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Rivastigmine in Dementia Associated with Parkinson

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Dementia An update on diagnostics and management Dennis Chan Senior Lecturer in Neurology Brighton and Sussex Medical School In Conclusion Disease-modifying ... – PowerPoint PPT presentation

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Title: Rivastigmine in Dementia Associated with Parkinson


1
Dementia An update on diagnostics and management
Dennis Chan Senior Lecturer in Neurology Brighton
and Sussex Medical School
2
The National Context
  • National Audit Office Report 2007
  • headline point on national performance?
  • VERY POOR

3
Summary 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.

4
Summary 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.

5
Conclusions
  • 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.

6
Conclusions
  • 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.

7
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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

11
The 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

12
Other 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

13
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15
Alzheimers disease
16
adapted from Jack et al. Brain 2009
17
SMI MCI
adapted from Jack et al. Brain 2009
18
Diagnostic 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

19
Lewy body dementia
20
Dementia 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

21
Symptomatology
  • Cognitive impairment
  • Fluctuation in cognition
  • Hallucinations
  • REM sleep behaviour disorder

22
Frontotemporal dementia
23
Frontotemporal lobar degeneration
  • Common cause of young onset dementia
  • second commonest degenerative cause after AD
  • Prototypical syndromes
  • Frontotemporal dementia
  • Progressive nonfluent aphasia
  • Semantic dementia

24
Treatment an update
25
Current treatment options
  • Alzheimers disease
  • ACHeI inhibitors
  • NMDA antagonist (memantine)
  • Vascular dementia
  • management of risk factors
  • Lewy body dementia
  • rivastigmine
  • Frontotemporal lobar degeneration
  • supportive
  • citalopram

26
Revised NICE guidelines March 2011
  • Cholinesterase inhibitors in mild as well as
    moderate AD
  • Memantine (Ebixa) in severe AD
  • Combination therapy not recommended

27
Treatment the future
28
Impaired Aß clearance
29
a-secretase promoters
Impaired Aß clearance
ß-, ?-secretase inhibitors
Heavy metal chelators
Statins
Anti-amyloid immunotherapy
NSAIDs
Anti-oxidants
Tau aggregation inhibitors
30
Drugs 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
31
Drugs 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
32
Bapineuzumab monoclonal Ab against N-terminus of
Aß42
Schenk et al. Nature (1999)
33
In 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?

34
In 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?

35
CHANGING THE PERCEPTION OF DEMENTIA
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