Title: Rivastigmine in Dementia Associated with Parkinson
1Dementia An update on diagnostics and management
Dennis Chan Senior Lecturer in Neurology Brighton
and Sussex Medical School
2The National Context
- National Audit Office Report 2007
- headline point on national performance?
- VERY POOR
3Summary points (1)
- Early diagnosis and intervention in dementia is
cost-effective - Only 33-50 of patients ever receive a formal
diagnosis. - In terms of the percentage of suitable patients
receiving anti-dementia drugs, UK performance is
below almost all northern and western European
nations. - In the UK the average reported time to diagnose
the disease is up to twice as long as in other
European countries. - Surveys revealed a lack of urgency among GPs
about diagnosis, due to the perception that
management options are limited. - Less than a third of GPs agreed that there were
satisfactory specialist services to meet need.
4Summary points (2)
- A wide range of screening tests are employed by
GPs, psychiatrists and others but specialist
knowledge is required to make the best use of
them brain scanning is recommended as a
diagnostic investigation by NICE but this is used
regularly by only 66 of community mental health
teams (CMHTs). - The role of CMHTs in diagnosis and early
treatment is inconsistent across the UK and
focuses mainly on people with severe mental
illness. - Earlier diagnosis may be cost-effective by
enabling more to be done to delay disease
progression. Having a clear diagnosis also
reduces the number and length of acute hospital
episodes and delays need for admission to more
expensive long-term care.
5Conclusions
- Dementia presents a significant and urgent
challenge to health and social care in terms of
cost and numbers of people affected. - Until 2005, the Department of Health and local
commissioners attached little priority to
dementia, partly due to the focus on cancer and
heart disease. - Services are not currently delivering value for
money to taxpayers or people with dementia and
their families. - Too few people are being diagnosed, or diagnosed
early. - Early, proven cost-effective, interventions are
not being made widely available. - The rapid ageing of the population means that
costs will rise and services are likely to become
increasingly inconsistent and unsustainable
without redesign.
6Conclusions
- Dementia presents a significant and urgent
challenge to health and social care in terms of
cost and numbers of people affected. - Until 2005, the Department of Health and local
commissioners attached little priority to
dementia, partly due to the focus on cancer and
heart disease. - Services are not currently delivering value for
money to taxpayers or people with dementia and
their families. - Too few people are being diagnosed, or diagnosed
early. - Early, proven cost-effective, interventions are
not being made widely available. - The rapid ageing of the population means that
costs will rise and services are likely to become
increasingly inconsistent and unsustainable
without redesign. - The opportunity now exists to address these
challenges.
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10- The development of multiple cognitive deficits
- manifested by both
- memory impairment
- one or more of the following
- aphasia
- apraxia
- agnosia
- disturbance of executive functioning
11The Dementias
- Degenerative
- Alzheimers disease
- Dementia with Lewy bodies/Parkinsons disease
dementia - Frontotemporal lobar degeneration
- Progressive supranuclear palsy
- Corticobasal degeneration
- Vascular
- Vascular dementia
- Cerebral amyloid angiopathy
- Post-stroke dementia
- Mixed degenerative and vascular dementia
12Other diseases associated with cognitive
impairment
- Prion diseases
- Metabolic disorders
- HIV-related dementia
- Wernicke encephalopathy
- Encephalitis
- Viral
- Paraneoplastic
- autoimmune
- Systemic diseases
- Vasculitis
- Space-occupying lesions
- tumours
- Depression
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15Alzheimers disease
16adapted from Jack et al. Brain 2009
17SMI MCI
adapted from Jack et al. Brain 2009
18Diagnostic criteria for AD (revised 2011)
- Probable AD
- Fulfils criteria for dementia
- insidious onset, progressive decline
- absence of other explanation for cognitive
decline - eg vascular dementia, Lewy body dementia
- Probable AD with biomarker evidence
- abnormal CSF levels of amyloid/tau
- abnormal amyloid-PET scanning
- hippocampal atrophy on MRI
- Possible AD
- atypical clinical course
- aetiologically mixed
- eg concomitant vascular disease
19Lewy body dementia
20Dementia with Lewy Bodies
- Second commonest degenerative dementia
- 10-15 at autopsy
- Two defined syndromes
- Dementia with Lewy bodies (DLB)
- Parkinsons disease with dementia (PDD)
- The one year rule
21Symptomatology
- Cognitive impairment
- Fluctuation in cognition
- Hallucinations
- REM sleep behaviour disorder
22Frontotemporal dementia
23Frontotemporal lobar degeneration
- Common cause of young onset dementia
- second commonest degenerative cause after AD
- Prototypical syndromes
- Frontotemporal dementia
- Progressive nonfluent aphasia
- Semantic dementia
24Treatment an update
25Current treatment options
- Alzheimers disease
- ACHeI inhibitors
- NMDA antagonist (memantine)
- Vascular dementia
- management of risk factors
- Lewy body dementia
- rivastigmine
- Frontotemporal lobar degeneration
- supportive
- citalopram
26Revised NICE guidelines March 2011
- Cholinesterase inhibitors in mild as well as
moderate AD - Memantine (Ebixa) in severe AD
- Combination therapy not recommended
27Treatment the future
28Impaired Aß clearance
29a-secretase promoters
Impaired Aß clearance
ß-, ?-secretase inhibitors
Heavy metal chelators
Statins
Anti-amyloid immunotherapy
NSAIDs
Anti-oxidants
Tau aggregation inhibitors
30Drugs Potential Launch by 2012
Phase III Agents LY2062430 (Amyloid beta MaB) Dimebon (Mitochondrial function) Bapineuzumab (MaB) Semagacestat (Amyloid beta peptide) Gammagard (Immunoglobulin) Rosiglitazone XR (TZD) Aricept modified release (ACheI) Ebixa modified release (NMDA antagonist)
Generics Donepezil Rivastigmine Galantamine Memantine
gt250 compounds currently in testing 10 in Phase
III trials
31Drugs Potential Launch by 2012
Phase III Agents LY2062430 (Amyloid beta MaB) Dimebon (Mitochondrial function) Bapineuzumab (MaB) Semagacestat (Amyloid beta peptide) Gammagard (Immunoglobulin) Rosiglitazone XR (TZD) Aricept modified release (ACheI) Ebixa modified release (NMDA antagonist)
Generics Donepezil Rivastigmine Galantamine Memantine
gt250 compounds currently in testing 10 in Phase
III trials
32Bapineuzumab monoclonal Ab against N-terminus of
Aß42
Schenk et al. Nature (1999)
33In Conclusion
- Different diseases have different biological
signatures - these will inform diagnostics and treatment
- Novel diagnostic techniques will be required
- Disease-modifying treatments will soon be
available - Future management of dementia will increasingly
focus on treatment of the underlying pathology - Alzheimers disease as a preventable disorder?
34In Conclusion
- Disease-modifying treatments will soon be
available - Earlier diagnosis is an imperative
- Different diseases have different biological
signatures - these will inform diagnostics and treatment
- Novel diagnostic techniques will be required
- The greatest challenge of all?
35CHANGING THE PERCEPTION OF DEMENTIA