The Alzheimer's Disease Neuroimaging Initiative: Annual change in biomarkers and clinical outcomes.
BACKGROUND
The Alzheimer's Disease Neuroimaging Initiative Phase 1 (ADNI-1) is a multisite prospective study designed to examine potential cerebrospinal fluid and imaging markers of Alzheimer's disease (AD) and their relationship to cognitive change. The objective of this study was to provide a global summary of the overall results and patterns of change observed in candidate markers and clinical measures over the first 2 years of follow-up.


METHODS
Change was summarized for 210 normal controls, 357 mild cognitive impairment, and 162 AD subjects, with baseline and at least one cognitive follow-up assessment. Repeated measures and survival models were used to assess baseline biomarker levels as predictors. Potential for improving clinical trials was assessed by comparison of precision of markers for capturing change in hypothetical trial designs.


RESULTS
The first 12 months of complete data on ADNI participants demonstrated the potential for substantial advances in characterizing trajectories of change in a range of biomarkers and clinical outcomes, examining their relationship and timing, and assessing the potential for improvements in clinical trial design. Reduced metabolism and greater brain atrophy in the mild cognitive impairment at baseline are associated with more rapid cognitive decline and a higher rate of conversion to AD. Use of biomarkers as study entry criteria or as outcomes could reduce the number of participants required for clinical trials.


CONCLUSIONS
Analyses and comparisons of ADNI data strongly support the hypothesis that measurable change occurs in cerebrospinal fluid, positron emission tomography, and magnetic resonance imaging well in advance of the actual diagnosis of AD.
Beckett
Laurel A
LA
Department of Public Health Sciences, University of California, Davis, CA, USA. labeckett@ucdavis.edu
Harvey
Danielle J
DJ
Gamst
Anthony
A
Donohue
Michael
M
Kornak
John
J
Zhang
Hao
H
Kuo
Julie H
JH
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003952:Diagnostic Imaging; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011877:Radionuclide Imaging
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
Ann Neurol. 2000 Apr;47(4):430-9
10762153
Neuroimage. 2010 Jun;51(2):654-64
20202480
Neurosignals. 2008;16(1):19-23
18097156
Ann Neurol. 2009 Apr;65(4):403-13
19296504
Eur Radiol. 2010 Mar;20(3):674-82
19760240
Neurology. 2003 Apr 22;60(8):1374-7
12707450
Neurology. 2009 Oct 13;73(15):1193-9
19822868
Brain. 2009 May;132(Pt 5):1355-65
19339253
J Neuropathol Exp Neurol. 2003 Nov;62(11):1087-95
14656067
Neurology. 2009 Sep 8;73(10):754-60
19587325
Alzheimers Dement. 2008 Jan;4(1):38-48
18631949
Lancet Neurol. 2006 Mar;5(3):228-34
16488378
Alzheimers Dement. 2005 Jul;1(1):55-66
17476317
Brain. 2009 Apr;132(Pt 4):1067-77
19251758
Biometrics. 1982 Dec;38(4):963-74
7168798
Clin Pharmacol Ther. 2009 Oct;86(4):438-41
19710641
Neurology. 2007 Dec 11;69(24):2197-204
17568013
Alzheimer Dis Assoc Disord. 2001 Aug;15 Suppl 1:S8-18
11669509
Neuroimaging Clin N Am. 2005 Nov;15(4):869-77, xi-xii
16443497
Eur J Nucl Med Mol Imaging. 2003 Aug;30(8):1104-13
12764551
Neurobiol Aging. 2011 Jul;32(7):1207-18
19660834
Neuron. 2002 Jan 31;33(3):341-55
11832223
Neuroimage. 2009 Dec;48(4):668-81
19615450