Rodriguez-Campos A, et al. Parkinsonism is associated to fronto-caudate disconnectivity and cognition in schizophrenia. Psychiatry Res Neuroimaging. 2018;277:1–6. https://doi.org/10.1016/j.pscychresns.2018.04.009.

    Article  PubMed  Google Scholar 

  35. 35.

    Cummings JL, Henchcliffe C, Schaier S, Simuni T, Waxman A, Kemp P. The role of dopaminergic imaging in patients with symptoms of dopaminergic system neurodegeneration. Brain. 2011;134(Pt 11):3146–66. https://doi.org/10.1093/brain/awr177.

    Article  PubMed  Google Scholar 

  36. 36.

    Shimizu S, Namioka N, Hirose D, Kanetaka H, Hirao K, Hatanaka H, et al. Comparison of diagnostic utility of semi-quantitative analysis for DAT-SPECT for distinguishing DLB from AD. J Neurol Sci. 2017;377:50–4. https://doi.org/10.1016/j.jns.2017.03.040.

    Article  PubMed  Google Scholar 

  37. 37.

    Jellinger KA, Attems J. Does striatal pathology distinguish Parkinson disease with dementia and dementia with Lewy bodies? Acta Neuropathol. 2006;112(3):253–60. https://doi.org/10.1007/s00401-006-0088-2.

    Article  PubMed  Google Scholar 

  38. 38.

    Halliday GM, Song YJ, Harding AJ. Striatal beta-amyloid in dementia with Lewy bodies but not Parkinson’s disease. J Neural Transm (Vienna). 2011;118(5):713–9. https://doi.org/10.1007/s00702-011-0641-6.

    CAS  Article  Google Scholar 

  39. 39.

    Brilliant MJ, Elble RJ, Ghobrial M, Struble RG. The distribution of amyloid beta protein deposition in the corpus striatum of patients with Alzheimer’s disease. Neuropathol Appl Neurobiol. 1997;23(4):322–5.

    CAS  Article  Google Scholar 

  40. 40.

    O’Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol. 2004;61(6):919–25. https://doi.org/10.1001/archneur.61.6.919.

    Article  PubMed  Google Scholar 

  41. 41.

    Walker Z, Costa DC, Walker RW, Lee L, Livingston G, Jaros E, et al. Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison. Neurology. 2004;62(9):1568–72.

    CAS  Article  Google Scholar 

  42. 42.

    Joling M, Vriend C, van der Zande JJ, Lemstra AW, van den Heuvel OA, Booij J, et al. Lower (123)I-FP-CIT binding to the striatal dopamine transporter, but not to the extrastriatal serotonin transporter, in Parkinson’s disease compared with dementia with Lewy bodies. NeuroImage Clinical. 2018;19:130–6. https://doi.org/10.1016/j.nicl.2018.04.009.

    Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Chung SJ, Yoo HS, Oh JS, Kim JS, Ye BS, Sohn YH, et al. Effect of striatal dopamine depletion on cognition in de novo Parkinson’s disease. Parkinsonism Relat Disord. 2018;51:43–8. https://doi.org/10.1016/j.parkreldis.2018.02.048.

    Article  PubMed  Google Scholar 

  44. 44.

    Roselli F, Pisciotta NM, Perneczky R, Pennelli M, Aniello MS, De Caro MF, et al. Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: a 123I-FP-CIT SPECT study. Mov Disord. 2009;24(14):2097–103. https://doi.org/10.1002/mds.22702.

    Article  PubMed  Google Scholar 

  45. 45.

    Ziebell M, Andersen BB, Pinborg LH, Knudsen GM, Stokholm J, Thomsen G, et al. Striatal dopamine transporter binding does not correlate with clinical severity in dementia with Lewy bodies. J Nucl Med. 2013;54(7):1072–6. https://doi.org/10.2967/jnumed.112.114025

  46. 46.

    Siepel FJ, Dalen I, Gruner R, Booij J, Bronnick KS, Buter TC, et al. Loss of dopamine transporter binding and clinical symptoms in dementia with Lewy bodies. Mov Disord. 2016;31(1):118–25. https://doi.org/10.1002/mds.26327.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Shimizu S, Hirao K, Kanetaka H, Namioka N, Hatanaka H, Hirose D, et al. Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2016;43(1):184–92. https://doi.org/10.1007/s00259-015-3146-y.

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Ravina B, Eidelberg D, Ahlskog JE, Albin RL, Brooks DJ, Carbon M, et al. The role of radiotracer imaging in Parkinson disease. Neurology. 2005;64(2):208–15. https://doi.org/10.1212/01.wnl.0000149403.14458.7f.

    CAS  Article  PubMed  Google Scholar 

Download references


This research was supported by a grant from the Korea Health Technology R&D Project through the Korean Healthy Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI16C1118).

Author information



Corresponding authors

Correspondence to Jungho Cha or Phil Hyu Lee.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material


(PDF 192 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chung, S.J., Lee, Y.H., Yoo, H.S. et al. Distinct FP-CIT PET patterns of Alzheimer’s disease with parkinsonism and dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 46, 1652–1660 (2019). https://doi.org/10.1007/s00259-019-04315-6

Download citation


  • Alzheimer’s disease
  • Dementia with Lewy bodies
  • Dopamine transporter
  • Parkinsonism