PPMI Prodromal cohort Hyposmia - ppmi-info.org · PPMI Prodromal cohort . Hyposmia . Danna Jennings, MD Institute of Neurodegenerative disorders May 7, 2014 PPMI 2014 Annual Meeting

PPMI Prodromal cohort Hyposmia

Danna Jennings, MD Institute of Neurodegenerative disorders

May 7, 2014

PPMI 2014 Annual Meeting

Prodromal Cohort for PPMI

Hyposmic Subjects RBD Subjects

DAT imaging

Eligible for PPMI Not eligible for PPMI

80% Mild to moderate DAT 20% Min to No-DAT Min to No-DAT

500-700 Subjects scanned

Advantages/Disadvantages of using hyposmia to screen for prodromal PD

Advantages

• Generalizable • Practical • Graspable • Screening at home • Relatively inexpensive • UPSIT is a sensitive for PD • Broad outreach increases

PD awareness

Disadvantages • Requires extensive

outreach • Those willing to do test

at home may not be willing to engage in clinic activities

• UPSIT lacks specificity for PD

Phenoconversion

P A R S

Year 2 Year 4

DAT deficit at BL (n=23, 11%) 7 (30%) 14 (61%)

Indeterminant at BL (n=34) 1 (3%) 2 (6%)

No DAT deficit at BL (n=146) 2 (1%) 4 (3%)

DAT deficit any scan (n=38) 10 (28%) 18 (47%)

Baseline: n=203 Year 2: n=177 (87% retention) Year 4: n=139 (66% retention, so far)

PARS 4 year Longitudinal Hyposmic Data

Surveys completed (mail, on line)

UPSITs mailed to subjects

UPSITs returned, hyposmics identified, referred to sites

Complete Imaging

Enrollment (if deemed eligible)

P-PPMI Hyposmic Cohort:

Process for Identifying Prodromal Subjects

Olfactory Core

PPMI Sites

Site # Site Name Subjects referred Consented Eligible Enrolled

001 Univ of Rochester 0* 006 Oregon Health Sci Univ 26 7 2 2 007 Baylor College of Med 17 012 The Parkinson's Institute 29 3 018 Univ of Pennsylvania 51 6 3 3 019 Univ of S Florida 13 023 Univ Calif San Diego 25 3 028 Johns Hopkins 19 032 Emory 11 1 034 IND 75 24 3 2 040 Boston Univ 16 1 057 Univ of Alabama 21 3 088 Northwestern 20 1 1 089 Univ Cinncinati 0* 096 Univ Washington/VA Puget Sound 0* 120 Cleveland Clinic 17 5 1 1 154 Banner Research Institute 18 9 196 PD and Mov Dis Center of Boca Raton 7 289 University of Tubingen - Germany 1 1 290 Paracelisus-Elena Klinik - Germany 0 291 Univ of Innsbruck - Austria 0 295 Imerial College London -England 11 327 University of Salerno - Italy 3

Hyposmic Enrollment by Site

*recent activation or not yet activated

6296 Eligible Surveys

3820 61% Returned UPSITs

535 14% Hyposmics

64 12% Completed Imaging 8 12% DAT deficit

P-PPMI Olfactory Cohort

Hyposmic Recruitment: How long does it take?

Eligible Survey

Returned UPSIT

Complete Imaging

Hyposmic Recruitment: How long does it take?

Eligible Survey

Returned UPSIT

Complete Imaging

• 28 days (range 1-453, median 21)

• 77 days (range 22-207, median 64)



535 14% Hyposmics

64 12% Completed Imaging

8 12% DAT deficit

P-PPMI Olfactory Cohort : Surveys

0

200

400

600

800

1000

1200

1400

Paper

Online

68% online surveys 32% paper surveys

All Eligible Ineligible n=7365 n=6439 n=926 MJFF 2861 2626 (92%) 235 (8%) Friend/Family 2196 1746 (80%) 450 (20%) Site Activities 1109 1006 (91%) 103 (9%) Mailing 121 111 (92%) 10 (8%) Other/unknown 1341 950 (71%) 391 (29%)

MJFF

Friend/Family

Site Activities

Mailing

Other/unnknown

0

500

1000

1500

2000

newsletters, emails, events

FTF MJFF website

Smell Surveys – Referral Sources

Reason ineligible zip code 488 (53%) diagnosis of PD 197 (21%) incomplete survey 142 (15%) age <60 85 (9%) diagnosis of AD 14 (2%)

MJFF Referrals

Site Referrals

Referral sources for all returning a survey

0

500

1000

1500

2000

Doctor or HC provider

Site Local media



535 14% Hyposmics


P-PPMI Olfactory Cohort: Returned UPSITs

0

100

200

300

400

500

600

700

800

all hyposmic normosmics (n=3820) (n=535) (n=3285) age (range) 67.9 (60-94) 69.7 (60-92) 67.6 (60-94) gender

male 1284 (34%) 214 (40%) 1070 (33%) female 2536 (66%) 321 (60%) 2215 (67%)

race caucasian 3737 (98%) 531 (99%) 3225 (98%)

asian 27 (<1%) 3 (<1%) 24 (<1%) black/AA 27 (<1%) 0 27 (1%)

Amer Indian 9 (<1%) 1 (<1%) 9 (<1%)

loss of sense of smell yes 823 (22%) 419 (78%) 404 (13%) no 2382 (62%) 84 (16%) 2298 (70%)

unsure 615 16%) 32 (6%) 583 (18%) family history

1st degree 980 (26%) 131 (24%) 849 (26%) 2nd degree 227 (6%) 33 (6%) 194 (6%) any relative 1165 (31%) 122 (23%) 1043 (32%)

none/unknown 2613 (68%) 371 (69%) 2242 (68%) laxatives

yes 401 (10%) 64 (12%) 337 (10%) no 3382 (88%) 460 (86%) 2922 (89%)

unsure 37 (2%) 11 (2%) 26 (1%) BM frequency

< 1 /day 721 (19%) 129 (24%) 5921 (18%) once/day 1953 (51%) 266(50%) 1687 (51%) twice/day 877 (23%) 112 (21%) 765 (23%)

three or more/day 269 (7%) 28 (5%) 241 (7%)

UPSIT Completers: Demographics

all hyposmic normosmics (n=3820) (n=535) (n=3285) age (range) 67.9 (60-94) 69.7 (60-92) 67.6 (60-94) gender

male 1284 (34%) 214 (40%) 1070 (33%) female 2536 (66%) 321 (60%) 2215 (67%)

race caucasian 3737 (98%) 531 (99%) 3225 (98%)

asian 27 (<1%) 3 (<1%) 24 (<1%) black/AA 27 (<1%) 0 27 (1%)

Amer Indian 9 (<1%) 1 (<1%) 9 (<1%)


unsure 615 16%) 32 (6%) 583 (18%) family history



yes 401 (10%) 64 (12%) 337 (10%) no 3382 (88%) 460 (86%) 2922 (89%)


< 1 /day 721 (19%) 129 (24%) 5921 (18%) once/day 1953 (51%) 266(50%) 1687 (51%) twice/day 877 (23%) 112 (21%) 765 (23%)

three or more/day 269 (7%) 28 (5%) 241 (7%)

UPSIT Completers: Demographics

hyposmic consented declined (n=535) (n=64) (n=379) age (range) 69.7 (60-92) 69.7 (60-82) 70.6 (60-92) gender

male 214 (40%) 24 (36%) 138 (36%) female 321 (60%) 40 (64%) 241 (64%)

race caucasian 531 (99%) 64 (100%) 364 (96%)

asian 3 (<1%) 0 (0%) 9 (2%) black/AA 0 (0%) 0 (0%) 3 (1%)

Amer Indian 1 (<1%) 0 (0%) 2 (<1%)


unsure 32 (6%) 11 (3%) 63 (17%) family history



yes 64 (12%) 6 (9%) 50 (13%) no 460 (86%) 58 (91%) 321 (85%)


< 1 /day 129 (24%) 14 (22%) 90 (24%) once/day 266 (50%) 37 (57%) 180 (47%) twice/day 112 (21%) 10 (16%) 79 (21%)

three or more/day 28 (5%) 3 (5%) 30 (8%)

Hyposmic (Consent and declined): Demographics

hyposmic consented declined (n=535) (n=64) (n=379) age (range) 69.7 (60-92) 69.7 (60-82) 70.6 (60-92) gender

male 214 (40%) 24 (36%) 138 (36%) female 321 (60%) 40 (64%) 241 (64%)

race caucasian 531 (99%) 64 (100%) 364 (96%)

asian 3 (<1%) 0 (0%) 9 (2%) black/AA 0 (0%) 0 (0%) 3 (1%)

Amer Indian 1 (<1%) 0 (0%) 2 (<1%)


unsure 32 (6%) 11 (3%) 63 (17%) family history



yes 64 (12%) 6 (9%) 50 (13%) no 460 (86%) 58 (91%) 321 (85%)


< 1 /day 129 (24%) 14 (22%) 90 (24%) once/day 266 (50%) 37 (57%) 180 (47%) twice/day 112 (21%) 10 (16%) 79 (21%)

three or more/day 28 (5%) 3 (5%) 30 (8%)

Hyposmic (Consent and declined): Demographics



535 14% Hyposmics


P-PPMI Olfactory Cohort: Imaging Visits

0

2

4

6

8

10

12

14

P-PPMI Olfaction compared to PARS

P-PPMI PARS 6296 Eligible Surveys 9398

3820 61% Returned UPSITs 53% 4999

535 14% Hyposmics 13% 669

64 12% Completed Imaging 30% 203 8 12% DAT deficit 11% 23

P-PPMI PARS 6296 Eligible Surveys 9398

3820 61% Returned UPSITs 53% 4999

535 14% Hyposmics 13% 669

64 12% Completed Imaging 30% 203 8 12% DAT deficit 11% 23

P-PPMI Olfaction compared to PARS

Differences between PPMI Olfaction and PARS

• Outreach more centralized by email, social media

• LPs required • Visits 3-4 times/yr • Provide info about risk

(80% with DAT deficit scan)

• Outreach by local mailings and site recruitment

• LPs optional • Annual Visits • Little info about risk

PPMI PARS

Where are all the hyposmics?

Hyposmics N=535

Consented and

imaged n=64

Declined site referral/no response

n=160

Females not referred n=76

Declined participation at site n=219

(65 were contacted w/ no response)

In process N=16

28% (7/2) of mailing responders* 25% (8/2) support group* 20% (13/62) of those from local media 19% (12/119) of friends and family 8% (6/74) of those from site 7% (21/310) of those from MJFF

Referral Source All eligible

(n=535) Consented to

Imaging (n=64)

Declined (at any point in process)

(n=379) MJFF 310 (58%) 21 (33%) 158 (42%) Friends/Family 119 (22%) 12 (19%) 84 (22%) Local media 62 (12%) 13 (20%) 49 (13%) Site 74( 14%) 6 (9%) 49( 13%) Mailing 7 (1%) 2 (3%) 5 (1%) Support group 8 (1%) 2 (3%) 5 (1%) Unknown 48 (9%) 6 (9%) 29 (8%)

Hyposmic Referral Sources

Referral Sources of subjects most likely to consent

Reasons for Decline – at the Site Level (n=219)

Reason for decline # declined Contact attempted, no response 65 (30%) Lumbar puncture** 34 (16%) Not interested 29 (14%) Time commitment 30 (14%) Exclusionary medical condition 24 (11%) Travel/transportation 19 (9%) Other 11 (5%) Datscan 6 (3%)

**If LP were not required there would be roughly 30 less decliners and 1.5 times more subjects who would have been eligible (estimate 15 eligible vs 10).

Contact attempted, no response Lumbar puncture

Not interested

Time commitment

Exclusionary medical condition Travel/transportation Other

0

20

40

60

80

100

120

140

Phone Clinic visit Email Mail

Method of Contact for Decliners

Eligible Subjects (n=10)

Site Age Gender Referral Source Race PD Family Hx

Laxative/Stool

softener use

Bowel Movement Frequency

Notes decreased sense of

smell

UPSIT - total

correct UPSIT

percentile

006 OHSU 73 M MJFF Website White/Caucasian Unsure No Once per day Yes 19 6

006 OHSU 62 F Local news article

White/Caucasian None No Three per day Unsure 22 2

018 UPENN 66 F ABC Philadelphia

White/Caucasian

Biological Father No Less than once

per day Yes 23 5

018 UPENN 66 F MJFF

Newsletter;Email or Event

White/Caucasian None No Once per day No 22 5

018 UPENN 74 F Local Newspaper

White/Caucasian None No Once per day Yes 12 3

034 IND 63 M Local Newspaper

White/Caucasian None No Once per day No 16 2

034 IND 81 M Google/Website

White/Caucasian None No Once per day Yes 12 5

034 IND 82 M Friend or Family Member

White/Caucasian None Yes Once per day No 18 10

088 Northwestern 68 F MJFF Website White/Caucasia

n None No Less than once per day Yes 13 1

120 Cleve Clinic 60 M

Doctor or Medical Care

Provider

White/Caucasian

Biological Father,Paternal

Aunts and Uncles

No Once per day Yes 18 4

Olfactory Recruitment…it’s all about the numbers

P-PPMI Triple surveys

Triple surveys, increase consent rate to 17%

Triple surveys, remove LP requirement

Double surveys, consent rate to 20%

Double surveys, consent rate to 20%, remove LP requirement

6296 18,000 18,000 18,000 12,000 12,000

3820 61% Returned UPSITs 10980 10980 10980 7320 7320

535 14% Hyposmics 1537.2 1537.2 1537.2 1024.8 1024.8

64 12% Completed

Imaging 184.5 261.3 276.7 205.0 307.4 8 12% DAT deficit 22.1 31.4 33.2 24.6 36.9

Reaching the Olfactory Destination

• 30 subjects (24 DAT deficit, 6 no DAT deficit) and enrolled by end of 2014 (60% males)

• Increase percent of individuals willing to consent – Modify an aspect of the protocol – re-contact declining

subjects – Additional support to sites to reach out to subjects – Modify messaging at initial visit/phone call

• Double the number of surveys – Local media – Engage existing cohorts (Alz Prevention Registry; genetics

gene negative individuals) – Focused mailings with local references – Complete surveys at the clinic/event

• Increase Percentage of Eligible subjects – Increase male:female ratio by monitoring female referrals to

site

“You can’t change the wind, but you can adjust the sails.” Jimmy Dean

Documents

PPMI Prodromal cohort Hyposmia - ppmi-info.org · PPMI Prodromal cohort . Hyposmia . Danna Jennings, MD Institute of Neurodegenerative disorders May 7, 2014 PPMI 2014 Annual Meeting