1. 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

2. 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)

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

4. 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.

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

6. 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)

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

8. 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)

9. 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)

10. 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)

11. 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

12. 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