Presentation is loading. Please wait.

Presentation is loading. Please wait.

©2012 MFMER | 3188678-1 ADNI Clinical Core Paul Aisen Ron Petersen Michael Donohue Jennifer Salazar.

Published byDamon Boone Modified over 8 years ago

Similar presentations

Presentation on theme: "©2012 MFMER | 3188678-1 ADNI Clinical Core Paul Aisen Ron Petersen Michael Donohue Jennifer Salazar."— Presentation transcript:

1 ©2012 MFMER | 3188678-1 ADNI Clinical Core Paul Aisen Ron Petersen Michael Donohue Jennifer Salazar

2 ADNI 2 Enrollment Update ADNI2 enrollment closed - July 1, 2013 New ADNI2 subjects enrolled: 767 (not including baseline fails) ADNI 1 continuations to ADNI 2: 276 ADNI GO continuations to ADNI 2: 120 Total Enrolled in ADNI 2: 1,033 ((767 totaled enrolled in ADNI2 - 130 reported discontinuations) + 276 ADNI1 rollovers + 120 ADNIGO rollovers) ©2012 MFMER | 3188678-2

3 ©2012 MFMER | 3188678-3 ADNI2 Cumulative Enrollment by Cohort – April 2014

4 ©2012 MFMER | 3188678-4 CN n=184 SMC n=103 EMCI n=301 LMCI n=160 AD n=142 Combined n=891P Age (yrs) 73.4 (6.3) 72.2 (5.6) 71.3 (7.4) 71.9 (7.7) 74.6 (8.1) 72.5 (7.3) <0.001 Female 94 (51%) 61 (61%) 132 (44%) 75 (47%) 57 (40%) 419 (47%) 0.021 Education 16.5 ( 2.5) 16.7 (2.6) 16.0 (2.7) 16.5 (2.6) 15.8 (2.6) 16.3 (2.6) 0.009 CDR-SB 0.0 (0.1) 0.01 (0.2) 1.3 (0.8) 1.8 (1.0) 4.5 (1.7) 1.5 (1.7) <0.001 ADAS 13 9.2 (4.5) 8.7 (4.3) 12.7 (5.4) 18.8 ( 7.1) 31.0 (8.3) 15.5 (9.6) <0.001 MMSE 29.0 (1.3) 29.0 (1.2) 28.3 (1.6) 27.6 (1.8) 23.1 (2.1) 27.6 (2.6) <0.001 Part. ECog 1.3 (0.3) 1.6 (0.3) 1.8 (0.5) 1.9 (0.6) 1.7 (0.5) <0.001 Study Part. Ecog 1.2 (0.3) 1.3 (0.3) 1.6 (0.5) 1.9 (0.7) 2.7 (0.7) 1.7 (0.7) <0.001 ADNI GO + 2 Baseline

5 ADNI 1+ GO + 2 Projected Dropouts ©2012 MFMER | 3188678-5 NCEMCILMCIAD Reported 5%7%13%19% 14 months* 11%13%19%21% *projections include reported dropouts and late data entry; assumes 14 months late in data entry = dropout

6 ©2012 MFMER | 3188678-6 Assumes no data in 14 months = dropout

7 ©2012 MFMER | 3188678-7 Assumes no data in 14 months = dropout

8 ©2014 MFMER | 3343740-8 Dx ADAS 13 50 40 30 20 10 0 CNSMCEMCILMCIAD MMSE Dx 21 CNSMCEMCILMCIAD 24 27 30 CDRSB Dx 0 CNSMCEMCILMCIAD 2.5 5.0 7.5 10.0

9 ©2014 MFMER | 3343740-9 ECog Self Total Dx CNSMCEMCILMCIAD 1 2 3 Dx CNSMCEMCILMCIAD ECog Partner Total

10 ©2014 MFMER | 3343740-10 ECog Total Dx Self 1 2 3 Partner CN SelfPartner SMC SelfPartner EMCI SelfPartner LMCI SelfPartner AD 4

11 ©2014 MFMER | 3343740-11 Participant 1 1 2 3 4 234 Study partner ECog Memory Score Count 4 8 12 16 Dx (corr) CN (0.34) SMC (0.25) EMCI (0.25) LMCI (0.28) AD (-0.01)

12 ©2014 MFMER | 3343740-12 Study partner Participant 1 1 2 3 4 23 ECog Total Score Count 2 4 6 8 Dx (corr) CN (0.40) SMC (0.27) EMCI (0.23) LMCI (0.24) AD (0.18)

13 ©2014 MFMER | 3343740-13 ADAS 13 ADAS 13 change Month -5 0 Mean and 95% CI 0 5 10 15 6122436 AD LMCI EMCI SMC CN

14 ©2014 MFMER | 3343740-14 MMSE MMSE change Month -2 0 Mean and 95% CI 0 6122436 -4 AD LMCI EMCI SMC CN

15 NL to MCI (1+GO+2)* ©2012 MFMER | 3188678-15 * Imputed baseline AV45 where not observed

16 NL to MCI (GO+2) ©2012 MFMER | 3188678-16

17 EMCI to AD (GO+2) ©2012 MFMER | 3188678-17

18 LMCI to AD (1+GO+2) ©2012 MFMER | 3188678-18

19 LMCI to AD (GO+2) ©2012 MFMER | 3188678-19

20 ADNI3 CLINICAL CORE Paul Aisen Ron Petersen Mike Donohue Mike Weiner

21 ADNI3 Primary Aim  Validate biomarkers for clinical trials  To guide ADNI3, we need to reach consensus on the direction of future AD trials

22 ADNI3 additional goals  Address gaps in our understanding of the clinical spectrum of AD  Utilize biomarker advances (eg tau PET) to further elucidate AD neurobiology  Evaluate outcome measures, including computerized cognitive assessments  Facilitate new and promising trial designs

23 Focus on early stage disease?  Biggest gaps are early  Very early trials may be optimal for disease- modification. The likelihood of major, useful advances in AD dementia trials may be small.  There is certainly a need for drug development in AD dementia, including disease-modifiers, cognitive enhancers and behavioral therapies. But such trials are based on clinical/cognitive/behavioral measures that are fairly well established.

24 ADNI2 cohorts  Normal: CDR=0, no subjective complaints, LogMem nl, MMSE 24-30, age>=65 or 70 (adjusted periodically, wider range for minorities)  SMC: CDR=0, subjective complaints, LogMem nl, MMSE 24-30, age>=65 or 70 (adjusted periodically)  EMCI: CDR=.5, LogMem 1sd below norm, MMSE 24- 30, age 55-90  LMCI: CDR=.5, LogMem 1.5sd below norm, MMSE 24- 30, age 55-90  Mild AD: CDR=.5-1, dementia, LogMem 1.5sd below norm, MMSE 20-26, age 55-90

25 ADNI3 clinical trial aims  Study the utility of imaging and biochemical markers in prodromal and preclinical AD trials  Optimize cognitive and PRO-type measures in prodromal and preclinical AD trials  Facilitate primary prevention trials (?), ie, treatment before brain amyloid is elevated  This would be new territory and somewhat risky  In favor: primary prevention is the ultimate goal, and ADNI must lead the way  Against: Is industry interested? Can we find an efficient way to study individuals not yet at the preclinical stage?

26 These aims suggest:  Drop AD dementia from ADNI?  Continue indefinite follow-up of other existing ADNI2 cohorts  Add new biomarkers (tau PET)  Manage overall subject burden (drop FDG PET?)  Include: cognitive measures optimized for clinically normal subjects, computerized assessments, PROs, possibly explore functional performance testing  Reduce lower age limit (?)  Consider ways to enrich young normal for risk of AD (FHx, APOE, vascular risk, subjective concerns …)

27 Specific ideas for ADNI3  Drop AD dementia  Combine LMCI, EMCI  Reduce lower age limit on normal, but with enrichment based on risk  Focus on intermediate amyloid PET suvr group?

28 Example: new subjects for ADNI3 AgeCDRMemory concerns Risk Young normal at risk50-600+ or -E4 carrier or known amyloid PET positive or CSF positive or strongly positive family history Normals60-900+ or - MCI50-900.5+ continue ADNI2 normal, SMC, EMCI, (LMCI?) drop ADNI2 AD cohort, subjects that have converted to AD dementia

29 Do we need younger subjects?  Perhaps: primary prevention will target middle age  Or: why not study transition to amyloid positivity in older individuals?

30 ADNI3 schedule, new and carry- over  Semiannual: mail-in assessments  Annual: MRI, blood, NP tests, computerized tests, PROs  Biennial: amyloid PET, tau PET, LP

31 Other ideas  Mild BehavioraI Impairment (Jesse Cedarbaum)  New biomarker approaches (ophthalmologic?)  Web-based recruitment/testing  Home-based (snail mail?) assessments  Utilize 23 and me data

Download ppt "©2012 MFMER | 3188678-1 ADNI Clinical Core Paul Aisen Ron Petersen Michael Donohue Jennifer Salazar."

Similar presentations

Methods for Studies in Preventing Cognitive Loss and Dementia

Methods for Studies in Preventing Cognitive Loss and Dementia
K OREAN ADNI … WHERE ARE WE NOW Seol-Heui Han, MD, PhD. On behalf of Preparatory Committee for K-ADNI Seol-Heui Han, MD, PhD. On behalf of Preparatory.

K OREAN ADNI … WHERE ARE WE NOW Seol-Heui Han, MD, PhD. On behalf of Preparatory Committee for K-ADNI Seol-Heui Han, MD, PhD. On behalf of Preparatory.
Speed of processing, the missing measure in early detection of MCI? Ruth O’Hara March 13 th 2001 Yogesh Shah.

Speed of processing, the missing measure in early detection of MCI? Ruth O’Hara March 13 th 2001 Yogesh Shah.
The Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing AUSTRALIAN ADNI. July 2010 UPDATE.

The Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing AUSTRALIAN ADNI. July 2010 UPDATE.
Department of Neurology, Mayo Clinic Arizona

Department of Neurology, Mayo Clinic Arizona
December, 2010. NEED FOR VALIDATED BIOMARKERS FOR AD TRIALS Biomarkers useful in Phase 2 to make decisions about Phase 3 (e.g. doses) Biomarkers useful.

December, NEED FOR VALIDATED BIOMARKERS FOR AD TRIALS Biomarkers useful in Phase 2 to make decisions about Phase 3 (e.g. doses) Biomarkers useful.
ADNI PiB Amyloid Imaging Chet Mathis University of Pittsburgh.

ADNI PiB Amyloid Imaging Chet Mathis University of Pittsburgh.
DIAN Treatment Trials An Update Sunday February 10, 2013 4:00 to 6:00 PM CST Presented by Randall Bateman MD DIAN Therapeutic Trials Unit Director DIAN.

DIAN Treatment Trials An Update Sunday February 10, :00 to 6:00 PM CST Presented by Randall Bateman MD DIAN Therapeutic Trials Unit Director DIAN.
Disclosures/Conflicts Consulting: GE Healthcare Bayer Abbott Elan/Janssen Synarc Genentech Merck.

Disclosures/Conflicts Consulting: GE Healthcare Bayer Abbott Elan/Janssen Synarc Genentech Merck.
Alzheimer’s Disease Neuroimaging Initiative STEERING COMMITTEE April

Alzheimer’s Disease Neuroimaging Initiative STEERING COMMITTEE April
ADNI 3 Clinical Core Plans

ADNI 3 Clinical Core Plans
CSF tau Is it an informative biomarker of AD pathology Chris Clark Alzheimer’s Disease Center University of Pennsylvania.

CSF tau Is it an informative biomarker of AD pathology Chris Clark Alzheimer’s Disease Center University of Pennsylvania.
Mild Cognitive Impairment as a Target for Drug Development Steven H. Ferris, Ph.D. Silberstein Aging and Dementia Research Center New York University School.

Mild Cognitive Impairment as a Target for Drug Development Steven H. Ferris, Ph.D. Silberstein Aging and Dementia Research Center New York University School.
MCI Clinical Trial Design FDA Advisory Committee Meeting March 13, 2001 Gaithersburg, MD Michael Grundman, MD, MPH Alzheimer’s Disease Cooperative Study.

MCI Clinical Trial Design FDA Advisory Committee Meeting March 13, 2001 Gaithersburg, MD Michael Grundman, MD, MPH Alzheimer’s Disease Cooperative Study.
Alzheimer's Disease – Current Status; Future Perspectives

Alzheimer's Disease – Current Status; Future Perspectives
Ethical issues in disclosing AD biomarker results Helen FK Chiu Professor of Psychiatry, The Chinese University of Hong Kong.

Ethical issues in disclosing AD biomarker results Helen FK Chiu Professor of Psychiatry, The Chinese University of Hong Kong.
Risk of Developing Alzheimer’s Disease in Persons with MCI

Risk of Developing Alzheimer’s Disease in Persons with MCI
EPAD update José Luis Molinuevo Worldwide-ADNI Update Meeting Friday, July 17, 2015 Washington, D.C.

EPAD update José Luis Molinuevo Worldwide-ADNI Update Meeting Friday, July 17, 2015 Washington, D.C.
Dementia in Clinical Practice Mary Ann Forciea MD Clinical Prof of Medicine Division of Geriatric Medicine UPHS Photo: Nat Geographic.

Dementia in Clinical Practice Mary Ann Forciea MD Clinical Prof of Medicine Division of Geriatric Medicine UPHS Photo: Nat Geographic.
How To Improve Memory Performance and Keep Your Brain Young Gary W. Small, MD Parlow-Solomon Professor on Aging Professor of Psychiatry & Biobehavioral.

How To Improve Memory Performance and Keep Your Brain Young Gary W. Small, MD Parlow-Solomon Professor on Aging Professor of Psychiatry & Biobehavioral.

Similar presentations

Ads by Google