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 CounsellClinical Reader & Hon Consultant in Neurology

Chronic Disease Research GroupDivision of Applied Health Sciences

www.abdn.ac.uk

Overview

• Aims of current grant

• Brief overview of PINE

• Results

• Implications / impact on patients and carers

• Future plans

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

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

www.abdn.ac.uk

Methods 2: assessmentsBaseline 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)

www.abdn.ac.uk

Methods 3: carers and controlsCarers• 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

www.abdn.ac.uk

Methods 4: follow-upAll 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

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)

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

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) 71.9 78.4 79.0 78.4 76.8 74.9

Male 58% 72% 67% 58% 61% 62%

Caucasian 99% 97% 100% 100% 100% 96%Lives alone 26% 38% 30% 26% 18% 33%Depcat 1&2 52% 38% 67% 53% 30% 46%

Family Hx 15% 5% 9% 9% 12% 5%Smoker 42% 59% 60% 58% 58% 61%Vascular dis 30% 54% 37% 51% 45% 32%Duration (m) 15 19 12 16 12 -Treated 12% 26% 9% 16% 9% -

Baseline characteristics

www.abdn.ac.uk

Baseline characteristics

PD Vascular DLB Park plus Other Controls

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% 74% 54% 19%UPDRS (m) 25 31 33 34 21 4

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 15 18 13 21 20 -

www.abdn.ac.uk

Patient survival by diagnosis

PD Vascular DLB Park plus Other Controls

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)

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)

www.abdn.ac.uk

Institutionalisation by diagnosis

Median time to instit in mths

(95% CI)PD NE

Vasc 58 (30-74)

P plus 51 (30-72)

DLB 27 (17-37)

www.abdn.ac.uk

Dementia in PD vs controls

Median time in mths

PD (n=51) 103Control (n=10) NE

PD vs control adjusted HR 6.4 (95% CI 3.1, 13.5)

www.abdn.ac.uk

PD Vascular DLB Park plus Controls

Yr 0 3 5 0 3 5 0 3 5 0 3 5 0 3 5Dead 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)

www.abdn.ac.uk

Motor function in PD survivors vs controls

Slight worsening over 3 yrs but no different from controls

www.abdn.ac.uk

GDS-15 in PD survivors vs controls

Greater deterioration in PD patients vs controls over 3 yrs

GDS ≥ 5 Yr 0 Yr 1 Yr 2 Yr 3

PD 30% 39% 44% 52%

Control 11% 14% 14% 15%

www.abdn.ac.uk

MMSE in PD survivors vs controls

Greater deterioration in PD patients vs controls over 3 yrs

MMSE <24 Yr 0 Yr 1 Yr 2 Yr 3

PD 8% 8% 9% 13%

Control 1% 2% 4% 2%

www.abdn.ac.uk

EQ-5D in PD survivors vs controls

www.abdn.ac.uk

PDQ-39 in PD survivors

www.abdn.ac.uk

Motor complications

PD Vascular DLB Park plus

Motor fluctuations 18% 0% 0% 2%

Dyskinesias 25% 0% 5% 5%

Motor fluctuations Dyskinesias

www.abdn.ac.uk

• Greater likelihood of death– older age, ever smoked, no tremor, [Rx in 1st 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

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 carerprognosis

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)

www.abdn.ac.uk

Baseline carer characteristics 1PD carers

(126)

Other Parkinsonism carers

(65)

All carers

(191)

AVERAGE AGE (yrs) 65.7 65.4 65.6PERCENTAGE FEMALE 71% 86% 73%

RELATIONSHIPspouse/partnerchildother

77%17%6%

66%31%3%

73%22%5%

EMPLOYMENTemployedUnemployed/retired

29%71%

31%69%

30%70%

HOW LONG KNOWN Average no. of years 49 50 49

www.abdn.ac.uk

Change in time spent caringPD Carers Other Park carers All Carers

BL(126)

3 years(97)

BL(65)

3 years(33)

BL(191)

3 years(130)

HOW LONG CARING ?

Not at all 39% 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?

averagerange

0.5 1(0-3)

1 2(1-10)

0.5 1

www.abdn.ac.uk

EQ5D Utility score over time

www.abdn.ac.uk

EQ5D VAS over time

www.abdn.ac.uk

GDS15 over time

GDS ≥ 5 Yr 0 Yr 3

PD 15% 14%

Other Park

23% 33%

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

www.abdn.ac.uk

Carer burden-”not at all” at 3 yearsPD Carers Other Park carers All Carers

BL(126)

3 years(97)

BL(65)

3 years(33)

BL(191)

3 years(130)

InconvenienceDisturbed sleepPhysical strainConfining/restrictingFamily adjustmentsChanges to plansOther time demandsEmotional adjustmentsUpsetting behaviourPerson changedWork adjustmentsFinancial strainCompletely overwhelming

64%71%70%62%75%70%69%58%75%34%85%88%60%

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%51%33%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%51%22%74%85%50%

www.abdn.ac.uk

Predictors of burden at baselinePD Carers Other Park carers All carers

Carer depression Carer depression Carer depression

Female carer Female carer

Carer is youngerPatient 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

www.abdn.ac.uk

Carer burden over time

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

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

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

www.abdn.ac.uk

Parkinson’s UK CSO NIHRRS Macdonald Trust BMA Doris Hillier BUPA FoundationNHS Grampian Endowments SPRING/local Park UK University of Aberdeen

Thank you to our funders

www.abdn.ac.uk

Any questions?