Effect of centrally acting ACE inhibitors on Alzheimer’s disease progress: A retrospective longitudinal study using SLAM BRC Case register Dr Gayan Perera Epidemiologist Institute of Psychiatry, King’s College London SLAM Biomedical Research Centre & Dementia Unit

Effect of centrally acting ACE inhibitors on Alzheimer’s disease progress Studies show a positive relationship between hypertension and cognitive decline (Framingham study, Honolulu-Asia Aging Study) Clinical trials have shown inconclusive results on ACE inhibitors on dementia Perindopril, a Central-ACEIs protect against cognitive impairment compared to Enalapril and Imidapril (Non-Central-ACEIs) in mouse models Rate of cognitive decline was lower among patients who newly started on C-ACEIs compared to patients not on any C-ACEIs (Gao et al, 2014)

Objectives Compare cognitive trajectories for those who received: Centrally Acting ACE inhibitors (C-ACEIs) Non-centrally Acting ACE inhibitors (NC-ACEIs) AChEIs

Methods Population: All patients diagnosed with AD diagnosed at any point during 1st Jan 2000 and 31st May 2014 and receiving AChEIs Exposure: Centrally Acting ACE Inhibitors, Non-centrally Acting ACE Inhibitors, No ACE inhibitors Outcome: All MMSE scores from the date of AD up to 3 years were used to model cognitive trajectories.

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. 1.3 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 Ref: Perera et al., 2015 ( BMJ Open)

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

Cognitive decline among AD patients receiving ACE inhibitors Patients receiving centrally Acting ACE inhibitors (n=1,234, MMSE points=5,734) Patients receiving non-centrally acting ACE inhibitors (n=145, MMSE points= 487) Patients not receiving ACE inhibitors (n=4,206, MMSE points=21,765) Time since AD diagnosis (years) Time since AD diagnosis (years) Time since AD diagnosis (years)

Cognitive decline among dementia patients receiving ACE inhibitors Patients receiving centrally Acting ACE inhibitors (n=1,234, MMSE points=5,734) Patients receiving non-centrally acting ACE inhibitors (n=145, MMSE points= 487) MMSE slope   Centrally Acting ACE inhibitors Non-Centrally Acting ACE inhibitors Slope difference (MMSE per year) P value 0- 1 year 0.44 -0.24 0.68 0.03 1- 3 years -1.12 -0.30 -0.40 0.36 Time since AD diagnosis (years) Time since AD diagnosis (years)

Cognitive decline among dementia patients receiving ACE inhibitors Patients receiving centrally Acting ACE inhibitors (n=1,234, MMSE points=5,734) Patients not receiving ACE inhibitors (n=4206, MMSE points=21,765) MMSE slope   Centrally Acting ACE inhibitors No ACEIs Slope difference (MMSE per year) P value 0- 1 year 0.44 -0.06 0.50 0.02 1- 3 years -1.12 -0.92 -0.10 0.48 Time since dementia diagnosis (years) Time since dementia diagnosis (years)

Conclusion During 1st year after diagnosis of dementia cognitive improvement was significantly better for those who received Centrally acting ACE inhibitors compared with those who received non-centrally acting ACE inhibitors or those who did not receive any ACE inhibitors. Further research is needed using RCTs Electronic Psychiatric Case Registers as a research tool for Asian countries

Acknowledgement Prof. Robert Stewart (Professor of Psychiatric Epidemiology, Clinical Informatics & consultant in old age psychiatry) Prof. Rob Howard (Professor of Old Age Psychiatry, formerly at SLAM/ IOPPN) Dr. Karim Fazal (SPR in Psyhiatry) Funding: The data resource and researcher 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 researchers and not necessarily those of the NHS, the NIHR or the Department of Health in the United Kingdom. Thank you