Demenz mit Lewy-Körpern

Kernaussagen

Die Assoziation eines demenziellen Syndroms und einer parkinsonoiden extrapyramidalmotorischen Symptomatik ist häufig. Allgemein etablierte Konsensuskriterien erlauben die Diagnose einer Lewy-Körper-Demenz – allerdings schließt diese auf klinischen Kriterien basierende Diagnose auch die Diagnose einer Demenz anderer Ätiologie nicht aus. Im klinischen Alltag treten häufig Mischformen mit begleitender Alzheimer-Erkrankung oder vaskulärer Enzephalopathie auf.

Klinisch bedeutsam ist die Vorsicht bei der Anwendung neuroleptischer Substanzen bei älteren Personen mit demenzieller Symptomatik. Symptome, die im Erwachsenenalter gut auf eine neuroleptische Behandlung ansprechen, z. B. Wahn oder Halluzinationen, sind bei Patienten mit kognitiven Einschränkungen nur mit Vorsicht anzuwenden, da zumindest begleitend eine Neuroleptika-Empfindlichkeit in Assoziation zum Vorliegen von Lewy-Körpern bestehen kann. Außer in Notfallsituationen sollte daher bevorzugt auch bei diesen Patienten zunächst mit einer cholinergen Medikation begonnen werden.

• Literatur

• 1 McKeith IG, Galasko D, Kosaka K et al. Consensus Guidelines for the Clinical and Pathologic Diagnosis of Dementia with Lewy Bodies (DLB): report of the Consortium on DLB International Workshop. Neurology 1996; 47: 1113-1124
• 2 Luis CA, Barker WW, Gajaraj K et al. Sensitivity and specificity of three clinical criteria for dementia with Lewy bodies in an autopsy-verified sample. Int J Geriatr Psychiatry 1999; 14: 526-533
• 3 Serby M, Samuels SC. Diagnostic criteria for dementia with Lewy bodies reconsidered. Am J Geriatr Psychiatry 2001; 9: 212-216
• 4 McKeith IG, Dickson DW, Lowe J et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology 2005; 65: 1863-1872
• 5 Vann Jones SA, O’Brien JT. The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies. Psychol Med 2013; 1-11
• 6 Okazaki H, Lipkin LE, Aronson SM. Diffuse intracytoplasmic ganglionic inclusions (Lewy type) associated with progressive dementia and quadriparesis in flexion. J Neuropathol Exp Neurol 1961; 20: 237-244
• 7 Dikiy I, Eliezer D. Folding and misfolding of alpha-synuclein on membranes. Biochim Biophys Acta 2012; 1818: 1013-1018
• 8 Husnjak K, Dikic I. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu Rev Biochem 2012; 81: 291-322
• 9 Goedert M, Spillantini MG, Del TK et al. 100 years of lewy pathology. Nat Rev Neurol 2013; 9: 13-24
• 10 McKeith I, Del Ser T, Spano P et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000; 356: 2031-2036
• 11 Brown DF, Dababo MA, Bigio EH et al. Neuropathologic evidence that the Lewy body variant of Alzheimer disease represents coexistence of Alzheimer disease and idiopathic Parkinson disease. J Neuropathol Exp Neurol 1998; 57: 39-46
• 12 Hamilton RL. Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol 2000; 10: 378-384
• 13 Clinton LK, Blurton-Jones M, Myczek K et al. Synergistic interactions between abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci 2010; 30: 7281-7289
• 14 Barber R, Scheltens P, Gholkar A et al. White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzheimer’s disease, vascular dementia, and normal aging. J Neurol Neurosurg Psychiatry 1999; 67: 66-72
• 15 Londos E, Passant U, Brun A et al. Clinical Lewy body dementia and the impact of vascular components. Int J Geriatr Psychiatry 2000; 15: 40-49
• 16 McKeith I, Mintzer J, Aarsland D et al. Dementia with Lewy bodies. Lancet Neurol 2004; 3: 19-28
• 17 Lee DR, Taylor JP, Thomas AJ. Assessment of cognitive fluctuation in dementia: a systematic review of the literature. Int J Geriatr Psychiatry 2012; 27: 989-998
• 18 Cagnin A, Gnoato F, Jelcic N et al. Clinical and cognitive correlates of visual hallucinations in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2013; 84: 505-510
• 19 Rolma G, Jelcic N, Gnoato F et al. Combined duloxetine and benzodiazepine-induced visual hallucinations in prodromal dementia with Lewy bodies. Gen Hosp Psychiatry 2013; doi:
• 20 Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to lewy bodies in the temporal lobe. Brain 2002; 125: 391-403
• 21 Ditter SM, Mirra SS. Neuropathologic and clinical features of Parkinson’s disease in Alzheimer’s disease patients. Neurology 1987; 37: 754-760
• 22 Liu Y, Stern Y, Chun MR et al. Pathological correlates of extrapyramidal signs in Alzheimer’s disease. Ann Neurol 1997; 41: 368-374
• 23 Aarsland D, Perry R, Larsen JP et al. Neuroleptic sensitivity in Parkinson’s disease and parkinsonian dementias. J Clin Psychiatry 2005; 66: 633-637
• 24 Ferman TJ, Boeve BF, Smith GE et al. Dementia with Lewy bodies may present as dementia and rem sleep behavior disorder without parkinsonism or hallucinations. J Int Neuropsychol Soc 2002; 8: 907-914
• 25 Hibi S, Yamaguchi Y, Umeda-Kameyama Y et al. The high frequency of periodic limb movements in patients with Lewy body dementia. J Psychiatr Res 2012; 46: 1590-1594
• 26 Del Ser T, Munoz DG, Hachinski V. Temporal pattern of cognitive decline and incontinence is different in Alzheimer’s disease and diffuse Lewy body disease. Neurology 1996; 46: 682-686
• 27 Postuma RB, Gagnon JF, Pelletier A et al. Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord 2013; 28: 597-604
• 28 Chiba Y, Fujishiro H, Iseki E et al. Retrospective survey of prodromal symptoms in dementia with Lewy bodies: comparison with Alzheimer’s disease. Dement Geriatr Cogn Disord 2012; 33: 273-281
• 29 Stubendorff K, Aarsland D, Minthon L et al. The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson’s disease with dementia. PLoS ONE 2012; 7: e45451
• 30 Vardy E, Holt R, Gerhard A et al. History of a suspected delirium is more common in dementia with Lewy bodies than Alzheimer’s disease: a retrospective study. Int J Geriatr Psychiatry 2013; doi:
• 31 Creese B, Ballard C, Aarsland D et al. Determining the association of the 5httlpr polymorphism with delusions and hallucinations in Lewy body dementias. Am J Geriatr Psychiatry 2013; doi:
• 32 Thaipisuttikul P, Lobach I, Zweig Y et al. Capgras syndrome in dementia with Lewy bodies. Int Psychogeriatr 2013; 25: 843-849
• 33 Gomperts SN, Locascio JJ, Marquie M et al. Brain amyloid and cognition in Lewy body diseases. Mov Disord 2012; 27: 965-973
• 34 Litvan I, MacIntyre A, Goetz CG et al. Accuracy of the clinical diagnoses of Lewy body disease, Parkinson disease, and dementia with Lewy bodies: a clinicopathologic study. Arch Neurol 1998; 55: 969-978
• 35 Minoshima S, Foster NL, Sima AA et al. Alzheimer’s disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol 2001; 50: 358-365
• 36 Meeus B, Theuns J, Van BC. The genetics of dementia with Lewy bodies: what are we missing?. Arch Neurol 2012; 69: 1113-1118
• 37 Salmon DP, Galasko D, Hansen LA et al. Neuropsychological deficits associated with diffuse Lewy body disease. Brain Cogn 1996; 31: 148-165
• 38 Hansen L, Salmon D, Galasko D et al. The Lewy body variant of Alzheimer’s disease: a clinical and pathologic entity. Neurology 1990; 40: 1-8
• 39 Sahgal A, Galloway PH, McKeith IG et al. Matching-to-sample deficits in patients with senile dementias of the Alzheimer and Lewy body types. Arch Neurol 1992; 49: 1043-1046
• 40 Shimomura T, Mori E, Yamashita H et al. Cognitive loss in dementia with Lewy bodies and Alzheimer disease. Arch Neurol 1998; 55: 1547-1552
• 41 Doubleday EK, Snowden JS, Varma AR et al. Qualitative performance characteristics differentiate dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2002; 72: 602-607
• 42 Yoshizawa H, Vonsattel JP, Honig LS. Early neuropsychological discriminants for Lewy body disease: an autopsy series. J Neurol Neurosurg Psychiatry 2013; doi:
• 43 Collerton D, Burn D, McKeith I et al. Systematic review and meta-analysis show that dementia with Lewy bodies is a visual-perceptual and attentional-executive dementia. Dement Geriatr Cogn Disord 2003; 16: 229-237
• 44 Noe E, Marder K, Bell KL et al. Comparison of dementia with Lewy bodies to Alzheimer’s disease and Parkinson’s disease with dementia. Mov Disord 2004; 19: 60-67
• 45 Simard M, van Reekum R, Myran D. Visuospatial impairment in dementia with Lewy bodies and Alzheimer’s disease: a process analysis approach. Int J Geriatr Psychiatry 2003; 18: 387-391
• 46 Hamilton JM, Salmon DP, Galasko D et al. A comparison of episodic memory deficits in neuropathologically-confirmed dementia with Lewy bodies and Alzheimer’s disease. J Int Neuropsychol Soc 2004; 10: 689-697
• 47 Simard M, van Reekum R, Myran D et al. Differential memory impairment in dementia with Lewy bodies and Alzheimer’s disease. Brain Cogn 2002; 49: 244-249
• 48 Simard M, van Reekum R, Cohen T. A review of the cognitive and behavioral symptoms in dementia with Lewy bodies. J Neuropsychiatry Clin Neurosci 2000; 12: 425-450
• 49 Ziebell M, Andersen BB, Pinborg LH et al. Striatal dopamine transporter binding does not correlate with clinical severity in dementia with Lewy bodies. J Nucl Med 2013; doi:
• 50 Siepel FJ, Rongve A, Buter TC et al. (123I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study. Br Med J open 2013; 3
• 51 Colloby SJ, McParland S, O’Brien JT et al. Neuropathological correlates of dopaminergic imaging in Alzheimer’s disease and Lewy body dementias. Brain 2012; 135: 2798-2808
• 52 Nakatsuka T, Imabayashi E, Matsuda H et al. Discrimination of dementia with Lewy bodies from Alzheimer’s disease using voxel-based morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registration through exponentiated lie algebra. Neuroradiology 2013; 55: 559-566
• 53 Chow N, Aarsland D, Honarpisheh H et al. Comparing hippocampal atrophy in Alzheimer’s dementia and dementia with Lewy bodies. Dement Geriatr Cogn Disord 2012; 34: 44-50
• 54 King AE, Mintz J, Royall DR. Meta-analysis of 123I-mibg cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord 2011; 26: 1218-1224
• 55 Wennstrom M, Surova Y, Hall S et al. Low CSF levels of both alpha-synuclein and the alpha-synuclein cleaving enzyme neurosin in patients with synucleinopathy. PLoS ONE 2013; 8: e53250
• 56 Schoonenboom NS, Reesink FE, Verwey NA et al. Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology 2012; 78: 47-54
• 57 Slaets S, Le BN, Martin JJ et al. Cerebrospinal fluid abeta1-40 improves differential dementia diagnosis in patients with intermediate p-tau181p levels. J Alzheimers Dis 2013; doi:
• 58 Zhang ZX, Roman GC. Worldwide occurence of Parkinson’s disease: an updated review. Neuroepidemiology 1993; 12: 195-208
• 59 Mayeux R, Stern Y, Rosenstein R. An estimate of the prevalence of dementia in idiopathic Parkinson’s disease. Arch Neurol 1988; 45: 260-262
• 60 Marder K, Flood P, Cote L et al. A pilot study of risk factors for dementia in Parkinson’s disease. Mov Disord 1990; 5: 151-161
• 61 Aarsland D, Andersen K, Larsen JP et al. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol 2003; 60: 387-392
• 62 Riepe MW, Kassubek J, Tracik F et al. Screening for cognitive impairment in Parkinson’s disease – which marker relates to disease severity?. J Neural Transm 2006; 113: 1463-1468
• 63 Pillon B, Ertle S, Deweer B et al. Memory for spatial location in ‘de novo’ parkinsonian patients. Neuropsychologia 1997; 35: 221-228
• 64 Pillon B, Deweer B, Agid Y et al. Explicit memory in Alzheimer’s, Huntington’s, and Parkinson’s diseases. Arch Neurol 1993; 50: 374-379
• 65 Pillon B, Dubois B, Lhermitte F et al. Heterogeneity of cognitive impairment in progressive supranuclear palsy, Parkinson’s disease, and Alzheimer’s disease. Neurology 1986; 36: 1179-1185
• 66 Saint-Cyr JA, Taylor AE, Lang AE. Procedural learning and neostriatal dysfunction in man. Brain 1988; 111: 941-959
• 67 Owen AM, Doyon J, Petrides M et al. Planning and spatial working memory: a positron emission tomography study in humans. Eur J Neurosci 1996; 8: 353-364
• 68 Owen AM, James M, Leigh PN et al. Fronto-striatal cognitive deficits at different stages of Parkinson’s disease. Brain 1992; 115: 1727-1751
• 69 Holthoff VA, Vieregge P, Kessler J et al. Discordant twins with Parkinson’s disease: positron emission tomography and early signs of impaired cognitive circuits. Ann Neurol 1994; 36: 176-182
• 70 Rinne JO, Portin R, Ruottinen H et al. Cognitive impairment and the brain dopaminergic system in Parkinson disease: [18f]fluorodopa positron emission tomographic study. Arch Neurol 2000; 57: 470-475
• 71 Boller F, Mizutani T, Roessmann U et al. Parkinson disease, dementia, and Alzheimer disease: clinicopathological correlations. Ann Neurol 1980; 7: 329-335
• 72 Laakso MP, Partanen K, Riekkinen P et al. Hippocampal volumes in Alzheimer’s disease, Parkinson’s disease with and without dementia, and in vascular dementia: an MRI study. Neurology 1996; 46: 678-681
• 73 Gotham AM, Brown RG, Marsden CD. ‘frontal’ cognitive function in patients with Parkinson’s disease ‘on’ and ‘off’ levodopa. Brain 1988; 111: 299-321
• 74 Levy G, Schupf N, Tang MX et al. Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol 2002; 51: 722-729
• 75 Litvan I, Agid Y, Goetz C et al. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology 1997; 48: 119-125
• 76 Pillon B, Blin J, Vidailhet M et al. The neuropsychological pattern of corticobasal degeneration: comparison with progressive supranuclear palsy and Alzheimer’s disease. Neurology 1995; 45: 1477-1483
• 77 Schneider JA, Watts RL, Gearing M et al. Corticobasal degeneration: neuropathologic and clinical heterogeneity. Neurology 1997; 48: 959-969
• 78 Kertzman C, Robinson DL, Litvan I. Effects of physostigmine on spatial attention in patients with progressive supranuclear palsy. Arch Neurol 1990; 47: 1346-1350
• 79 Pillon B, Dubois B, Ploska A et al. Severity and specificity of cognitive impairment in Alzheimer’s, huntington’s, and Parkinson’s diseases and progressive supranuclear palsy. Neurology 1991; 41: 634-643
• 80 Robbins TW, James M, Lange KW et al. Cognitive performance in multiple system atrophy. Brain 1992; 115: 271-291
• 81 Ballard C, Aarsland D, Francis P et al. Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: pathophysiology, clinical features, and pharmacological management. Drugs Aging 2013; doi:
• 82 Rolinski M, Fox C, Maidment I et al. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson’s disease dementia, and cognitive impairment in Parkinson’s disease. Cochrane Database Syst Rev 2012; (3) CD006504
• 83 Riepe MW, Wilkinson D, Forstl H et al. Additive scales in degenerative disease – calculation of effect sizes and clinical judgment. BMC Med Res Methodol 2011; 11: 169
• 84 Mori E, Ikeda M, Kosaka K. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial. Ann Neurol 2012; 72: 41-52