will we ever have effective treatments for dementia? robert howard king’s college london...
Post on 22-Dec-2015
217 Views
Preview:
TRANSCRIPT
Will we ever have effective treatments for dementia?
Robert HowardKing’s College London
robert.j.howard@kcl.ac.uk
Objectives of presentation
Review evidence for treatments for (i) cognitive symptoms and function(ii) behavioural symptoms and psychosis(iii) potential disease modification in AD
Hope – 2 reasons to be optimistic about the future
What the evidence shows for cholinesterase inhibitor treatment of cognition and function
Mild, moderate and severe AD – modest improvements in cognitive function and ADLs
No effect on overall decline
Withdrawal effect involving worsening cognition and function and earlier nursing home placement
What happens when cholinesterase inhibitor therapy is stopped? The DOMINO trial
Direc tion o f improv ement
0
1
2
3
4
5
6
7
8
9
10
11
sM
MS
E
0 6 18 30 52Vis i t Week
Dis c ontinue donepez i l
Replac e wi th memantine
Continue donepez i l
Add memantine
Direc tion o f improv ement
22
24
26
28
30
32
34
36
38
40
42
BA
DL
S
0 6 18 30 52Vis i t Week
What the evidence shows for treatment of behavioural symptoms and psychosis
Only risperidone is convincingly superior to placebo in treatment of agitation, aggression and psychosis in AD
Psychosis returns when treatment stops
Dementia drugs ineffective in AD
Disease modification in Alzheimer’s diseaseAn elusive Holy Grail
No shortage of translationally-identified targets
Anti-amyloid (immunotherapy, anti-aggregation, γ- and β-secretase inhibitors)Neurotransmitter-basedMetabolic and neurotrophic drugsRegenerative approachesGlial cell modulatorsAnti-tau proteinopathy
The difficult truth is that everything (so far) has failed
Repurposing trials are perfect for NHS
Dec-13
Feb-14
Apr-14
Jun-14
Aug-14
Oct-14
Dec-14
Feb-15
Apr-15
Jun-15
Aug-15
Oct-15
Dec-15
0
50
100
150
200
250
300
350
400
450
0 0 0 0 0 5 1530
5070
90115
140165
190215
245
275
305
335
365
395
425
455480MADE Trial recruitment
Randomisations achieved Adjusted Target
Cum
ulati
ve R
ando
misa
tions
In conclusion
Current symptomatic treatments make modest but measurable differences to cognition and function
Behavioural disturbance and psychosis have an evidence-based and licensed treatment
Difficult to predict timetable for discovery of disease modifying drugs or lifestyle interventions with impact, but live in hope
top related