1. www.abdn.ac.uk Medium-term prognosis of an incident cohort of people with Parkinson’s and their carers vs a community-based control group Carl Counsell Clinical Reader & Hon Consultant in Neurology Chronic Disease Research Group Division of Applied Health Sciences

2. www.abdn.ac.uk Overview Aims of current grant Brief overview of PINE Results Implications / impact on patients and carers Future plans

3. www.abdn.ac.uk establish the medium-term prognosis of PD + other park: –survival, disability, motor progression, quality of life, motor and non-motor complications. compare some of these aspects of prognosis with an age- gender matched control group. identify factors that predict worse outcome in PD document the prognosis of carers with regards to quality of life, burden of care, and mood. Aims of the grant

4. www.abdn.ac.uk PINE Study Methods 1: Incidence period / population: Pilot: 18 months Nov 2002 – April 2004 (149,000 in 18 GPs) Main: 36 months April 2006 – March 2009 (317,000 in 37 GPs) Ascertainment: –Referrals from GPs –Referrals from hospital consultants –Hand-searching referral letters (neurology & DOME) –Electronic searching (GP, hospital discharge data) –Screening over 65 and over 75’s Inclusion Criteria –Parkinsonism (  2 of tremor, bradykinesia, rigidity, instability) –First suspicion during incident period –Not drug-induced

5. www.abdn.ac.uk Methods 2: assessments Baseline assessment 1: ? eligible –standard history and examination including motor UPDRS –clinical diagnosis If eligible  given study info & offered consent (a) None (b) Notes review (c) Survival (d) Full Baseline assessment 2: –Risk factors –Complete UPDRS and timed tests –Cognitive function (MMSE, MMP) –Disability (Schwab & England, Barthel ADL index) –Quality of life (Euroquol, PDQ-39) –Mood (GDS-15)

6. www.abdn.ac.uk Methods 3: carers and controls Carers Each patient was asked to nominate a carer Regular assessment of the carer’s own QoL, mood and carer burden (as well as proxy assessment of the patient’s QoL and disability) Controls Matched for general practice, age and sex Undergo the same assessments as the patients

7. www.abdn.ac.uk Methods 4: follow-up All patients were invited to undergo long-term follow-up: Notes based Survival tagging Yearly assessment (at home if reqd) Interim assessments as required At each contact, the diagnosis is reviewed Discuss issue of PM / brain donation if appropriate Carers and controls also undergo annual follow-up

8. www.abdn.ac.uk Baseline characteristics Survival vs controls Disease progression vs controls –institutionalisation –dementia –dead or dependent –motor function, quality of life, mental health Motor complications Predictors of survival and independent survival in PD Patient Results (as of 31/3/13, all 3 yrs FU, median 5 yrs FU)

9. www.abdn.ac.uk 377 patients 361 pts Parkinson’s disease 203 (56%) Dementia with lewy bodies 43 (12%) Parkinson’s plus 43 (12%) Vascular park 39 (11%) Non-eligible 33 (9%) 266 controls No consent 16 (4%) 262 controls Withdrew 4 (1.5%) Parkinsonian 2 No consent 2 Lost to follow-up n=3 Study Flow chart: latest diagnosis

10. www.abdn.ac.uk PD (n=203) Vascular (n=39) DLB (n=43) Park plus (n=43) Other (n=33) Controls (n=262) Age (yrs) 71.978.479.078.476.8 74.9 Male58%72%67%58%61%62% Caucasian99%97%100% 96% Lives alone 26% 38%30%26%18% 33% Depcat 1&2 52%38%67%53%30%46% Family Hx 15%5%9% 12%5% Smoker 42%59%60%58% 61% Vascular dis 30%54%37%51%45% 32% Duration (m) 1519121612 - Treated 12%26%9%16%9% - Baseline characteristics

11. www.abdn.ac.uk Baseline characteristics PDVascularDLBPark plusOtherControls Tremor 86%46%70%44%79% 13% Slowness 66%64%65%63%39% 8% Balance 30%69%67%81%42% 24% Falls 38%64%74% 54% 19% UPDRS (m) 25313334214 H-Y ≥3 26%50%58%64%36%- GDS-15 ≥5 30%64%30%73%58% 11% S-E <80 26%60%65%58%33% 6% MMSE <24 8%42%62%25%14% 1% PDQ-39 1518132120 -

12. www.abdn.ac.uk Patient survival by diagnosis PDVascularDLBPark plusOtherControls Deaths by 31/3/13 77 (38%)29 (75%)35 (81%)33 (77%)18 (54%) 57 (22%) Median survival in mths (95% CI) 92 (75-109) 25 (13-37) 39 (25-54) 32 (25-54) 63 (40-87) NE PMs 40 (21%) 7 (12%) PD vs control adjusted HR 2.0 (95% CI 1.3, 3.1)

13. www.abdn.ac.uk PD patient survival by age Median survival in mths (95% CI) <70yrs (n=61) NE ≥70yrs (n=142) 80 (69-91)

14. www.abdn.ac.uk Institutionalisation by diagnosis Median time to instit in mths (95% CI) PD NE Vasc58 (30-74) P plus51 (30-72) DLB27 (17-37)

15. www.abdn.ac.uk Dementia in PD vs controls Median time in mths PD (n=51) 103 Control (n=10)NE PD vs control adjusted HR 6.4 (95% CI 3.1, 13.5)

16. www.abdn.ac.uk PDVascularDLBPark plusControls Yr 035035035035 035 Dead 0%18%29%0%56%69%0%44%77%0%56%72% 0%11%18% Dead or dep 26% 47%68%60%94%100%65%97%100%58%95%100% 6%21%41% Death or dependency by diagnosis At 3 yrs: PD vs control adjusted OR = 2.3 (95% CI 1.2, 4.4)

17. www.abdn.ac.uk Motor function in PD survivors vs controls Slight worsening over 3 yrs but no different from controls

18. www.abdn.ac.uk GDS-15 in PD survivors vs controls Greater deterioration in PD patients vs controls over 3 yrs GDS ≥ 5Yr 0Yr 1Yr 2Yr 3 PD30%39%44%52% Control11%14% 15%

19. www.abdn.ac.uk MMSE in PD survivors vs controls Greater deterioration in PD patients vs controls over 3 yrs MMSE <24Yr 0Yr 1Yr 2Yr 3 PD8% 9%13% Control1%2%4%2%

20. www.abdn.ac.uk EQ-5D in PD survivors vs controls

21. www.abdn.ac.uk PDQ-39 in PD survivors

22. www.abdn.ac.uk Motor complications PDVascularDLBPark plus Motor fluctuations 18%0% 2% Dyskinesias 25%0%5% Motor fluctuationsDyskinesias

23. www.abdn.ac.uk Greater likelihood of death –older age, ever smoked, no tremor, [Rx in 1 st yr ?] –NOT gender, Depcat, living alone, vascular disease, baseline GDS/motor UPDRS/MMSE/H-Y Greater likelihood of death or dependency at 3 yrs –baseline disability (S&E) or UPDRS –NOT age, gender, Depcat, living alone, smoking, vascular disease, tremor, baseline GDS/MMSE/H-Y Greater likelihood of dementia –older age, baseline cognitive function, lack of tremor Predictors of poor outcomes in PD patients

24. www.abdn.ac.uk Carers in the PINE study: Aims describe the impact (burden) of caring for someone with Parkinson’s over time identify factors (patient and carer) that predict carer prognosis

25. www.abdn.ac.uk Annual carer assessments Update on any health problems Current medication Employment status/hours per week Any care/help given to patient (hours per day) and for how long Carer’s quality of life and health state (Euroquol-5D & VAS) Mood (GDS15) Impact of caring (Crossroads ABC scale)

26. www.abdn.ac.uk Baseline carer characteristics 1 PD carers (126) Other Parkinsonism carers (65) All carers (191) AVERAGE AGE (yrs)65.765.465.6 PERCENTAGE FEMALE71%86%73% RELATIONSHIP spouse/partner child other 77% 17% 6% 66% 31% 3% 73% 22% 5% EMPLOYMENT employed Unemployed/retired 29% 71% 31% 69% 30% 70% HOW LONG KNOWN Average no. of years495049

27. www.abdn.ac.uk Change in time spent caring PD CarersOther Park carersAll Carers BL (126) 3 years (97) BL (65) 3 years (33) BL (191) 3 years (130) HOW LONG CARING ? Not at all39%29%20%9%32%24% Less than 6 months 26%3%20%3%24%3% More than 6 months 34%66%58.4%76%42%68.5% HOW MANY HOURS PER DAY? average range 0.51 (0-3) 12 (1-10) 0.51

28. www.abdn.ac.uk EQ5D Utility score over time

29. www.abdn.ac.uk EQ5D VAS over time

30. www.abdn.ac.uk GDS15 over time GDS ≥ 5Yr 0Yr 3 PD15%14% Other Park 23%33%

31. www.abdn.ac.uk CROSSROADS ABC SCALE Measures carer strain/burden “Living with or caring for someone with a condition like Parkinson’s may cause stress or disruption to your life” 13 items

32. www.abdn.ac.uk Carer burden-”not at all” at 3 years PD CarersOther Park carersAll Carers BL (126) 3 years (97) BL (65) 3 years (33) BL (191) 3 years (130) Inconvenience Disturbed sleep Physical strain Confining/restricting Family adjustments Changes to plans Other time demands Emotional adjustments Upsetting behaviour Person changed Work adjustments Financial strain Completely overwhelming 64% 71% 70% 62% 75% 70% 69% 58% 75% 34% 85% 88% 60% 64% 68% 55% 65% 61% 62% 57% 61% 26% 76% 90% 56% 54% 61% 55% 46% 65% 55% 54% 52% 55% 15% 75% 85% 40% 51% 33% 42% 30% 51% 33% 24% 12% 67% 70% 33% 62% 68% 66% 58% 71% 66% 65% 57% 67% 27% 82% 86% 53% 59% 63% 59% 49% 59% 53% 59% 51% 22% 74% 85% 50%

33. www.abdn.ac.uk Predictors of burden at baseline PD CarersOther Park carersAll carers Carer depression Female carer Carer is younger Patient is dependent (low score on Barthel) Patient is dependent (low score on Barthel) Patient’s impairment (severity of PD) Patient has memory problems Patient is younger

34. www.abdn.ac.uk Carer burden over time

35. www.abdn.ac.uk Benefits to people with PD? Better understanding of prognosis → better treatment of patients and carers Higher level of death and dependency than previously thought esp atypical park and older onset PD despite best medical Rx Slight decline in non-motor aspects of disease over first 3yrs Carer outcomes relatively stable over 3 yrs Need for allied health input (?) and care (resources) Maximise QoL early in elderly

36. www.abdn.ac.uk Future plans for PINE study Further follow-up of cohort (funded to Feb 2016) Further analysis –Systematic reviews of prognosis –Prognostic modelling –Importance of co-morbidity –Carer/proxy outcomes Collaborative data pooling project

37. www.abdn.ac.uk Research Team Doctors –Carl Counsell (PI), Angus Macleod, Kate Taylor, David McGhee Research nurses –Clare Harris, Hazel Forbes, Anne Hayman, Joanne Gordon Secretary –Pam Rebecca, Susan Kilpatrick, Aileen Sylvester Information technology –Katie Wilde, David Dawson, Alasdair McDougal, Val Angus Statistician –Shona Fielding, Neil Scott Co-investigators –Amanda Lee

38. www.abdn.ac.uk Parkinson’s UK CSO NIHR RS Macdonald Trust BMA Doris Hillier BUPA Foundation NHS Grampian Endowments SPRING/local Park UK University of Aberdeen Thank you to our funders

39. www.abdn.ac.uk Any questions?