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Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Ronald C. Petersen, PhD, MD Co-Director, Clinical Core Mayo Clinic College of Medicine Rochester, MN Alzheimer’s Disease International Toronto March 28, 2011
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Disclosures Pfizer, Inc. (Wyeth): Chair, DMC
Janssen Alzheimer’s Immunotherapy Program (Elan): Chair, DMC Elan Pharmaceuticals: Consultant GE Healthcare: Consultant Funding: National Institute on Aging U01 AG006786, P50 AG , R01 AG011378, R01 AG and the Robert and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program
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FUNDED BY NATIONAL INSTITUTE ON AGING
NIBIB,NIMH,NINR,NINDS,NCRR,NIDA and CIHR M. Weiner, P. Aisen, R Petersen, C. Jack, W. Jagust, J Trojanowski, L. Shaw, A. Toga, L. Beckett, D. Harvey, C Mathis, A. Gamst. R. Green, A Saykin, J Morris, L Thal (D) Neil Buckholz, David Lee, Mark Schmidt Industry Scientific Advisory Board (ISAB) And Site PIs, Study Coordinators and 821 subjects enrolled in 58 Sites in US and Canada
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ADNI Structure Executive Committee Clinical Core MRI Core PET Core
Biomarker Core Biostatistics Core Informatics Core Genetics Core Neuropathology Core
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GOALS OF ADNI Validate biomarkers as measures of change
Validate biomarkers as diagnostics or predictors: symptomatic and presymptomatic Optimize biomarker methods Standardize biomarker methods Establish a world-wide network for clinical AD studies and treatment trials
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ADNI All data in public database: UCLA/LONI/ADNI: No embargo of data
Naturalistic study of AD progression 200 NORMAL 4 yrs 400 MCI 4 yrs 200 AD 2 yrs Visits every 6 months 57 sites Clinical, blood, LP Cognitive Tests 1.5T MRI Some also have 3.0T MRI (25%) FDG-PET (50%) PiB-PET (approx 100) All data in public database: UCLA/LONI/ADNI: No embargo of data
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AD Progression Abnormal Normal Time Pre-symptomatic EMCI LMCI Dementia
CSF abeta42 MRI hippocampal volume Function (ADL) Amyloid imaging CSF Tau FDG PET Cognitive performance Jack et al: Lancet Neurology, 2010
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AD Progression Abnormal Normal Time Pre-symptomatic EMCI LMCI Dementia
CSF abeta42 MRI hippocampal volume Function (ADL) Amyloid imaging CSF Tau FDG PET Cognitive performance Jack et al: Lancet Neurology, 2010
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AD Progression Abnormal Normal Time Pre-symptomatic EMCI LMCI Dementia
CSF abeta42 MRI hippocampal volume Function (ADL) Amyloid imaging CSF Tau FDG PET Cognitive performance Jack et al: Lancet Neurology, 2010
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AD Progression Abnormal Normal Time Pre-symptomatic EMCI LMCI Dementia
CSF abeta42 MRI hippocampal volume Function (ADL) Amyloid imaging CSF Tau FDG PET Cognitive performance Jack et al: Lancet Neurology, 2010
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AD Progression Abnormal Normal Time Pre-symptomatic EMCI LMCI Dementia
CSF abeta42 MRI hippocampal volume Function (ADL) Amyloid imaging CSF Tau FDG PET Cognitive performance Jack et al: Lancet Neurology, 2010
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Ron Petersen, Mayo Clinic
Clinical Core Paul Aisen, UCSD Ron Petersen, Mayo Clinic
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ADNI Conversion Rates 15 NL 229 MCI 398 AD 192 12+2 158+2 215 225 192
Year Normal MCI MCI AD 0-1 1.4% ( ) 16.0% ( ) 1-2 2.4% ( ) 23.9% ( ) 2-3 0.0% ( ) 9.5% ( ) Petersen, Ronald C MN
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ADNI Withdrawal Rates P<0.001 p<0.001
Petersen, Ronald C MN
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ADAS Cog 11 Petersen, Ronald C MN
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ADAS Cog Change Petersen, Ronald C MN
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Summary Clinical groups are performing as expected
MCI to AD rates are accelerating from 16%/yr to 24%/yr Significant variability in clincal instruments Opportunity for imaging and fluid biomarkers to define subsets
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POWER CALCULATIONS Hypothetical clinical trial
Two arms: Treatment and Placebo Estimate the sample size/arm required to detect a significant treatment effect 1 year trial 25% slowing of rate of change two-sided tests, alpha=0.05, 80% power 23 ADNI publications on longitudinal change
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POWER OF CLINICAL/COGNITIVE TESTS 25% CHANGE 1YR STUDY (2 ARM) :
AD (155 Subjects) Test Sample Size MMSE 803 RAVLT 607 ADAS 592 CDR SOB 449
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Test Sample Size RAVLT 6056 ADAS 4547 MMSE 3879 CDR SOB 853
POWER OF CLINICAL/COGNITIVE TESTS 25% CHANGE 1YR STUDY (2 ARM) : MCI (355 Subjects) Test Sample Size RAVLT 6056 ADAS 4547 MMSE 3879 CDR SOB 853
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Clifford Jack MD Mayo Clinic 60 publications on MRI
MRI CORE Clifford Jack MD Mayo Clinic 60 publications on MRI
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FREESURFER PARCELATION
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Feb-09; N. Schuff
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Mean Cortical Thickness Change over 12 Months
Diagnosed as AD +2% Diagnosed as NC Scale ranges from -20% (cyan) to +20% (yellow) -2% Lateral View Medial View Holland et al. 24
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Baseline White Matter Hyperintensities
Normal and MCI had similar WMH distributions; increased WMH burden in AD with suggestions of anterior-posterior progression Normal MCI AD
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1.5T MRI Comparisons - AD (n=69)
Lab Variable SS/arm Alexander L. Hippo. Formation 334 Dale Whole Brain 207 Schuff - FS Hippocampus 201 Ventricles 132 126 Studholme Temporal lobe % change 123 119 Studhome CV - % change 106 Fox VBSI % change 105 BSI % change 71 Thompson 54
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William Jagust UC Berkeley 12 papers on PET
PET CORE William Jagust UC Berkeley 12 papers on PET
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Normal Aging vs. Alzheimer’s Disease FDG PET
AD
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FDG-PET ANALYSIS Jagust Lab
Composite ROI - Based on published coordinates 29
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Statistical ROI of12-Month CMRgl declines
Defined using data from 27 training-set patients using bootstrap with replacement Number of AD patients per group needed in a 12-month multi-center RCT to detect a 25% treatment effect with power=80%, p=0.05 & no need to correct for multiple comparisons FDG PET ADAS-COG MMSE Characterized in 29 test-set patients (excluding HiRez & HRRT scanners) Reiman et al Banner Alzheimer Institute
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PET Comparisons - AD (n=36)
Lab Variable SS/arm Foster hypometabolism1 638 hypometabolism2 549 Jagust ROI-avg 412 Reiman CV-fROI 96
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PET Comparisons - MCI (n=81)
Lab Variable SS/arm Jagust ROI-avg 7649 Foster hypometabolism1 1876 hypometabolism2 1280 Reiman CV - fROI 280
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First Conclusion In general atrophy, measured by MRI is a more sensitive and robust measure of rate of change Hippocampus, ventricles, not that different With the exception of Eric Reiman’s statistically generated ROI, PET measures have less statistical power to detect a slowing of change than MRI BUT PET may be more sensitive to detect a treatment effect which improves function!!!
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John Trojanowski, U Penn
Biomarker Core John Trojanowski, U Penn Les Shaw, U Penn
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John Trojanowski, Les Shaw, U Penn.
BIOMARKERS John Trojanowski, Les Shaw, U Penn. 24 papers on biomarkers Tau and pTau181p concentrations are highest in AD compared to NC and next highest in MCI vs NC. Ab1-42 is lowest in AD, highest in NC and intermedicate in MCI. Tau/Ab1-42 and pTau/Ab1-42 Ratio values are highest in AD compared to NC and next highest in MCI vs NC. These differences Are expected for these ADNI populations and comparable with data from published studies. 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, P-Tau 181P/Ab1-42. Mann-Whitney test
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Survival analyses for ADNI MCI subjects:
progression to AD for BASELINE CSF biomarkers > or < cutpoints Ab42<192 pg/mL t-tau/Ab42>0.39 As of June 28, 2010 riskTAA2>0.34
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Lower CSF Aβ1-42 is Associated with Increased Rates of Atrophy in MCI
Consistent with the view that MCI patients with low CSF Aβ1–42 have the AD
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ADNI: HC atrophy and CSF Aβ
Ab1-42 <192pg/mL Ab1-42 >192pg/mL ALL -5.6±4.7 -2.6±4.1 AD -8.0±5.9 -4.2±3.5 MCI -4.8±3.6 -2.9±3.7 NC -3.6±3.2 -2.2±4.3
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PiB Imaging Chet Mathis, U Pitt
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PIB Imaging: Chet Mathis
FDG PIB
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Follow-Up of PIB-Positive ADNI MCI’s
ADNI PiB MCI’s N = 65, 12 mo. follow-up PiB(-) Converters to AD 3 PiB(+) Converters to AD 21
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Follow-Up of ADNI PiB Controls
ADNI PiB Ctrl’s N = 19, 12 mo. follow-up PiB(-) Converters to MCI 0 PiB(+) Converters to MCI 2
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PIB vs CSF Biomarkers: A
Total N = 55 (11 Control, 34 MCI, 10 AD) Penn Autopsy Sample (56 AD, 52 Cog normal) 192 pg/ml
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PREDICTING TIME TO CONVERSION
Time to conversion from MCI to AD (using Cox proportional hazards) is predicted by Baseline ADAS-cog FAQ Use of acetylcholinesterase inhibitors Baseline biomarkers: hippocampus, FDG PET, PIB PET, CSF
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PREDICTING RATE OF ADAS COG-11 CHANGE
In controls: Hippocampal volume In MCI: ApoE, CSF AB and tau, FDG PET, PIB PET, hippocampal and ventricular volumes In AD: CSF tau and FDG PET
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PREDICTING FUTURE RATE OF HIPPOCAMPAL ATROPHY
Controls: CSF AB and tau MCI: APOE, CSF AB and tau, FDG and PIB PET AD: CSF AB and tau
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INFORMATICS CORE Arthur Toga UCLA
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ADNI Extensions ADNI GO ADNI 2 World Wide ADNI
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NIA GRAND OPPORTUNITES (GO) GRANT
GO grant ($24 million from NIA) will Add a cohort of 200 early MCI subjects (EMCI) LPs on 100% of these new subjects Follow controls/MCI an additional year F18 amyloid imaging on ALL existing and new ADNI/GO subjects (AV-45) Complete analysis of all ADNI data
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ADNI 2 Clinical Core
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Mild Cognitive Impairment
Normal MCI AD ADNI GO ADNI 2 (EMCI) ADNI 1 (LMCI) 0.5 1 CDR
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Alzheimer’s Disease Neuroimaging Initiative
Normal LMCI AD ADNI 1 EMCI ADNI GO EMCI LMCI AD ADNI 2 Normal
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SCOPE OF ADNI 2 ADNI2 ($69 million) will:
Continue to follow more than 400 controls and MCI from ADNI 1 for 5 more years Enroll: 100 additional EMCI (supplements 200 from GO) 150 new controls, LMCI, and AD MRI at 3,6, months and annually F18 amyloid (AV-45)/FDG baseline and Yr2 LP on all subjects at enrollment Genetics
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9/2009 N. Schuff
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SUMMARY Standardized methods Rate of change: MRI Predictors: many
Earlier diagnosis: caution Clinical trial design Data sharing World wide impact
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These slides and much more at ADNI-INFO.ORG
All data at
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MANY THANKS TO NIA: Drs Hodes and Buckholz
Industry Scientific Advisory Board Foundation for NIH ADNI Core leaders and Core members ADNI Site PIs Our volunteer subjects
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ADNI 1 Private Partner Scientific Board: 20 companies/2 non-profits
PIB/PET Supplement : Alzheimer’s Association and GE Healthcare Cerebrospinal Fluid Extension: Alzheimer’s Association, AstraZeneca, Cure Alzheimer’s Fund, Merck, Pfizer and an anonymous foundation Genome-Wide Genotyping :Gene Network Sciences, Merck, Pfizer and an anonymous foundation Genome-Wide Genotyping Genetic Analysis: NIBIB, Merck, Pfizer and an anonymous foundation
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Publications Trojanowski JQ. Searching for the biomarkers of Alzheimer’s. Practical Neurol., 3:30-34, 2004. Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack CR, Jagust W, Trojanowski JQ, Toga AW, Beckett L.: Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative (ADNI), Alzheimer’s & Dementia 1:55-66, PMID PMC Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack C, Jagust W, Trojanowski JQ, Toga AW, Beckett L. The Alzheimer’s Disease Neuroimaging Initiative. Neuroimaging Clin N Am, 15(4):869-77, PMID PMC Fukuyama H. Neuroimaging in mild cognitive impairment. Rinsho Shinkeigaku, 46(11):791-4, PMID Iwatsubo T. Beta-and gamma-secretases. Rinsho Shinkeigaku, 46(11):925-6, PMID Leow AD, Klunder AD, Jack CR Jr, Toga AW, Dale AM, Bernstein MA, Britson PJ, Gunter JL, Ward CP, Whitwell JL, Borowski BJ, Fleisher AS, Fox NC, Harvey D, Kornak J, Schuff N, Studholme C, Alexander GE, Weiner MW, Thompson PM; ADNI Preparatory Phase Study.: Longitudinal stability of MRI for mapping brain change using tensor-based morphometry. Neuroimage, 31(2):627-40, PMID PMC Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack C, Jagust W, Trojanowski JQ, Toga AW, Beckett LA. Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative. Cognition and Dementia, 5(4):56-62, 2006. Arai H. Alzheimer’s Disease Neuroimaging Initiative and mild cognitive impairment. RinshoShinkeigaku, 47(11):905-7, PMID Fletcher PT, Powell S, Foster NL, Joshi SC. Quantifying metabolic asymmetry modulo structure in Alzheimer’s disease. Inf Process Med Imaging, 20:446-57, PMID Ihara Y. Overview on Alzheimer’s disease. Rinsho Shinkeigaku, 47(11):902-4, PMID Murayam S, Saito Y. Neuropathology of mild cognitive impairment Alzheimer’s disease. Rinsho Shinkeigaku, 47(11): 912-4, PMID Haschke M, Zhang YL, Kahle C, Klawitter J, Korecka M, Shaw LM, Christians U. HPLC-atmospheric pressure chemical ionization MS/MS for quantification of 15-F2t-isoprostane in human urine and plasma. Clinical Chemestry, 53: , 2007.PMID Shaw LM, Korecka M, Clark CM, Lee VM-Y, and Trojanowski JQ. Biomarkers of neurodegenertaion for diagnosis and monitoring therapeutics. Nat. Rev. Drug Discovery, 6: , 2007.PMID Fan Y, Batmanghelich N, Clark CM, Davatzikos C, the Alzheimer’s Disease Neuroimaging Initiative. Spatial Patterns of Brain Atrophy in MCI Patients, Identified via High-Dimensional Pattern Classification, Predict Subsequent Cognitive Decline. NeuroImage, 39(4): , PMID Hampel H, Burger K, Teipel SJ, Bokde ALW, Zetterberg H, Blennow K. Core Candidate Neurochemical and Imaging Biomarkers of Alzheimer’s Disease. Alzheimer’s & Dementia, 4(1):38-48, PMID Nestor SM, Rupsingh R, Borrie M, Smith M, Accomazzi V, Wells JL, Fogarty J, Bartha R, and the Alzheimer’s Disease Neuroimaging Initiative. Ventricular Enlargement as a Possible Measure of Alzheimer’s Disease Progression Validated Using the Alzheimer’s Disease Neuroimaging Initiative Database. Brain 131(Pt 9): , PMID PMC
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Shaw LM. PENN biomarker core of the Alzheimer’s Disease Neuroimaging Initiative. Neurosignals, 16(1):19-23, PMID PMC Visser PJ, Verhey FRJ, Boada M, Bullock R, De Deyn PP, Frisoni GB, Frolich L, Hampel H, Jolles J, Jones R, Minthon L, Nobili F, Olde Rikkert M, Ousset P-J, Rigaurd A-S, Scheltens P, Soininen H, Spiru L, Touchon J, Tsolaki M, Vellas B, Wahlund LO, Wilcock G, Winblad B, DESCRIPA study group. Development of Screening Guidelines and Clinical Criteria for Predementia Alzheimer’s Disease. Neuroepidemiology, 30: , PMID Boyes RG, Gunter JL, Frost C, Janke AL, Yeatman T, Hill DL, Bernstein MA, Thompson PM, Weiner MW, Schuff N, Alexander GE, Killiany RJ, Decarli C, Jack CR, Fox NC, for the ADNI study.: Intensity non-uniformity corrections using N3 on 3-T scanners with multichannel phased array coils. Neuroimage, 39(4): , PMID PMC Jack CR Jr, Bernstein MA, Fox NC, Thompson P, Alexander G, Harvey D, Borowski B, Britson PJ, Whitwell J, Ward C, Dale AM, Felmlee JP, Gunter JL, Hill DL, Killiany R, Schuff N, Fox-Bosetti, S, Lin C, Studholme C, Decarli CS, Gunnar Krueger, Ward HA, Metzger GJ, Scott KT, Mallozzi R, Blezek D, Levy J, Debbins JP, Fleisher AS, Albert M, Green R, Bartzokis G, Glover G, Mugler J, Weiner MW, ADNI Study. The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods. J Magn Reson Imaging, 27(4):685-91, PMID PMC Hua X, Leow AD, Lee S, Klunder AD, Toga A, Lepore N, Chou Y-Y, Brun C, Chiang M-C, Barysheva M, Jack Jr. CR, Bernstein MA, Britson PJ, Ward CP, Whitwell JL, Borowski B, Fleisher AS, Fox NC, Boyes RG, Barnes J, Harvey D, Kornak J, Schuff N, Boreta L, Alexander GE, Weiner MW, Thompson PM, the Alzheimer’s Disease Neuroimaging Initiative. 3D characterization of brain atrophy in Alzheimer’s disease and mild cognitive impairment using tensor-based morphometry. NeuroImage, 41(1):19-34, PMID PMC Frisoni GB, Henneman WJP, Weiner MW, Scheltens P, Vellas B, Reynish E, Hudecova J, Hampel H, Burger K, Blennow K, Waldemar G, Johannsen P, Wahlund L-O, Zito G, Rossini PM, Winblad B, Barkhof F, Alzheimer’s Disease Neuroimaging Initiative. The pilot European Alzheimer’s Disease Neuroimaging Initiative of the European Alzheimer’s Disease Consortium. Alzheimer’s & Dementia, 4(4): , PMID PMC Morra JH, Tu Z, Apostolova LG, Green AE, Avedissian C, Madsen SK, Parikshak N, Hua X, Toga AW, Jack CR Jr, Weiner MW, Thompson PM, the Alzheimer’s Disease Neuroimaging Initiative. Validation of a fully automated 3D hippocampal segmentation method using subjects with Alzheimer’s disease mild cognitive impairment , and elderly controls. Neuroimage, 43(1): 59-68, PMID PMC Hua X, Leow AD, Parikshak N, Lee S, Chiang MC, Toga AW, Jack CR Jr, Weiner MW, Thompson PM, the Alzheimer’s Disease Neuroimaging Initiative. Tensor-based morphometry as a neuroimaging biomarker for Alzheimer’s disease: An MRI study of 676 AD, MCI, and normal subjects. NeuroImage, 43(3):458-69, PMID PMC in Process – NIHMSID 78543 Becker RE, Greig NH. Alzheimer’s disease drug development: old problems require new priorities. CNS Neurol Disord Drug Targets, 7(6): , PMID Clark CM, Davatzikos C, Borthakur A, Newberg A, Leight S, Lee VM-Y, Trojanowski JQ. Biomarkers for early detection of Alzheimer pathology. NeuroSignals, 16:11-18, 2008 PMID Mormino EC, Kluth JT, Madison CM, Rabinovici GD, Baker SL, Miller BL, Koeppe RA, Mathis CA, Weiner MW, Jagust WJ, and the Alzheimer’s Disease Neuroimaging Initiative. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain, 132(Pt 5): , PMID PMC
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Morra JH, Tu Z, Apostolova LG, Green AE, Avedissian C, Madsen SK, Parikshak N, Toga AW, Jack CR Jr, Schuff N, Weiner MW, Thompson PM, The Alzheimer’s Disease Neuroimaging Initiative. Automated mapping of hippocampal atrophy in 1-year repeat MRI data from 490 subjects with Alzheimer’s disease, mild cognitive impairment, and elderly controls. Neuroimage, 45(1 Suppl):S3-15, PMID PMC Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee V, Trojanowski JQ, Alzheimer’s Disease Neuroimaging Initiative. Cerebrospinal Fluid Biomarker Signature in Alzheimer’s Disease Neuroimaging Initiative Subjects. Ann Neurol, 65(4):403-13, PMID PMC Morra J, Tu Z, Apostolova LG, Green AE, Avedissian C, Madsen SK, Parikshak N, Hua X, Toga AW, Jack CR, Schuff N, Weiner MW, Thompson PM. Automated 3D Mapping of Hippocampal Atrophy and its Clinical Correlates in 400 Subjects with Alzheimer's Disease, Mild Cognitive Impairment, and Elderly Controls, Human Brain Mapping, 30(9): , PMID PMC Misra C, Fan Y, Davatzikos C. Baseline and longitudinal patterns of brain atrophy in MCI patients, and their use in prediction of short-term conversion to AD: Results from ADNI. NeuroImage, 44(4): , PMID PMC Leow AD, Yanovsky I, Parikshak N, Hua X, Lee S, Toga AW, Jack CR Jr, Bernstein MA, Britson PJ, Gunter JL, Ward CP, Borowski B, Shaw LM, Trojanowski JQ, Fleisher AS, Harvey D, Kornak J, Schuff N, Alexander GE, Weiner MW, Thompson PM, Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s Disease Neuroimaging Initiative: A One-Year Follow-up Study Using Tensor-Based Morphometry Correlating Degenerative Rates, Biomarkers and Cognition. Neuroimage. 45(3):645-55, PMID PMC Langbaum JBS, Chen K, Lee W, Reschke C, Bandy D, Fleisher AS, Alexander GE, Foster NL, Weiner MW, Koeppe RA, Jagust WJ, Reiman EM, and the Alzheimer’s Disease Neuroimaging Initiative. Categorical and Correlational Analyses of Baseline Fluorodeoxyglucose Positron Emission Tomography Images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). NeuroImage, 45: , PMID PMC Weiner MW. Editorial: Imaging and Biomarkers Will be Used for Detection and Monitoring Progression of Early Alzheimer’s Disease. J Nutr Health Aging, 13(4):332, PMID Schuff N, Woerner N, Boreta L, Kornfield T, Shaw LM, Trojanowski JQ, Thompson PM, Jack CR Jr, Weiner MW, and the Alzheimer's Disease Neuroimaging Initiative. MRI of Hippocampal Volume Loss in Early Alzheimer’s Disease in Relation to ApoE Genotype and Biomarkers. Brain. 132(Pt 4): , PMID PMC McEvoy LK, Fennema-Notestine C, Cooper JC, Hagler D Jr, Holland D, Karow DS, Pung CJ, Brewer JB, Dale AM for the Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s Disease: Quantitative structural neuroimaging for detection and prediction clinical and structural changes in mild cognitive impairment. Radiology, 251(1): , PMID PMC Carrillo MC, Sanders CA, Katz RG. Maximizing the Alzheimer's Disease Neuroimaging Initiative II. Alzheimers Dement. May;5(3):271-5, PMID: Bossa MN, Zacur E, Olmos S. Tensor-based morphometry with mappings parameterized by stationary velocity fields in Alzheimer's disease neuroimaging initiative. Med Image Comput Comput Assist Interv. 12(Pt 2):240-7, PMID:
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Chupin M, Gerardin E, Cuingnet R, Boutet C, Lemieux L, Lehericy S, Benali H, Garnero L, Colliot O. Fully Automatic Hippocampus Segmentation and Classification in Alzheimer’s Disease and Mild Cognitive Impairment Applied on Data from ADNI. Hippocampus, 19(6): , PMID PMC Jack Jr. CR, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS, Shiung MM, Gunter JL, Boeve BF, Kemp BJ, Weiner M, Petersen RC, and the Alzheimer’s Disease Neuroimaging Initiative. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain, 132(Pt 5): , PMID PMC Potkin SG, Guffanti G, Lakatos A, Turner JA, Kruggel F, Fallon JH, Saykin AJ, Orro A, Lupoli S, Salvi E, Weiner M, Macciardi F. Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer’s disease. PLoS ONE, 4(8):e , PMID PMC Chou YY, Leporé N, Avedissian C, Madsen SK, Parikshak N, Hua X, Shaw LM, Trojanowski JQ, Weiner MW, Toga AW, Thompson PM; The Alzheimer's Disease Neuroimaging Initiative. Mapping Correlations Between Ventricular Expansion and CSF Amyloid and Tau Biomarkers in 240 Subjects with Alzheimer’s Disease, Mild Cognitive Impairment and Elderly Controls. NeuroImage, 46(2): , PMID PMC Kovacevic S, Rafii MS, Brewer BJ and the Alzheimer’s Disease Neuroimaging Initiative. High-throughput, Fully-automated Volumetry for Prediction of MMSE and CDR Decline in Mild Cognitive Impairment. Alzheimer Disease and Associated Disorders, 23(2): , PMID PMC Clarkson MJ, Ourselin S, Neilsen C, Leung KK, Barnes J, Whitwell JL, Gunter JL, Hill D, Weiner MW, Jack CR, Fox NC. Comparison of Phantom and Registration Scaling Corrections using the ADNI Cohort. NeuroImage, 47(4): , PMC Hua X, Lee S, Yanovsky I, Leow AD, Chou YY, Ho AJ, Gutman B, Toga AW, Jack CR Jr., Bernstein MA, Reiman EM, Harvey DJ, Kornak J, Schuff N, Alexander GE, Weiner MW, Thompson PM, the Alzheimer’s Disease Neuroimaging Initiative. Optimizing power to track brain degeneration in Alzheimer’s disease and mild cognitive impairment with tensor-based morphometry: An ADNI study of 515 subjects. Neuroimage, 48(4):668-81, PMID PMC In Process – NIHMSID Hinrichs C, Singh V, Mukherjee L, Xu G, Chung MK, Johnson SC; Alzheimer's Disease Neuroimaging Initiative. Spatially augmented LP boosting for AD classification with evaluations on the ADNI dataset. Neuroimage, 48(1):138-49, PMC Gunter JL, Bernstein MA, Borowski BJ, Ward CP, Britson PJ, Felmlee JP, Schuff N, Weiner M, Jack CR. Measurement of MRI scanner performance with the ADNI phantom. Med Phys, 36(6): , PMC King RD, George AT, Jeon T, Hynan LS, Youn TS, Kennedy DN, Dickerson B and the Alzheimer’s Disease Neuroimaging Initiative. Characterization of atrophic changes in the cerebral cortex using fractal dimensional analysis. Brain Imaging and Behavior, 3(2):154-66, 2009. Petersen RC, and Trojanowski JQ. Use of Alzheimer’s Disease biomarkers: Potentially yes for clinical trials, but not yet for clinical practice. JAMA, 302(4):436-7, PMID: PMC Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner M, Knopman DS, Petersen RC, Jack Jr CR, and the Alzheimer’s Disease Neuroimaging Initiative. MRI and CSF biomarkers in normal, MCI, AD: Diagnostic discrimination and cognitive correlations. Neurol., 73: , 2009a. PMID PMC
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Vemuri P, Wiste HJ, Weigand SD, Shaw LM, Trojanowski JQ, Weiner M, Knopman DS, Petersen RC, Jack Jr CR, and the Alzheimer’s Disease Neuroimaging Initiative. MRI and CSF biomarkers in normal, MCI, AD: Predicting future clinical change. Neurol., 73: , 2009b. PMID PMC McDonald CR, McEvoy LK, Gharapetian L, Fennema-Notestine C, Hagler DJ Jr, Holland D, Koyama A, Brewer JB, Dale AM; Alzheimer's Disease Neuroimaging Initiative. Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. Neurology, 73(6):457-65, PMC Querbes O, Aubry F, Pariente J, Lotterie JA, Demonet JF, Duret V, Puel M, Berry I, Fort JC, Celsis P; the Alzheimer's Disease Neuroimaging Initiative. Early Diagnosis of Alzheimer’s Disease Using Cortical Thickness: Impact of Cognitive Reserve. Brain, 132(8): , PMID PMC Risacher SL, Saykin AJ, West JD, Shen L, Firpi HA, McDonald BC, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Baseline MRI Predictors of Conversion from MCI to Probable AD in the ADNI Cohort. Current Alzheimer Research, 6: , PMID PMC Jagust WJ, Landau SM, Shaw LM, Trojanowski JQ, Koeppe RA, Reiman EM, Foster NL, Petersen RC, Weiner MW, Price JC, Mathis CA, and the Alzheimer’s Disease Neuroimaging Initiative. Relationships between biomarkers in aging and dementia. Neurology, 73:1193-9, PMID: PMC Petersen RC. Commentary on “A roadmap for the prevention of dementia II: Leon Thal Symposium A national registry on aging. Alzheimer’s & Dementia, 5(2):105-7, PMID: PMC Petersen RC. Early Diagnosis of Alzheimer’s Disease: Is MCI too late? Curr Alzheimer Res, 6(4):324-30, PMID: Petersen RC, Jack Jr, CR. Imaging and Biomarkers in Early Alzheimer’s Disease and Mild Cognitive Impairment. Clinical Pharmacology and Therapeutics, 86(4):438-41, PMID Huang A, Abugharbieh R, Tam R; Alzheimer's Disease Neuroimaging Initiative. A hybrid geometric-statistical deformable model for automated 3-D segmentation in brain MRI. IEEE Trans Biomed Eng, 56(7): , PMID Cruchaga C, Kauwe JS, Bertelsen S, Nowotny P, Shah AR, et. al. SNPs in the regulatory subunit of calcineurin are associated with CSF tau protein levels, brain mRNA levels. Alzheimer’s and Dementia, 5(4 Suppl1):P471-P472, 2009. Hirschman C. Alzheimer’s Disease Neuroimaging Initiative (ADNI) Generates Promising Early Findings. Connections: News from the Alzheimer’s Disease Education and Referral (ADEAR) Center, National Institute on Aging, Fall 2009. Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, Brewer JB, Dale AM. One-year brain atrophy evident in healthy aging. J Neurosci, 29(48): , PMID PMC Mortamet B, Bernstein MA, Jack CR Jr, Gunter JL, Ward C, Britson PJ, Meuli R, Thiran JP, Krueger G; Alzheimer's Disease Neuroimaging Initiative. Automatic quality assessment in structural brain magnetic resonance imaging. Magn Reson Med. Aug; 62(2):365-72, PMID: PMCID: PMC Buerger K, Frisoni G, Uspenskaya O, Ewers M, Zetterberg H, Geroldi C, Binetti G, Johannsen P, Rossini PM, Wahlund LO, Vellas B, Blennow K, Hampel H. Validation of Alzheimer's disease CSF and plasma biological markers: the multicentre reliability study of the pilot European Alzheimer's Disease Neuroimaging Initiative (E-ADNI). Exp Gerontol. Sep;44(9):579-85, PMID:
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Cummings JL. Integrating ADNI results into Alzheimer's disease drug development programs. Neurobiol Aging. Aug; 31(8): , 2010 PMID: De Meyer G, Shapiro F, Vanderstichele H, Vanmechelen E, Engelborghs S, De Deyn PP, Coart E, Hansson O, Minthon L, Zetterberg H, Blennow K, Shaw L, Trojanowski JQ; for the Alzheimer's Disease Neuroimaging Initiative. Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People. Arch Neurol. Aug; 67(8): , PMID: Fan M, Liu B, Zhou Y, Zhen X, Xu C, Jiang T; the Alzheimer's Disease Neuroimaging Initiative. Cortical thickness is associated with different apolipoprotein E genotypes in healthy elderly adults. Neurosci Lett. Aug 2; 479(3):332-6, PMID: Korecka M, Clark CM, Lee VM, Trojanowski JQ, Shaw LM. Simultaneous HPLC-MS-MS quantification of 8-iso-PGF(2alpha) and 8,12-iso-iPF(2alpha) in CSF and brain tissue samples with on-line cleanup.J Chromatogr B Analyt Technol Biomed Life Sci. Aug 15; 878(24): , PMID: McEvoy LK, Edland SD, Holland D, Hagler DJ, Roddey JC, Fennema-Notestine C, Salmon DP, Koyama AK, Aisen PS, Brewer JB, Dale AM; For the Alzheimer’s Disease Neuroimaging Initiative. Neuroimaging Enrichment Strategy for Secondary Prevention Trials in Alzheimer Disease. Alzheimer Dis Assoc Disord. Jul/Sep; 24(3): , 2010 PMID: Fjell AM, Walhovd KB, Fennema-Notestine C, McEvoy LK, Hagler DJ, Holland D, Blennow K, Brewer JB, Dale AM; the Alzheimer’s Disease Neuroimaging Initiative. Brain Atrophy in Healthy Aging Is Related to CSF Levels of A{beta}1-42. Cereb Cortex. Sep; 20(9): , 2010 PMID: Schneider LS, Kennedy RE, Cutter GR; Alzheimer’s Disease Neuroimaging Initiative. Requiring an amyloid-beta1-42 biomarker for prodromal Alzheimer's disease or mild cognitive impairment does not lead to more efficient clinical trials. Alzheimers Dement. Sep;6(5):367-77, PMID: PMC [Available on 2011/9/1] Llano DA, Laforet G, Devanarayan V; The Alzheimer's Disease Neuroimaging Initiative. Derivation of a New ADAS-cog Composite Using Tree-based Multivariate Analysis: Prediction of Conversion From Mild Cognitive Impairment to Alzheimer Disease. Alzheimer Dis Assoc Disord. Sep 22. [Epub ahead of print] PMID: Wu X, Chen K, Yao L, Ayutyanont N, Langbaum JB, Fleisher A, Reschke C, Lee W, Liu X, Alexander GE, Bandy D, Foster NL, Thompson PM, Harvey DJ, Weiner MW, Koeppe RA, Jagust WJ, Reiman EM; Alzheimer's Disease Neuroimaging Initiative. Assessing the reliability to detect cerebral hypometabolism in probable Alzheimer's disease and amnestic mild cognitive impairment. J Neurosci Methods. Oct 15;192(2):277-85, PMID: King RD, Brown B, Hwang M, Jeon T, George AT; Alzheimer's Disease Neuroimaging Initiative. Fractal dimension analysis of the cortical ribbon in mild Alzheimer's disease. Neuroimage. Nov 1;53(2): Epub 2010 Jun 25. PMID: PMC [Available on 2011/11/1] Shen L, Kim S, Risacher SL, Nho K, Swaminathan S, West JD, Foroud T, Pankratz N, Moore JH, Sloan CD, Huentelman MJ, Craig DW, Dechairo BM, Potkin SG, Jack CR Jr, Weiner MW, Saykin AJ; the Alzheimer's Disease Neuroimaging Initiative. Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort. Neuroimage. Nov; 53(3): , 2010.PMID: PMC [Available on 2011/7/1/]
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Vounou M, Nichols TE, Montana G; the Alzheimer's Disease Neuroimaging Initiative. Discovering genetic associations with high-dimensional neuroimaging phenotypes: A sparse reduced-rank regression approach. Neuroimage. Nov 15;53(3): , PMID: Stein JL, Hua X, Lee S, Ho AJ, Leow AD, Toga AW, Saykin AJ, Shen L, Foroud T, Pankratz N, Huentelman MJ, Craig DW, Gerber JD, Allen AN, Corneveaux JJ, Dechairo BM, Potkin SG, Weiner MW, M Thompson P; the Alzheimer's Disease Neuroimaging Initiative. Voxelwise genome-wide association study (vGWAS). Neuroimage. Nov; 53(3): , PMID: PMC Habeck C, Stern Y; Alzheimer’s Disease Neuroimaging Initiative. Multivariate data analysis for neuroimaging data: overview and application to Alzheimer's disease. Cell Biochem Biophys. Nov;58(2):53-67, PMID: Murphy EA, Holland D, Donohue M, McEvoy LK, Hagler DJ Jr, Dale AM, Brewer JB; Alzheimer's Disease Neuroimaging Initiative. Six-month atrophy in MTL structures is associated with subsequent memory decline in elderly controls. Neuroimage. Dec;53(4):1310-7, PMID: PMC [Available on 2011/12/1] Kauwe JS, Cruchaga C, Bertelsen S, Mayo K, Latu W, Nowotny P, Hinrichs AL, Fagan AM, Holtzman DM, Alzheimer's Disease Neuroimaging Initiative, Goate AM. Validating Predicted Biological Effects of Alzheimer's Disease Associated SNPs Using CSF Biomarker Levels. J Alzheimers Dis. 21(3):833-42, 2010.PMID: McDonald CR, Gharapetian L, McEvoy LK, Fennema-Notestine C, Hagler DJ Jr, Holland D, Dale AM; Alzheimer's Disease Neuroimaging Initiative. Relationship between regional atrophy rates and cognitive decline in mild cognitive impairment. Neurobiol Aging May 13. [Epub ahead of print] PMID: PMC [Available on 2011/11/1] Cuingnet R, Gerardin E, Tessieras J, Auzias G, Lehéricy S, Habert MO, Chupin M, Benali H, Colliot O; The Alzheimer's Disease Neuroimaging Initiative. Automatic classification of patients with Alzheimer's disease from structural MRI: A comparison of ten methods using the ADNI database. Neuroimage Jun 11. [Epub ahead of print] PMID: Dickerson BC, Wolk DA; the Alzheimer's Disease Neuroimaging Initiative. Dysexecutive versus amnesic phenotypes of very mild Alzheimer's disease are associated with distinct clinical, genetic and cortical thinning characteristics. J Neurol Neurosurg Psychiatry Jun 20. [Epub ahead of print] PMID: Davatzikos C, Bhatt P, Shaw LM, Batmanghelich KN, Trojanowski JQ. Prediction of MCI to AD conversion, via MRI, CSF biomarkers, and pattern classification. Neurobiol Aging Jun 29. [Epub ahead of print] PMID: Jun G, Naj AC, Beecham GW, Wang LS, et al. Meta-analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions With APOE Genotypes. Arch Neurol Sep 3. [Epub ahead of print] PMID:
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Abstracts Weiner MW, Thal L, Jack C, Jagust W, Toga A, Beckett L, Peterson R: Alzheimer’s disease neuroimaging initiative, Alzheimer’s Disease and Parkinson’s Diseases: Insights, Progress and Perspectives 7th International Conference, Sorrento, Italy March 9-13, 2005. Weiner MW, Thal L, Petersen R, Jagust W, Trojanowski J, Toga A, Beckett L, Jack C.: Alzheimer’s disease neuroimaging initiative. Poster from 2nd Congress of the International Society for Vascular Behavioural and Cognitive Disorders, Florence, Italy, June 8-12, 2005. Weiner MW, Thal LJ, Petersen RC, Jack Jr. CR, Jagust W, Trojanowski JQ, Beckett LA. Imaging biomarkers to monitor treatment effects for Alzheimer’s Disease trials: The Alzheimer’s Disease Imaging Initiative. Alzheimer’s Association 10th International Conference on Alzheimer’s Disease and Related Disorders. Madrid, Spain. 2(3 Suppl 1): S311 (P2-254). July 15-20, 2006. Weiner MW, Thal L, Petersen R, Jack C, Jagust W, Trojanowski J, Shaw L, Toga A, Beckett L, Stables L, Mueller S, Lorenzen P, Schuff N. MRI of Alzheimer’s and Parkinson’s: The Alzheimer’s Disease Neuroimaging Initiative (ADNI-Info.Org). Neurodegenerative Dis, 4(Suppl 1):276, 832, 2007. Gunter JL, Bernstein MA, Britson PJ, Felmlee JP, Schuff N, Weiner M, Jack CR.: MRI system tracking and correction using the ADNI phantom. Alzheimer’s & Dementia, 3(3 Suppl 2):S109 P Second Alzheimer’s Association International Conference on Prevention of Dementia, Washington, DC. June 9-12, 2007. Fletcher PT, Wang AY, Tasdizen T, Chen K, Jagust WJ, Koeppe RA, Reiman EM, Weiner MW, Minoshima S, Foster NL.: Variability of Normal Cerebral Glucose Metabolism from the Alzheimer’s Disease Neuroimaging Initiative (ADNI): Implication for Clinical Trials. Annals of Neurology, 62(Suppl 11):S52-3. American Neurological Association 132nd Annual Meeting, Washington, DC. October 7-10, 2007. Chen K, Reiman EM, Alexander GE, Lee W, Reschke C, Smilovici O, Bandy D, Weiner MW, Koeppe RA, Jagust WJ.: Six-month cerebral metabolic declines in Alzheimer’s Disease, amnestic mild cognitive impairment and elderly normal control groups: Preliminary findings from the Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s & Dementia, 3(3 Suppl 2):S174 O Second Alzheimer’s Association International Conference on Prevention of Dementia, Washington, DC. June 9-12, 2007. Chen K, Reiman EM, Alexander GE, Smilovici O, Lee W, Reschke C, Bandy D, Foster NL, Weiner MW, Koeppe RA, Jagust WJ.: The pattern and severity of FDG PET abnormalities in Alzheimer’s Disease and amnestic mild cognitive impairment: Preliminary findings from the Alzheimer’s Disease Neuroimaging Initiative. Alzheimer’s & Dementia, 3(3 Suppl 2):S103 P Second Alzheimer’s Association International Conference on Prevention of Dementia, Washington, DC. June 9-12, 2007. Alexander GE, Chen K, Reiman EM, Aschenbrenner M, Merkley TL, Hanson KD, Dale AM, Berstein MA, Kornak J, Schuff N, Fox NC, Thompson PM, Weiner MW, Jack CR Jr.: Regional gray matter reductions in Alzheimer’s dementia and amnestic mild cognitive impairment: Preliminary findings from the Alzheimer’s Disease Neuroimaging Initiative using voxel-based morphomety. Alzheimer’s & Dementia, 3(3 Suppl 2):S102 P-020. Second Alzheimer’s Association International Conference on Prevention of Dementia, Washington, DC, June 9-12, 2007. Weiner MW, Thal L, Petersen R, Jack C, Jagust W, Trojanowski J, Shaw L, Toga A, Beckett L.: The Alzheimer’s Disease Imaging Initiative: Progress report. Alzheimer’s & Dementia, 3(3 Suppl 2):S174 O Second Alzheimer’s Association International Conference on Prevention of Dementia, Washington, DC. June 9-12, 2007.
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Weiner MW, Aisen P, Petersen R, Jack C, Jagust W, Trojanowski J, Shaw L, Toga A, Beckett L, Gamst A. Alzheimer’s Disease Neuroimaging Initiative (ADNI): Progress Report. 11th International Conference on Alzheimer’s Disease, Chicago, IL, 2008. Weiner MW. Alzheimer’s Disease Neuroimaging Initiative (ADNI): Progress Report. S , Page T99, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Reiman EM, Chen K, Ayutyanont N, Lee W, Bandy D, Reschke C, Alexander GE, Weiner MW, Koeppe RA, Foster NL, Jagust WJ. Twelve-Month Cerebral Metabolic Declines in Probable Alzheimer’s Disease and Amnestic Mild Cognitive Impairment: Preliminary Findings From the Alzheimer’s Disease Neuroimaging Initiative (ADNI), 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Schuff N, Woerner N, Boreta L, Kornfield T, Jack Jr. CR, Weiner MW. Rate of Hippocampal Atrophy in the Alzheimer’s Disease Neuroimaging Initiative (ADNI): Effects of ApoE4 and Value of Additional MRI Scans. O , Page T164, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Donohue M, Aisen P, Gamst A, Weiner M. Using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Data to Improve Power For Clinical Trials, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Alexander GE, Hanson KD, Chen K, Reiman EM, Bernstein MA, Kornak J, Schuff NW, Fox NC, Thompson PM, Weiner MW, Jack CR. Six-Month MRI Gray Matter Declines in Alzheimer Dementia Evaluated by Voxel-Based Morphometry with Multivariate Network Analysis: Preliminary Findings from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). IC-03-06, Page T8, & P1-216, Page T273, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Landau SM, Madison C, Wu D, Cheung C, Foster N, Reiman E, Koeppe R, Weiner M, Jagust WJ. Pinpointing Change in Alzheimer’s Disease: Longitudinal FDG-PET Analysis From the Alzheimer’s Disease Neuroimaging Initiative (ADNI). PI-258, Page T291, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Gunter JL, Borowski B, Bernstein M, Ward C, Britson P, Felmlee J, Schuff N, Weiner M, Jack C. Systematics of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Phantom. P2-011, Page T369, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Gunter JL, Borowski B, Britson P, Bernstein M, Ward C, Felmlee J, Schuff N, Weiner M, Jack C. Alzheimer’s Disease Neuroimaging Initiative (ADNI) Phantom and Scanner Longitudinal Performance. P2-012, Page T370, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Lee W, Langbaum JBS, Chen K, Recshke C, Bandy D, Alexander GE, Foster NL, Weiner MW, Koeppe RA, Jagust WJ, Reiman EM. Categorical and Correlational Analyses of Baseline Fluorodeoxyglucose Positron Emission Tomography Images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). IC-P1-036, Page T23 & P2-037, Page T379, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008. Petersen RC, Aisen P, Beckett L, Donohue M, Weng Q, Salmon D, Weiner M. Alzheimer’s Disease Neuroimaging Initiative (ADNI): Baseline Characteristics. P3-040, Page T528, 11th International Conference on Alzheimer’s Disease and Related Disorders, Chicago, IL, 2008.
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