認知症診療ガイドライン2017_700_第7章.indd

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1 7 Lewy CQ 7 1 Lewy dementia with Lewy bodies DLB DLB Diagnostic and Statistical Manual of Mental Disorders, Fifth EditionDSM DLB C 1976 Lewy Lewy 20% Alzheimer DLB Parkinson Parkinsons disease with dementia PDD 4.3%Lewy Lewy body diseaselbd Lewy LBD Parkinson PDD pure autonomic failurepaf Lewy Lewy DLB 2 3 SPECT PET probable DLB 1 1 probable DLB 1 possible DLB 3 REM sleep behavior disorderrbd % 73% 4 7 Lewy CQ

2 1DLB DLB 22 probable DLB1 possible DLB probable DLB1 possible DLB probable DLB SPECT PET 4 CT MRI SPECTPET MIBG 5DLB 6 DLB PDD Parkinson Lewy LBDDLB PDD 1 DLB Lewy α McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodiesthird report of the DLB Consortium. Neurology Lewy major neurocognitive disorder with Lewy bodies DSM5 5 A B Cprobable Lewy possiblelewy probable Lewy possiblelewy a b c 2 a b D DSM Lewy

3 2013 DSM5 Lewy major neurocognitive disorder with Lewy bodies Lewy mild neurocognitive disorder with Lewy bodies 5 2 DLB DLB 6 Alzheimers disease ,9 6,9 68 7,8 9 DLB DLB RBD 3DLB DLB SPECT PET MIBG 4 CT MRI SPECTPET FDGPET cingulate island sign Probable DLB a2 b1 1 Probable DLB Possible DLB a1 b1 DLB a DLB b 7 Lewy DLB PDD Parkinson Lewy Lewy Body DiseaseDLB PDD 1 DLB 1 McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodiesfourth consensus report of the DLB Consortium. Neurology CQ

4 10 metaiodobenzylguani dinemibg DLB 11,12 DLB DLB probable DLB 2005 DLB RBD 1Gelpi E, NavarroOtano J, Tolosa E, et al. Multiple organ involvement by alphasynuclein pathology in Lewy body disorders. Mov Disord 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 McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodiesthird report of the DLB Consortium. Neurology Ferman TJ, Boeve BF, Smith GE, et al. Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology American Psychiatric AssociationDiagnostic and Statistical manual of Mental Disorders, Fifth edition DSM5. American psychiatric Publishing, Boeve BF. Mild cognitive impairment associated with underlying Alzheimers disease versus Lewy body disease. Parkin sonism and Related Disorders S1S41S44. 7Jicha GA, Schmitt FA, Abner E, et al. Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease. Neurobiology of Aging Auning E, Rongve A, Fladby T, et al. Early and Presenting Symptoms of Dementia with Lewy Bodies. Dement Geriatr Cogn Disord Chiba Y, Fujishiro H Iseki E, et al, Retrospective Survey of Prodromal Symptoms in Dementia with Lewy Bodies Comparison with Alzheimers Disease. Dement Geriatr Cogn Disord Cummings JL. Toward a molecular neuropsychiatry of neurodegenerative diseases. Ann Neurol Yoshita M, Arai H, Arai H et al. Diagnostic accuracy of 123Imetaiodobenzylguanidine myocardial scintigraphy in dementia with Lewy bodiesa multicenter study. PLoS One e Oda H, Ishii K, Terashima A, et al. Myocardial scintigraphy may predict the conversion to probable dementia with Lewy bodies. Neurology McKeith IG, Boeve BF, Dickson DW, et al. Diagnosis and management of dementia with Lewy bodiesfourth consensus report of the DLB Consortium. Neurology PubMed #1 "Lewy Body Disease/diagnosis" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body"and diagnosis TIOR diagnoses TIOR diagnostic TIAND "Early Diagnosis" MeshOR early OR "diagnostic criteria" OR "diagnostic accuracy" OR "diagnostic classification" TIOR "Diagnosis, Differential" Mesh OR "differential diagnosis" #1 Lewy /TH OR Lewy /TI OR /TIAND SH,,, X,, OR /TH OR /TIAND /TH OR /TI OR /AL Lewy

5 CQ 7 2 Lewy dementia with Lewy bodies DLBParkinson Parkinsons disease with dementiapdd 1Lewy Lewy body diseaselbd Lewy 2DLB PDD DLB PDD LBD 1 3 DLB 1 PDD 1. DLB PDD DLB α Lewy DLB 1 Parkinson PD Parkinson PDD 1 PDD 1 DLB DLB PDD DLB PDD DLB DLB Alzheimer 3 PDD DLB PDD DLB DLB PDD α LBD 4 PDD 12 Parkinson Parkinson Lewy CQ

6 1PDD core features 1Queen Square Brain Bank Parkinson 2Parkinson 1 1 spontaneous attention focused attention attentional task 1 bradyphrenia 2 PDD PDD DSM NINDSAIREN probable vascular dementia 1 3 Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinsons disease. Mov Disord, ICD probable PDD possible PDD probable PDD A B PDD PDD C 1 D 1 possible PDD A B 1 C 1 1 D 1 Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinsons disease. Mov Disord, ICD Lewy

7 PDD 6,7 α Lewy Alzheimer Alzheimer Alzheimer LBD 1McKeith 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 McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodiesthird report of the DLB Consortium. Neurology Morra LF, Donovick PJ. Clinical presentation and differential diagnosis of dementia with Lewy bodiesa review. Int J Geriatr Psychiatry Lippa CF, Duda JE, Grossman M, et al. DLB and PDD boundary issuesdiagnosis, treatment, molecular pathology, and biomarkers. Neurology Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinsons disease. Mov Disord ICD PubMed #1 "Lewy Body Disease/diagnosis" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body"and diagnosis TIOR diagnoses TIOR diagnostic TI AND "Parkinson Disease" MeshAND Dementia MeshOR "Cognition Disorders" Mesh OR "Parkinsons disease dementia" OR "Parkinson disease dementia" OR PDDOR "Lewy Body Disease/diagnosis" MeshOR "Lewy body" OR "Lewy bodies"and "Dementia/diagnosis" MajrAND "Parkinson Disease/diagnosis" MeshOR "Parkinson disease" AND diagnosis TI AND criteria OR "Diagnosis, Differential" MeshOR "Incidence" MeshOR "differential diagnosis" TI OR "pathologic diagnosis" #1 Lewy /TH OR Lewy /TI OR /TIAND Parkinson /TH OR Parkinson /TI OR /TIAND /TH OR /TI OR /TH OR /TI OR /TI Lewy CQ

8 CQ 7 3 Lewy dementia with Lewy bodies DLB DLB metaiodobenzylguanidinemibg CT/MRI SPECT/FDGPET 1A DLB 123 IMIBG SPECT PD DLB 2014 DLB 123 IMIBG 1 Alzheimer IMIBG DLB Alzheimer 96.1% 90.7% 3 DLB DLB 123 IMIBG 93% 100% 100% 98% 90% 76% 49% 97% 4 1DLB 2 3 selective serotonin reuptake inhibitor SSRI serotoninnorepinephrine reuptake inhibitorsnri MAOB Parkinson Lewy

9 5 5 MRI VoxelBased Specific Regional Analysis System for Alzheimers DiseaseVSRAD 6 Alzheimer DLB Alzheimer DLB DLB Alzheimer 7 25 probable DLB 68% 8 DLB MIBG 9 DLB MIBG MRI VSRAD PET DLB Alzheimer ChEPET ChE 10 Parkinson DLB α α α DLB 11 DLB Aβ DLB DLB 237 CQ MIBG 3 polysomnographypsg REM sleep without atoniarwa REM sleep behavior disorderrbd 90% 1Yoshita M, et al. Diagnostic Accuracy of 123IMetaIodobenzylguanidine Myocardial Scintigraphy in Dementia with Lewy BodiesA Multicenter Study. PLoS ONE e McKeith I, OBrien J, Walker Z, et al.dlb Study Group. Sensitivity and specificity of dopamine transporter imaging with 123IFPCIT SPECT in dementia with Lewy bodiesa phase III, multicentre study. Lancet Neurol Shimizu S, Hirao K, Kanetaka H, et al. Utility of the combination of DAT SPECT and MIBG myocardial scintigraphy in differentiating dementia with Lewy bodies from Alzheimers disease. Eur J Nucl Med Mol Imaging Tiraboschi P, Corso A, Guerra UP, et al.scilla Working Group. 123I2β carbomethoxy3β 4iodophenylN 3fluoropropylnortropane single photon emission computed tomography and 123 Imetaiodobenzylguanidine myocar dial scintigraphy in differentiating dementia with lewy bodies from other dementiasa comparative study. Ann Neurol. 7 Lewy CQ

10 Nakatsuka T, Imabayashi E, Matsuda H, et al. Discrimination of dementia with Lewy bodies from Alzheimers disease using voxelbased morphometry of white matter by statistical parametric mapping 8 plus diffeomorphic anatomic registra tion through exponentiated Lie algebra. Neuroradiology Fujishiro H, et al. A follow up study of nondemented patients with primary visual cortical hypometabolismprodromal dementia with Lewy bodies. J Neurol Sci, Tateno M, Kobayashi S, Shirasaka T, et al. Comparison of the usefulness of brain perfusion SPECT and MIBG myocardial scintigraphy for the diagnosis of dementia with Lewy bodies. Dement Geriatr Cogn Disord Hanyu H, Shimizu S, Hirao K, et al. Comparative value of brain perfusion SPECT and 123IMIBG myocardial scin tigraphy in distinguishing between dementia with Lewy bodies and Alzheimers disease. Eur J Nucl Med Mol Imaging Shimada H, Hirano S, Shinotoh H, et al. Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. Neurology Zhou B, Wen M, Yu WF, et al. The Diagnostic and Differential Diagnosis Utility of Cerebrospinal Fluid α Synuclein Levels in Parkinsons DiseaseA MetaAnalysis. Parkinsons Dis Maetzler W, Stapf AK, Schulte C, et al. Serum and cerebrospinal fluid uric acid levels in Lewy body disordersassociations with disease occurrence and amyloidβ pathway. J Alzheimers Dis PubMed #1 "Lewy Body Disease/diagnosis" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body"and diagnosis TIOR diagnoses TIOR diagnostic TI AND "Diagnostic Imaging" MeshOR "3Iodobenzylguanidine/diagnostic use" MeshOR "Dopamine Plasma Membrane Transport Proteins" Mesh OR "magnetic resonance imaging" OR "singlephoton emission computed tomography" OR "positron emission tomography" OR DAT scan* OR neuroimaging OR MRI OR SPECT OR MIBG OR PETOR "Lewy Body Disease/cerebrospinal fluid" MajrOR "Lewy Body Disease/radionuclide imaging" MeshOR "Lewy body" TIOR "Lewy bodies" TI AND dementia TI AND diagnosis TI OR diagnoses TI OR diagnostic TI AND "Fluorodeoxyglucose F18/diagnostic use" MeshOR "3Iodobenzylguanidine/diagnostic use" MeshOR "Dopamine Plasma Membrane Transport Proteins/analysis" MajrOR Metaiodobenzylguanidine OR metaiodobenzylguanidine OR MIBG #1 Lewy /TH OR Lewy /TI OR /TIAND SH,,, X,, OR /THAND /TH OR "Dopamine Plasma Membrane Transport Proteins"/ TH OR DAT OR DATscan OR DAT OR MRI/TI OR OR OR OR OR SPECT/TI OR OR OR OR OR OR Iobenguane/TH OR MIBG OR PET/TI OR OR Lewy

11 CQ 7 4 Lewy dementia with Lewy bodies DLB DLB Alzheimer DLB C DLB Alzheimer 16 1,2 DLB Alzheimer 7 DLB 6 5,8 DLB 9 1Stavitsky K, Brickman AM, Scarmeas N, et al. The progression of cognition, psychiatric symptoms, and functional abilities in dementia with Lewy bodies and Alzheimer disease. Arch Neurol Lopez OL, Wisniewski S, Hamilton RL, et al. Predictors of progression in patients with AD and Lewy bodies. Neurology Ballard C, OBrien J, Morris CM, et al. The progression of cognitive impairment in dementia with Lewy bodies, vascular dementia and Alzheimers disease. Int J Geriatr Psychiatry Helmes E, Bowler JV, Merskey H, et al. Rates of cognitive decline in Alzheimers disease and dementia with Lewy bodies. Dement Geriatr Cogn Disord Williams MM, Xiong C, Morris JC, et al. Survival and mortality differences between dementia with Lewy bodies vs Alzheimer disease. Neurology Hanyu H, Sato T, Hirao K, et al. Differences in clinical course between dementia with Lewy bodies and Alzheimers disease. Eur J Neurol Breitve MH, Chwiszczuk LJ, Hynninen MJ, et al. A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimers disease. Alzheimers Res Ther Matsui Y, Tanizaki Y, Arima H, et al. Incidence and survival of dementia in a general population of Japanese elderlythe Hisayama study. J Neurol Neurosurg Psychiatry Stubendorff K, Hansson O, Minthon L, et al. Differences in survival between patients with dementia with Lewy bodies and patients with Alzheimers diseasemeasured from a fixed cognitive level. Dement Geriatr Cogn Disord Lewy PubMed #1 "Lewy Body Disease" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body" CQ

12 AND "Disease Progression" MeshOR "Prognosis" MeshOR clinical course* OR progression OR prognosisor "Lewy Body Disease" MajrOR "Lewy body" OR "Lewy bodies"and dementia TI AND "Disease Progression" MeshOR "Prognosis" MeshOR clinical course* OR progression TIOR prognosis TI #1 Lewy /TH OR Lewy /TI OR /TIAND SHOR /TH OR /TI OR /AL Lewy

13 CQ 7 5 Lewy dementia with Lewy bodies DLB DLB A DLB behavioral and psychological symptoms of dementiabpsd 1 DLB DLB BPSD 診断 認知機能障害 (CQ7 6 参照 ) 認知症の行動 心理症状 (BPSD) (CQ7 7 参照 ) 自律神経障害 (CQ7 8 参照 ) パーキンソニズム (CQ7 9 参照 ) 認知機能の変動視空間認知障害遂行機能障害注意力障害処理速度の低下 幻覚妄想 1 興奮 2 うつ 3 アパシー レム期睡眠行動異常 (RBD) 日中の眠気 起立性低血圧 1 排尿障害 2 便秘 3 発汗障害 筋強剛寡動安静時振戦姿勢反射障害 7 Lewy 社会的交流 環境刺激 認知行動療法適切なケア ( パーソンセンタードケア ) コリンエステラーゼ阻害薬ドネペジル ( アリセプトは保険適用 ) リバスチグミン コリンエステラーゼ阻害薬 1 NMDA 受容体拮抗薬 ( メマンチン ) 2 抑肝散 1 2( 低カリウム血症に注意 ) 非定型抗精神薬 1 2 ( 過敏性に注意 ) SSRI/SNRI 3 日光浴など環境刺激日中の社会活動参加 クロナゼパム ( ラメルテオンドネペジルほか ) 臥床中頭部挙上 1 塩分摂取 1 弾性ストッキング 1 膀胱訓練 2 水 食物繊維摂取 3 ドロキシドパ 1 ミドドリン 1 フルドロコルチゾン 1 緩下剤 3 消化管蠕動改善薬 3 運動療法歩行 姿勢矯正訓練 抗 Parkinson 病薬レボドパドパミンアゴニスト (BPSD 悪化に注意 ) 1DLB 中の は症状 療の 1 の症状には 1 の薬剤 用 部の 療につ は適 用 CQ

14 3 DLB 2003 DLB 1 1McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodiesthird report of the DLB Consortium. Neurology PubMed #1 "Lewy Body Disease" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body" AND "Cognition Disorders/therapy" MeshOR cognition disorder* OR cognitive disorder*and therapy OR therapeutic OR treatment OR "Lewy Body Disease/drug therapy" MajrOR "Lewy body" TIOR "Lewy bodies" TI AND donepezil OR rivastigmine OR "Dementia/drug therapy" MajrAND "Parkinson Disease/ complications" Mesh AND "Cognition/drug effects" MajrOR cognitive function* OR cognitive assessment* OR cognitive subscale*and improve* #1 Lewy /TH OR Lewy /TI OR /TIAND /TH OR /TI OR /TIAND SH,,,,,,, OR /TH OR /TI OR /TI Lewy

15 CQ 7 6 Lewy dementia with Lewy bodies DLB DLB 1B DLB 1 DLB 10 randomized controlled trialrct clinical global impression of changecgic Parkinson cognitive impairment in Parkinsons diseasecindpd Parkinson Parkinsons disease with dementiapdddlb 6 PDD ADL DLB 1 2 Lewy DLB/PDD ChEI a. 4 DLB 5 mg10 mg Mini Mental State ExaminationMMSENeuropsychi atric InventoryNPI2 4 NPI10 10 mg 52 NPI4 5 BPSD CQ mg 10 mg 6 DLB Phase MMSE 10 mg 5 mg 7 PDD 8 Lewy CQ

16 診断 日常生活に支障があるか? はい *1 コリンエステラーゼ阻害薬 いいえ 定期的診察 生活環境整備 経過観察易怒性, 攻撃性など陽性の BPSD があるはい抑肝散, 場合により非定型抗精神病薬 *2 を考慮 早期から明確なパーキンソニズムを合併しているレボドパの併用 *3 を考慮はい *1 DLB にはアリセプトのみ保険適用. (PDD にはリバスチグミン, ドネペジルの有効性のエビデンスがあるが, わが国での保険適用なし ) *2 過敏症に十分に注意する. *3 幻視 妄想などの精神症状の増悪に注意する. 1DLB/PDD b. DLB RCT MMSE 9 PDD RCT Alzheimers Disease Assessment Scale cognitive subscaleadascog 10 PDD EFNS 1 A AAN 2 B 11 c. DLB 24 ADAScog NMDA 72 DLB PDD 24 RCT AQT CGIC Wang 1 Matsunaga 14 1Wang HF, Yu JT, Tang SW, et al. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinsons disease, Parkinsons disease dementia, and dementia with Lewy bodiessystematic review with metaanalysis and trial sequential analysis. J Neurol Neurosurg Psychiatry Rolinski M, Fox C, Maidment I, et al. Cholinesterase inhibitors for dementia with Lewy bodies, Parkinsons disease dementia and cognitive impairment in Parkinsons disease. Cochrane Database Syst Rev CD Lewy

17 3Matsunaga S, Kishi T, Yasue I, Iwata N. Cholinesterase Inhibitors for Lewy Body DisordersA MetaAnalysis. Int J Neuropsychopharmacol Mori E, Ikeda M, Kosaka K. Donepezil for dementia with Lewy bodiesa randomized, placebocontrolled trial. Donepez ildlb Study Investigators. Ann Neurol Ikeda M, Mori E, Kosaka K, et al.donepezildlb Study Investigators. Longterm safety and efficacy of donepezil in patients with dementia with Lewy bodiesresults from a 52week, openlabel, multicenter extension study. Dement Geriatr Cogn Disord Mori E, Ikeda M, Nagai R, et al. Longterm donepezil use for dementia with Lewy bodiesresults from an openlabel extension of Phase III trial. Alzheimers Res Ther Ikeda M, Mori E, Matsuo K, et al. Donepezil for dementia with Lewy bodiesa randomized, placebocontrolled, confir matory phase III trial. Alzheimers Res Ther Dubois B, Tolosa E, Katzenschlager R, et al. Donepezil in Parkinsons disease dementiaa randomized, doubleblind efficacy and safety study. Mov Disord McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodiesa randomised, doubleblind, placebocontrolled international study. Lancet Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinsons disease. N Engl J Med Poewe W, Gauthier S, Aarsland D, et al. Diagnosis and management of Parkinsons disease dementia. Int J Clin Pract Edwards K, Royall D, Hershey L, et al. Efficacy and safety of galantamine in patients with dementia with Lewy bodiesa 24week openlabel study. Dement Geriatr Cogn Disord Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinsons disease dementia or dementia with Lewy bodiesa doubleblind, placebocontrolled, multicentre trial. Lancet Neurol Matsunaga S, Kishi T, Iwata N. Memantine for Lewy body disorderssystematic review and metaanalysis. Am J Geriatr Psychiatry PubMed #1 "Lewy Body Disease" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body" AND "Cognition Disorders/therapy" MeshOR cognition disorder* OR cognitive disorder*and therapy OR therapeutic OR treatment OR "Lewy Body Disease/drug therapy" MajrOR "Lewy body" TIOR "Lewy bodies" TI AND donepezil OR rivastigmine OR "Dementia/drug therapy" MajrAND "Parkinson Disease/ complications" Mesh AND "Cognition/drug effects" MajrOR cognitive function* OR cognitive assessment* OR cognitive subscale*and improve* #1 Lewy /TH OR Lewy /TI OR /TIAND /TH OR /TI OR /TIAND SH,,,,,,, OR /TH OR /TI OR /TI 7 Lewy CQ

18 CQ 7 7 Lewy dementia with Lewy bodies DLB behavioral and psychological symptoms of dementiabpsd REM sleep behavior disorderrbd 1BPSD 2RBD 2C DLB BPSD DLB BPSD 1 5 mg10 mg 12 Neuropsychiatric Inven torynpi2 NPI4 1 DLB BPSD 2 randomized controlled trialrct NPI4 3 BPSD DLB 63 4 NPI 4 DLB BPSD 5 DLB BPSD 6 DLB 7 Parkinson DLB Lewy

19 mg/ 8 DLB DLB 23 PDD 9 Alzheimer mg 120 mg/ PDD mg/ 31 DLB citalopram 12 Mini Mental State ExaminationMMSE 65% 11 Alzheimer 29 DLB 12 5 mg/ DLB 8 DLB mg/2 BPSD mg/ 13 DLB BPSD RBD RBD mg/ 14 DLB DLB DLB DLB Mori E, Ikeda M, Kosaka K, et al. Donepezil for dementia with Lewy bodiesa randomized, placebocontrolled trial. Ann Neurol Ikeda M, Mori E, Matsuo K, et al. Donepezil for dementia with Lewy bodiesa randomized, placebocontrolled, confir matory phase III trial. Alzheimers Res Ther McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodiesa randomised, doubleblind, placebocontrolled international study. Lancet Iwasaki K, Kosaka K, Mori H, et al. Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan, a traditional Japanese medicine. Psychogeriatrics Emre M, Tsolaki M, Bonuccelli U, et al. Memantine for patients with Parkinsons disease dementia or dementia with Lewy bodiesa randomised, doubleblind, placebocontrolled trial. Lancet Neurol McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodiesthird report of the DLB Consortium. Neurology Takahashi H, Yoshida K, Sugita T, et al. Quetiapine treatment of psychotic symptoms and aggressive behavior in patients with dementia with Lewy bodiesa case series. Prog Neuropsychopharmacol Biol Psychiatry Kurlan R, Cummings J, Raman R, et al. Quetiapine for agitation or psychosis in patients with dementia and parkinsonism. Neurology Lewy CQ

20 10Workman RH Jr, Orengo CA, Bakey AA, et al. The use of risperidone for psychosis and agitation in demented patients with Parkinsons disease. J Neuropsychiatry Clin Neurosci Culo S, Mulsant BH, Rosen J, et al. Treating neuropsychiatric symptoms in dementia with Lewy bodiesa randomized controlledtrial. Alzheimer Dis Assoc Disord Cummings JL, Street J, Masterman D, et al. Efficacy of olanzapine in the treatment of psychosis in dementia with Lewy bodies. Dement Geriatr Cogn Disord Walker Z, Grace J, Overshot R, et al. Olanzapine in dementia with Lewy bodiesa clinical study. Int J Geriatr Psychiatry Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorderdemographic, clinical and laboratory findings in 93 cases. Brain Pt Shinno H, Kamei M, Nakamura Y, et al. Successful treatment with YiGan San for rapid eye movement sleep behavior disorder. Prog Neuropsychopharmacol Biol Psychiatry Nomura T, Kawase S, Watanabe Y, et al. Use of ramelteon for the treatment of secondary REM sleep behavior disorder. Intern Med Ringman JM, Simmons JH. Treatment of REM sleep behavior disorder with donepezila report of three cases. Neurology Ramelteon Shinno H, Inami Y, Inagaki T, et al. Effect of YiGan San on psychiatric symptoms and sleep structure at patients with behavioral and psychological symptoms of dementia. Prog Neuropsychopharmacol Biol Psychiatry PubMed #1 "Lewy Body Disease" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body" AND "behavioral psychological symptom dementia" OR BPSDAND therapy OR therapeutic OR treatmentor "Behavioral Symptoms/therapy" MeshOR "REM sleep" OR sleep disorder*and therapy OR therapeutic OR treatment OR "Sleep Disorders/therapy" Mesh OR "Lewy Body Disease/psychology" MeshOR "Lewy body" TIOR "Lewy bodies" TI AND dementia TI AND mental impairment* OR behavioural symptom* TI AND "Lewy Body Disease/drug therapy" MajrOR "Delusions/drug therapy" MajrOR "Psychotic Disorders/drug therapy" MajrOR "Dementia/drug therapy" MajrAND "Dementia/psychology" Mesh OR "REM Sleep Behavior Disorder/drug therapy" MajrOR "REM Sleep Behavior Disorder/drug therapy" MeshAND "REM Sleep Behavior Disorder/physiopathology" Mesh AND "Nootropic Agents" MeshOR "Antipsychotic Agents" MeshOR "Drugs, Chinese Herbal" MeshOR "Dibenzothiazepines" MeshOR "Anticonvulsants" Mesh OR "Clonazepam" MeshOR "Cholinesterase Inhibitors" Mesh #1 Lewy /TH OR Lewy /TI OR /TIAND SH,,,,,,, OR /TH OR /TI OR /TIAND /TH OR /TI OR /TH OR /TI OR /TH OR /TI OR /TH OR /TI Lewy

21 CQ 7 8 Lewy dementia with Lewy bodies DLB DLB Parkinson Parkinsons diseasepd 2C DLB PD PD 1 29 DLB 97%83% 66%28% mmhg 10 mmhg α PD 5 DLB PD DLB 6 selective sero tonin reuptake inhibitorsssri serotoninnorepinephrine reuptake inhibitorsnri M2 7 7 Lewy CQ

22 1 ABCDEF A Abdominal binder B Bolus treatment and headofbed up C Counter maneuvers to raise orthostatic BP D Drugs E Education F Fluid and salt DLB Low PA, Tomalia VA. Orthostatic HypotensionMechanisms, Causes, Management. J Clin Neurol Low PA, Tomalia VA. Orthostatic HypotensionMechanisms, Causes, Management. J Clin Neurol Horimoto Y, Matsumoto M, Akatsu H, et al. Autonomic dysfunctions in dementia with Lewy bodies. J Neurol Pathak A, Senard JM. Pharmacology of orthostatic hypotension in Parkinsons diseasefrom pathophysiology to manage ment. Expert Rev Cardiovasc Ther Henry R, Rowe J, OMahony D. Haemodynamic analysis of efficacy of compression hosiery in elderly fallers with ortho static hypotension. Lancet Woitalla D, Kassubek J, Timmermann L, et al. Reduction of gastrointestinal symptoms in Parkinsons disease after a switch from oral therapy to rotigotine transdermal patcha noninterventional prospective multicenter trial. Parkinsonism Relat Disord Orme S, Morris V, Gibson W, et al. Managing urinary incontinence in patients with dementiapharmacological treatment options and considerations. Drugs Aging Sakakibara R, Uchiyama T, Yoshiyama M, et al. Preliminary communicationurodynamic assessment of donepezil hydro chloride in patients with Alzheimers disease. Neurourol Urodyn PubMed #1 "Lewy Body Disease" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body" AND "Autonomic Nervous System Diseases/therapy" MeshOR "Constipation/therapy" MeshOR "Hyperhidrosis/ therapy" Mesh OR "Dysuria/therapy" Mesh OR autonomic dysfunction* OR orthostatic hypotensi* OR constipation* OR hyperhidrosis OR dysuriaand therapy OR therapeutic OR treatmentor "Parkinson Disease/ therapy" MajrOR Parkinsons disease*and orthostatic hypotensi* OR GI symptom* OR GI complaint*and improve*or "Urination Disorders/drug therapy" MajrOR "Urinary Bladder Diseases/drug therapy" Majr #1 Lewy /TH OR Lewy /TI OR /TIAND /TH OR /TI OR /TI OR /TI OR /TH OR /TI OR /TH OR /TI OR /TI OR /TH OR /TI Lewy

23 CQ 7 9 Lewy dementia with Lewy bodies DLB DLB 2C DLB randomized controlled trial RCTParkinson Parkinsons diseasepd 1,2 PD 2 DLB 2 3,4 5 DLB 6 PD 7 7 1Molloy S, McKeith IG, OBrien JT, et al. The role of levodopa in the management of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodiesthird report of the DLB Consortium. Neurology Ahlskog JE, Muenter MD. Frequency of levodoparelated dyskinesias and motor fluctuations as estimated from the cumu lative literature. Mov Disord Hong JY, Oh JS, Lee I, et al. Presynaptic dopamine depletion predicts levodopainduced dyskinesia in de novo Parkinson disease. Neurology Whone AL, Watts RL, Stoessl AJ, et al. Slower progression of Parkinsons disease with ropinirole versus levodopathe REALPET study. Ann Neurol Goldman JG, Goetz CG, Brandabur M, et al. Effects of dopaminergic medications on psychosis and motor function in dementia with Lewy bodies. Mov Disord Moretti DV, Binetti G, Zanetti O, et al. Nonergot dopamine agonist rotigotine as a promising therapeutic tool in atypical parkinsonism syndromesa 24 months pilot observational openlabel study. Neuropharmacology Lewy CQ

24 PubMed #1 "Lewy Body Disease" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body" AND "Parkinsonian Disorders/therapy" MeshOR "Neurologic Manifestations/therapy" MeshOR Parkinsonian disorder* OR Parkinsonism OR dyskinesia OR motor dysfunction*and therapy OR therapeutic OR treatment OR "Parkinson Disease/drug therapy" MajrOR Parkinson disease* TIABOR Parkinsons disease* TIABAND therapy TIABOR intervention* TIABAND "Lewy Body Disease/drug therapy" MeshOR "Lewy body" TIOR "Lewy bodies" TI AND dementia TIAND therapy TIOR management TI OR "Dyskinesias" MajrOR dyskinesia* TI #1 Lewy /TH OR Lewy /TI OR /TIAND SH,,,,,,, OR /TH OR /TI OR /TIAND /TH OR /TI OR Parkinson /TI OR /TI OR /TH OR /TI OR /TH OR /TI Lewy

25 CQ 7 10 Lewy dementia with Lewy bodies DLB DLB D DLB DLB behavioral and psychological symptoms of dementiabpsd 1 DLB BPSD 2 3 BPSD 4 DLB DLB 1,5 Parkinson DLB 7 1McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodiesthird report of the DLB Consortium. Neurology Ballard C, Aarsland D, Francis P, et al. Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodiespathophysiology, clinical features, and pharmacological management. Drugs Aging Boot BP, McDade EM, McGinnis SM, et al. Treatment of dementia with Lewy bodies. Curr Treat Options Neurol Brodaty H, Arasaratnam C. Metaanalysis of nonpharmacological interventions for neuropsychiatric symptoms of dementia. Am J Psychiatry Kudo Y, Imamura T, Sato A, et al. Risk factors for falls in communitydwelling patients with Alzheimers disease and dementia with Lewy bodieswalking with visuocognitive impairment may cause a fall. Dement Geriatr Cogn Disord Lewy PubMed CQ

26 #1 "Lewy Body Disease/therapy" MeshOR Lewy body disease* OR "Lewy body dementia" OR "dementia with Lewy body"and therapy OR therapeutic OR treatment OR rehabilitation OR intervention* AND "Rehabilitation" MeshOR rehabilitation* OR "Psychotherapy" MeshOR "Social Support" MeshOR psychosocial intervention* OR "Lewy Body Disease/therapy" MeshOR "Lewy body" TIOR "Lewy bodies" TIAND dementia TI AND therapy TIOR management TI AND specific intervention* OR nonpharmacologic OR cognitive behavioral intervention*or "Dementia/therapy" MajrAND "Phototherapy" Mesh #1 Lewy /TH OR Lewy /TI OR /TIAND SHOR /TH OR /TI OR /TH OR /TI OR /TI OR /TI OR /TI OR /TH OR /TI OR /TI OR /TI Lewy