인지기능장애의치료적접근 / 이상현 연수강좌 인지기능장애의치료적접근 이상현국민건강보험일산병원가정의학과 치매는치료가모두같을까? 1 The earliest deficit in Alzheimer's is a physiologic lesion in the hippocampus; as the disease progresses, it causes structural damage manifest as cell loss, plaques, and tangles in the brain. Vascular Dementia 진단 치매 뇌경색관련증상및뇌영상소견 치매와뇌혈관성질환의관련성 관련성 중풍후 3 개월내치매발생했거나 인지기능장애가급격히혹은단계적 (step-wise) 장애 주의 단순히치매의심환자에서 MRI 에서작은허혈성병변이보인다고혈관성치매라고진단내리면안된다. Frontotemporal Lobar Degeneration 50-60 세 (range 21-80) Behavior, judgment, language, personality Inability to make long-term plans, incorrect social behavior, impaired impulse control (spending, appetite, sexual desire0 Subgroups Frontotemporal dementia (FTD) Progressive non-fluent aphasia (PNFA) Semantic dementia (SD) Difficulty to manage day activities d/t judgement & behavioral problems Cf: memory deficits in AD Tx??? AchE inhibitors? often respond adversely to cholinesterase inhibitors with increased agitation and insomnia SSRI antipsychotics 109
연수강좌 Dementia with Lewy bodies Normal Pressure Hydrocephalus 2ndary degenerative dementia (Bx of Dementia : 15-25%) Cognitive findings Varying degree of memory impairment Visuospatial problems fluctuation Visual hallucinations Parkinson feature Masked face, Rigidity, (Tremor is unusual) 치매가파킨슨증세보다먼저발생했거나, 파킨슨증세발생 1 년이내치매발생 Tx 인지기능 항콜린에스테라제 이상행동 항정신병약물과민 (neuroleptic sensitivity) Clozapine, olanzapine, quetiapine 우울 SSRI 운동기능장애 소량항파킨슨약물 (L-dopa, dopamine agonist) clinical triad of NPH 1) progressive gait abnormality 2) urinary incontinence 3) impairment of mental function 67 세여성 3 개월후 2006.10.24 F/U 해보면좋아지나, 나빠지나. MoCA :23 점 110
인지기능장애의치료적접근 / 이상현 8 개월후 2007.7.3 2008.11.11 MoCA :27 점 MMSE:28 점 2009.7.14 8 개월후 Stages of Dementia Mild (CDR 1, GDS 4,5) MMSE 20-26 기억력장애 Moderate (CDR 2, GDS 6) MMSE 10-19 인지장애명백 일상생활수행능력 (IADL) 장애 행동장애 Severe (CDR 3, GDS 7) MMSE < 9 언어장애 식사, 의복입기등기본적생활수행능력 (ADL) 장애 MMSE : 23 점 효과차이? Cochrane 2006 Cholinesterase 억제제는비슷할까? 16 111
연수강좌 A/E : vomiting Cochrane 2006 A/E : Wt. loss Cochrane 2006 17 18 GI S/E Rivastigmine & Galantamine with food Wt loss Rivastigmine Drug interaction Donepezil & Galantamine metabolized by hepatic cytochrome P450 isoenzyme SSRI 와함께투여시농도증가, 항경련제는농도감소 Rivastigmine hydrolyzed by brain esterases Insomnia Donepezil (Aricept) 어떻게복용하나? 5 mg for 4wk => 10 mg hs 취침전 ( 위장관부작용감소 ) 불면증, 악몽있으면아침투여 효과 ADAS-Cog 2-3 점증가. 5 년후에도위약군과차이 상대적장점은? 위장관부작용 / 체중감소부작용적다. 약물상호작용 SSRI : donepezil 약물농도증가 항경련제 : 약물농도감소 Rivastigmine (Exelon) 어떻게투여하나? (2) 1.5 mg bid for 2wk => 2 주마다증량 3mg bid => 4.5mg bid => max 6mg bid 특징 Butyryl-cholinesterase (BuChE) 동시억제 Cytochrome p450 과무관 부작용 12mg 투여시 40-50% N/V 24% 체중감소 (7%) Galantamine (Reminyl) 특징 Allosteric modulation Nicotine Receptor 도자극하여 Ach 분비량증가효과 어떻게투여하나? 8mg for 4 wk => 16mg for 4 wk => max 24mg for 4wk 부작용 고용량 (16-24mg) 에서위장관부작용 (12-16%) 11% 환자에서체중감소 (7%) 112
인지기능장애의치료적접근 / 이상현 교체기준 A. 3 개월째인지기능평가 좋아지거나비슷하면 => 약물효과 나빠지면 => 교체고려 (AD 평균 MMSE 점수감소는 3.3 점 / 년 ) B. 부작용 Memantine (Ebixa ) 어떻게투여? 5mg (1 st wk) => 5mg bid(2 nd wk) => 10mg / 5mg(3 rd wk) => 10mg bid (4 th wk) 특징 Cytochrome P450 과무관 부작용 어지러움증, 환각, 두통 (5-6%) BPSD 치료약물들은비슷할까? Behavior Medications Hallucinations/delusions Risperidone 0.25-2 mg, divided doses Quetiapine 25-400 mg, divided doses Agitation Cholinesterase inhibitors Trazadone 25-100 mg daily Comparison of Atypical Antipsychotics Drug Dosages Advantages Disadvantages (mg/day) Risperidone 0.25-1.5 Non-sedating (dementia) EPS increase with dose Orthostatic hypotension Chronic anxiety Acute anxiety lnsomnia Sertraline 50-100 mg qd Escitalopram 10 mg qd Buspirone 5-15 mg tid Lorazepam 0.5 mg PO / IM Trazadone 25-100 mg qhs Zolpidem 5-10 mg qhs Olanzapine 2.5-5.0 Low EPS Anticholinergic effects (dementia) Weight gain Quetiapine 25-200 Low EPS Sedation, Orthostatic hypotension 113
연수강좌 언제까지사용할것인가? 연구결과들 (AchI) 초기 : 인지기능 / 일상생활활동호전 9-12 개월 : 위약군보다는좋지만투여전상태 5 년추적결과 : 치료군이상대적차이를보임 결론 지속적투여가도움 언제까지? 치매말기 한두단어말, 대소변식사전적의존, 운동기능상실 Cf: 약끊고서급속히악화되면재투약고려 114