認知症診療ガイドライン2017_200_第2章.indd

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1 2 behavioral and psychological symptoms of dementia BPSD BPSD BPSD 18 2

2 2 1,2 1 CQ frontotemporal lobar degeneration FTLD 3. 3 a. CQ

3 1 1 Alzheimer Lewy Alzheimer Alzheimer Lewy Alzheimer Lewy Alzheimer Alzheimer b. 20 2

4 2 想起する時期 即時 出来事記憶 ( 短期 ) 記憶 近時記憶 遠隔記憶 刺激 ~ 数秒程度 ~ 数日程度 1 出来事記憶 る ~ 年 1 c CQ2 6 Sylvius 5. Alzheimer Lewy Lewy posterior cortical atrophy PCA Alzheimer 6. CQ

5 7. 1 Sachdev PS, Blacker D, Blazer DG, et al. Classifying neurocognitive disorders the DSM 5 approach. Nat Rev Neurol DSM

6 2 2 2 behavioral and psycholog ical symptoms of dementia BPSD BPSD CQ BPSD 1 3 European Alzheimer Disease Consortium 2,354 Alzheimer Neuropsychiatric Inventory NPIBPSD hyperactivity psychosis affective symptoms apathy 4 4,5 BPSD 1. agitation irritability frontotemporal lobar degeneration FTLD 2. Alzheimer Lewy dementia with Lewy bodies DLB DLB BPSD CQ

7 3. Alzheimer Alzheimer DLB DLB DLB 4. FTLD Alzheimer Alzheimer BPSD DLB FTLD 1 Cerejeira J, Lagarto L, Mukaetova Ladinska EB. Behavioral and psychological symptoms of dementia. Front Neurol Finkel SI, Costa e Silva J, Cohen G, et al. Behavioral and psychological signs and symptoms of dementia a consensus statement on current knowledge and implications for research and treatment. Int Psychogeriatr Suppl Ikeda M, Fukuhara R, Shigenobu K, et al. Dementia associated mental and behavioural disturbances in elderly people in the community findings from the first Nakayama study. J Neurol Neurosurg Psychiatry Aalten P, Verthey FRJ, Boziki M, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium Part. Dement Geriatr Cogn Disord Aalten P, Verthey FRJ, Boziki M, et al. Consistency of neuropsychiatric syndromes across dementias results from the European Alzheimer Disease Consortium. Part. Dement Geriatr Cogn Disord

8 2 Mini Mental State Examination MMSE 2 3 2C CQ MMSE MMSE 1 HDS R MMSE HDS R MMSE 20 mild cognitive impairment MCIMontreal Cognitive Assessment Japanese version MoCA J Addenbrooke s Cognitive Examination Revised ACE R151 CQ4B 4 MMSE 2 Alzheimer s Disease Assessment Scale cognitive subscale Japanese version ADAS Jcog Alzheimer Alzheimer 1 Severe Impairment Battery SIB 3,4 Severe Cognitive Impairment Rating Scale SCIRS 5,6 CQ

9 1 MMSE HDS R MoCA J MoCA ACE ACE R N D test N COGNISTAT COGNISTAT ADAS Jcog Alzheimer SIB SIB WAIS Wechsler 3 RCPM Raven JART JART WMS R Wechsler RBMT Rivermead ROCFT Rey BVRT Benton S PA WAB WAB SLTA ROCFT Rey Kohs Kohs VPTA CAT BIT BIT TMT FAB Frontal Assessment Battery WCST Wisconsin BADS BADS Velayudhan L, Ryu SH, Raczek M, et al. Review of brief cognitive tests for patients with suspected dementia. Int Psycho geriatr Wouters H, Appels B, van der Flier WM, et al. Improving the accuracy and precision of cognitive testing in mild dementia. J Int Neuropsychol Soc Saxton J, McGonigle Gibson KL, Swihart A, et al. Assessment of the severely impaired patient description and validation of a new neuropsychological test battery. Psychol Assess SIB ADCS ADL Choe JY, Youn JC, Park JH, et al. The Severe Cognitive Impairment Rating Scale an instrument for the assessment of cognition in moderate to severe dementia patients. Dement Geriatr Cogn Disord Severe Cognitive Impairment Rating Scale

10 2 PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis OR diagnoses OR diagnostic OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR cognitive disorder* TI AND diagnosis OR diagnoses OR diagnostic AND "Neuropsychological Tests" Majr OR neuropsychological test* TI OR "Psychiatric Status Rating Scales" Majr OR assessment scale* TI #1 /TH OR /TI OR /TH OR /TI OR /TI AND /TH OR /TI OR /TI OR /TH OR /TI CQ

11 CQ 2 4 behavioral and psycholog ical symptoms of dementia BPSD activities of daily living ADL BPSD Neuropsychiatric Inventory NPI ADL Physical Self Maintenance Scale PSMS Clinical Dementia Rating CDR 2C BPSD ADL 1 1. BPSD NPI NPI NPI Q 1 NPI NHBehavioral Pathology in Alzheimer s Disease Behave AD25 4 Cohen Mansfield Agitation Inventory CMAI 29 agitated behavior 7 Behave AD Stereotypy Rating Inventory SRI frontotemporal lobar degeneration FTLD 2. ADL ADL PSMS ADL 6 Instrumental Activities of Daily Living Scale IADL ADL 8 2 Alzheimer s Disease Cooper 28 2

12 2 Study Activities of daily living inventory ADCS ADL 19 ADCS ative ADL severe N N ADL Alzheimer Disability Assessment for Dementia DAD 3. CDR CDR 0.5 MCI CDR 6 3 N 5 10 Clinician s Interview Based Impression of Change plus Caregiver Input CIBIC plus ADL 3 Mental Function Impairment Scale MENFISDAD Behave AD 1 Neuropsychiatric Inventory NPI ADL Behavioral Pathology in Alzheimer s Disease Behave AD Cohen Mansfield Agitation Inventory CMAI Stereotypy Rating Inventory SRI Physical Self Maintenance Scale PSMS Instrumental Activities of Daily Living Scale IADL N N ADL Alzheimer s Disease Cooperative Study Activities of daily living inventory ADCS ADL Disability Assessment for Dementia DAD Erlangen Test of Activities of Daily Living E ADL Test Direct Assessment of Functional Status DAFS Direct Assessment of Functional Abilities DAFA Test of Everyday Functional Abilities TEFA Independent Living Scales ILS Clinical Dementia Rating CDR N NM Clinician s Interview Based Impression of Change plus Caregiver Input CIBIC plus CQ

13 1 Luttenberger K, Schmiedeberg A, Graessel E. Activities of daily living in dementia revalidation of the E ADL test and suggestions for further development. BMC Psychiatry Sikkes SA, de Lange de Klerk ES, Pijnenburg YA, et al. A systematic review of instrumental activities of daily living scales in dementia room for improvement. J Neurol Neurosurg Psychiatry Duara R, Loewenstein DA, Greig Custo MT, et al. Diagnosis and staging of mild cognitive impairment, using a modifica tion of the clinical dementia rating scale the mcdr. Int J Geriatr Psychiatry Nakamura Y, Usui M, Nishikawa T, et al. CIBIC Plus J assessment using a videotaped method in Alzheimer s disease patients. Dement Geriatr Cogn Dis Extra PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis OR diagnoses OR diagnostic OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR cognitive disorder* TI AND diagnosis OR diagnoses OR diagnostic AND "Neuropsychological Tests" Majr OR neuropsychological test* TI OR "Psychiatric Status Rating Scales" Majr OR assessment scale* TI #1 /TH OR /TI OR /TH OR /TI OR /TI AND /TH OR /TI OR /TI OR /TH OR /TI 30 2

14 2 2 5 quality of life QOL CQ QOL 2C QOL QOL QOL 1 QOL 1 2 QOL Medical Outcome Study Short Form 36 Item Health Survey SF 36EuroQol Instrument EQ 5D 1 QOL 15 3 QOL 1 QOL Medical Outcome Study Short Form 36 Item Health Survey SF 36 EuroQol Instrument EQ 5D WHO QOL 26 Quality of Life in Alzheimer s Disease QoL AD Dementia Quality of Life DQOL Bath Assessment of Subjective Quality of Life in Dementia BASQID QOL D Dementia Care Mapping DCM Alzheimer s Disease Related Quality of Life ADRQL Quality of Life Measure for People with Dementia QUALIDEM CQ

15 Quality of Life in Alzheimer s Disease QoL AD 4 Alzheimer 5 QOL Dementia Quality of Life DQOL 6,7 QOL Bath Assessment of Subjective Quality of Life in Dementia BASQID 8 QOL D 9 QOL Alzheimer s Disease Related Quality of Life ADRQL 10 QOL Quality of Life Measure for People with Dementia QUALIDEM 11 Dementia Care Mapping DCM 12,13 1 Smith S, Lamping D, Banerjee S, et al. Measurement of health related quality of life for people with dementia develop ment of a new instrument DEMQOL and an evaluation of current methodology. Health Technol Assess Gräske J, Meyer S, Wolf Ostermann K. Quality of life ratings in dementia care across sectional study to identify factors associated with proxy ratings. Health Qual Life Outcomes Perales J, Cosco TD, Stephan BC, et al. Health related quality of life in the Cambridge City over 75s Cohort CC75C development of a dementia specific scale and descriptive analyses. BMC Geriatr Logston RG, Gibbons LE, McCurry SM, et al. Quality of life in Alzheimer s disease patient and caregiver reports. J Ment Health Aging Matsui T, Nakaaki S, Murata Y, et al. Determinants of the quality of life in Alzheimer s disease patients as assessed by the Japanese version of the Quality of Life Alzheimer s disease scale. Dement Geriatr Cogn Disord Brod M, Stewart AL, Sands L, et al. Conceptualization and measurement of quality of life in dementia the dementia quality of life instrument DQoL. Gerontologist Dementia Quality of Life Instrument Trigg R, Skevington SM, Jones RW. How can we best assess the quality of life of people with dementia? the Bath Assess ment of Subjective Quality of Life in Dementia BASQID. Gerontologist Terada S, Ishizu H, Fujisawa Y, et al. Development and evaluation of a health related quality of life questionnaire for the elderly with dementia in Japan. Int J Geriatr Psychiatry Rabins PV, Kasper JD, Kleinman L, et al. Concepts and methods in the development of the ADRQL an instrument for assessing health related quality of life in persons with Alzheimer s disease. J Ment Health Aging Ettema TP, Dröes RM, de Lange J, et al. QUALIDEM development and evaluation of a dementia specific quality of life instrumentvalidation. Int J Geriatr Psychiatry Kitwood T, Bredin K. Towards a theory of dementia care personhood and well being. Ageing Soc Dawn Brooker Quality of life Dementia Care Mapping DCMWell being and Ill being Value WIB PubMed #1 "Dementia" Majr OR dementia TI OR "Cognition Disorders" Majr OR cognition disorder* TI OR cognitive disorder* TI AND "Neuropsychological Tests" Majr OR neuropsychological test* TI OR "Psychiatric Status Rating Scales" Majr OR scale* TIAND "Quality of Life" Majr OR "quality of life" TI #1 /TH OR /TI OR /TH OR /TI OR /TI AND /TH OR /TI OR /TI OR /TH OR /TI AND / TH OR /TI OR "Quality of Life"/TI 32 2

16 2 2 6 primary progressive aphasia PPA 1/23 C CQ 1 3 MRI SPECT/PET / 1 / / / / PPA 2,3 / / / PPA Western Aphasia Battery WAB 4,5 PPA3 1/3 2 5,6 PPA / frontotemporal lobar degenera tion FTLD 77% 51% TDP 43 26%Alzheimer 21% FTLD CQ

17 1 / MRI SPECT/PET / Sylvius Sylvius Gorno Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology %15% TDP 43 73%Alzheimer 12% FTLD 36% 11% TDP 43 24%Alzheimer 56% 7,8 / FTLD tau FTLD TDP Alzheimer 1 Gorno Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology Josephs KA, Duffy JR, Strand EA, et al. Characterizing a neurodegenerative syndrome primary progressive apraxia of speech. Brain Josephs KA, Duffy JR, Strand EA, et al. Syndromes dominated by apraxia of speech show distinct characteristics from agrammatic PPA. Neurology Ash S, Evans E, O Shea J, et al. Differentiating primary progressive aphasias in a brief sample of connected speech. Neurology Wicklund MR, Duffy JR, Strand EA, et al. Quantitative application of the primary progressive aphasia consensus criteria. Neurology Botha H, Duffy JR, Whitwell JL, et al. Classification and clinicoradiologic features of primary progressive aphasia PPA and apraxia of speech. Cortex Harris JM, Gall C, Thompson JC, et al. Classification and pathology in primary progressive aphasia. Neurology Harris JM, Jones M. Pathology in primary progressive aphasia syndromes. Curr Neurol Neurosci Rep

18 2 PubMed #1 "Aphasia, Primary Progressive/classification" Majr OR "primary progressive aphasia" TI AND classification OR "Aphasia, Primary Progressive/diagnosis" Mesh OR "primary progressive aphasia" TI AND diagnosis OR diagnoses OR diagnostic AND "Neuropsychological Tests" Mesh OR neuropsychological test* TI AND assessment* OR "Aphasia, Primary Progressive/diagnosis" Majr OR "primary progressive aphasia" TI AND diagnosis OR diagnoses OR diagnostic OR "Aphasia, Primary Progressive/diagnosis" Mesh OR "primary progressive aphasia" TI AND diagnosis OR diagnoses OR diagnostic AND "Neuropsychological Tests" Mesh OR neuropsychological test* TI AND three variant* OR variant* AND criteria TI OR "Diagnosis, Differential" Mesh OR "differential diagnosis" TI OR classification TI OR classification SH OR assessment* TI #1 /TH OR /TI AND /TH OR /AL OR /AL OR /AL OR /TH OR /AL OR /AL CQ

19 CQ 2 7 CT MRI 2 1,2 10 ICD DSM 5 4 /Alzheimer National Institute on Aging Alzheimer s Association workgroup NIA AA 5 CT MRI 6 8 B 12 human immunodeficiency virus HIV 6 8 1,

20 2 認知症 ( 広義 ) の疑い 除外 除外 加齢に伴う健忘 ( 正常範囲内 ) 軽度認知障害 除外薬剤誘発性, 意識障害 ( せん妄など ) うつ病, 妄想性障害, 特殊なてんかん 鑑別 内科的疾患 : 代謝性疾患, 内分泌系疾患, 感染症, アルコール性などによる認知症外科的疾患 : 正常圧水頭症, 慢性硬膜下出血, 脳腫瘍など 認知症 ( 変性性 血管性 ) の疑い 鑑別 変性性認知症を臨床症状, 画像 検査所見により鑑別 鑑別 鑑別 画像上, 脳血管障害の存在脳血管病変の部位に一致した認知機能障害 神経症状段階的進行 Alzheimer 型認知症 : 出来事記憶障害取り繕い, 物盗られ妄想画像上, 側頭葉内側の萎縮が目立つ FTLD: 限局性脳萎縮 ( 前頭 側頭葉 ) 性格変化や反道徳的行為失語症, 記憶障害は比較的軽度 VaD 鑑別 DLB: 幻視, 症状が動揺性錐体外路徴候 鑑別 鑑別 CJD: 進行が速いミオクローヌス脳波上の PSD DWl における大脳皮質の高信号 他の神経変性疾患 (PSP,CBD,HD など ) 1 VaD vascular dementia, FTLD frontotemporal lobar degeneration, DLB dementia with Lewy bodies, CJD Creutzfeldt Jakob disease, PSD periodic synchronous discharge, DWI diffusion weighted image, PSP progressive supranuclear palsy, CBD corticobasal degeneration, HD Huntington s disease 1 Galvin JE, Sadowsky CH. Practical guidelines for the recognition and diagnosis of dementia. J Am Board Fam Med Moore A, Patterson C, Lee L, et al. Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia recommendations for family physicians. Can Fam Physician World Health Organization. International Statistical Classification of Diseases and Related Health Problems. 10th Revision. Geneva World Health Organization American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM 5. Arlington, VA American Psychiatric Association McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer s disease recommenda tions from the National Institute on Aging Alzheimer s Association workgroups on diagnostic guidelines for Alzheimer s disease. Alzheimers Dement Noel Storr AH, McCleery JM, Richard E, et al. Reporting standards for studies of diagnostic test accuracy in dementia The STARDdem Initiative. Neurology Sorbi S, Hort J, Erkinjuntti T, et al. EFNS ENS Guidelines on the diagnosis and management of disorders associated with dementia. Eur J Neurol Ngo J, Holroyd Leduc JM. Systematic review of recent dementia practice guidelines. Age Ageing CQ

21 PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis TI OR diagnoses TI OR diagnostic TI OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR "cognitive dysfunction" TI AND diagnosis TI OR diagnoses TI OR diagnostic TI AND "Diagnosis, Differential" Majr OR "differential diagnosis" TI OR "Diagnostic Errors" Majr OR diagnostic error* TI OR misdiagnosis TI #1 /MTH OR /TI OR /MTH OR /TI AND SH,,, X,, OR /TH OR /TI AND /MTH or /TI or /MTH or /TI 38 2

22 2 CT/MRI MRI SPECT MIBG 2 8 1B CQ CT/MRI 1 MRI CT MRI 1 2 MRI 2 2 MRI T1 T2 FLAIR 3 Creutzfeldt Jakob T2 * susceptibility weighted imaging SWI voxel based morphometry VBM voxel based specific regional analysis system for Alzheimer s disease VSRAD VSRAD Z Alzheimer Z SPECT SPECT 123 I IMP 99m Tc ECD SPECT 3D SSP ezis Alzheimer 4 FDG PET SPECT 5 Lewy MIBG MIBG I FP CIT Lewy Alzheimer β Aβ 7 Aβ 11 C PIB 18 F Florbetapir 18 F Flutemetamol 18 F Florbe taben 8 PET CQ6 6 CQ

23 Alzheimer 型認知症, DLB, 他の変性疾患もしくは血管性認知症 びまん性 あり あり 大脳萎縮 あり なし あり 正常加齢軽度認知障害早期 DLB bvftd CBD 前頭葉 限局性葉性 側頭葉 テント下 頭頂葉 / 後頭葉 海馬限局 中脳を含む Alzheimer 型認知症, HS( 非対称性 ) MAPT( 前方 > 後方 ) 左右差あり PNFA ( 後部前頭葉 島回萎縮 ) 左右差あり SD,LPA( 後方 > 前方 ) bvftd( 前方 > 後方 ) PCA,CBD,DLB 1 DLB dementia with Lewy bodies, bvftd behavioral variant frontotemporal dementia, CBD corticobasal degeneration, PNFA progressive nonfluent aphasia, SD semantic dementia, PCA posterior cortical atrophy, PSP progressive supranuclear palsy, MAPT microtubule associated protein tau, HS hippocampal sclerosis Harper L, Barkhof F, Scheltens P, et al. An algorithmic approach to structural imaging in dementia. J Neurol Neurosurg Psychiatry PSP MR アーチファクト : flow voids や側頭骨由来の信号 信号変化の評価 石灰化鉄沈着 ( 微小出血以外 ) デオキシヘモグロビン出血性転移性腫瘍びまん性軸索障害 厳密に葉性に分布 (1 つ以上 ) 脳微小出血 T2 * 低信号 加えて / もしくは 加えて / もしくは DWI 高信号 FLAIR/T2 高信号領域 あり なし あり 血管性変化らしくない 優位半球における脳動脈領域, 連合野, 分水嶺領域 大脳白質に分布戦略的部位局在視床 ( 両側 ) 脳小血管病による VCI CAA 深部脳領域 ( 基底核, 視床, 脳幹 ) 線条体もしくは新皮質 血管性らしい白質病変 加えて / もしくは 多巣性 融合性高信号領域 感染, 炎症, 脱髄性疾患, 白質ジストロフィーもしくは白質脳症 単一穿通枝領域 最近の深部小梗塞 高血圧性脳小血管病 CJD 深部灰白質に分布 ( 視床を含む基底核 ) 脳小血管病による VCI 側頭葉極の病変 加えて FLAIR 画像で中心性の脳脊髄液信号と周囲を取り囲む高信号 血管性らしい皮質下高信号領域 CADASIL 血管性病変によるラクナ梗塞 2 MRI FLAIR fluid attenuated inversion recovery, CAA cerebral amyloid angiopathy, CADASIL cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, CJD Creutzfeldt Jakob disease, VCI vascular cognitive impairment Harper L, Barkhof F, Scheltens P, et al. An algorithmic approach to structural imaging in dementia. J Neurol Neurosurg Psychiatry

24 2 11C PBB3 18F T F THK Filippi M, Agosta F, Barkhof F, et al. EFNS task force the use of neuroimaging in the diagnosis of dementia. Eur J Neurol e131 e Harper L, Barkhof F, Scheltens P, et al. An algorithmic approach to structural imaging in dementia. J Neurol Neurosurg Psychiatry Mortimer AM, Likeman M, Lewis TT. Neuroimaging in dementia a practical guide. Pract Neurol Yeo JM, Lim X, Khan Z, et al. Systematic review of the diagnostic utility of SPECT imaging in dementia. Eur Arch Psychi atry Clin Neurosci Shivamurthy VK, Tahari AK, Marcus C, et al. Brain FDG PET and the diagnosis of dementia. AJR Am J Roentgenol W76 W85. 6 King AE, Mintz J, Royall DR. Meta analysis of 123I MIBG cardiac scintigraphy for the diagnosis of Lewy body related disorders. Mov Disord Pearson SD, Ollendorf DA, Colby JA. Amyloid β positron emission tomography in the diagnostic evaluation of alzheimer disease summary of primary findings and conclusions. JAMA Intern Med Johnson KA, Minoshima S, Bohnen NI, et al. Update on appropriate use criteria for amyloid PET imaging dementia experts, mild cognitive impairment, and education. Amyloid Imaging Task Force of the Alzheimer s Association and Society for Nuclear Medicine and Molecular Imaging. Alzheimers Dement e106 e109. PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis TI OR diagnoses TI OR diagnostic TI OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR "cognitive dysfunction" TI AND diagnosis TI OR diagnoses TI OR diagnostic TIAND "Diagnostic Imaging" Majr OR imaging TI OR neuroimaging TI OR MRI TI OR CT TI OR SPECT TI OR PET TI OR MIBG TI #1 /MTH OR /TI OR /MTH OR /TI AND SH,,, X,, OR /TH OR /TI AND /MTH or /TI or MRI/TI and CT/TI or SPECT/TI or PET/TI or MIBG/TI CQ

25 CQ 2 9 β42 Aβ42 Alzheimer B B 12 human immunodeficiency virus HIV 1 2 Alzheimer β42 Aβ42 3,4 Aβ42 Aβ PET 5 Alzheimer International Working Group IWG2 6 National Institute on Aging Alzheimer s Association work group NIA AA 7 Aβ42 Alzheimer Aβ42 1,2 1 Lewy Alzheimer α 8 Creutzfeldt Jakob

26 2 1 Alzheimer Aβ42 Alzheimer Lewy α Parkinson / FTLD TDP GRN Creutzfeldt Jakob RT QUIC RT QUIC real time quaking induced conversion 1 Ahmed RM, Paterson RW, Warren JD, et al. Biomarkers in dementia clinical utility and new directions. J Neurol Neurosurg Psychiatry Noel Storr AH, Flicker L, Ritchie CW, et al. Systematic review of the body of evidence for the use of biomarkers in the diagnosis of dementia. Alzheimers Dement e96 e Agarwal R, Tripathi CB. Diagnostic Utility of CSF Tau and Aβ 42 in Dementia A Meta Analysis. Int J Alzheimers Dis van Harten AC, Kester MI, Visser PJ, et al. Tau and p tau as CSF biomarkers in dementia a meta analysis. Clin Chem Lab Med Wurtman R. Biomarkers in the diagnosis and management of Alzheimer s disease. Metabolism Suppl 1 S Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer s disease the IWG 2 criteria. Lancet Neurol McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer s disease recommenda tions from the National Institute on Aging Alzheimer s Association workgroups on diagnostic guidelines for Alzheimer s disease. Alzheimers Dement Lim X, Yeo JM, Green A, et al. The diagnostic utility of cerebrospinal fluid alpha synuclein analysis in dementia with Lewy bodies a systematic review and meta analysis. Parkinsonism Relat Disord Mattsson N, Andreasson U, Persson S, et al. CSF biomarker variability in the Alzheimer s Association quality control program. Alzheimers Dement PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis TI OR diagnoses TI OR diagnostic TI OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR "cognitive dysfunction" TI AND diagnosis TI OR diagnoses TI OR diagnostic TIAND "Biological Markers" Majr OR biological marker* TI OR biomarker* TI OR "Hematologic Tests" Mesh OR hematologic test* TI OR blood test* TI OR "Cerebrospinal Fluid" Mesh OR "cerebrospinal fluid" TI OR "cerebrospinal fluid" SH #1 /MTH OR /TI OR /MTH OR /TI AND SH,,, X,, OR /TH OR /TI AND /MTH OR / TI OR /TI OR /TH OR /TI OR /TI OR /TH OR /TI CQ

27 CQ non pitting Behçet ,3 Argyll Robertson Wernicke Huntington Lewy Parkinson Creutzfeldt Jakob Alzheimer B 12 Lewy Lewy

28 2 1 Ames D, Burns A, O Brien J Dementia, Fourth edition. Boca Raton, Fl CRC Press Idiaquez J, Roman GC. Autonomic dysfunction in neurodegenerative dementias. J Neurol Sci PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis TI OR diagnoses TI OR diagnostic TI OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR "cognitive dysfunction" TI AND diagnosis TI OR diagnoses TI OR diagnostic TI AND "Physical Examination" Mesh OR physical examination* TI OR physical finding* TI #1 /MTH OR /TI OR /MTH OR /TI AND SH,,, X,, OR /TH OR /TI AND /MTH OR /TI OR /TI CQ

29 CQ B Alzheimer Parkinson 2 12% % Parkinson NSAIDs 4 5 GABA GABA 46 2

30 2 6 7 Beers Parkinson NSAIDs H 2 2 Parkinson γ CQ

31 2 HMG CoA B 2b 1 1a n1 D 3 base.html 1 Larson EB, Kukull WA, Buchner D, et al. Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med Moore AR, O Keeffe ST. Drug induced cognitive impairment in the elderly. Drugs Aging Brain Nerve Carrière I, Fourrier Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population the 3 city study. Arch Intern Med Rudolph JL, Salow MJ, ANgelini MC, et al. The anticholinergic risk scale and anticholinergic adverse effects in older 48 2

32 2 Arch Intern Med persons. 6 Billioti de Gage S, Bégaud B, Bazin F, et al. Benzodiazepine use and risk of dementia prospective population based study. BMJ e Zhong G, Wang Y, Zhang Y, et al. Association between Benzodiazepine use and dementia A meta analysis. PLoS One e Campanelli CM. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc menu_tenpu_base.html PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis TI OR diagnoses TI OR diagnostic TI OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR "cognitive dysfunction" TI AND diagnosis TI OR diagnoses TI OR diagnostic TI AND "Physiological Effects of Drugs" Mesh OR "Pharmacologic Actions/adverse effects" Mesh OR "Chemicals and Drugs Category" Majr AND "adverse effects" SH #1 /MTH OR /TI OR /MTH OR /TI AND SH,,, X,, OR /TH OR /TI AND SH,, OR /TH OR /MTH CQ

33 CQ 2 12 Mendel APOE Alzheimer Alzheimer APOE ε4 APOE Alzheimer Mendel 1 Alzheimer APP PSEN1 PSEN Alzheimer ,2 Lewy SNCA frontotemporal lobar degeneration FTLD 2 3 FTLD MAPT GRN 1 Alzheimer APOE 4 6 Alzheimer APOE ε4 Alzheimer APOE ε4 7 Alzheimer APOE 8,9 Alzheimer

34 2 1 Mendel 発症年Alzheimer OMIM* Amyloid precursor protein APP q21.3 APP Aβ, tauopathy Presenilin 1 PSEN q24.2 Presenilin 1 Aβ, tauopathy Presenilin 2 PSEN q42.13 Presenilin 2 Aβ, tauopathy OMIM* Microtubule asso ciated protein tau MAPT q21.31 tau tauopathy Progranulin GRN q21.31 progranulin, granulin TDP 43 prote inopathy Chromatin modi fying protein 2B CHMP2B p11.2 charged multive sicular body protein 2b P62 positive inclusion Valosin con taining protein VCP p13.3 transitional endoplasmic reticulum ATPase TDP 43 prote inopathy Chromosome 9 open reading frame 72 C9orf p21.2 chromosome 9 open reading frame 72 TDP 43 prote inopathy Lewy OMIM* α synuclein SNCA q22.1 α synuclein synucleinopathy OMIM* CADASIL NOTCH p13.12 Notch3 vasculopathy of small arteries CARASIL HTRA q26.13 Htra1 vasculopathy of small arteries * Online Mendelian Inheritance in Man CADASIL cerebral autosomal dominant arteriop athy with subcortical infarcts and leukoencephalopathy, CARASIL cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy [ 歳 ] 齢** ** PSEN1 (n=87) APP (n=23) MAPT (n=51) 1 Alzheimer FTDP 17 PSEN1 Alzheimer 44 8 APP 54 9 MAPT ** p 0.01 CQ

35 剖検なし ALS を伴わない認知症の家族歴あり 認知症と ALS の家族歴あり 家族歴なし bvftd PNFA bvftd SD CBS PSP 記憶障害 SD FTD ALS bvftd, PNFA,CBS, 記憶障害 頭頂葉症状を伴う 頭頂葉症状を伴わない 頭頂葉症状を伴う 頭頂葉症状を伴わない 研究的診断 MAPT,GRN, TARDBP,FUS, C9orf72 の検査を考慮 検査をしても変異はみつかりにくい 研究的検査もしくは検査を行わない GRN もしくは検査を行わない GRN MAPT GRN MAPT GRN MAPT GRN 陰性であれば MAPT 陰性であれば GRN 陰性であれば MAPT 陰性であれば GRN 陰性であれば MAPT 陰性であれば GRN 陰性であれば PSEN 1 2, APP 陰性であれば研究的検査 陰性であれば研究的検査 陰性であれば研究的検査 陰性であれば研究的検査 陰性であれば MAPT 2 ALS amyotrophic lateral sclerosis, bvftd behavioral variant frontotemporal dementia, CBS corticobasal syndrome, FTD frontotem poral dementia, FUS fused in sarcoma, MAPT microtubule associated protein tau, GRN progranulin, PNFA progressive nonfluent aphasia, PSP progressive supranuclear palsy, SD semantic dementia Pelicano Paulos J, Massano J. Clinical, genetic and neuropathological features of frontotemporal dementia an update and guide. Acta Med Port Kasuga K, Kikuchi M, Tokutake T, et al. Systematic review and meta analysis of Japanese familial Alzheimer s disease and FTDP 17. J Hum Genet Bettens K, Sleegers K, Van Broeckhoven C. Genetic insights in Alzheimer s disease. Lancet Neurol Pelicano Paulos J, Massano J. Clinical, genetic and neuropathological features of frontotemporal dementia an update and guide. Acta Med Port Schellenberg GD, Montine TJ. The genetics and neuropathology of Alzheimer s disease. Acta Neuropathol Arribas Ayllon M. The ethics of disclosing genetic diagnosis for Alzheimer s disease do we need a new paradigm? Br Med Bull Howard KL, Filley CM. Advances in genetic testing for Alzheimer s disease. Rev Neurol Dis Miyashita A, Wen Y, Kitamura N, et al. Lack of genetic association between TREM2 and late onset Alzheimer s disease in a Japanese population. J Alzheimers Dis Goldman JS, Hahn SE, Catania JW, et al. Genetic counseling and testing for Alzheimer disease joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet Med Šerý O, Povová J, Balcar VJ. Perspectives in genetic prediction of Alzheimer s disease. Neuro Endocrinol Lett Lambert JC, Ibrahim Verbaas CA, Harold D, et al. Meta analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer s disease. Nat Genet Cassidy MR, Roberts JS, Bird TD, et al. Comparing test specific distress of susceptibility versus deterministic genetic 52 2

36 2 for Alzheimer s disease. Alzheimers Dement testing PubMed #1 "Dementia/diagnosis" Majr OR dementia TI AND diagnosis TI OR diagnoses TI OR diagnostic TI OR "Cognition Disorders/diagnosis" Majr OR cognition disorder* TI OR "cognitive dysfunction" TI AND diagnosis TI OR diagnoses TI OR diagnostic TI AND "Genetic Testing" Mesh OR "Heterozygote Detection" Mesh OR "Genetic Predisposition to Disease" Mesh OR "Molecular Diagnostic Techniques" Mesh OR "Mutation" Majr OR genetic test* OR genetic diagnos* OR mutation TI #1 /MTH OR /TI OR /MTH OR /TI AND SH,,, X,, OR /TH OR /TI AND /TH OR /TI OR /TI OR /TI OR /TI OR /TI CQ