Skip to main content

Advertisement

SpringerLink
Log in

Progression of grey and white matter brain damage in Parkinson's disease: a critical review of structural MRI literature

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

The current review summarizes the current knowledge on longitudinal cortical and subcortical grey and white matter MRI findings assessed using T1-weighted and one-tensor diffusion-weighted MRI in Parkinson’s disease (PD) patients. Results were reviewed according to disease duration, disease severity and cognitive impairment. The most consistent findings are those showing a progressive cortical atrophy accumulation in caudate, putamen, temporal/hippocampal, frontal and parietal areas in de novo PD cases and in the early/middle phase of the disease, with the achievement of a plateau in the later stage. Analyzing results according to the patient cognitive status, only a few studies used longitudinal MRI metrics to predict mild cognitive impairment or dementia conversion in PD patients, suggesting that atrophy of the hippocampus, fronto-temporal areas, caudate, thalamus and accumbens might play a role in this process. Stratifying patients according to disease severity, findings appear partially controversial, although showing a progressive atrophy of basal ganglia over 1 year of follow up and a widespread cortical thinning over 3–6 years in mild to moderate PD patients. Finally, microstructural damage of the main motor and associative WM tracts seems to be present, and rapidly progress, even in the early phase of PD. The utility of structural MRI metrics as biomarkers of PD progression and their role in improving the accuracy of disease progression prediction is still debated.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag AE, Lang AE (2017) Parkinson disease. Nat Rev Dis Primers 3:17013. https://doi.org/10.1038/nrdp.2017.13

    Article  PubMed  Google Scholar 

  2. Tolosa E, Wenning G, Poewe W (2006) The diagnosis of Parkinson's disease. Lancet Neurol 5(1):75–86. https://doi.org/10.1016/S1474-4422(05)70285-4

    Article  PubMed  Google Scholar 

  3. Braak H, Bohl JR, Muller CM, Rub U, de Vos RA, Del Tredici K (2006) Stanley Fahn Lecture 2005: the staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered. Mov Disorders 21(12):2042–2051. https://doi.org/10.1002/mds.21065

    Article  Google Scholar 

  4. Prange S, Metereau E, Thobois S (2019) Structural imaging in Parkinson's Disease: new developments. Curr Neurol Neurosci Rep 19(8):50. https://doi.org/10.1007/s11910-019-0964-5

    Article  PubMed  Google Scholar 

  5. Yang J, Burciu RG, Vaillancourt DE (2018) Longitudinal progression markers of Parkinson's Disease: current view on structural imaging. Curr Neurol Neurosci Rep 18(12):83. https://doi.org/10.1007/s11910-018-0894-7

    Article  CAS  PubMed  Google Scholar 

  6. De Micco R, Russo A, Tessitore A (2018) Structural MRI in idiopathic Parkinson's Disease. Int Rev Neurobiol 141:405–438. https://doi.org/10.1016/bs.irn.2018.08.011

    Article  CAS  PubMed  Google Scholar 

  7. Caspell-Garcia C, Simuni T, Tosun-Turgut D, Wu IW, Zhang Y, Nalls M, Singleton A, Shaw LA, Kang JH, Trojanowski JQ, Siderowf A, Coffey C, Lasch S, Aarsland D, Burn D, Chahine LM, Espay AJ, Foster ED, Hawkins KA, Litvan I, Richard I, Weintraub D, Parkinson's Progression Markers I (2017) Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease. PLoS One 12(5):e0175674. https://doi.org/10.1371/journal.pone.0175674

  8. Mollenhauer B, Zimmermann J, Sixel-Doring F, Focke NK, Wicke T, Ebentheuer J, Schaumburg M, Lang E, Trautmann E, Zetterberg H, Taylor P, Friede T, Trenkwalder C, DeNoPa Study G (2016) Monitoring of 30 marker candidates in early Parkinson disease as progression markers. Neurology 87(2):168–177. https://doi.org/10.1212/WNL.0000000000002651

  9. Tessa C, Lucetti C, Giannelli M, Diciotti S, Poletti M, Danti S, Baldacci F, Vignali C, Bonuccelli U, Mascalchi M, Toschi N (2014) Progression of brain atrophy in the early stages of Parkinson's disease: a longitudinal tensor-based morphometry study in de novo patients without cognitive impairment. Hum Brain Mapp 35(8):3932–3944. https://doi.org/10.1002/hbm.22449

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sampedro F, Martinez-Horta S, Marin-Lahoz J, Pagonabarraga J, Kulisevsky J (2019) Longitudinal intracortical diffusivity changes in de-novo Parkinson's disease: A promising imaging biomarker. Parkinsonism Relat Disord 68:22–25. https://doi.org/10.1016/j.parkreldis.2019.09.031

    Article  PubMed  Google Scholar 

  11. Sampedro F, Marin-Lahoz J, Martinez-Horta S, Pagonabarraga J, Kulisevsky J (2019) Dopaminergic degeneration induces early posterior cortical thinning in Parkinson's disease. Neurobiol Dis 124:29–35. https://doi.org/10.1016/j.nbd.2018.11.001

    Article  CAS  PubMed  Google Scholar 

  12. Lewis MM, Du G, Lee EY, Nasralah Z, Sterling NW, Zhang L, Wagner D, Kong L, Troster AI, Styner M, Eslinger PJ, Mailman RB, Huang X (2016) The pattern of gray matter atrophy in Parkinson's disease differs in cortical and subcortical regions. J Neurol 263(1):68–75. https://doi.org/10.1007/s00415-015-7929-7

    Article  PubMed  PubMed Central  Google Scholar 

  13. Melzer TR, Myall DJ, MacAskill MR, Pitcher TL, Livingston L, Watts R, Keenan RJ, Dalrymple-Alford JC, Anderson TJ (2015) Tracking Parkinson's Disease over one year with multimodal magnetic resonance imaging in a group of older patients with moderate disease. PLoS ONE 10(12):e0143923. https://doi.org/10.1371/journal.pone.0143923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sterling NW, Wang M, Zhang L, Lee EY, Du G, Lewis MM, Styner M, Huang X (2016) Stage-dependent loss of cortical gyrification as Parkinson disease "unfolds". Neurology 86(12):1143–1151. https://doi.org/10.1212/WNL.0000000000002492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nurnberger L, Gracien RM, Hok P, Hof SM, Rub U, Steinmetz H, Hilker R, Klein JC, Deichmann R, Baudrexel S (2017) Longitudinal changes of cortical microstructure in Parkinson's disease assessed with T1 relaxometry. NeuroImage Clinical 13:405–414. https://doi.org/10.1016/j.nicl.2016.12.025

    Article  PubMed  Google Scholar 

  16. Ibarretxe-Bilbao N, Junque C, Segura B, Baggio HC, Marti MJ, Valldeoriola F, Bargallo N, Tolosa E (2012) Progression of cortical thinning in early Parkinson's disease. Mov Disord 27(14):1746–1753. https://doi.org/10.1002/mds.25240

    Article  PubMed  Google Scholar 

  17. Jia X, Liang P, Li Y, Shi L, Wang D, Li K (2015) Longitudinal study of gray matter changes in Parkinson Disease. AJNR Am J Neuroradiol 36(12):2219–2226. https://doi.org/10.3174/ajnr.A4447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Campabadal A, Uribe C, Segura B, Baggio HC, Abos A, Garcia-Diaz AI, Marti MJ, Valldeoriola F, Compta Y, Bargallo N, Junque C (2017) Brain correlates of progressive olfactory loss in Parkinson's disease. Parkinsonism Relat Disord 41:44–50. https://doi.org/10.1016/j.parkreldis.2017.05.005

    Article  PubMed  Google Scholar 

  19. Wee N, Wen MC, Kandiah N, Chander RJ, Ng A, Au WL, Tan LC (2016) Neural correlates of anxiety symptoms in mild Parkinson's disease: a prospective longitudinal voxel-based morphometry study. J Neurol Sci 371:131–136. https://doi.org/10.1016/j.jns.2016.10.021

    Article  PubMed  Google Scholar 

  20. Hanganu A, Bruneau MA, Degroot C, Bedetti C, Mejia-Constain B, Lafontaine AL, Chouinard S, Monchi O (2017) Depressive symptoms in Parkinson's disease correlate with cortical atrophy over time. Brain Cogn 111:127–133. https://doi.org/10.1016/j.bandc.2016.11.001

    Article  PubMed  Google Scholar 

  21. Baba T, Kikuchi A, Hirayama K, Nishio Y, Hosokai Y, Kanno S, Hasegawa T, Sugeno N, Konno M, Suzuki K, Takahashi S, Fukuda H, Aoki M, Itoyama Y, Mori E, Takeda A (2012) Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson's disease: a 3 year longitudinal study. Brain 135(Pt 1):161–169. https://doi.org/10.1093/brain/awr321

    Article  PubMed  Google Scholar 

  22. Ibarretxe-Bilbao N, Ramirez-Ruiz B, Junque C, Marti MJ, Valldeoriola F, Bargallo N, Juanes S, Tolosa E (2010) Differential progression of brain atrophy in Parkinson's disease with and without visual hallucinations. J Neurol Neurosurg Psychiatry 81(6):650–657. https://doi.org/10.1136/jnnp.2009.179655

    Article  PubMed  Google Scholar 

  23. Uribe C, Segura B, Baggio HC, Abos A, Garcia-Diaz AI, Campabadal A, Marti MJ, Valldeoriola F, Compta Y, Bargallo N, Junque C (2019) Progression of Parkinson's disease patients' subtypes based on cortical thinning: 4-year follow-up. Parkinsonism Relat Disord. https://doi.org/10.1016/j.parkreldis.2019.05.012

    Article  PubMed  Google Scholar 

  24. Garcia-Diaz AI, Segura B, Baggio HC, Uribe C, Campabadal A, Abos A, Marti MJ, Valldeoriola F, Compta Y, Bargallo N, Junque C (2018) Cortical thinning correlates of changes in visuospatial and visuoperceptual performance in Parkinson's disease: a 4-year follow-up. Parkinsonism Relat Disord 46:62–68. https://doi.org/10.1016/j.parkreldis.2017.11.003

    Article  CAS  PubMed  Google Scholar 

  25. Hanganu A, Bedetti C, Degroot C, Mejia-Constain B, Lafontaine AL, Soland V, Chouinard S, Bruneau MA, Mellah S, Belleville S, Monchi O (2014) Mild cognitive impairment is linked with faster rate of cortical thinning in patients with Parkinson's disease longitudinally. Brain 137(Pt 4):1120–1129. https://doi.org/10.1093/brain/awu036

    Article  PubMed  Google Scholar 

  26. Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ, Duncan GW, Mollenhauer B, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn DJ, O'Brien JT (2017) Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson's disease. Neurobiol Aging 55:78–90. https://doi.org/10.1016/j.neurobiolaging.2017.03.012

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ, Duncan GW, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn DJ, O'Brien JT (2015) Baseline and longitudinal grey matter changes in newly diagnosed Parkinson's disease: ICICLE-PD study. Brain 138(Pt 10):2974–2986. https://doi.org/10.1093/brain/awv211

    Article  PubMed  PubMed Central  Google Scholar 

  28. Uribe C, Segura B, Baggio HC, Campabadal A, Abos A, Compta Y, Marti MJ, Valldeoriola F, Bargallo N, Junque C (2018) Differential progression of regional hippocampal atrophy in aging and Parkinson's Disease. Front Aging Neurosci 10:325. https://doi.org/10.3389/fnagi.2018.00325

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gorges M, Kuntz B, Del Tredici K, Schmidt DG, Muller HP, Ludolph AC, Dupuis L, Kassubek J (2019) Morphological MRI investigations of the hypothalamus in 232 individuals with Parkinson's disease. Mov Disord 34(10):1566–1570. https://doi.org/10.1002/mds.27814

    Article  PubMed  Google Scholar 

  30. Foo H, Mak E, Chander RJ, Ng A, Au WL, Sitoh YY, Tan LC, Kandiah N (2017) Associations of hippocampal subfields in the progression of cognitive decline related to Parkinson's disease. NeuroImage Clinical 14:37–42. https://doi.org/10.1016/j.nicl.2016.12.008

    Article  PubMed  Google Scholar 

  31. Ramirez-Ruiz B, Marti MJ, Tolosa E, Bartres-Faz D, Summerfield C, Salgado-Pineda P, Gomez-Anson B, Junque C (2005) Longitudinal evaluation of cerebral morphological changes in Parkinson's disease with and without dementia. J Neurol 252(11):1345–1352. https://doi.org/10.1007/s00415-005-0864-2

    Article  PubMed  Google Scholar 

  32. Gee M, Dukart J, Draganski B, Wayne Martin WR, Emery D, Camicioli R (2017) Regional volumetric change in Parkinson's disease with cognitive decline. J Neurol Sci 373:88–94. https://doi.org/10.1016/j.jns.2016.12.030

    Article  PubMed  Google Scholar 

  33. Zhou C, Guan XJ, Guo T, Zeng QL, Gao T, Huang PY, Xuan M, Gu QQ, Xu XJ, Zhang MM (2019) Progressive brain atrophy in Parkinson's disease patients who convert to mild cognitive impairment. CNS Neurosci Ther. https://doi.org/10.1111/cns.13188

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wen MC, Ng A, Chander RJ, Au WL, Tan LC, Kandiah N (2015) Longitudinal brain volumetric changes and their predictive effects on cognition among cognitively asymptomatic patients with Parkinson's disease. Parkinsonism Relat Disord 21(5):483–488. https://doi.org/10.1016/j.parkreldis.2015.02.014

    Article  PubMed  Google Scholar 

  35. Camicioli R, Sabino J, Gee M, Bouchard T, Fisher N, Hanstock C, Emery D, Martin WRW (2011) Ventricular dilatation and brain atrophy in patients with Parkinson's Disease with incipient dementia. Mov Disord 26(8):1443–1450. https://doi.org/10.1002/mds.23700

    Article  PubMed  Google Scholar 

  36. Compta Y, Pereira JB, Rios J, Ibarretxe-Bilbao N, Junque C, Bargallo N, Camara A, Buongiorno M, Fernandez M, Pont-Sunyer C, Marti MJ (2013) Combined dementia-risk biomarkers in Parkinson's disease: a prospective longitudinal study. Parkinsonism Relat Disord 19(8):717–724. https://doi.org/10.1016/j.parkreldis.2013.03.009

    Article  PubMed  Google Scholar 

  37. Low A, Foo H, Yong TT, Tan LCS, Kandiah N (2019) Hippocampal subfield atrophy of CA1 and subicular structures predict progression to dementia in idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 90(6):681–687. https://doi.org/10.1136/jnnp-2018-319592

    Article  PubMed  Google Scholar 

  38. Foo H, Mak E, Yong TT, Wen MC, Chander RJ, Au WL, Sitoh YY, Tan LC, Kandiah N (2017) Progression of subcortical atrophy in mild Parkinson's disease and its impact on cognition. Eur J Neurol 24(2):341–348. https://doi.org/10.1111/ene.13205

    Article  CAS  PubMed  Google Scholar 

  39. Chan LL, Ng KM, Yeoh CS, Rumpel H, Li HH, Tan EK (2016) Putaminal diffusivity Correlates with disease progression in Parkinson's Disease: prospective 6-year study. Medicine 95(6):e2594. https://doi.org/10.1097/MD.0000000000002594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Pozorski V, Oh JM, Adluru N, Merluzzi AP, Theisen F, Okonkwo O, Barzgari A, Krislov S, Sojkova J, Bendlin BB, Johnson SC, Alexander AL, Gallagher CL (2018) Longitudinal white matter microstructural change in Parkinson's disease. Hum Brain Mapp 39(10):4150–4161. https://doi.org/10.1002/hbm.24239

    Article  PubMed  PubMed Central  Google Scholar 

  41. Rau YA, Wang SM, Tournier JD, Lin SH, Lu CS, Weng YH, Chen YL, Ng SH, Yu SW, Wu YM, Tsai CC, Wang JJ (2019) A longitudinal fixel-based analysis of white matter alterations in patients with Parkinson's disease. NeuroImage Clinical 24:102098. https://doi.org/10.1016/j.nicl.2019.102098

    Article  PubMed  PubMed Central  Google Scholar 

  42. Zhang Y, Wu IW, Tosun D, Foster E, Schuff N, Parkinson's Progression Markers I (2016) Progression of regional microstructural degeneration in Parkinson's Disease: a multicenter diffusion tensor imaging study. PLoS ONE 11(10):e0165540. https://doi.org/10.1371/journal.pone.0165540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Taylor KI, Sambataro F, Boess F, Bertolino A, Dukart J (2018) Progressive decline in gray and white matter integrity in de novo Parkinson's Disease: an analysis of Longitudinal Parkinson progression markers initiative diffusion tensor imaging data. Front Aging Neurosci 10:318. https://doi.org/10.3389/fnagi.2018.00318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Minett T, Su L, Mak E, Williams G, Firbank M, Lawson RA, Yarnall AJ, Duncan GW, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn D, O'Brien JT (2018) Longitudinal diffusion tensor imaging changes in early Parkinson's disease: ICICLE-PD study. J Neurol 265(7):1528–1539. https://doi.org/10.1007/s00415-018-8873-0

    Article  PubMed  Google Scholar 

  45. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24(2):197–211. https://doi.org/10.1016/s0197-4580(02)00065-9

    Article  PubMed  Google Scholar 

  46. Braak H, Rub U, Del Tredici K (2006) Cognitive decline correlates with neuropathological stage in Parkinson's disease. J Neurol Sci 248(1–2):255–258. https://doi.org/10.1016/j.jns.2006.05.011

    Article  PubMed  Google Scholar 

  47. Peng C, Trojanowski JQ, Lee VM (2020) Protein transmission in neurodegenerative disease. Nat Rev Neurol 16(4):199–212. https://doi.org/10.1038/s41582-020-0333-7

    Article  CAS  PubMed  Google Scholar 

  48. Fereshtehnejad SM, Zeighami Y, Dagher A, Postuma RB (2017) Clinical criteria for subtyping Parkinson's disease: biomarkers and longitudinal progression. Brain 140:1959–1976. https://doi.org/10.1093/brain/awx118

    Article  PubMed  Google Scholar 

Download references

Funding

None.

Author information

Authors and Affiliations

  1. Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy

    Elisabetta Sarasso, Federica Agosta, Noemi Piramide & Massimo Filippi

  2. Vita-Salute San Raffaele University, Milan, Italy

    Elisabetta Sarasso, Federica Agosta, Noemi Piramide & Massimo Filippi

  3. Laboratory of Movement Analysis, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Elisabetta Sarasso

  4. Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

  5. Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Massimo Filippi

Authors
  1. Elisabetta Sarasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Federica Agosta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noemi Piramide
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimo Filippi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ES, AF, and NP drafted the manuscript and revised it. MF revised the manuscript.

Corresponding author

Correspondence to Massimo Filippi.

Ethics declarations

Conflicts of interest

E. Sarasso and N. Piramide have nothing to disclose. F. Agosta is Section Editor of NeuroImage: Clinical; has received speaker honoraria from Biogen Idec and Novartis; and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), and the European Research Council. M. Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Availability of data and material

The complete search line is reported in the supplementary material.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 12 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sarasso, E., Agosta, F., Piramide, N. et al. Progression of grey and white matter brain damage in Parkinson's disease: a critical review of structural MRI literature. J Neurol 268, 3144–3179 (2021). https://doi.org/10.1007/s00415-020-09863-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-020-09863-8

Keywords

Search

Navigation