Abstract
Previous studies reported an association between cortical Lewy body (LB) formation and dementia in Parkinson's disease (PD). However, it is unclear whether cognitive decline in this disorder is related to specific patterns of LB distribution within the cerebral cortex. Moreover, the prediction of cognitive status based on concomitant assessment of LB and Alzheimer's disease lesions has led to conflicting results. We performed a clinicopathological study in 22 elderly PD patients in whom parkinsonism preceded cognitive decline by at least 3 years. Cognitive status was assessed prospectively using the clinical dementia rating scale (CDR); quantitative assessment of LB, neurofibrillary tangles (NFT), and senile plaques (SP) was performed in Brodmann areas 9, 21, 24, 40 and the entorhinal cortex. Statistical analysis was performed using both correlation coefficients and logistic regression models. There was a highly significant correlation between CDR scores and regional LB scores in the entorhinal cortex and area 24. LB and SP densities in the entorhinal cortex accounted for 36.2% and 19.3% of the variability in CDR scores. LB densities in area 24 could explain 25.2% of this variability. NFT densities did not predict cognitive status. In multivariate models only LB densities in the entorhinal cortex and anterior cingulate cortex were significantly associated with CDR scores. These results imply that an assessment of LB pathology limited to the entorhinal cortex and area 24 may be sufficient to predict cognition in PD. They also suggest that LB formation in limbic areas may be crucial for the development of PD dementia.
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Aarsland D, Tandberg E, Larsen JP, Cummings JL (1996) Frequency of dementia in Parkinson disease. Arch Neurol 53:538–542
Apaydin H, Ahlskog E, Parisi JE, Boeve BF, Dickson DW (2002) Parkinson disease neuropathology. Arch Neurol 59:102–112
Braak H, Braak E (1990) Cognitive impairment in Parkinson's disease: amyloid plaques, neurofibrillary tangles and neuropil threads in the cerebral cortex. J Neural Transm 2:45–47
Braak H, Braak E, Yilmazer D, Vos RA de, Jansen EN, Bohl J (1996) Pattern of brain destruction in Parkinson's disease and Alzheimer's disease. J Neural Transm 103:455–490
Braak H, Del Tredici K, Bohl J, Bratzke H, Braak E (2000) Pathological changes in the parahippocampal region in select non-Alzheimer's dementias. Ann N Y Acad Sci 911:221–239
Churchyard A, Lees AJ (1997) The relationship between dementia and direct involvement of the hippocampus and amygdala in Parkinson's disease. Neurology 49:1570–1576
Delacourte A, Flament S, Dibe EM, Hublau P, Sablonniere B, Hemon B, Sherrer V, Defossez A (1990) Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease. Demonstration with a panel of antibodies against Tau proteins. Acta Neuropathol 80:111–117
Devinsky O, Morrell MJ, Vogt BA (1995) Contributions of anterior cingulate cortex to behaviour. Brain 118:279–306
Duyckaerts C, Gaspar P, Costa C, Bonnet A-M, Hauw J-J (1993) Dementia in Parkinson's disease. Morphometric data. Adv Neurol 60:447–455
Hansen LA (1997) The Lewy body variant of Alzheimer disease. J Neural Transm Suppl 51:83–93
Harding AJ, Stimson E, Henderson JM, Halliday GM (2002) Clinical correlates of selective pathology in the amygdala of patients with Parkinson's disease. Brain 125:2431–2445
Heyman A, Fillenbaum GG, Gearing M, Mirra SS, Welsh-Bohmer KA, Peterson B, Pieper C (1999) Comparison of Lewy body variant of Alzheimer's disease with pure Alzheimer's disease: Consortium to Establish a Registry for Alzheimer's Disease, Part XIX. Neurology 52:1839–1844
Hurtig HI, Trojanowski JQ, Galvin J, Ewbank D, Schmidt ML, Lee VM, Clark CM, Glosser G, Stern MB, Gollomp SM, Arnold SE (2000) Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease. Neurology 54:1916–1921
Ince P, Irving D, MacArthur F, Perry RH (1991) Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson's disease and non-demented elderly control patients. J Neurol Sci 106:142–151
Ito K, Nagano-Saito A, Kato T, Arahata Y, Nakamura A, Kawasumi Y, Hatano K, Abe Y, Yamada T, Kachi T, Brooks DJ (2002) Striatal and extrastriatal dysfunction in Parkinson's disease with dementia: a 6-[18F]fluoro-l-dopa PET study. Brain 125:1358–1365
Jendroska K, Lees AJ, Poewe W, Daniel SE (1996) Amyloid β-peptide and the dementia of Parkinson's disease. Mov Disord 11:647–653
Kim KS, Miller DL, Sapienza VG, Chen CCJ, Vai C, Grundke-Iqbal I, Curry JR, Wisniewski HM (1988) Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide. Neurosci Res Commun 2:121–130
Lippa CF, Smith TW, Swearer JM (1994) Alzheimer's disease and Lewy body disease: a comparative clinicopathological study. Ann Neurol 35:81–88
Mahler ME, Cummings JL (1990) Alzheimer disease and the dementia of Parkinson disease: comparative investigations. Alzheimer Dis Assoc Disord 4:133–149
Marder K, Tang MX, Cote L, Stern Y, Mayeux R (1995) The frequency and associated risk factors for dementia in patients with Parkinson's disease. Arch Neurol 52:695–701
Mattila PM, Roytta M, Torikka H, Dickson DW, Rinne JO (1998) Cortical Lewy bodies and Alzheimer-type changes in patients with Parkinson's disease. Acta Neuropathol 95:576–582
Mattila PM, Rinne JO, Helenius H, Dickson DW, Röyttä M (2000) Alpha-synuclein-immunoreactive cortical Lewy bodies are associated with cognitive impairment in Parkinson's disease. Acta Neuropathol 100:285–290
Mayeux R, Chen J, Mirabello E, Marder K, Bell K, Dooneief G, Cote L, Stern Y (1990) An estimate of the incidence of dementia in idiopathic Parkinson's disease. Neurology 40:1513–1517
Mayeux R, Denaro J, Hemenegildo N, Marder K, Tang MX, Cote LJ, Stern Y (1992) A population-based investigation of Parkinson's disease with and without dementia: relationship to age and gender. Arch Neurol 49:492–497
McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, Vos RA de, Wilcock GK, Jellinger KA, Perry RH (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124
McKeith IG, Ballard CG, Perry RH, Ince PG, O'Brien JT, Neill D, Lowery K, Jaros E, Barber R, Thompson P, Swann A, Fairbairn AF, Perry EK (2000) Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology 54:1050–1058
Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43:2412–2414
Newell KL, Hyman BT, Growdon JH, Hedley-Whyte ET (1999) Application of the National Institute on Aging (NIA)-Reagan Institute criteria for the neuropathological diagnosis of Alzheimer disease. J Neuropathol Exp Neurol 58:1147–1155
Perl DP, Olanow CW, Calne D (1998) Alzheimer's disease and Parkinson's disease: distinct entities or extremes of a spectrum of neurodegeneration? Ann Neurol 44:S19–S31
Perry RH, Irving D, Blessed G, Fairbairn A, Perry EK (1990) Senile dementia of Lewy body type. A clinically and neuropathologically distinct type of Lewy body dementia in the elderly. J Neurol Sci 95:119–139
Sutcliffe RLG, Prior R, Mawby B, McQuillan WJ (1985) Parkinson's disease in the district of the Northampton Health Authority, United Kingdom: a study of prevalence and disability. Acta Neurol Scand 72:363–379
Tison F, Dartigues JF, Auriacombe S, Letenneur L, Boller F, Alperovitch A (1995) Dementia in Parkinson's disease: a population-based study in ambulatory and instituionalized individuals. Neurology 45:705–708
Tyrrell PJ, Sawle GV, Ibanez V, Bloomfield PM, Leenders KL, Frackowiak RS, Rossor MN (1990) Clinical and positron emission tomographic studies in the "extrapyramidal syndrome" of dementia of the Alzheimer type. Arch Neurol 47:1318–1323
Vallet PG, Guntern R, Hof PR, Golaz J, Delacourte A, Robakis NK, Bouras C (1992) A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease. Acta Neuropathol 83:170–178
Vogt BA, Finch DM, Olson CR (1992) Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. Cereb Cortex 2:435–443
Ward CD, Gibb WR (1990) Research diagnosis criteria for Parkinson's disease. Adv Neurol 53:245–249
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Supported by grant AG05138 from the National Institutes of Health, Bethesda, MD (P.R.H.), and by grant 31-52997.97 from the Fonds National Suisse de la Recherche Scientifique, Bern, Switzerland (P.G., C.B.).
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Kövari, E., Gold, G., Herrmann, F.R. et al. Lewy body densities in the entorhinal and anterior cingulate cortex predict cognitive deficits in Parkinson's disease. Acta Neuropathol 106, 83–88 (2003). https://doi.org/10.1007/s00401-003-0705-2
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DOI: https://doi.org/10.1007/s00401-003-0705-2