Neil Buckholtz, Ph.D.

National Institute on Aging/NIH

70 yo Normal

72 yo MCI

74 yo AD

CMRgI Abnormalities in Probable Alzheimers Dementia

From Reiman et al, New Engl J Med 1996

Importance of Brain Imaging/Fluid Biomarkers in Alzheimers Disease

1) Tools for research 2) Identifying markers for detection of early brain changes in pathogenesis of AD 3) Assessing brain markers of disease progression 4) Potential surrogate markers for assessment of interventions

Cognitive Continuum
Normal

Mild Cognitive Impairment

Alzheimer's Disease

CP926864- 35

MILD COGNITIVE IMPAIRMENT ORIGINAL CRITERIA

MEMORY COMPLAINT MEMORY IMPAIRED FOR AGE NORMAL GENERAL COGNITIVE FUNCTION NORMAL ACTIVITIES OF DAILY LIVING NOT DEMENTED

Mild Cognitive Impairment

MCI AD 12%/yr
100 90 80 70 60 50 Initial 12 exam 24 Months 36 48

Control AD 1-2%/yr
100 90 80 70 60 50 Initial 12 exam 24 36 Months 48

Petersen RC et al: Arch Neurol 56:303-308, 1999

CP926864- 12

New Diagnostic Criteria

The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on workgroups on diagnostic guidelines for Alzheimer's disease. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. Alzheimers Dement. 2011 May;7(3):263-9. The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Albert MS, Dekosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. Alzheimers Dement. 2011 May;7(3):270-9. Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Alzheimers Dement. 2011 May;7(3):280-92.

GOALS OF THE ADNI: LONGITUDINAL MULTI-SITE OBSERVATIONAL STUDY

Major goal is collection of data and samples to establish a brain imaging, biomarker, and clinical database in order to identify the best markers for following disease progression and monitoring treatment response Determine the optimum methods for acquiring, processing, and distributing images and biomarkers in conjunction with clinical and neuropsychological data in a multi-site context Validate imaging and biomarker data by correlating with neuropsychological and clinical data. Rapid public access of all data and access to samples

STUDY DESIGN-ADNI1
MCI (n= 400): 0, 6, 12, 18, 24, 36 months AD (n= 200): 0, 6, 12, 24 months Controls (n= 200): 0, 6, 12, 24, 36 months Clinical/neuropsychological evaluations, MRI (1.5 T) at all time points FDG PET at all time points in 50% 3 T MRI at all time points in 25% PIB sub-study on 120 subjects Blood and urine at all time points from all subjects; CSF from 50% of subjects 0, 1 yr, 2 yr (subset); DNA and immortalized cell lines from all subjects GWAS study

ADNI Public-Private Partnership Structure

Private/Philanthropic + Public
ADNI Executive Steering Committee
PET Core: Berkeley: Jagust MRI Core: Mayo: Jack Clinical Core: UCSD: Aisen Mayo: Petersen

FDA
NIBIB and other ICs

PI: Mike Weiner

Administrative Core: UCSF
Biomarkers Core: UPenn: Trojanowski/ Shaw Genetics Core: Indiana,Saykin

Publications Core: Harvard: Green Informatics Core: UCLA: Toga

Biostatistics Core: UCD: Beckett Pathology Core: WashU: Morris

57 Clinical Sites: ADNI PIs and Cores

ADNI 2 Private Partner Scientific Board

23 companies, 1 government entity and 2 non-profit organizations

ADNI MRI Standardization Methods

Steps taken before Subject Enrollment Began

Our goal: Standardization of image qualities (CNR, spatial resolution, resistance to artifact, reliability) across sites/platforms, and consistency across time in the face of ongoing upgrades Site equipment survey determine technical specifications for each potential scanner in the study, select optimum scanner at each site Create a generic, non-platform specific MRI protocol Organize vendor support With vendor support, create a platform specific protocol for each scanner 91 scanners, 48 distinct compiled versions of the ADNI protocol Deliver protocol to each scanner electronically, not manual creation Create an ADNI MRI procedures manual and deliver to sites Phone/email training of MRI site personnel by ADNI MR tech Site certification phantom and human volunteer scans

Ongoing Standardization Methods During Study

Recertification of scanners after upgrades (79 scanners re- certified to date, some numerous times) Hands-on trouble shooting by ADNI technical personal (ie MR physicist, MR tech, radiologist) QA of images: visual + electronic inspection in 3 areas protocol compliance electronically check every relevant MRI parameter against the master protocol for that system for each image acquired in the study, also identify scanner upgrades that were not reported by sites Visual inspection and rating of image quality request patient re scan if necessary Identify medical abnormalities for inclusion/exclusion as well as medical care purposes

MRI PHANTOM

Data and Sample Sharing

Goal is rapid public access of all raw and processed data Central repository for all QAd MRI and PET [Laboratory of Neuroimaging, UCLA (LONI)] Clinical data base at UCSD is linked to LONI Databases- in the public domain, available to all qualified investigators Sample sharing-Resource Allocation Review Committee No special access Data Sharing & Publication Committee (DPC) -ADNI Data Use Agreement

ADNI1 Demographics
Normal controls (n=229)
Age, mean (SD) Female (%) Years of education, mean (SD) Apolipoprotein E e4: Positive (%) 76.4 (5.0) 48.0 15.6 (3.1)

MCI (n=398)
75.3 (7.5) 35.4 16.0 (2.9)

AD (n=192)
75.8 (7.4) 47.4 14.7 (3.1)

P 0.15 0.002 <0.001

26.6

53.5

65.6

<0.001

CP1307278-1

Subject Evaluation
Baseline/screening eval and q 6 mo.
Labs, Apo E Hamilton(S) Beck MMSE ANART ADAS-cog NPI CDR ADL

Neuropsyc(B and q 6 mo)

Logical Memory(S) AVLT BNT Trails A &B Symbol digit Clock drawing Category fluency

ADAS Cog 11

3003731-7

MMSE

3003731-9

ADNI Progression Rates

Year 0-1 1-2 Normal MCI 1.4% (0.0-3.2) 2.4% (0.0-4.7) MCI AD 16.0% (11.3-20.4) 23.9% (19.0-29.5)

Mean Cortical Thickness Change over 12 Months

Diagnosed as AD

+2%

Diagnosed as NC

-2%

Lateral View

Medial View

Holland et al.

12 month CMRgl Decline in AD

12 month CMRgl Decline in MCI

P<0.001

P<0.001

Kewei Chen, Ph.D., Eric M. Reiman, M.D. Banner Alzheimer's Institute Translational Genomics Research Institute University of Arizona Arizona Alzheimers Consortium Phoenix, Arizona, USA

P<0.001

Statistical ROIs of 12-Month CMRglDecline

AD

MCI

Human Amyloid Imaging in AD Using Pittsburgh Compound-B

Appearance in expected gray matter areas

Very little retention

Absence in areas where there is no amyloid

Absence of retention in gray matter

Klunk et al., Annals of Neurology 2004

PIB Imaging:
Chet Mathis

FDG

PIB

Mean Cortical SUVR

2.5

1.5

Cutoff > 1.46 PIB+ (Berkeley Data)

1

Normals MCI AD 9/19 (47%) 47/63 (68%)17/19 (89%) PIB+ PIB+ PIB+

Follow-Up of PIB-Positive ADNI MCIs

ADNI PiB MCIs
N = 65, 12 mo. follow-up

PiB(-) Converters to AD PiB(+)

18 3 47

Converters to AD 21

Prediction of Conversion (3 yrs):AIBL Study

Rowe et al
HC (n=106) MCI (n=65)

PiB-ve Subjects:
Converters to naMCI

74
2 (3%)

PiB-ve Subjects:
Converters to AD: Converters to DLB: Converters to FTD:

20
1 2 1 1 45 32 (5%) (10%) (5%) (5%)

PiB+ve Subjects:
Converters to MCI/AD

32
8 (25%)

Converters to VaD: PiB+ve Subjects: Converters to AD

(71%)

Follow-Up of ADNI PiB Controls

ADNI PiB Ctrls
N = 19, 24 mo. follow-up

PiB(-)

10

Converters to MCI 0
PiB(+) 9

Converters to MCI 2

Total Tau, p-Tau181p and Ab1-42 in CSF of ADNI subjects at Baseline using a bioanalytically validated xMAP Luminex immunoassay system and Innogenetics immunoassay reagents
Clinical Core Leslie M Shaw, John Trojanowski University of Pennsylvania Medical Center

ADNI BASELINE CSF biomarker concentrations show the expected average differences between AD and MCI and NC
AD (n=102)
MeanSD

Tau
12258

Ab1-42
14341

P-Tau181P Tau/Ab1-42 P-Tau181P/Ab1-42

4220 0.90.5 0.30.2

MCI (n=200)
MeanSD

10361

16455

3518

0.80.6

0.30.2

NC (n=114)
MeanSD

7030

20655

2515

0.40.3

0.10.1

p<0.0001, for each of the 5 biomarker tests for AD vs NC and for MCI vs NC. For AD vs MCI:p<0.005, Tau; p<0.01, Ab1-42; p<0.01, P-Tau 181P; p<0.0005, Tau/Ab1-42; p<0.005, PTau 181P/Ab1-42. Mann-Whitney test for statistical differences used for these non-normally distributed data sets.

ADNI baseline visit CSF biomarkers-general statistics separated by APO E4+/concentration (pg/mL) ratio

group ( apo E genotype) AD4+ (n=70) AD4-(n=30) Normal distribution (4+, 4-) p value

Tau 121.4153.07 122.0767.92 no, yes 0.77

Ab 1-42 131.6127.42 171.2753.07 yes,yes p<0.0001* * parametric test

P-Tau 181P 42.2419.32 40.4321.72 no, yes 0.47

Tau/Ab 1-42 0.970.48 0.80.49 no, yes 0.12

P-Tau181P/Ab 1-42 0.340.19 0.270.17 no, yes 0.10

Control4+(n=27) Control4-(n=87) Normal distribution (4+, 4-) p value

80.4840.23 66.3225.97 no, no 0.11

156.8548.50 220.7147.95 yes, no p<0.0001

32.320.93 22.5511.14 no, no 0.03

0.570.37 0.330.19 no, no p<0.0001

0.240.19 0.110.09 no, no p<0.0001

MCI4+(n=105) MCI4-(n=91) Normal distribution (4+, 4-) p value

118.4267.32 86.3146.93 no, no p<0.0001

143.0841.12 186.3359.48 no, no p<0.0001

40.5818.20 30.3316.71 no, no p<0.0001

0.930.71 0.550.40 no, no p<0.0001

0.320.19 0.200.15 no, no p<0.0001

**p value calculated using Mann-Whitney test for each biomarker in each study group, segregated by APO E4, except for the one instance for which both 4+ & 4- subgroups were both normally distributed. Each value in the table is the mean + SD for the respective biomarker concentration in CSF.

CSF biomarker cutpoints established using CSFs collected from ADNI-independent autopsy-based AD and age-matched cognitively normal

subjects
Tau
ROC AUC Threshold values Sensitivity (%) Specificity (%) Test accuracy (%)
Positive predictive value (%) Negative predictive value (%)

Ab1-42
0.913 192 ng/mL 6.4 76.9 87.0 81.8

pTau181p
0.753 23 ng/mL 67.9 73.1 73.1 67.9

Tau/Ab1- pLR TAA tau181p/Ab1-42 42

0.917 0.39 85.7 84.6 85.2 85.7 0.856 0.10 91.1 71.2 81.5 77.3 0.938 0.22 100 76.9 88.9 82.4

0.831 93 ng/mL 69.6 92.3 80.6 90.7

73.8

95.2

70.4

84.6

88.1

100

MCI converters to AD at YEAR 1(n=37)

MCI converters to normal

Ab1-42 concentrations in CSF, collected at the baseline visit, of 37 ADNI MCI subjects who at their one year visit converted to a diagnosis of probable AD. The data points for the MCIAD converters are presented as a horizontal dot plot with the x axis scale identical to that of the Ab1-42 frequency plot for the entire ADNI MCI group. The vertical line indicates the Ab1-42 cutoff concentration obtained from ROC analysis of an ADNI-independent cohort of autopsy-based AD subjects CSF.

PIB vs CSF Biomarkers: Ab

Total N = 55 (11 Control, 34 MCI, 10 AD)
300
MCI AD

250

Control

CSF Ab 1-42

200

Penn Autopsy Sample (56 AD, 52 Cog normal) 192 pg/ml

150

100

50.0 1 1.2 1.4 1.6 1.8 2 2.2 2.4

Mean Cortical SUVR

ADNI Plasma and CSF Proteomics Studies

GOAL: Leverage ADNI Plasma and CSF samples to assess the utility of existing AD biomarker panels studies. PLASMA STUDY: Baseline and 1 year ADNI plasma samples analyzed using RBM190 analyte multiplex immunoassay platform (Luminex xMAP) containing proteins previously reported in the literature to be altered as a result of cancer, cardiovascular disease, metabolic disorders, inflammation, Alzheimers disease All data posted to ADNI website and available as of Nov, 2010 Project Team - completed statistical analyses; finalizing manuscript CSF STUDY: ADNI CSF samples to be sent to RBM for analysis (July, 2011) Additional studies planned to qualify a Multiple Reaction Monitoring (MRM) Mass Spectrometry panel and to examine Beta-Site APP Cleaving Enzyme (BACE-1) levels and enzymatic activity in CSF.

Plasma RBM studies

Using data from two independent cohorts (Penn & WU) we identified 16 analytes that were associated with MCI and AD and 5 of them were validated in a third independent cohort (ADNI). In addition two of the five analytes that were validated in the final step correlated with the CSF A 1-42 and tau. Validation of new potential biomarkers using independent cohorts is a powerful and essential screening and validation tool. More work needed on analytes that were replicated in 2 cohorts (Penn&WU, WU&ADNI, Penn&ADNI)

Hippocampal atrophy rates (L+R) free surfer data in ADNI subjects with CSF Ab1-42 >192 pg/mL or <192 pg/mL Hippocampal % atrophy rates (BL12 mos), for ADNI subjects with Ab1-42< 192 or >192 pg/mL
Ab1-42 <192pg/mL Ab1-42 >192pg/mL

ALL AD MCI NC

-5.64.7
-8.05.9 -4.83.6 -3.63.2

-2.64.1
-4.23.5 -2.93.7 -2.24.3

These data show that in ADNI AD, MCI and NC subjects the rate of hippocampal atrophy increases at a significantly higher rate in subjects with Ab1-42 <192 pg/mL cutoff concentration compared to those >192 pg/mL

Feb-09; N. Schuff

POWER OF CLINICAL/COGNITIVE TESTS 25% CHANGE 1YR STUDY (2 ARM) : AD

Test MMSE RAVLT ADAS CDR SOB

Sample Size 803 607 592 449

1.5T MRI Comparisons - AD (n=69)

Lab Alexander

Variable L. Hippo. Formation

SS/arm 334

Dale
Schuff - FS Dale Dale

Whole Brain
Hippocampus Ventricles Hippocampus Ventricles CV - % change VBSI % change

207
201 132 126 119 106 105

Studholme
Schuff - FS Studhome Fox

Temporal lobe % change 123

Fox
Thompson

BSI % change
CV - % change

71
54
45

ADNI Genotyping
Initial goal: high density genome wide scan Identified major microarray platforms for GWAS Compared marker selection strategies, HapMap coverage of genome, performance & reliability, as well as cost/sample Illumina platform was selected by consensus of the Genetics Committee & ISAB for this project TGen (Phoenix, AZ) was selected to perform the assays Illumina Human 610-Quad

Shen et al 2010: Overview

FreeSurfer: 56 volume or cortical thickness measures Baseline MRI Scans 142 QTs QCed genotyping data 530,992 SNPs

GWAS of Imaging Phenotypes

VBM: 86 GM density measures

Strong associations represented by heat maps

GWAS of candidate QT

VBM of candidate SNP

Refined modeling of candidate association

Conclusion: Imaging Gene Discovery

Gene Identification with Imaging Deep Phenotypes: GWAS

Structural MRI + 600k SNPs = GRIN2b as Novel Risk Factor for MTL deficits in Alzheimers
Stein et al 2010; ADNI

Amyloid Gene Pathway PET Study: [11C]PiB

DHCR24 (seladin selective AD indicator cholesterol synthesis pathway)

Swaminathan et al, Brain Imaging & Behavior (2012)

DOI 10.1007/s11682-011-9136-1

Continue to follow all EMCI, LMCI and NC from ADNI 1 and ADNI GO for 5 more years Enroll:

100 additional EMCI (supplements 200 from GO) 150 new controls, LMCI, and AD

3T MRI at 3, 6, months and annually F18 amyloid (AV-45)/FDG every other year LP on 100% of subjects at enrollment Genetics

Normal

MCI

AD

ADNI 2 ADNI 1 (EMCI) (LMCI)

0.5 CDR

1
3004153-1

Inclusion Criteria for ADNI GO & 2*

CN CDR MMSE 26 0 24-30 EMCI 0.5 24-30 LMCI AD 0.5 0.5-1 24-30 20-

LM-DR (cut-off scores)

Educ 0-7 8-15 16

Dementia

EMCI have milder memor dysfunction than LMCI approximately 0.5-1.5 SD below the mean for CN. They are CDR 0.5 as are LMCI. LMCI were 1.5 SD below the mean for memo function.

3 5 9 No

3-6 5-9 9-11 No

2 4 8

2 4 8

No Yes

* Ron Petersen

FDG-PET

CSF A42 Cog Amyloid imaging CSF tau

MRI hipp

Fxn

The eMCI group: selected to be intermediate between NC and later MCI, at baseline.

Baseline eMCI yellow is intermediate in ADAS-Cog between NC (green) and MCI (blue).

Also intermediate in complete cortical florbetapir index; considerable heterogeneity in all groups except perhaps AD (red).

Volumetric summaries and FDG-PET measures show eMCI more like NC at baseline.

ECog Memory
4
Self Partner

0 CN EMCI LMCI AD

2012 MFMER | 3188678-56

New functional measure: everyday cognitive function (ECog). Can be self-reported or informant-reported (better!)

ADNI GO/2 Florbetapir (N=602)

56/194 29% positive

Frequency

89/212
42% positive

83/132 63% positive

1.11 threshold
ADNI Data processed with freesurfer & whole cerebellum reference
51/64 80% positive

Florbetapir cortical mean

fibrillar A deposition in ADNI subject groups

in comparison with 78 cognitively normal APOE e4 non-carriers

AD (n=53)
MCI (n=78)

eMCI (n=150)

0.05 Banner Alzheimers Institute

P-value

e-14

in comparison with 78 cognitively normal APOE e4 non-carriers

cerebral glucose hypometabolism in ADNI patients

AD (n=53)

MCI (n=78)

eMCI (n=150)

0.05

p-value Banner Alzheimers Institute

e-16

cerebral glucose hypometabolism in 51 A-positive eMCI patients

in comparison with 99 A-negative eMCI patients

0.05

P-value

e-4

Banner Alzheimers Institute

ADNI GO & ADNI 2 CSF biomarkers

(pg/mL)

Ab1-42

t-tau
(pg/mL)

p-tau181
(pg/mL)

t-tau/Ab1-42

p-tau/Ab1-42

Normal
(107)

23371

7334

41.320

0.370.27

0.210.15

EMCI
(192)

23172*

8153**

44.428** *

0.450.49* ***

0.240.22**** *

LMCI
(66)

18168

10355

63.840

0.680.45

0.420.31

AD
(25)
* Ab1-42:

15152

13459

70.133

0.970.49

0.540.33

p<0.000001 vs AD; p<0.00001 vs LMCI, p=0.83 vs NL. ** t-tau: p<0.000005 vs AD, p<0.005 vs LMCI, p=0.86 vs NL. ***p-tau181:p<0.0005 vs AD, p<0.00005 vs LMCI; p=0.91 vs NL. **** t-tau/ Ab1-42: p<0.0000001 vs AD, p<0.00005 vs LMCI, p=0.99 vs NL *****p-tau / Ab : p< 0.00005 vs AD, p<0.000001 vs LMCI; p=0.96 vs NL.

Baseline ADAScog results in ADNI subjects with CSF Ab1-42 >192 pg/mL or <192 pg/mL
Baseline ADAScog results for ADNI subjects (meanSD) with Ab1-42 <192 pg/mL or >192 pg/mLAb1-42 Ab
1-42

<192pg/m L

>192pg/m L

ALL
n=385

18.28.4 11.34.9 15.25.7 21.56.1 30.37.7

12.06.4 9.44.2 11.85.4 15.87.4 29.78.4

<0.000 1 0.078 <0.000 5 <0.005 0.75

NC
n=106

EMCI
n=190

LMCI
n=65

AD
n=24

Baseline AV45 SUVR results in ADNI subjects with CSF Ab1-42 >192 pg/mL or <192 pg/mL SUVR Baseline AV45
results for ADNI subjects (meanSD) with Ab1-42 <192 pg/mL or >192 Abpg/mLAb
1-42 1-42

<192pg/m >192pg/m L L

ALL
n=246

1.60.23 1.50.22 1.50.21 1.60.27 1.60.25

1.20.11 1.20.09 1.20.13 1.20.09 1.10.21

<0.000 1 <0.000 1 <0.000 1 <0.000 5 <0.05

NC
n=53

EMCI
n=148

LMCI
n=32

AD
n=13

AV45 SUVR vs CSF Ab1-42 in ADNI GO and ADNI 2 sub

ALL

NC Spearmans r=-0.74
AV45 SUVR

Spearmans r=-0.73
AV45 SUVR

Ab1-42, pg/mL

Ab1-42, pg/mL

1.28 SUVR cutpoint as described by Landau and Jagust (ADNI web site)

EMCI to LMCI
1.0 strata ApoE=e4+ ApoE=e4

0.8

p = 0.001 Probability
0.6

0.4

0.2

0.0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

Years
ApoE=e4 ApoE=e4+

142 139 91 82 79 57

59 29

53 21

39 17

36 12

27 6

18 4

6 0

2 0

Numbers at risk

Standardization: imaging, biomarkers Neuroscience: relationships among biomarker trajectories elucidate neurobiology Trials: new understanding of biomarkers has facilitated interventional studies in very early AD Data sharing: ADNI has demonstrated the power of real-time public data sharing Collaboration: academia, industry, non-profits, regulatory agencies world-wide

9/2009 N. Schuff

http://www.adni-info.org http://www.loni.ucla.edu/ADNI

Parkinsons disease FTD Autism

World-Wide Standardization
Alzheimers Association efforts to standardize CSF and hippocampal volume measures

CAMD
Utilization of ADNI data to develop documents to qualify CSF and MRI measures for regulatory purposes to FDA and EMA for enrolling subjects at high risk

National Alzheimers Project Act (NAPA) Update

Draft framework for National Plan to Address Alzheimers proposed January 2012
National Plan released May 15

http://aspe.hhs.gov/daltcp/napa/

NAPA Goals 1. Prevent and effectively treat Alzheimers disease by 2025 2. Optimize care quality and efficiency 3. Expand patient and family support 4. Enhance public awareness and engagement 5. Track progress and drive improvement

Identify Research Strategies for Alzheimers Disease

NIH/NIA hosted AD Research Summit May 14-15, 2012 Research recommendations released May 18 http://www.nia.nih.gov/newsroom/alzheimersdisease-research-summit-2012-recommendations Day One Webcast http://videocast.nih.gov/summary.asp?Live=11196

ADNI Data Investigators

Total Investigators Approved Investigators Disapproved Investigators

3135 2931 204

ADNI Data Applications

Disapproved Applications (204)

28

Asked to clarify Nonsense users

176

ADNI Data Applications by Sector (cumulative)

1800 1600 1400 1200 1000 800 600 400 200 0 2007

2008

2009

University/Research Pharmaceutical Biotech Scanner Mfg Government Other

2010 2011

Other Government Scanner Mfg Biotech Pharmaceutical University/Research

ADNI Data Users

Investigators (3135) by degree type:

B.A. 92 B.S. 270 M.A. 70 M.S. 550 M.D. 644 Ph.D. 1509

Countries with ADNI Data Applicants

Countries with ADNI data applicants

Data Archived and Downloaded

140,000 images archived (raw and processed) 1.2 million image downloads 90,000 downloads of non-image data (clinical, genetic, proteomic, summary) from 36 countries

ADNI Manuscripts
504 manuscripts utilized ADNI data
Published Epub ahead of print In Press Under revision In submission 274 16 8 2 191

Withdrawn Under review by DPC

11 2

ADNI Manuscripts (reviewed)

Of the 504 manuscripts that utilized ADNI data, 469 were submitted for ADNI DPC Review
11 Met initial criteria 238 220

Required one revision Withdrawn

ADNI Manuscripts (not reviewed)

35 manuscripts were not submitted to the ADNI DPC for review
Compliant with ADNI policies Non-compliant with ADNI policies 6 29

Reasons authors cited for not submitting manuscripts for review: Didnt submit this time, but will in the future (19) Forgot to submit, but have since (3) No response (8) Author reported paper to us after publication (5)