A bit of history

1
A bit of history

• Alzheimers disease named after Alois Alzheimer
  who first described it back in 1906
• Now dementia affects 24 million people
  world-wide, 60 in developing countries.
• 0.5 million people in UK.
• Comes third in disability indices.

2
Dementia

• Loss of intellectual functions including memory.
• Deterioration in ability to carry out day to day
  activities.
• Changes in social behaviour.

3
Alzheimers dementia

• Most common form.
• Behaviour changes often take form of apathy and
  social withdrawal but also behavioural
  disturbance.
• Leads to death of selected nerve cells in the
  CNS.
• Average survival post diagnosis 8-10 years.

4
Vascular dementia

• Role of vascular events in aetiology of dementia
  poorly understood.
• Onset may be abrupt or may be stepwise
  progression.
• Physical problems are more common than in AD.

5
Lewy body dementia

• Fluctuation of awareness from day to day.
• Signs of Parkinsonism
• Visual hallucinations or delusions.
• Similar to dementia seen in patients with
  Parkinsons disease (affects 75 after 10 years).

6
The others

• Fronto-temporal dementia.
• CJD.
• Mixed dementia.

7
Diagnosis

• History
• Ideally using diagnostic criteria eg. DSM4
• Cognitive testing
• MMSE
• Screening for reversible causes
• Only if clinically indicated
• Assess for depression
• Imaging
• CT /- SPECT

8
Non-pharmacological interventions

• Supporting care givers
• Cognitive stimulation
• Environment design
• Physical activities
• Recreational activities

9
Cholinesterase inhibitors

• Inhibit the enzymatic breakdown of acetylcholine.
• Efficacy on reducing cognitive decline of three
  main drugs the same.
• Donepezil possibly better tolerated.
• Long term use may delay institutionalisation.

10
Donepezil

• Can be used to treat cognitive decline in
  mild-mod AD and vascular dementia.
• Reduces psychotic symptoms and some behavioural
  problems in mild-mod AD.
• Treatment daily doses of 5mg or above.

11
Galantamine

• Can be used for treatment of cognitive decline in
  AD and mixed dementias.
• Can be used for Mx of associated symptoms
  including functional ability in AD.
• Higher doses up to 24mg/day more effective slow
  dose escalation improves tolerability.

12
Rivastigmine

• Shown to reduce cognitive decline and improve
  associated symptoms in patients with AD and Lewy
  body dementia.

13
Memantine

• NMDA receptor antagonist.
• Small benefits in wide range of measures and
  activities of daily living in patients with
  mild-mod AD and vascular dementia but not
  statistically significant.
• Insufficient evidence to back up its use.

14
Ginkgo Biloba

• Studies looked at use in dementias
• Has a positive effect on cognition and function
  but less than cholinesterase inhib.
• Benefit most pronounced in advanced AD.
• Safe though interacts with medicines e.g.
  increased clotting time on warfarin.
• Needs to be used for 1 year to see improvements.

15
Use of Antipsychotics

• Are effective for treatment of behavioural
  problems.
• Older and atypical forms have similar efficacy.
• Risk of stroke with atypical antipsychotics.
• Significant SE profile needs monitored.
• No causal link to accelerated progression of
  dementia.

16
Things that dont work

• Anti-inflammatories
• Hydroxychloroquine
• Prednisolone
• Melatonin
• Oestrogens
• Selegiline

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The cholinesterase inhibitors debate

• Use limited by NICE to moderate dementia (MMSE
  10-20).
• Yearly cost of 1000/pt.
• 1/3 of patients stop after 3mths due to SE.
• Challenged in courts on basis that economic model
  not released for scrutiny.
• Are rigid cut-offs in MMSE a fair way to assess
  eligibility for treatment?

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The cholinesterase inhibitors debate

• Less than 20 of patients with dementia treated
  with these meds.
• Cost 30 more in UK than Europe.
• Poor standard of care compared to other countries
• 1/3 of patients receive a formal diagnosis
• Use of cholinesterase inhibitors less widespread.

19
Current NICE guidelines

• Donepezil, Galantamine and Rivastigmine used in
  mild-mod severe AD
• MMSE 10-20
• Initiated by specialist
• R/V every 6/12
• Only continued if MMSE gt 10 and clinically
  worthwhile.

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Current NICE guidelines

• Memantine not recommended
• Patients already on Tx can continue until
  considered appropriate to stop.