a bit of history alzheimer's disease – named after alois
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A bit of historyA bit of history
Alzheimer’s disease – named after Alzheimer’s disease – named after Alois Alzheimer who first described it Alois Alzheimer who first described it back in 1906back in 1906
Now dementia affects 24 million Now dementia affects 24 million people world-wide, 60% in developing people world-wide, 60% in developing countries.countries.
0.5 million people in UK.0.5 million people in UK. Comes third in disability indices.Comes third in disability indices.
DementiaDementia
Loss of intellectual functions Loss of intellectual functions including memory.including memory.
Deterioration in ability to carry out Deterioration in ability to carry out day to day activities.day to day activities.
Changes in social behaviour.Changes in social behaviour.
Alzheimers dementiaAlzheimers dementia
Most common form.Most common form. Behaviour changes often take form of Behaviour changes often take form of
apathy and social withdrawal but also apathy and social withdrawal but also behavioural disturbance.behavioural disturbance.
Leads to death of selected nerve cells Leads to death of selected nerve cells in the CNS.in the CNS.
Average survival post diagnosis 8-10 Average survival post diagnosis 8-10 years.years.
Vascular dementiaVascular dementia
Role of vascular events in aetiology Role of vascular events in aetiology of dementia poorly understood.of dementia poorly understood.
Onset may be abrupt or may be Onset may be abrupt or may be stepwise progression.stepwise progression.
Physical problems are more common Physical problems are more common than in AD.than in AD.
Lewy body dementiaLewy body dementia
Fluctuation of awareness from day to Fluctuation of awareness from day to day.day.
Signs of ParkinsonismSigns of Parkinsonism Visual hallucinations or delusions.Visual hallucinations or delusions. Similar to dementia seen in patients Similar to dementia seen in patients
with Parkinson’s disease (affects 75% with Parkinson’s disease (affects 75% after 10 years).after 10 years).
The othersThe others
Fronto-temporal dementia.Fronto-temporal dementia. CJD.CJD. Mixed dementia.Mixed dementia.
DiagnosisDiagnosis
HistoryHistory Ideally using diagnostic criteria eg. DSM4Ideally using diagnostic criteria eg. DSM4
Cognitive testingCognitive testing MMSEMMSE
Screening for reversible causesScreening for reversible causes Only if clinically indicatedOnly if clinically indicated Assess for depressionAssess for depression
ImagingImaging CT +/- SPECTCT +/- SPECT
Non-pharmacological Non-pharmacological interventionsinterventions
Supporting care giversSupporting care givers Cognitive stimulationCognitive stimulation Environment designEnvironment design Physical activitiesPhysical activities Recreational activitiesRecreational activities
Cholinesterase inhibitorsCholinesterase inhibitors
Inhibit the enzymatic breakdown of Inhibit the enzymatic breakdown of acetylcholine.acetylcholine.
Efficacy on reducing cognitive decline Efficacy on reducing cognitive decline of three main drugs the same.of three main drugs the same.
Donepezil possibly better tolerated.Donepezil possibly better tolerated. Long term use may delay Long term use may delay
institutionalisation.institutionalisation.
DonepezilDonepezil
Can be used to treat cognitive decline Can be used to treat cognitive decline in mild-mod AD and vascular dementia.in mild-mod AD and vascular dementia.
Reduces psychotic symptoms and some Reduces psychotic symptoms and some behavioural problems in mild-mod AD.behavioural problems in mild-mod AD.
Treatment daily doses of 5mg or above.Treatment daily doses of 5mg or above.
GalantamineGalantamine
Can be used for treatment of cognitive Can be used for treatment of cognitive decline in AD and mixed dementias.decline in AD and mixed dementias.
Can be used for Mx of associated Can be used for Mx of associated symptoms including functional ability symptoms including functional ability in AD.in AD.
Higher doses up to 24mg/day more Higher doses up to 24mg/day more effective; slow dose escalation effective; slow dose escalation improves tolerability.improves tolerability.
RivastigmineRivastigmine
Shown to reduce cognitive decline Shown to reduce cognitive decline and improve associated symptoms in and improve associated symptoms in patients with AD and Lewy body patients with AD and Lewy body dementia.dementia.
MemantineMemantine
NMDA receptor antagonist.NMDA receptor antagonist. Small benefits in wide range of Small benefits in wide range of
measures and activities of daily living measures and activities of daily living in patients with mild-mod AD and in patients with mild-mod AD and vascular dementia but not vascular dementia but not statistically significant.statistically significant.
Insufficient evidence to back up its Insufficient evidence to back up its use.use.
Ginkgo BilobaGinkgo Biloba
Studies looked at use in dementiasStudies looked at use in dementias Has a positive effect on cognition and Has a positive effect on cognition and
function but less than cholinesterase inhib.function but less than cholinesterase inhib. Benefit most pronounced in advanced AD.Benefit most pronounced in advanced AD. Safe though interacts with medicines e.g. Safe though interacts with medicines e.g.
increased clotting time on warfarin.increased clotting time on warfarin. Needs to be used for 1 year to see Needs to be used for 1 year to see
improvements.improvements.
Use of AntipsychoticsUse of Antipsychotics
Are effective for treatment of Are effective for treatment of behavioural problems.behavioural problems.
Older and atypical forms have similar Older and atypical forms have similar efficacy.efficacy.
Risk of stroke with atypical Risk of stroke with atypical antipsychotics.antipsychotics.
Significant SE profile – needs monitored.Significant SE profile – needs monitored. No causal link to accelerated No causal link to accelerated
progression of dementia.progression of dementia.
Things that don’t workThings that don’t work
Anti-inflammatoriesAnti-inflammatories HydroxychloroquineHydroxychloroquine PrednisolonePrednisolone MelatoninMelatonin OestrogensOestrogens SelegilineSelegiline
The cholinesterase inhibitors The cholinesterase inhibitors debatedebate
Use limited by NICE to moderate dementia Use limited by NICE to moderate dementia (MMSE 10-20). (MMSE 10-20).
Yearly cost of £1000/pt.Yearly cost of £1000/pt. 1/3 of patients stop after 3mths due to SE.1/3 of patients stop after 3mths due to SE. Challenged in courts on basis that Challenged in courts on basis that
economic model not released for scrutiny.economic model not released for scrutiny. Are rigid cut-offs in MMSE a fair way to Are rigid cut-offs in MMSE a fair way to
assess eligibility for treatment?assess eligibility for treatment?
The cholinesterase inhibitors The cholinesterase inhibitors debatedebate
Less than 20% of patients with Less than 20% of patients with dementia treated with these meds.dementia treated with these meds.
Cost 30% more in UK than Europe.Cost 30% more in UK than Europe. Poor standard of care compared to Poor standard of care compared to
other countriesother countries 1/3 of patients receive a formal 1/3 of patients receive a formal
diagnosisdiagnosis Use of cholinesterase inhibitors less Use of cholinesterase inhibitors less
widespread.widespread.
Current NICE guidelinesCurrent NICE guidelines
Donepezil, Galantamine and Donepezil, Galantamine and Rivastigmine used in mild-mod Rivastigmine used in mild-mod severe ADsevere AD MMSE 10-20MMSE 10-20 Initiated by specialistInitiated by specialist R/V every 6/12R/V every 6/12 Only continued if MMSE >= 10 and Only continued if MMSE >= 10 and
clinically worthwhile.clinically worthwhile.
Current NICE guidelinesCurrent NICE guidelines
Memantine not recommended Memantine not recommended Patients already on Tx can continue Patients already on Tx can continue
until considered appropriate to stop.until considered appropriate to stop.