Brain Topography

, Volume 32, Issue 1, pp 142–160 | Cite as

Patterns of Grey Matter Atrophy at Different Stages of Parkinson’s and Alzheimer’s Diseases and Relation to Cognition

  • Jonas Kunst
  • Radek Marecek
  • Patricia Klobusiakova
  • Zuzana Balazova
  • Lubomira Anderkova
  • Nela Nemcova-Elfmarkova
  • Irena RektorovaEmail author
Original Paper


Using MRI, a characteristic pattern of grey matter (GM) atrophy has been described in the early stages of Alzheimer’s disease (AD); GM patterns at different stages of Parkinson’s disease (PD) have been inconclusive. Few studies have directly compared structural changes in groups with mild cognitive impairment (MCI) caused by different pathologies (AD, PD). We used several analytical methods to determine GM changes at different stages of both PD and AD. We also evaluated associations between GM changes and cognitive measurements. Altogether 144 subjects were evaluated: PD with normal cognition (PD-NC; n = 23), PD with MCI (PD-MCI; n = 24), amnestic MCI (aMCI; n = 27), AD (n = 12), and age-matched healthy controls (HC; n = 58). All subjects underwent structural MRI and cognitive examination. GM volumes were analysed using two different techniques: voxel-based morphometry (VBM) and source-based morphometry (SBM), which is a multivariate method. In addition, cortical thickness (CT) was evaluated to assess between-group differences in GM. The cognitive domain z-scores were correlated with GM changes in individual patient groups. GM atrophy in the anterior and posterior cingulate, as measured by VBM, in the temporo-fronto-parietal component, as measured by SBM, and in the posterior cortical regions as well as in the anterior cingulate and frontal region, as measured by CT, differentiated aMCI from HC. Major hippocampal and temporal lobe atrophy (VBM, SBM) and to some extent occipital atrophy (SBM) differentiated AD from aMCI and from HC. Correlations with cognitive deficits were present only in the AD group. PD-MCI showed greater GM atrophy than PD-NC in the orbitofrontal regions (VBM), which was related to memory z-scores, and in the left superior parietal lobule (CT); more widespread limbic and fronto-parieto-occipital neocortical atrophy (all methods) differentiated this group from HC. Only CT revealed subtle GM atrophy in the anterior cingulate, precuneus, and temporal neocortex in PD-NC as compared to HC. None of the methods differentiated PD-MCI from aMCI. Both MCI groups showed distinct limbic and fronto-temporo-parietal neocortical atrophy compared to HC with no specific between-group differences. AD subjects displayed a typical pattern of major temporal lobe atrophy which was associated with deficits in all cognitive domains. VBM and CT were more sensitive than SBM in identifying frontal and posterior cortical atrophy in PD-MCI as compared to PD-NC. Our data support the notion that the results of studies using different analytical methods cannot be compared directly. Only CT measures revealed some subtle differences between HC and PD-NC.


Parkinson’s disease Alzheimer’s disease Mild cognitive impairment Voxel-based morphometry Source-based morphometry Cortical thickness 



The authors acknowledge and deeply thank our participants for their commitment to our research project. We acknowledge also the core facility MAFIL of CEITEC supported by the MEYS CR (LM2015062 Czech-BioImaging funded by Ministry of Education, Youth and Sports of the Czech Republic).


The work was supported by the EU Joint Programming initiative within Neurodegenerative Diseases, funded by the Norwegian Strategic Research Council (JPND, APGeM—Preclinical genotype-phenotype predictors of Alzheimer’s disease and other dementias, Grant Agreement Number 3056-00001) and by the 15-33854A Grant from the Czech Ministry of Health (Ministerstvo Zdravotnictví Ceské Republiky).

Compliance with Ethical Standards

Conflict of interest

All author declares that they have no conflict of interest to disclose.


  1. Agosta F, Canu E, Stojković T, Pievani M, Tomić A, Sarro L et al (2013) The topography of brain damage at different stages of Parkinson’s disease. Hum Brain Mapp 34(11):2798–2807. Google Scholar
  2. Almeida OP, Burton EJ, McKeith I, Gholkar A, Burn D, O’Brien JT (2003) 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 16(2):57–63. Google Scholar
  3. Anderkova L, Eliasova I, Marecek R, Janousova E, Rektorova I (2015) Distinct pattern of gray matter atrophy in mild Alzheimer’s disease impacts on cognitive outcomes of noninvasive brain stimulation. J Alzheimer’s Dis 48(1):251–260. Google Scholar
  4. Anderkova L, Barton M, Rektorova I (2017) Striato-cortical connections in Parkinson’s and Alzheimer’s diseases: relation to cognition. Mov Disord 32(6):917–922. Google Scholar
  5. Apostolova LG, Steiner CA, Akopyan GG, Dutton RA, Hayashi KM, Toga AW et al (2007) Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease. Arch Neurol 64(10):1489–1495. Google Scholar
  6. Apostolova LG, Beyer M, Green AE, Hwang KS, Morra JH, Chou Y-Y et al (2010) Hippocampal, caudate, and ventricular changes in Parkinson’s disease with and without dementia. Mov Disord 25(6):687–695. Google Scholar
  7. Ashburner J, Csernansky JG, Davatzikos C, Fox NC, Frisoni GB, Thompson PM (2003) Computer-assisted imaging to assess brain structure in healthy and diseased brains. Lancet Neurol 2(2):79–88. Google Scholar
  8. Besser LM, Litvan I, Monsell SE, Mock C, Weintraub S, Zhou X-H, Kukull W (2016) Mild cognitive impairment in Parkinson’s disease versus Alzheimer’s disease. Parkinsonism Relat Disord 27:54–60. Google Scholar
  9. Beyer MK, Janvin CC, Larsen JP, Aarsland D (2007) A magnetic resonance imaging study of patients with Parkinson’s disease with mild cognitive impairment and dementia using voxel-based morphometry. J Neurol Neurosurg Psychiatry 78(3):254–259. Google Scholar
  10. Binetti G, Cappa SF, Magni E, Padovani A, Bianchetti A, Trabucchi M (1996) Disorders of visual and spatial perception in the early stage of Alzheimer’s disease. Ann N Y Acad Sci 777:221–225Google Scholar
  11. Biundo R, Calabrese M, Weis L, Facchini S, Ricchieri G, Gallo P, Antonini A (2013) Anatomical correlates of cognitive functions in early Parkinson’s disease patients. PLoS ONE 8(5):e64222. Google Scholar
  12. Brück A, Kurki T, Kaasinen V, Vahlberg T, Rinne JO (2004) Hippocampal and prefrontal atrophy in patients with early non-demented Parkinson’s disease is related to cognitive impairment. J Neurol Neurosurg Psychiatry 75(10):1467–1469. Google Scholar
  13. Burnham SC, Bourgeat P, Doré V, Savage G, Brown B, Laws S et al (2016) Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer’s disease pathophysiology (SNAP) or Alzheimer’s disease pathology: a longitudinal study. Lancet Neurol 15(10):1044–1053. Google Scholar
  14. Burton EJ, McKeith IG, Burn DJ, Williams ED, O’Brien JT (2004) Cerebral atrophy in Parkinson’s disease with and without dementia: a comparison with Alzheimer’s disease, dementia with Lewy bodies and controls. Brain 127(Pt 4):791–800. Google Scholar
  15. Camicioli R, Moore MM, Kinney A, Corbridge E, Glassberg K, Kaye JA (2003) Parkinson’s disease is associated with hippocampal atrophy. Mov Disord 18(7):784–790. Google Scholar
  16. Cavanna AE, Trimble MR (2006) The precuneus: a review of its functional anatomy and behavioural correlates. Brain 129(Pt 3):564–583. Google Scholar
  17. Chételat G, Landeau B, Eustache F, Mézenge F, Viader F, de la Sayette V et al (2005) Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. NeuroImage 27(4):934–946. Google Scholar
  18. Compta Y, Parkkinen L, O’Sullivan SS, Vandrovcova J, Holton JL, Collins C et al (2011) Lewy- and Alzheimer-type pathologies in Parkinson’s disease dementia: which is more important? Brain 134(Pt 5):1493–1505. Google Scholar
  19. Compta Y, Ibarretxe-Bilbao N, Pereira JB, Junqué C, Bargalló N, Tolosa E et al (2012) Grey matter volume correlates of cerebrospinal markers of Alzheimer-pathology in Parkinson’s disease and related dementia. Parkinsonism Relat Disord 18(8):941–947. Google Scholar
  20. Compta Y, Pereira JB, Ríos J, Ibarretxe-Bilbao N, Junqué C, Bargalló N et al (2013) Combined dementia-risk biomarkers in Parkinson’s disease: a prospective longitudinal study. Parkinsonism Relat Disord 19(8):717–724. Google Scholar
  21. Dalaker TO, Larsen JP, Bergsland N, Beyer MK, Alves G, Dwyer MG et al (2009) Brain atrophy and white matter hyperintensities in early Parkinson’s disease. Mov Disord 24(15):2233–2241. Google Scholar
  22. Dalaker TO, Zivadinov R, Larsen JP, Beyer MK, Cox JL, Alves G et al (2010) Gray matter correlations of cognition in incident Parkinson’s disease. Mov Disord 25(5):629–633. Google Scholar
  23. Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D et al (2006) An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage 31(3):968–980. Google Scholar
  24. Dickerson BC, Bakkour A, Salat DH, Feczko E, Pacheco J, Greve DN et al (2009a) The cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex 19(3):497–510. Google Scholar
  25. Dickerson BC, Feczko E, Augustinack JC, Pacheco J, Morris JC, Fischl B, Buckner RL (2009b) Differential effects of aging and Alzheimer’s disease on medial temporal lobe cortical thickness and surface area. Neurobiol Aging 30(3):432–440. Google Scholar
  26. Du A-T, Schuff N, Kramer JH, Rosen HJ, Gorno-Tempini ML, Rankin K et al (2007) Different regional patterns of cortical thinning in Alzheimer’s disease and frontotemporal dementia. Brain 130(Pt 4):1159–1166. Google Scholar
  27. Duncan GW, Firbank MJ, O’Brien JT, Burn DJ (2013) Magnetic resonance imaging: a biomarker for cognitive impairment in Parkinson’s disease? Mov Disord 28(4):425–438. Google Scholar
  28. Ferreira LK, Diniz BS, Forlenza OV, Busatto GF, Zanetti MV (2011) Neurostructural predictors of Alzheimer’s disease: a meta-analysis of VBM studies. Neurobiol Aging 32(10):1733–1741. Google Scholar
  29. Gasca-Salas C, García-Lorenzo D, Garcia-Garcia D, Clavero P, Obeso JA, Lehericy S, Rodríguez-Oroz MC (2017) Parkinson’s disease with mild cognitive impairment: severe cortical thinning antedates dementia. Brain Imaging Behav. Google Scholar
  30. Hanganu A, Bedetti C, Degroot C, Mejia-Constain B, Lafontaine A-L, Soland V et al (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. Google Scholar
  31. Hutton C, Draganski B, Ashburner J, Weiskopf N (2009) A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging. NeuroImage 48(2):371–380. Google Scholar
  32. Ibarretxe-Bilbao N, Junque C, Marti MJ, Tolosa E (2011) Brain structural MRI correlates of cognitive dysfunctions in Parkinson’s disease. J Neurol Sci 310(1–2):70–74. Google Scholar
  33. Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, Van Deerlin V et al (2012) Neuropathologic substrates of Parkinson disease dementia. Ann Neurol 72(4):587–598. Google Scholar
  34. Irwin DJ, Lee VM-Y, Trojanowski JQ (2013) Parkinson’s disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies. Nat Rev Neurosci 14(9):626–636. Google Scholar
  35. Jack CR (2014) PART and SNAP. Acta Neuropathol 128(6):773–776. Google Scholar
  36. Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS et al (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12(2):207–216. Google Scholar
  37. Jack CR, Knopman DS, Chételat G, Dickson D, Fagan AM, Frisoni GB et al (2016) Suspected non-Alzheimer disease pathophysiology: concept and controversy. Nat Rev Neurol 12(2):117–124. Google Scholar
  38. Jellinger KA, Seppi K, Wenning GK, Poewe W (2002) Impact of coexistent Alzheimer pathology on the natural history of Parkinson’s disease. J Neural Transm 109(3):329–339. Google Scholar
  39. Lee E-Y, Sen S, Eslinger PJ, Wagner D, Shaffer ML, Kong L et al (2013) Early cortical gray matter loss and cognitive correlates in non-demented Parkinson’s patients. Parkinsonism Relat Disord 19(12):1088–1093. Google Scholar
  40. Lehericy S, Vaillancourt DE, Seppi K, Monchi O, Rektorova I, Antonini A et al (2017) The role of high-field magnetic resonance imaging in parkinsonian disorders: pushing the boundaries forward. Mov Disord 32(4):510–525. Google Scholar
  41. Li Y-O, Adali T, Calhoun VD (2007) Estimating the number of independent components for functional magnetic resonance imaging data. Hum Brain Mapp 28(11):1251–1266. Google Scholar
  42. Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, Petersen RC et al (2012) Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: movement disorder society task force guidelines. Mov Disord 27(3):349–356. Google Scholar
  43. Liu Y, Paajanen T, Zhang Y, Westman E, Wahlund L-O, Simmons A et al (2010) Analysis of regional MRI volumes and thicknesses as predictors of conversion from mild cognitive impairment to Alzheimer’s disease. Neurobiol Aging 31(8):1375–1385. Google Scholar
  44. Lyoo IK, Sung YH, Dager SR, Friedman SD, Lee J-Y, Kim SJ et al (2006) Regional cerebral cortical thinning in bipolar disorder. Bipolar Disord 8(1):65–74. Google Scholar
  45. Madhyastha TM, Askren MK, Boord P, Zhang J, Leverenz JB, Grabowski TJ (2015) Cerebral perfusion and cortical thickness indicate cortical involvement in mild Parkinson’s disease. Mov Disord 30(14):1893–1900. Google Scholar
  46. Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ et al (2015) Baseline and longitudinal grey matter changes in newly diagnosed Parkinson’s disease: ICICLE-PD study. Brain 138(10):2974–2986. Google Scholar
  47. Mattis PJ, Niethammer M, Sako W, Tang CC, Nazem A, Gordon ML et al (2016) Distinct brain networks underlie cognitive dysfunction in Parkinson and Alzheimer diseases. Neurology 87(18):1925–1933. Google Scholar
  48. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement 7(3):263–269. Google Scholar
  49. Melzer TR, Watts R, MacAskill MR, Pitcher TL, Livingston L, Keenan RJ et al (2012) Grey matter atrophy in cognitively impaired Parkinson’s disease. J Neurol Neurosurg Psychiatry 83(2):188–194. Google Scholar
  50. Nagano-Saito A, Washimi Y, Arahata Y, Kachi T, Lerch JP, Evans AC et al (2005) Cerebral atrophy and its relation to cognitive impairment in Parkinson disease. Neurology 64(2):224–229. Google Scholar
  51. Nemcova-Elfmarkova N, Gajdos M, Rektorova I, Marecek R, Rapcsak SZ (2017) Neural evidence for defective top-down control of visual processing in Parkinson’s and Alzheimer’s disease. Neuropsychologia 106:236–244. Google Scholar
  52. Pan PL, Shi HC, Zhong JG, Xiao PR, Shen Y, Wu LJ et al (2013) Gray matter atrophy in Parkinson’s disease with dementia: evidence from meta-analysis of voxel-based morphometry studies. Neurol Sci 34(5):613–619. Google Scholar
  53. Pereira JB, Svenningsson P, Weintraub D, Brønnick K, Lebedev A, Westman E, Aarsland D (2014) Initial cognitive decline is associated with cortical thinning in early Parkinson disease. Neurology 82(22):2017–2025. Google Scholar
  54. Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV et al (2001) Current concepts in mild cognitive impairment. Arch Neurol 58(12):1985–1992Google Scholar
  55. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W et al (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30(12):1591–1601. Google Scholar
  56. Preston AR, Eichenbaum H (2013) Interplay of hippocampus and prefrontal cortex in memory. Curr Biol 23(17):R764–R773. Google Scholar
  57. Quental NBM, Brucki SMD, Bueno OFA (2013) Visuospatial function in early Alzheimer’s disease: the use of the visual object and space perception (VOSP) battery. PLoS ONE 8(7):e68398. Google Scholar
  58. Rektor I, Svátková A, Vojtíšek L, Zikmundová I, Vaníček J, Király A, Szabó N (2018) White matter alterations in Parkinson’s disease with normal cognition precede grey matter atrophy. PLoS ONE 13(1):e0187939. Google Scholar
  59. Rektorova I, Biundo R, Marecek R, Weis L, Aarsland D, Antonini A (2014) Grey matter changes in cognitively impaired Parkinson’s disease patients. PLoS ONE 9(1):e85595. Google Scholar
  60. Rodriguez-Oroz MC, Gago B, Clavero P, Delgado-Alvarado M, Garcia-Garcia D, Jimenez-Urbieta H (2015) The relationship between atrophy and hypometabolism: is it regionally dependent in dementias? Curr Neurol Neurosci Rep 15(7):44. Google Scholar
  61. Sack AT (2009) Parietal cortex and spatial cognition. Behav Brain Res 202(2):153–161. Google Scholar
  62. Song SK, Lee JE, Park H-J, Sohn YH, Lee JD, Lee PH (2011) The pattern of cortical atrophy in patients with Parkinson’s disease according to cognitive status. Mov Disord 26(2):289–296. Google Scholar
  63. Summerfield C, Junqué C, Tolosa E, Salgado-Pineda P, Gómez-Ansón B, Martí MJ et al (2005) Structural brain changes in Parkinson disease with dementia: a voxel-based morphometry study. Arch Neurol 62(2):281–285. Google Scholar
  64. Tae WS, Kim SH, Joo EY, Han SJ, Kim IY, Kim SI et al (2008) Cortical thickness abnormality in juvenile myoclonic epilepsy. J Neurol 255(4):561–566. Google Scholar
  65. Tam CWC, Burton EJ, McKeith IG, Burn DJ, O’Brien JT (2005) Temporal lobe atrophy on MRI in Parkinson disease with dementia: a comparison with Alzheimer disease and dementia with Lewy bodies. Neurology 64(5):861–865. Google Scholar
  66. Thompson PM, Hayashi KM, de Zubicaray G, Janke AL, Rose SE, Semple J et al (2003) Dynamics of gray matter loss in Alzheimer’s disease. J Neurosci 23(3):994–1005Google Scholar
  67. Tinaz S, Courtney MG, Stern CE (2011) Focal cortical and subcortical atrophy in early Parkinson’s disease. Mov Disord 26(3):436–441. Google Scholar
  68. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N et al (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15(1):273–289. Google Scholar
  69. Uribe C, Segura B, Baggio HC, Abos A, Marti MJ, Valldeoriola F et al (2016) Patterns of cortical thinning in nondemented Parkinson’s disease patients. Mov Disord 31(5):699–708. Google Scholar
  70. Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA et al (2013) Preclinical Alzheimer’s disease and its outcome: a longitudinal cohort study. Lancet Neurol 12(10):957–965. Google Scholar
  71. Weintraub D, Doshi J, Koka D, Davatzikos C, Siderowf AD, Duda JE et al (2011) Neurodegeneration across stages of cognitive decline in Parkinson disease. Arch Neurol 68(12):1562–1568. Google Scholar
  72. Weintraub D, Dietz N, Duda JE, Wolk DA, Doshi J, Xie SX et al (2012) Alzheimer’s disease pattern of brain atrophy predicts cognitive decline in Parkinson’s disease. Brain 135(Pt 1):170–180. Google Scholar
  73. Whitwell JL, Josephs KA, Murray ME, Kantarci K, Przybelski SA, Weigand SD et al (2008) MRI correlates of neurofibrillary tangle pathology at autopsy: a voxel-based morphometry study. Neurology 71(10):743–749. Google Scholar
  74. Xu L, Groth KM, Pearlson G, Schretlen DJ, Calhoun VD (2009) Source-based morphometry: the use of independent component analysis to identify gray matter differences with application to schizophrenia. Hum Brain Mapp 30(3):711–724. Google Scholar
  75. Xu Y, Yang J, Hu X, Shang H (2016) Voxel-based meta-analysis of gray matter volume reductions associated with cognitive impairment in Parkinson’s disease. J Neurol 263(6):1178–1187. Google Scholar
  76. Ye BS, Jeon S, Ham JH, Lee JJ, Lee JM, Lee HS, et al (2017) Dementia-predicting cognitive risk score and its correlation with cortical thickness in parkinson disease. Dement Geriatr Cogn Disord 44(3–4):203–212. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Medical FacultyMasaryk UniversityBrnoCzech Republic
  2. 2.Brain and Mind Research ProgrammeCEITEC Masaryk UniversityBrnoCzech Republic
  3. 3.Movement Disorders Centre, First Department of Neurology, St Anne’s University HospitalMasaryk UniversityBrnoCzech Republic

Personalised recommendations