Dementia

An update on diagnostics and management

Dennis Chan

Senior Lecturer in Neurology

Brighton and Sussex Medical School

The National Context

National Audit Office Report 2007

headline point on national performance?

VERY POOR

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.

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.

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.

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.

The development of multiple cognitive deficits The development of multiple cognitive deficits manifested by both:manifested by both:

•memory impairmentmemory impairment•one or more of the following:one or more of the following:

•aphasiaaphasia•apraxiaapraxia•agnosiaagnosia•disturbance of executive functioningdisturbance of executive functioning

The Dementias

Degenerative 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

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

Alzheimer’s disease

adapted from Jack et al. Brain 2009

adapted from Jack et al. Brain 2009

SMI MCI

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

Lewy body dementia

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”

Symptomatology

Cognitive impairment Fluctuation in cognition Hallucinations REM sleep behaviour disorder

Frontotemporal dementia

Frontotemporal lobar degeneration

Common cause of young onset dementia second commonest degenerative cause after AD

Prototypical syndromes Frontotemporal dementia Progressive nonfluent aphasia Semantic dementia

Treatment – an update

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

Revised NICE guidelines March 2011

Cholinesterase inhibitors in mild as well as moderate AD

Memantine (Ebixa™) in severe AD Combination therapy not recommended

Treatment – the future

Impaired Aβ clearance

Impaired Aβ clearance

NSAIDs

Anti-oxidants

Heavy metal chelators

Statins

Tau aggregation inhibitors

α-secretase promoters

ß-, γ-secretase inhibitors

Anti-amyloid immunotherapy

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

DonepezilRivastigmine Galantamine Memantine

>250 compounds currently in testing

~10 in Phase III trials

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

DonepezilRivastigmine Galantamine Memantine

>250 compounds currently in testing

~10 in Phase III trials

Bapineuzumab: monoclonal Ab against N-terminus of Aβ42

Schenk et al. Nature (1999)

In Conclusion

Different diseases have different biological signaturesthese 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?

In Conclusion

Disease-modifying treatments will soon be available

Earlier diagnosis is an imperative

Different diseases have different biological signaturesthese will inform diagnostics and treatment

Novel diagnostic techniques will be required

The greatest challenge of all?

CHANGING THE

PERCEPTION

OF DEMENTIA