Dementia care Update Stanley KF Tam Executive council member, Coordinator of Education & Publication Subcommittee, Hong Kong Alzheimer s Disease Association Honorary Clinical Assistant Professor, Faculty of MED, HKU Associate Consultant, Depart of MED, QEH / HKBH F/81 with Alzheimer s Disease referred to memory clinic, from private neurologist for impaired memory good past health, cataract with extraction c/o : Progressive memory lost over 3 years initially affect short term memory, gradually deteriorating recent few months, have problems in operating home electrical appliance deranged cooking technique change of personality very argumentative, very defensive, and protective sometimes very emotional MMSE 18/30: education up to secondary school level Orientation 6/10 Registration 3/3 Attention & calculation 1/5 Recall 1/3 Language 7/8 Praxia 0/1 Physical exam: Unremarkable including neurological exam Unremarkable blood test: CBP L / RFT, Ca PO4 Thyroid function VDRL Vitamin B12, Folate 1
Dementia An acquired syndrome of decline in memory and other cognitive functions > 55 illnesses can cause dementia Common causes of Dementia in HK 1. Alzheimer s Disease ( 阿爾茲海默氏症 ) 73.5 % 2. Vascular dementia 22.4 % 3. Others 4.1% Prevalence of dementia in the Hong Kong community a population survey in 2005/06 : Elderly Health Services, Department of Health and Department of Psychiatry, Chinese University of Hong Kong; 2006. The number of people with dementia worldwide is currently estimated at 35.6 million. This number will double by 2030 and more than triple by 2050. 2
Epidemiology of dementia in HK Epidemiology of dementia in HK In 2006, research findings from DH and CUHK showed that, about 1 in 10 community-dwelling population aged 70 or above had dementia, and 1 in 3 aged 85 or above had dementia Prevalence of dementia in the Hong Kong community a population survey in 2005/06 : Elderly Health Services, Department of Health and Department of Psychiatry, Chinese University of Hong Kong; 2006. Epidemiology of dementia in HK Assuming no increase in prevalence rates, the number of people aged 60+ with dementia will still increase from 0.11 million (2010) to 0.28 million (2036) 患者的數目 ( 萬 ) Number (Ten thousands) ( 資料來源 : 賽馬會流金頌計劃研究系列 : 老年癡呆症 ) Alzheimer s disease Multiple cognitive deficits manifested by memory impairment and one or more of apraxia, agnosia, aphasia or disturbance in executive functioning (ability to initiate, plan and execute daily tasks). Multiple cognitive deficits manifested by memory impairment and one or more of aphasia, apraxia, agnosia or disturbance in executive functioning (ability to initiate, plan and execute daily tasks). Significant impairment in social or occupational functioning Gradual onset and continuing cognitive decline Symptoms not due to neurologic, systemic or substance abuse conditions known to cause dementia 3
Neurocognitive Disorder (DSM-V) 1 The DSM-IV diagnoses of dementia is under the newly named entity major neurocognitive disorder (NCD). 2 The term dementia is not precluded from use. 3 Furthermore, a less severe level of cognitive impairment, mild NCD, which is a new disorder that permits the diagnosis of less disabling syndromes that may nonetheless be the focus of concern and treatment. Major Neurocognitive Disorder 1 Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains (complex attention, executive function, learning and memory, language, perceptual-motor, or social cognition) based on: Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and A substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or, in its absence, another quantified clinical assessment. Major Neurocognitive Disorder Mild Neurocognitive Disorder 2 3 4 The cognitive deficits interfere with independence in everyday activities (i.e., at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications). The cognitive deficits do not occur exclusively in the context of a delirium. The cognitive deficits are not better explained by another mental disorder (e.g., major depressive disorder, schizophrenia). 1 The cognitive deficits do not interfere with capacity for independence in everyday activities (i.e., complex instrumental activities of daily living such as paying bills or managing medications are preserved, but greater effort, compensatory strategies, or accommodation may be required). start Exelon 1.5 mg bd Gradually stepped up to 4.5mg bd over 4 months Pharmacology treatment 4
Drugs for Alzheimer s Disease 1 Disease modifying agents 2 Symptomatic treatment 3 Treatment of neuropsychiatric symptoms (psychosis, depression) Kaj Blennow Lancet 2006 Cholinergic Hypothesis in AD Acetylcholine (ACh) is important for learning & memory ACh is deficient in the brains of persons with AD, esp. in moderate to severe disease stages Loss of cholinergic neurons Enhanced ACh concentrations may improve memory Drugs for Alzheimer s Disease Acetyl-cholinesterase inhibitors (AChEIs) 膽鹼酯酵素抑制劑 remain the mainstay of symptomatic treatment. Two independent meta-analyses have confirmed the efficacy of these drugs with mild-to-moderate Alzheimer s disease. Ritchie CW. Am J Geriatr Psychiatry 2004 Lanctot KL. CMAJ 2003 Donepezil (Aricept) Galantamine (Reminyl) Rivastigmine (Exelon) Patient with (a) mild to moderate Alzheimer s disease and MMSE 10 26, (b) Without medical contraindication / precaution with C.I. and (c) patient is compliant or there is reliable caregiver to ensure compliance. [Geri / Neur / Psy specialists] start Exelon 1.5 mg bd Gradually stepped up to 4.5mg bd over 4 months Associated with reduced appetite, weight loss from 108 lb 103 lb No other GI symptom, denied other drug intake, no overdose of Exelon system enquiry & exam, blood test, stool for occult blood : unremarkable OGD refused stepped down Exelon, no improvement 5
mood low side crying during interview GDS 12/15 Add Fluoxetine 10mg om, switch Exelon to Aricept 5mg N 2 months later...(fluoxetine 10mg om + Aricept 5mg N) Same low mood, poor appetite, BW 100lb Stopped Aricept, keep Fluoxetine 10mg om Counseling to daughter: daughter criticize the patients overtly Counseling to patient: son being unemployed encourage more daytime activities and outdoor activities, introduce HKADA Alzheimer s Disease Association 4 weeks later, mood better, stepped up Fluoxetine Re-start Exelon patch 4.6mg / D stepped up to 9.5mg /D in 1 month Well tolerated Appetite improved BW 110lb Clinical experience suggests that introducing cholinesterase inhibitors at low doses, increasing the dose gradually, and administering the medication with meals may limit gastrointestinal side effects. Watch out for organic cause other than drug side effect. Look for and treat depression. Behavioral and psychological symptoms are common in Alzheimer s disease Proper assessment and intervention can benefit patient and career Behavioral and pharmacological intervention are equally important. 6
Exelon Transdermal 9.5 mg/24 h Patch Neurology 69 (Suppl 1) July 24, 2007 Dose Titration Rivastigmine Patch: Smooth Continuous Delivery Through the Skin Treatment groups (double-dummy, double-blind): Rivastigmine once-daily patch 20 cm 2 and placebo capsules Rivastigmine once-daily patch 10 cm 2 and placebo capsules Rivastigmine twice-daily capsules 3 12 mg/day and placebo patch Placebo patch and capsules Doses were titrated at 4-weekly intervals Patch 5 20 cm 2 Patch 5 10 cm 2 Weeks 1 4 Weeks 5 8 Weeks 9 12 Weeks 13 24 Patch 5 cm 2 Patch 10 cm 2 Patch 15 cm 2 Patch 20 cm 2 Patch 5 cm 2 Patch 10 cm 2 Rivastigmine (ng/ml) 30 20 10 0 Rivastigmine 10 cm 2 patch Rivastigmine 6 mg bid capsule 0 3 6 9 12 15 18 21 24 Time (h) Capsule 3 12 mg 3 mg/day 6 mg/day 9 mg/day 12 mg/day Placebo 10 cm 2 patch delivered average concentrations provided by an oral dose of 6 mg bid (12 mg per day), based on PK modeling Patients Receiving the Patch Demonstrated Improved Cognitive Functions Most Frequent Adverse Events Neurology 69 (Suppl 1) July 24, 2007 Neurology 69 (Suppl 1) July 24, 2007 7
Rivastigmine Patch shows Good Skin Tolerability Caregiver Preference for Patch versus Capsule None/slight/mild Moderate/severe % patients 100 90 80 70 60 50 40 30 20 10 0 93.3 92.4 6.7 7.6 Itching Redness 98.1 98.9 Oedema 1.9 1.1 Pain, stinging and/or burning % caregivers reporting a preference 80 60 40 20 0 72% Patch 28% Capsule Safety population C-ITT population Preference at 24 weeks (n = 985) p < 0.0001, patch versus capsule new patients : Start 4.6 mg D for at least 4 weeks. If well tolerated, step up to 9.5 mg D. For patients already receiving Exelon capsules : taking < 6 mg day oral Exelon : switch to the 4.6 mg D patch for at least 4 weeks taking 6 mg day oral Exelon : may switch directly to target 9.5 mg D patch. In both instances, the first patch should be applied the day after the last oral dose. Apply to: Upper and lower back Upper arm Chest The skin should be clean, dry and hairless before the patch is applied Normal daily activities, such as bathing, are permitted Donepezil for dementia due to Alzheimer s disease The Cochrane Library 2009, Issue 3 2006 3 years after starting treatment BW 111 lb walk unaided, mood OK, social smile, intake good self care OK, take cared by daughter mostly home bound, outdoor need assistance less initiation, less speech ear wax+ MMSE 13/30 (Jun/06) - 18/30 (Mar/03) Fluoxetine 20mg N, 1 st AChEI (max dose), add memantine 5mg om, olive oil for ear wax Donepezil is beneficial for people with mild, moderate and severe dementia due to Alzheimer s disease, in being associated with improvements in cognitive function and activities of daily living. Adverse effects were consistent with the cholinergic actions of the drug. Effects on cognition remained measurable and statistically significant at 52 weeks of treatment in one study. 8
Action of NMDA receptors antagonist in AD Benefits of NMDA receptors antagonist across domains in moderate to severe AD Memantine N-methyl-D-aspartate receptor (NMDAR) antagonist A central mechanism in learning and memory is long-term potentiation (LTP) which is mediated by the neurotransmitter glutamate via the NMDA receptor However, in AD, glutamate receptors of the NMDA type are overactivated, with the resulting continuous mild activation leading to neuronal damage and impairment of learning. Winblad et al. Memantine in Moderate to Severe Alzheimer s disease: a Meta-Analysis of Randomised Clinical Trials, Dement Geriatr Cogn Disord 2007;24:20-27 Memantine in mod-severe AD already receiving Donepezil Memantine in mod-severe AD already receiving Donepezil Tariot PN. JAMA 2004 Tariot PN. JAMA 2004 Memantine adverse effect 9
4 weeks after starting memantine daughter report: more cheerful, more conversation, more alert at day time thus more participation in day time activities step up to full dose 10mg bd in 6 months Nov 2006 report aggressiveness: shouting loud if against her wish, rushed to bank to get money daughter: care-giver stress, low mood step back memantine to 15mg/D, agitation resolved patient moved to live with son + DIL Sep 2009 6 years after starting treatment come to clinic FU walk unaided with daughter MMSE 10/30 live with son + DIL, sometimes cared by daughter during weekend need supervision / assistance in ADL e.g. toileting, bathing repeated face cleansing, searching behaviour especially night time no delusion, hallucination observed Severe Dementia noncompetitive antagonist of glutamate N- methyl-d-aspartate (NMDA) receptors, effective and safe in patients with moderate to severe Alzheimer s disease Donepezil is approved by the US FDA. Non-pharmacology treatment 10
Summary Management of Alzheimer s disease Assessment We do not have a cure but we do have treatments Management of Dementia pharmacological non-pharmacological Target: Delay progression Manage symptoms (cognitive, behavioral, psychological) Maintain functioning 11
FU Jan 2011 BW 111 lb walk unaided, mood OK, social smile, intake good self care OK, take cared by DIL, outdoor need assistance Exelon patch 9.5mg/D, Fluoxetine 10mg N, memantine 15mg/D 12