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

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

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

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)

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)

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

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

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)

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)

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

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

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.