BACKGROUND: Cortical changes associated with cognitive decline in Parkinson's disease (PD) are not fully explored and require investigations with established diagnostic classification criteria. OBJECTIVE: We used MRI source-based morphometry to evaluate specific differences in grey matter volume patterns across 4 groups of subjects: healthy controls (HC), PD with normal cognition (PD-NC), PD with mild cognitive impairment (MCI-PD) and PD with dementia (PDD). METHODS: We examined 151 consecutive subjects: 25 HC, 75 PD-NC, 29 MCI-PD, and 22 PDD at an Italian and Czech movement disorder centre. Operational diagnostic criteria were applied to classify MCI-PD and PDD. All structural MRI images were processed together in the Czech centre. The spatial independent component analysis was used to assess group differences of local grey matter volume. RESULTS: We identified two independent patterns of grey matter volume deviations: a) Reductions in the hippocampus and temporal lobes; b) Decreases in fronto-parietal regions and increases in the midbrain/cerebellum. Both patterns differentiated PDD from all other groups and correlated with visuospatial deficits and letter verbal fluency, respectively. Only the second pattern additionally differentiated PD-NC from HC. CONCLUSION: Grey matter changes in PDD involve areas associated with Alzheimer-like pathology while fronto-parietal abnormalities are possibly an early marker of PD cognitive decline. These findings are consistent with a non-linear cognitive progression in PD.

Brain and Mind Research Program Central European Institute of Technology Central European Institute of Technology Masaryk University Masaryk University Brno Czech Republic ; 1st Department of Neurology School of Medicine Masaryk University and St Anne's University Hospital Brno Czech Republic

Center for Parkinson's disease and Movement Disorder Fondazione Ospedale San Camillo Istituto di Ricovero e Cura a Carattere Scientifico Venice Lido Italy

Department of Neurology and Clinical Neuroscience Karolinska Institutet and Karolinska University Hospital Stockholm Sweden ; Centre for Age Related Diseases Stavanger University Hospital Stavanger Norway

Zobrazit více v PubMed

Svenningsson P, Westman E, Ballard C, Aarsland D (2012) Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment. Lancet Neurol 11: 697–707. PubMed

Aarsland D, Bronnick K, Williams-Gray C, Weintraub D, Marder K, et al. (2010) Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis. Neurology 75: 1062–9. PubMed PMC

Ibarretxe-Bilbao N, Tolosa E, Junque C, Marti MJ (2009) MRI and cognitive impairment in Parkinson's disease. Mov Disord 24 Suppl 2: S748–53. PubMed

Hattori T, Orimo S, Aoki S, Ito K, Abe O, et al. (2012) Cognitive status correlates with white matter alteration in Parkinson's disease. Hum Brain Mapp 33: 727–39. PubMed PMC

Melzer TR, Watts R, MacAskill MR, Pitcher TL, Livingston L, et al. (2012) Grey matter atrophy in cognitively impaired Parkinson's disease. J Neurol Neurosurg Psychiatry 83: 188–94. PubMed

Dalaker TO, Zivadinov R, Larsen JP, Beyer MK, Cox JL, et al. (2010) Gray matter correlations of cognition in incident Parkinson's disease. Mov Disord 25: 629–33. PubMed

Litvan I, Goldman JG, Tröster AI, Schmand BA, Weintraub D, et al. (2012) Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord 27: 349–56. PubMed PMC

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: 711–24. PubMed PMC

Kaspárek T, Marecek R, Schwarz D, Kucerova H, Marecek R, et al. (2010) Source-based morphometry of gray matter volume in men with first-episode schizophrenia. Hum Brain Mapp 31: 300–10. PubMed PMC

Ward CD, Gibb WR (1990) Research diagnostic criteria for Parkinson's disease. Adv Neurol 53: 245–9. PubMed

Mathuranath PS, Nestor PJ, Berrios GE, Rakowicz W, Hodges JR (2000) A brief cognitive test battery to differentiate Alzheimer's disease and frontotemporal dementia. Neurology 55: 1613–20. PubMed

Hummelova-Fanfrdlova Z, Rektorova I, Sheardova K, Bartos A, Linek V, et al. (2009) Ceska adaptace Addenbrookskeho kognitivnýho testu. Ceskoslovenska psychologie 53: 376–388.

Reyes MA, Perez-Lloret S, Roldan Gerschcovich E, Martin ME, Leiguarda R, et al. (2009) Addenbrooke's Cognitive Examination validation in Parkinson's disease. Eur J Neurol 16: 142–7. PubMed

Kaszás B, Kovács N, Balás I, Kállai J, Aschermann Z, et al. (2012) Sensitivity and specificity of Addenbrooke's Cognitive Examination, Mattis Dementia Rating Scale, Frontal Assessment Battery and Mini Mental State Examination for diagnosing dementia in Parkinson's disease. Parkinsonism Relat Disord 18: 553–6. PubMed

Rittman T, Ghosh BC, McColgan P, Breen DP, Evans J, et al. (2013) The Addenbrooke's Cognitive Examination for the differential diagnosis and longitudinal assessment of patients with parkinsonian disorders. J Neurol Neurosurg Psychiatry 84: 544–51. PubMed PMC

Krajcovicova L, Mikl M, Marecek R, Rektorova I (2012) The default mode network integrity in patients with Parkinson's disease is levodopa equivalent dose-dependent. J Neural Transm 119: 443–54. PubMed

Rektorova I, Krajcovicova L, Marecek R, Mikl M (2012) Default mode network and extrastriate visual resting state network in patients with Parkinson's disease dementia. Neurodegener Dis 10: 232–7. PubMed

McColgan P, Evans JR, Breen DP, Mason SL, Barker RA, et al. (2012) Addenbrooke's Cognitive Examination-Revised for mild cognitive impairment in Parkinson's disease. Mov Disord 27: 1173–7. PubMed

Emre M, Aarsland D, Brown R, Burn DJ, Duyckaerts C, et al. (2007) Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord 22: 1689–707. PubMed

Li YO, Adali T, Calhoun VD (2007) Estimating the number of independent components for functional magnetic resonance imaging data. Hum Brain Mapp 28: 1251–66. PubMed PMC

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: 791–800. PubMed

Nagano-Saito A, Washimi Y, Arahata Y, Kachi T, Lerch JP, et al. (2005) Cerebral atrophy and its relation to cognitive impairment in Parkinson disease. Neurology 64: 224–9. PubMed

Summerfield C, Junqué C, Tolosa E, Salgado-Pineda P, Gómez-Ansón B, et al. (2005) Structural brain changes in Parkinson disease with dementia: a voxel-based morphometry study. Arch Neurol 62: 281–5. PubMed

Tam CW, 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: 861–5. PubMed

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: 254–9. PubMed PMC

Song SK, Lee JE, Park HJ, Sohn YH, Lee JD, et al. (2011) The pattern of cortical atrophy in patients with Parkinson's disease according to cognitive status. Mov Disord 26: 289–96. PubMed

Weintraub D, Doshi J, Koka D, Davatzikos C, Siderowf AD, et al. (2011) Neurodegeneration across stages of cognitive decline in Parkinson disease. Arch Neurol 68: 1562–8. PubMed PMC

Biundo R, Formento-Dojot P, Facchini S, Vallelunga A, Ghezzo L, et al. (2011) Brain volume changes in Parkinson's disease and their relationship with cognitive and behavioural abnormalities. J Neurol Sci 310: 64–9. PubMed

Friston KJ, Ashburner J (2004) Generative and recognition models for neuroanatomy. Neuroimage 23: 21–4. PubMed

Haxby JV, Grady CL, Horwitz B, Ungerleider LG, Mishkin M, et al. (1991) Dissociation of object and spatial visual processing pathways in human extrastriate cortex. Proc Natl Acad Sci U S A 88: 1621–5. PubMed PMC

Weintraub D, Dietz N, Duda JE, Wolk DA, Doshi J, et al. (2012) Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease. Brain 135: 170–80. PubMed PMC

Apostolova L, Alves G, Hwang KS, Babakchanian S, Bronnick KS, et al. (2012) Hippocampal and ventricular changes in Parkinson's disease mild cognitive impairment. Neurobiol Aging 33: 2113–24. PubMed PMC

Pereira JB, Junqué C, Martí MJ, Ramirez-Ruiz B, Bargalló N, et al. (2009) Neuroanatomical substrate of visuospatial and visuoperceptual impairment in Parkinson's disease. Mov Disord 24: 1193–9. PubMed

Irwin DJ, White MT, Toledo JB, Xie SX, Robinson JL, et al. (2012) Neuropathologic substrates of Parkinson disease dementia. Ann Neurol 72: 587–98. PubMed PMC

Halliday GM, McCann H (2010) The progression of pathology in Parkinson's disease. Ann N Y Acad Sci 1184: 188–95. PubMed

Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, et al. (2011) The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol 106: 1125–65. PubMed PMC

Huang C, Mattis P, Perrine K, Brown N, Dhawan V, et al. (2008) Metabolic abnormalities associated with mild cognitive impairment in Parkinson disease. Neurology 70: 1470–7. PubMed PMC

Schmahmann JD, Sherman JC (1998) The cerebellar cognitive affective syndrome. Brain 121: 561–79. PubMed

Garrard P, Bradshaw D, Jäger HR, Thompson AJ, Losseff N, et al. (2002) Cognitive dysfunction after isolated brain stem insult. An underdiagnosed cause of long term morbidity. J Neurol Neurosurg Psychiatry 73: 191–4. PubMed PMC

Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 3: 201–15. PubMed

Leh SE, Petrides M, Strafella AP (2010) The neural circuitry of executive functions in healthy subjects and Parkinson's disease. Neuropsychopharmacology 35: 70–85. PubMed PMC

Poletti M, Emre M, Bonuccelli U (2011) Mild cognitive impairment and cognitive reserve in Parkinson's disease. Parkinsonism Relat Disord 17: 579e86. PubMed

Jech R, Mueller K, Schroeter ML, Ruzicka E (2013) Levodopa increases functional connectivity in the cerebellum and brainstem in Parkinson's disease. Brain in print. PubMed

Cerasa A, Messina D, Pugliese P, Morelli M, Lanza P, et al. (2011) Increased prefrontal volume in PD with levodopa-induced dyskinesias: a voxel-based morphometry study. Mov Disord 26: 807–12. PubMed

Aron AR, Obeso J (2012) Is executive control used to compensate for involuntary movements in levodopa-induced dyskinesia? Mov Disord 27: 339–40. PubMed

Biundo R, Calabrese M, Weis L, Facchini S, Ricchieri G, et al. (2013) Anatomical correlates of cognitive functions in early Parkinson's disease patients. PLoS One 8 5: e64222. PubMed PMC

Jones DT, Machulda MM, Vemuri P, McDade EM, Zeng G, et al. (2011) Age-related changes in the default mode network are more advanced in Alzheimer disease. Neurology 77: 1524–3. PubMed PMC

Jubault T, Brambati SM, Degroot C, Kullmann B, Strafella AP, et al. (2009) Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI. PLoS One 4 12: e8247. PubMed PMC

Fahn S, Elston RL, members of the UPDRS Development Committee (1987) Unified Parkinson's disease rating scale. In: Fahn S, Marsden CD, Goldstein M, Calne DB (eds). Recent developments in Parkinson's disease, vol. 2. Macmillan, New York, pp. 153–163.

Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, et al. (2010) Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord 25: 2649–53. PubMed

Giovagnoli AR, Del Pesce M, Mascheroni S, Simoncelli M, Laiacona M, et al. (1996) Trail Making Test: normative values from 287 normal adult controls. Neurol Sci 17: 305–309. PubMed

Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A (2002) Una versione abbreviata del test di Stroop. Dati normativi nella popolazione italiana. Nuova Riv Neurol 12: 111–115.

Appollonio I, Leone M, Isella V, Piamarta F, Consoli T, et al. (2005) The Frontal Assessment Battery (FAB): normative values in an italian population sample. Neurol Sci 26: 108–116. PubMed

Spinnler H (1987) Tognoni G (1987) Standardizzazione e taratura italiana di test neuropsicologici. Neurol Sci 6: 1–120. PubMed

Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A (2002) Rey-Osterrieth complex figure: normative values in an Italian population sample. Neurol Sci 22: 443–447. PubMed

Novelli G, Papagno C, Capitani E, Laiacona M, Vallar G, et al. (1986) Tre test clinici di ricerca e produzione lessicale: taratura su soggetti normali. Archo Psicol Neurol Psichiat 47: 477–506.

Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson's Disease

The reduction of hippocampal volume in Parkinson's disease

Gray Matter Changes in Parkinson's and Alzheimer's Disease and Relation to Cognition

Diffusion tensor and restriction spectrum imaging reflect different aspects of neurodegeneration in Parkinson's disease

White matter alterations in Parkinson's disease with normal cognition precede grey matter atrophy