1. An update on diagnostics and management
Dementia
An update on diagnostics and management
Dennis Chan
Senior Lecturer in Neurology
Brighton and Sussex Medical School

2. VERY POOR 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.

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 Vascular
Alzheimer’s disease
Dementia with Lewy bodies/Parkinson’s 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

15. Alzheimer’s 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)
Parkinson’s 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
Alzheimer’s 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 Aβ clearance

29. NSAIDs α-secretase promoters ß-, γ-secretase inhibitors
Impaired Aβ clearance
ß-, γ-secretase inhibitors
Heavy metal chelators
Statins
Anti-amyloid immunotherapy
NSAIDs
Anti-oxidants
Tau aggregation inhibitors

30. >250 compounds currently in testing ~10 in Phase III trials
Drugs
Potential Launch by 2012
Phase III Agents
LY (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
>250 compounds currently in testing
~10 in Phase III trials

31. >250 compounds currently in testing ~10 in Phase III trials
Drugs
Potential Launch by 2012
Phase III Agents
LY (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
>250 compounds currently in testing
~10 in Phase III trials

32. Bapineuzumab: monoclonal Ab against N-terminus of Aβ42
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
Alzheimer’s disease as a preventable disorder?

34. The greatest challenge of all?
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