1. Polypharmacy and specific medication profiles as predictors of treatment and health outcomes in dementia
Dr Christoph Mueller, NIHR Academic Clinical Lecturer
Dr Gayan Perera, Epidemiologist

2. None

3. Dementia

4. Dementia

5. Dementia

6. Dementia
Guthrie et al., 2012, BMJ; Barnett et al., 2012, Lancet

7. Polypharmacy

8. Psychotropics & Polypharmacy

9. Overview Mortality Polypharmacy Hospitalisation & A&E attendance
Cognitive decline
Polypharmacy
Psychiatric Medications
Acetylcholinesterase inhibitors (AChEIs)
Antidepressants
Antipsychotics (by indication)
Anticholinergics

10. SLAM Biomedical Research Centre (BRC) Case Register
King’s College London (KCL)
United Kingdom
London
South London
South London and Maudsley (SLAM)

11. BRC Case Register

12. Clinical Record Interactive Search
Methods - Linkages
Clinical Record Interactive Search
HES
Moor

13. Health of the Nation Outcome Scale (HoNOS65+)
Clinician rated problems:
0  - No problem
1  - Minor problem (sub threshold)
2  - Mild problem but definitely present
3  - Moderate problem
4  - Severe problem
Mental health problem scales:
Behavioral disturbance (aggressive behavior)
Non-accidental self-injury (self harm)
Problem-drinking or drug use
(Cognitive problems)
Hallucinations and/or delusions
Depressive symptoms
Problems related to physical illness/disability
No problem
(Score 0-1)
Problem present
(Score 2-4)
Functional problem scales:
Social or supportive relationships
Activities of daily living
Living conditions
Work and leisure activities – quality of daytime environment

14. MMSE
Perera et al., PLOS ONE, 2014

15. Dementia on the BRC case register
patients diagnosed between
12% severe / 44% moderate / 44% mild
58% AD / 29% VaD
Antidementia medication
Anticholinergic medication
Median
number of medications
4-6
medications
≥ 7 medications
≥ 10 medications
33%
43%
4.0
24%
16% 9%

16. 1. Polypharmacy – A&E attendance
Cumulative incidence (%)
Age & gender, MMSE adjusted HR (95% CI)
Fully adjusted HR (95% CI)
0-3 medications
57.1%
1 [reference]
4-6 medications
64.6%
1.27 ( )
1.21 ( )
> 7 medications
67.5%
1.54 ( )
1.40 ( )
Risk increase per additional medication
1.06 ( )
1.05 ( )
> 4 medications:
> 21% ⬆️ risk

17. 1. Polypharmacy - Hospitalisation
Cumulative incidence (%)
Age & gender, MMSE adjusted HR (95% CI)
Fully adjusted HR (95% CI)
0-3 medications
63.0%
1 [reference]
4-6 medications
69.2%
1.21 ( )
1.14 ( )
> 7 medications
75.9%
1.63 ( )
1.35 ( )
Risk increase per additional medication
1.06 ( )
1.04 ( )
> 4 medications:
> 14% ⬆️ risk

18. 1. Polypharmacy - Mortality
Cumulative incidence (%)
Age & gender adjusted HR (95% CI)
Fully adjusted HR (95% CI)
0-3 medications
21.2%
1 [reference]
4-6 medications
28.2%
1.37 ( )
1.32 ( )
> 7 medications
31.1%
1.61 ( )
1.44 ( )
Risk increase per additional medication
1.06 ( )
1.05 ( )
> 4 medications:
> 32% ⬆️ risk

19. 2. Acetylcholinesterase inhibitors - Mortality
AChEI prescribed
23% ⬇️ risk
Mueller et al., Age & Ageing, 2017

20. 3. Antidepressants - Mortality
Antidepressant receipt prior (and post) dementia diagnosis
Antidepressant receipt post dementia diagnosis only
Multivariate Cox regression models
Hazard ratio (95% CI)
Unadjusted
1.15 ( )
1.26 ( )
 Fully adjusted (for demographics, cognitive scores, and all HoNOS65+ subscales, and vascular co-morbidity)
1.20 ( )
1.25 ( )
Adjusted using propensity score as co-variate
1.22 ( )
1.22 ( )
Antidepressant prescribed:
> 22% ⬆️ risk
Mueller et al., JAMDA, 2017

21. 3. Antidepressants - Mortality
Patients with depressed mood± (n=483)
Patients with depressed mood and agitation/psychosis± (n=170)
Patients with agitation/psychosis, but not depressed mood± (n=653)
Patients without neuropsychiatric symptoms±
(n=3,975)
Antidepressant receipt prior (and post) dementia diagnosis
1.56 ( )
0.97 ( )
1.27 ( )
1.20 ( )
Antidepressant receipt post dementia diagnosis
1.11 ( )
1.91 ( )
1.31 ( )
1.22 ( )
Mueller et al., JAMDA, 2017

22. 4. Antipsychotics - Mortality

23. Treatment x factor interaction
4. Antipsychotics
Factor present
Factor not present
Treatment x factor interaction
% with event in Risperidone
% with event in Placebo
% with events in Placebo
Stroke risk:
Delusions
3.1%
2.0%
6.6%
1.2%
0.043
Depression
3.6%
5.6%
5.1%
1.3%
0.025
Mortality risk:
No death in Risperidone group
9.3%
4.4%
2.6%
<0.001
NSAIDs
5.2%
1.4%
3.4%
3.8%
0.021

24. 4. Antipsychotics - Mortality
Agitation & Psychosis (Ag+/Ps+)
n=320
No Agitation, but Psychosis (Ag-/Ps+)
n=401
Agitation, no Psychosis (Ag+/Ps-)
n=742
No agitation, No psychosis (Ag-/Ps-)
n=3,855

25. 4. Antipsychotics - Mortality
Agitation & Psychosis (Ag+/Ps+)
HR: 1.15 ( )
No Agitation, but Psychosis (Ag-/Ps+)
HR: 1.02 ( )
Agitation, no Psychosis (Ag+/Ps-)
HR: 1.26
( )
No agitation, No psychosis (Ag-/Ps-)
HR: 0.99
( )

26. 4. Antipsychotics - Mortality
Agitation & Psychosis (Ag+/Ps+)
HR: 1.15 ( )
No Agitation, but Psychosis (Ag-/Ps+)
HR: 1.02 ( )
Agitation, no Psychosis (Ag+/Ps-)
HR: 1.26
( )
No agitation, No psychosis (Ag-/Ps-)
HR: 0.99
( )
All dementia patients with psychosis (+/-Ag; n=721)
HR: 1.14 ( )
All dementia patients with depressed mood (+/-Ag, Ps; n=701)
HR: 1.06 ( )

27. 5. Anticholinergic medications (AChEI users)
Lu & Tune, 2003 Am J Geriatr Psychiatry

28. 5. Anticholinergic medications (AChEI users)

29. 5. Anticholinergic medications (AChEI users)

30. Conclusions

31. Thank you Acknowledgements: Dr Richard Hayes Professor Robert Stewart
BRC Nucleus Team