current treatments for dementia and future prospects...– qol does not improve with achis •...
TRANSCRIPT
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Current Treatments for Dementiaand Future Prospects
James Warner
St Charles Hospital, London
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DementiaCognitive
• Memory
• orientation
• language
• other cognitive abilities• planning
• organising
• problem solving
• praxis
Non-cognitive (BPSD)
• behavioural symptoms• agitation
• Wandering
• apathy
• psychotic symptoms• delusions
• hallucinations
• affective• depression
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Treatment of cognitivesymptoms
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Available drugs
• Acetylcholinesterase inhibitors (ACHIs)
– donepezil (Aricept)
– rivastigmine (Exelon)
– galantamine (Reminyl)
• NMDA agonist
– memantine
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A problem…..
• Evidence is confusing
– 5 outcomes
– 4 drugs
– 3 diseases
– 2 stages
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Efficacy of ACHIs
+712mg bdgalantamine
+++56mg bdrivastigmine
+410mgdonepezil
Adverseeffects
Numberneeded to
treat
DoseDrug
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• Sustained effects up to 240 weeks
– Improved over baseline for 38 weeks
– Benefit over placebo sustained
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• mild-moderate dementia
– Delays functional decline in by 5 months(NNT 7)
– No effect on Quality of life
• moderate-severe dementia (MMSE 5-17)
– Improve global state, preserves ADLs, andreduce carer stress
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Memantine
• Moderate to severe AD.
– Marginal improvements on cognition and ADL
• Mild to moderate AD.
– Marginal improvement on cognition
• ADAS-cog 0.99 (0.21 to 1.78)
– no significant effect on behaviour or activitiesof daily living
• Few side effects
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Other treatments for dementiacurrent evidence-base
??Statins
??NSAIDS
?+/-Ginkgo biloba
--Vitamin E
+/-+/-oestrogen
vascularAlzheimer’sdrug
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Non-drug treatments
• Reminiscence therapy
• Music therapy
• Reality orientation
• Exercise
• Cognitive training
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NICE recommendations
• Alzheimer’s disease only
• MMSE 10-20 (but caveats)
• Specialist initiation
• Least expensive drug
• Review (MMSE, function and behaviour)6-monthly (can be by GP)
• Continue while MMSE remains 10+
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Problems with NICE
• Alzheimer’s disease only
– Evidence for other dementias is mounting
• Not recommended for mild dementia
• Decision based on QALYs
– QoL does not improve with ACHIs
• Overlooks individual impact
• Stopping if MMSE < 10 is problematic
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55%Germany
61%France
64%US
68%Japan
76%Spain
84%Italy
percentageCountry
Proportion with AD receiving ACHIs
Source: Alzheimer Europe 2007
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33%UK
55%Germany
61%France
64%US
68%Japan
76%Spain
84%Italy
Drug treatment rateCountry
Proportion with AD receiving ACHIs
Source: Alzheimer Europe 2007
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Prescribing Observatoryfor Mental Health
• 2007 audit of 19 Trusts (54 PCTs)
– 1897 patients
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Prescribing Observatoryfor Mental Health
• 2007 audit of 19 Trusts (54 PCTs)
– 1897 patients
• 13% of eligible people received ACHIs
– 67% donepezil
– 20% galantamine
– 9% rivastigmine
• 50% prescribed in primary care
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Why are ACHIs not used?
• NICE guidance is too restrictive?
• Cost considerations?
• Lack of shared care?
• Concerns about evidence?
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Unanswered questions
• Can we predict who will respond?
• How long do the drugs work for?
• Is one CI better than another?
• Is earlier treatment relatively better?
• Do ACHIs work in other types of dementia?
• If one doesn’t work, is it worth tryinganother?
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Recommendations
• Do not let drugs dominate dementia care
– Maintain holistic approach
• All patients with AD/VaD should have trialof donepezil or galantamine
• Review after 3-6 months and stop if noteffective
• Do not rely on MMSE or NICE to guidedecisions on treatment
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Behavioural and PsychologicalSymptoms
of Dementia(BPSD)
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Extract from: Alzheimer A. Über eine eigenartigeErkrankung der Hirnrinde Allgemeine Zeitschrift furPsychiatrie und Psychisch-gerichtliche Medizin. 1907
“One of the first diseasesymptoms of a 51-year-oldwoman was a strong feeling ofjealousy towards her husband.Very soon she showed rapidlyincreasing memoryimpairments; she could notfind her way about her home,she dragged objects to andfro, hid herself, or sometimesthought that people were outto kill her, then she would startto scream loudly.”
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“From time to time shewas completely delirious,dragging her blanketsand sheets to and fro,calling for her husbandand daughter, andseeming to have auditoryhallucinations. Often shewould scream for hoursand hours in a horriblevoice.”
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0
10
20
30
40
50
60
70
apathy
depression
irrita
bility
anxiety
agitatio
n
delusions
disinhibition
wandering
mild
severe
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BPSDconsequences
• Associated with greater functionalimpairment
• Very distressing for individual
• Very distressing for carers
• Institutional care
• Overmedication
• Elder abuse
• Associated with increased mortality
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Treatment options
• Identify cause
• Wait and see?
• Education and counselling
• Prophylaxis
• Environmental modification
• Direct behavioural approaches
• Medication
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BPSD Drug Treatment
• Risperidone and haloperidol are effective
– Significant increased risk of stroke and death
• ACHIs- probably not effective
– More studies needed
• Benzodiazepines- probably effective
– More studies needed
• Carbamazepine- probably effective
– More studies needed
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BPSD management
• Drug treatment
– Last resort
– Should target specific symptoms
– Specialist initiation
– Regular review
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The future
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• Over 40 drugs in development
• Around 20 have potential diseasemodifying action
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Amyolid overproduction
Deposition of amyloid (plaques)
Inflammatory response
Abnormal tau phosphorylation
Neurofibrillary tangles
β and γ secretase inhibitors
Anti A β immunisation
Anti-inflammatory drugs
Tau kinase inhibitors
Tau aggregation inhibitors
DEMENTIA Cholinesterase inhibitors
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conclusions
• Drug treatments must not become focus ofmanagement
• Good evidence for ACHIs in Alzheimer’sdisease and Vascular dementia
– donepezil and galantamine safe and welltolerated
• Drug treatment of BPSD is last resort
• Several exciting developments awaited
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Thank You