1. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Effect of depression on survival among AD patients: An Application of CRIS in Dementia Research Dr Gayan Perera Senior Epidemiologist Institute of Psychiatry, Psychology & Neuroscience. King’s College London.

2. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Objectives  Predicting the Path of Cognitive Decline and survival in Dementia  Depression as a risk factor for survival of dementia patients  To Demonstrate Importance of Clinical Records Interactive Search (CRIS) in Mental Health Research

3. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Introduction: Dementia Characterised by cognitive impairment: measured using MMSE Prevalence of dementia is increasing Cost of dementia Dementia subtypes: AD Medication only delay progression of dementia Focus on primary prevention Risk factors of survival:

4. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk AD dx Death Reliable ability to predict prognosis and survival has far- reaching personal, social & economic implications. Factors that influence disease progression and mortality are not well understood. Background: Justification

5. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk AD dx Death Limitations: - Mental illness hx exclusion criterion - Self-report symptoms vs diagnosis - Psychological factors just not studied Stern et al. Jama 1997 Lapane et al. Neurology 2001 Walsh et al. Annals Intern Med 1990 Carlson et al. J Gerontology 2001 Tschanz et al. Neurology 2004 Background

6. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk AD dx DeathDepression dx Blazer et al. J Gerontol A Biol Sci Med Sci 2001 Furlanetto et al. Psychosomatics 2000 Lavretsky et al. Am J Psychiatry 2010 Diniz et al. Br J Psychiatry 2013 Ownby et al. Arch Gen Psychiatry 2006 Background ?

7. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk AD dx Death Depression dx Does depression (and/or anxiety) pre- or on- date of AD diagnosis affect survival? Study question

8. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk King’s College London (KCL) South London and Maudsley (SLAM) SLAM Biomedical Research Centre (BRC) Case Register United Kingdom London South London

9. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk The SLAM BRC-Mental Health Case Register Electronic Health Record The Patient Journey System (PJS) 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) Socio-demographics Correspondence letters Event notes Medication notes Clinical observations & investigations Ability to read Word/ PDF documents

10. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Today she scored 5/30 on the MMSE I reviewed Mrs. ZZZZZ on 6th March

11. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Why use mental health Case register data? Powerful tool to investigate ‘real world’ outcomes Symptoms, presentations, adverse events, specific service use Comorbidity Pharmacotherapy Large case samples Longitudinal data Outcomes – predictors (and response to interventions) Data linkage (Perera et al. (2009, British J of Psychiatry)

12. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Cohort: All patients diagnosed with AD for the first time and age 65 or over. Inclusion: Only included patients who were diagnosed with AD during 1 st Jan 2008 and 31 st Dec 2013. Census date: Survival analysis carried out using census point as 1 st June 2014 or the recorded death date. Survival analysis: Cox proportional-hazards regression Cognitive decline: longitudinal change in MMSE Methods

13. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Results Characteristics of the study population: Demographics Variable No depression on or before dementia diagnosis (n=3036) (%) Had depression on or before dementia diagnosis (n=941) (%) Age at dementia diagnosis <6523 (0.76%)18 (1.88%) 65- 69126 (4.15%)61 (6.36%) 70- 74337 (11.10%)108 (11.47%) 75- 79597 (19.66%)183 (19.6%) 80- 84817 (26.91%)255 (26.8%) 85- 89770 (25.36%)215 (22.84%) 90 & over366 (12.06%)101 (11.05%) Number of deceased patients1252 (41.24%)426 (45.46%) Average number of years of follow-up till census point (SD) 2.80 (1.55)2.58 (1.59) Gender Female1920 (63.24%)666 (70.7%) Male1115 (36.73%)275 (29.3%) Ethnicity European2400 (79.05%)776 (83.25%) Non-European563 (18.54%)155 (16.75%) Ethnicity missing73 (2.40%)10 (1.04%)

14. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Results Characteristics: Psychiatric measurements Variable No depression on or before dementia diagnosis (n=3036) (%) Had depression on or before dementia diagnosis (n=941) (%) Medications Psychotropic medication ever 1017 (33.50%)914 (97.13%) Antidepressants ever 486 (16.01%)886 (94.16%) Antipsychotics ever 225 (7.41)221 (23.49%) Anxiolytics ever 127 (4.18%)168 (17.85%) Hypnotics ever 98 (3.23%)128 (13.60%) Cognitive impairment after AD diagnosis Mean MMSE score (SD)18.48 (6.32)19.04 (6.18)

15. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Probability of survival of those AD patients with and without depression

16. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Predictors of mortality among AD patients

17. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Slope difference between two groups0.67(p value: 0. 81) Cognitive decline among AD patients with and without depression 2.4 (-0.31 to 4.13) 3.1 (0.59 to 4.94) Diagnosed with depression on or before AD (n=941) No diagnosis of depression on or before AD (n=3036)

18. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Cognitive decline among AD patients with and without depression -1.09 (-2.11 to -0.58) -1.02 (-1.71 to -0.76) Slope difference between two groups0.07 (p value: 0.61) Diagnosed with depression on or before AD (n=941) No diagnosis of depression on or before AD (n=3036)

19. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Findings Presence of depression before diagnosis of AD is associated with mortality However, presence of depression before diagnosis was not associated for cognitive decline among AD

20. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Conclusion Data can be used to investigate predictors of outcomes such as mortality – Depression before AD as a risk factor of survival of AD patients Hypothesis/ observations can be tested using ‘real world’ data – Survival analysis among AD patients Can be used to influence policy – To influence public health prevention strategy in AD

21. Biomedical Research Centre for Mental Health and Dementia Unit at South London and Maudsley NHS Foundation Trust the Institute of Psychiatry, King’s College London brc.slam.nhs.uk Acknowledgement Prof. Robert Stewart (Professor of Psychiatric Epidemiology, Clinical Informatics & consultant in old age psychiatry) CRIS team 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. Contact: gayan.perera@kcl.ac.ukgayan.perera@kcl.ac.uk Thank you