1. Treatment response in Alzheimer’s disease: An example of use of case registers
Dr Gayan Perera
Epidemiologist
Institute of Psychiatry, King’s College London
SLAM Biomedical Research Centre & Dementia Unit

2. Objectives
To demonstrate importance of Case Registers in the field of Psychiatry
To demonstrate response to AChEIs among dementia patients
To demonstrate response to AChEIs among different ethnic groups

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

4. The SLAM BRC-Mental Health Case Register
Coverage: Lambeth, Southwark, Lewisham, Croydon
Local population: c. 1.2 million
Clinical area: specialist mental health
Active patients: c. 39,000
Total inpatients: c. 2000
Total records: c. 250,000
(increasing by c. 20,000 per year)
Electronic Health Record
The Patient Journey System (PJS)
Socio-demographics
Correspondence letters
Event notes
Medication notes
Clinical observations & investigations
Ability to read Word documents and scanned PDF files
(Stewart et al., 2009, BMC Psychiatry)

5. Why use mental health Case register data? (Advantages over RCTs)
Powerful tool to investigate ‘real world’ outcomes
Pharmacotherapy
Comorbidity
Large case samples
Longitudinal data
Outcomes – predictors (and intervention response)
Symptoms, presentations, adverse events, Specific service use
(Perera et al. (2009, British J of Psychiatry)

6. Estimating response to AChEIs among dementia patients
Study design: Longitudinal cohort study
Patient cohort: All those patients who received AChEIs (Donepezil, Galantamine & Rivastigmine) and had at least 1 MMSE score before drug initiation and had at least 1 MMSE score after drug initiation
Exposure: Exposure to AChEIs
Primary outcome: Cognitive change in terms of MMSE scores
Confounding factors: Socio-demographics, Other drugs: Diabetes, Antipsychotics, anti-depressants, ACE inhibitors, anti-hypertensives etc.
Perera et al., Nov 2014, PLOS one

7. I reviewed Mrs. ZZZZZ on 6th March
Today she scored 5/30 on the MMSE

8. MMSE scores distribution of patients who received AChEIs
Patients receiving AChEI treatment
Sample size
2,460
Number of MMSE scores
10,669
Mean number of MMSE scores per patient (SD)
4.3 (0.51)
Mean MMSE score overall (SD)
19.9 (2.37)
Mean MMSE score at AChEI drug initiation (SD)
19.9 (5.08)
Mean MMSE score at first dementia diagnosis (SD)
20.3 (5.10)
Perera et al (PLOS one, Nov. 2014)

9. Response to AChEI treatment in terms of MMSE scores (Slope change in MMSE units per year)
+4.2 (+3.5, +4.9)
Most of the RCTs only collect data from 0 to 1 year after drug initiation
Slope change
-0.2 (-0.7, +0.2)
Perera et al (PLOS one, Nov. 2014)

10. Response to AChEIs by ethnicity (Slope change in MMSE units per year)
Black & Asian ethnic groups (n=386)
European ethnic groups (n=2044)
Slope change
+3.2 (+2.7, +3.7)
Slope change
+4.8 (+3.9, +5.7)
Slope difference in MMSE score 6 months and 1 year prior AChEI treatment is 1.6 (P= 0.02) 10

11. Conclusion
Our observational findings on treatment of AD using AChEIs are similar to UK (NICE) and European guidelines and meta-analysis of RCTs (Cochrane, 2009).
Further investigations required to explain response to treatment by Black and Asian ethnic minority groups
Case registers provide important real-life clinical evidence.
Opportunities for Asian countries to explore Case registers with advance in technology

12. Acknowledgement
Prof. Robert Stewart (Professor of Psychiatric Epidemiology, Clinical Informatics & consultant in old age psychiatry)
Prof. Matthew Hotopf (Director of BRC & Dementia Unit)
Prof. Simon Lovestone (Professor of Translational Neuroscience at University of Oxford and founder director of SLAM BRC Nucleus)
Funding:
The data resource and all authors are funded by the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King's College London.  
The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health in the United Kingdom.