Skip to main content
Top
Published in: Alzheimer's Research & Therapy 4/2014

Open Access 01-08-2014 | Review

Imaging as a biomarker in drug discovery for Alzheimer’s disease: is MRI a suitable technology?

Authors: Emilio Merlo Pich, Andreas Jeromin, Giovanni B Frisoni, Derek Hill, Andrew Lockhart, Mark E Schmidt, Martin R Turner, Stefania Mondello, William Z Potter

Published in: Alzheimer's Research & Therapy | Issue 4/2014

Login to get access

Abstract

This review provides perspectives on the utility of magnetic resonance imaging (MRI) as a neuroimaging approach in the development of novel treatments for Alzheimer’s disease. These considerations were generated in a roundtable at a recent Wellcome Trust meeting that included experts from academia and industry. It was agreed that MRI, either structural or functional, could be used as a diagnostic, for assessing worsening of disease status, for monitoring vascular pathology, and for stratifying clinical trial populations. It was agreed also that MRI implementation is in its infancy, requiring more evidence of association with the disease states, test-retest data, better standardization across multiple clinical sites, and application in multimodal approaches which include other imaging technologies, such as positron emission tomography, electroencephalography, and magnetoencephalography.
Literature
1.
go back to reference McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, 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: The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011, 7: 263-269. 10.1016/j.jalz.2011.03.005.PubMedCentralCrossRefPubMed McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, 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: The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011, 7: 263-269. 10.1016/j.jalz.2011.03.005.PubMedCentralCrossRefPubMed
2.
go back to reference Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, Harvey D, Jack CR, Jagust W, Liu E, Morris JC, Petersen RC, Saykin AJ, Schmidt ME, Shaw L, Shen L, Siuciak JA, Soares H, Toga AW, Trojanowski JQ, Alzheimer’s Disease Neuroimaging Initiative: The Alzheimer’s Disease Neuroimaging Initiative: a review of papers published since its inception. Alzheimers Dement. 2013, 9: e111-e194. 10.1016/j.jalz.2013.05.1769.PubMedCentralCrossRefPubMed Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Green RC, Harvey D, Jack CR, Jagust W, Liu E, Morris JC, Petersen RC, Saykin AJ, Schmidt ME, Shaw L, Shen L, Siuciak JA, Soares H, Toga AW, Trojanowski JQ, Alzheimer’s Disease Neuroimaging Initiative: The Alzheimer’s Disease Neuroimaging Initiative: a review of papers published since its inception. Alzheimers Dement. 2013, 9: e111-e194. 10.1016/j.jalz.2013.05.1769.PubMedCentralCrossRefPubMed
4.
go back to reference Moulder KL, Snider BJ, Mills SL, Buckles VD, Santacruz AM, Bateman RJ, Morris JC: Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther. 2013, 5: 48-10.1186/alzrt213.PubMedCentralCrossRefPubMed Moulder KL, Snider BJ, Mills SL, Buckles VD, Santacruz AM, Bateman RJ, Morris JC: Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther. 2013, 5: 48-10.1186/alzrt213.PubMedCentralCrossRefPubMed
5.
go back to reference Frisoni GB, Bocchetta M, Chételat G, Rabinovici GD, de Leon MJ, Kaye J, Reiman EM, Scheltens P, Barkhof F, Black SE, Brooks DJ, Carrillo MC, Fox NC, Herholz K, Nordberg A, Jack CR, Jagust WJ, Johnson KA, Rowe CC, Sperling RA, Thies W, Wahlund LO, Weiner MW, Pasqualetti P, Decarli C, ISTAART’s NeuroImaging Professional Interest Area: Imaging markers for Alzheimer disease: which vs how. Neurology. 2013, 81: 487-500. 10.1212/WNL.0b013e31829d86e8.PubMedCentralCrossRefPubMed Frisoni GB, Bocchetta M, Chételat G, Rabinovici GD, de Leon MJ, Kaye J, Reiman EM, Scheltens P, Barkhof F, Black SE, Brooks DJ, Carrillo MC, Fox NC, Herholz K, Nordberg A, Jack CR, Jagust WJ, Johnson KA, Rowe CC, Sperling RA, Thies W, Wahlund LO, Weiner MW, Pasqualetti P, Decarli C, ISTAART’s NeuroImaging Professional Interest Area: Imaging markers for Alzheimer disease: which vs how. Neurology. 2013, 81: 487-500. 10.1212/WNL.0b013e31829d86e8.PubMedCentralCrossRefPubMed
6.
go back to reference Frisoni GB, Fox NC, Jack CR, Scheltens P, Thompson PM: The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol. 2010, 6: 67-77. 10.1038/nrneurol.2009.215.PubMedCentralCrossRefPubMed Frisoni GB, Fox NC, Jack CR, Scheltens P, Thompson PM: The clinical use of structural MRI in Alzheimer disease. Nat Rev Neurol. 2010, 6: 67-77. 10.1038/nrneurol.2009.215.PubMedCentralCrossRefPubMed
7.
go back to reference Damoiseaux JS, Prater KE, Miller BL, Greicius MD: Functional connectivity tracks clinical deterioration in Alzheimer’s disease. Neurobiol Aging. 2012, 33: e19-30-CrossRef Damoiseaux JS, Prater KE, Miller BL, Greicius MD: Functional connectivity tracks clinical deterioration in Alzheimer’s disease. Neurobiol Aging. 2012, 33: e19-30-CrossRef
8.
go back to reference Ashford JW, Salehi A, Furst A, Bayley P, Frisoni GB, Jack CR, Sabri O, Adamson MM, Coburn KL, Olichney J, Schuff N, Spielman D, Edland SD, Black S, Rosen A, Kennedy D, Weiner M, Perry G: Imaging the Alzheimer brain. J Alzheimers Dis. 2011, 26 (Suppl 3): 1-27.PubMedCentralPubMed Ashford JW, Salehi A, Furst A, Bayley P, Frisoni GB, Jack CR, Sabri O, Adamson MM, Coburn KL, Olichney J, Schuff N, Spielman D, Edland SD, Black S, Rosen A, Kennedy D, Weiner M, Perry G: Imaging the Alzheimer brain. J Alzheimers Dis. 2011, 26 (Suppl 3): 1-27.PubMedCentralPubMed
10.
go back to reference Foster NL, Heidebrink JL, Clark CM, Jagust WJ, Arnold SE, Barbas NR, DeCarli CS, Turner RS, Koeppe RA, Higdon R, Minoshima S: FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer’s disease. Brain. 2007, 130: 2616-2635. 10.1093/brain/awm177.CrossRefPubMed Foster NL, Heidebrink JL, Clark CM, Jagust WJ, Arnold SE, Barbas NR, DeCarli CS, Turner RS, Koeppe RA, Higdon R, Minoshima S: FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer’s disease. Brain. 2007, 130: 2616-2635. 10.1093/brain/awm177.CrossRefPubMed
11.
go back to reference Reiman EM, Alzheimer’s Disease Biomarkers Working Group for the Alliance for Aging R: Fluorodeoxyglucose positron emission tomography: emerging roles in the evaluation of putative Alzheimer’s disease-modifying treatments. Neurobiol Aging. 2011, 32 (Suppl 1): S44-S47.PubMedCentralCrossRefPubMed Reiman EM, Alzheimer’s Disease Biomarkers Working Group for the Alliance for Aging R: Fluorodeoxyglucose positron emission tomography: emerging roles in the evaluation of putative Alzheimer’s disease-modifying treatments. Neurobiol Aging. 2011, 32 (Suppl 1): S44-S47.PubMedCentralCrossRefPubMed
12.
go back to reference Yamane T, Ikari Y, Nishio T, Ishii K, Ishii K, Kato T, Ito K, Silverman DH, Senda M, Asada T, Arai H, Sugishita M, Iwatsubo T, J-ADNI Study Group: Visual-statistical interpretation of 18 F-FDG-PET images for characteristic Alzheimer patterns in a multicenter study: inter-rater concordance and relationship to automated quantitative evaluation. AJNR Am J Neuroradiol. 2014, 35: 244-249. 10.3174/ajnr.A3665.CrossRefPubMed Yamane T, Ikari Y, Nishio T, Ishii K, Ishii K, Kato T, Ito K, Silverman DH, Senda M, Asada T, Arai H, Sugishita M, Iwatsubo T, J-ADNI Study Group: Visual-statistical interpretation of 18 F-FDG-PET images for characteristic Alzheimer patterns in a multicenter study: inter-rater concordance and relationship to automated quantitative evaluation. AJNR Am J Neuroradiol. 2014, 35: 244-249. 10.3174/ajnr.A3665.CrossRefPubMed
13.
go back to reference Duara R, Gross-Glenn K, Barker WW, Chang JY, Apicella A, Loewenstein D, Boothe T: Behavioral activation and the variability of cerebral glucose metabolic measurements. J Cereb Blood Flow Metab. 1987, 7: 266-271. 10.1038/jcbfm.1987.62.CrossRefPubMed Duara R, Gross-Glenn K, Barker WW, Chang JY, Apicella A, Loewenstein D, Boothe T: Behavioral activation and the variability of cerebral glucose metabolic measurements. J Cereb Blood Flow Metab. 1987, 7: 266-271. 10.1038/jcbfm.1987.62.CrossRefPubMed
14.
go back to reference Shipley SM, Frederick MC, Filley CM, Kluger BM: Potential for misdiagnosis in community-acquired PET scans for dementia. Neurol Clin Pract. 2013, 3: 305-312. 10.1212/CPJ.0b013e318296f2df.PubMedCentralCrossRefPubMed Shipley SM, Frederick MC, Filley CM, Kluger BM: Potential for misdiagnosis in community-acquired PET scans for dementia. Neurol Clin Pract. 2013, 3: 305-312. 10.1212/CPJ.0b013e318296f2df.PubMedCentralCrossRefPubMed
15.
go back to reference Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, Klunk WE, Ashford E, Yoo K, Xu ZX, Loetscher H, Santarelli L: Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012, 69: 198-207. 10.1001/archneurol.2011.1538.CrossRefPubMed Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, Klunk WE, Ashford E, Yoo K, Xu ZX, Loetscher H, Santarelli L: Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol. 2012, 69: 198-207. 10.1001/archneurol.2011.1538.CrossRefPubMed
16.
go back to reference Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, Schneider JA, Arora A, Carpenter AP, Flitter ML, Joshi AD, Krautkramer MJ, Lu M, Mintun MA, Skovronsky DM, AV-45-A16 Study Group: Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol. 2012, 11: 669-678. 10.1016/S1474-4422(12)70142-4.CrossRefPubMed Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH, Schneider JA, Arora A, Carpenter AP, Flitter ML, Joshi AD, Krautkramer MJ, Lu M, Mintun MA, Skovronsky DM, AV-45-A16 Study Group: Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol. 2012, 11: 669-678. 10.1016/S1474-4422(12)70142-4.CrossRefPubMed
17.
go back to reference Frisoni GB, Jack CR: Harmonization of magnetic resonance-based manual hippocampal segmentation: a mandatory step for wide clinical use. Alzheimers Dement. 2011, 7: 171-174. 10.1016/j.jalz.2010.06.007.CrossRefPubMed Frisoni GB, Jack CR: Harmonization of magnetic resonance-based manual hippocampal segmentation: a mandatory step for wide clinical use. Alzheimers Dement. 2011, 7: 171-174. 10.1016/j.jalz.2010.06.007.CrossRefPubMed
18.
go back to reference McEvoy LK, Brewer JB: Quantitative structural MRI for early detection of Alzheimer’s disease. Expert Rev Neurother. 2010, 10: 1675-1688. 10.1586/ern.10.162.PubMedCentralCrossRefPubMed McEvoy LK, Brewer JB: Quantitative structural MRI for early detection of Alzheimer’s disease. Expert Rev Neurother. 2010, 10: 1675-1688. 10.1586/ern.10.162.PubMedCentralCrossRefPubMed
19.
go back to reference Sperling R, Salloway S, Brooks DJ, Tampieri D, Barakos J, Fox NC, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Lieberburg I, Arrighi HM, Morris KA, Lu Y, Liu E, Gregg KM, Brashear HR, Kinney GG, Black R, Grundman M: Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 2012, 11: 241-249. 10.1016/S1474-4422(12)70015-7.PubMedCentralCrossRefPubMed Sperling R, Salloway S, Brooks DJ, Tampieri D, Barakos J, Fox NC, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Lieberburg I, Arrighi HM, Morris KA, Lu Y, Liu E, Gregg KM, Brashear HR, Kinney GG, Black R, Grundman M: Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol. 2012, 11: 241-249. 10.1016/S1474-4422(12)70015-7.PubMedCentralCrossRefPubMed
20.
go back to reference Binnewijzend MA, Kuijer JP, Benedictus MR, van der Flier WM, Wink AM, Wattjes MP, van Berckel BN, Scheltens P, Barkhof F: Cerebral blood flow measured with 3D pseudocontinuous arterial spin-labeling MR imaging in Alzheimer disease and mild cognitive impairment: a marker for disease severity. Radiology. 2013, 267: 221-230. 10.1148/radiol.12120928.CrossRefPubMed Binnewijzend MA, Kuijer JP, Benedictus MR, van der Flier WM, Wink AM, Wattjes MP, van Berckel BN, Scheltens P, Barkhof F: Cerebral blood flow measured with 3D pseudocontinuous arterial spin-labeling MR imaging in Alzheimer disease and mild cognitive impairment: a marker for disease severity. Radiology. 2013, 267: 221-230. 10.1148/radiol.12120928.CrossRefPubMed
21.
go back to reference Gold BT, Jiang Y, Powell DK, Smith CD: Multimodal imaging evidence for axonal and myelin deterioration in amnestic mild cognitive impairment. J Alzheimers Dis. 2012, 31 (Suppl 3): S19-S31.PubMedCentralPubMed Gold BT, Jiang Y, Powell DK, Smith CD: Multimodal imaging evidence for axonal and myelin deterioration in amnestic mild cognitive impairment. J Alzheimers Dis. 2012, 31 (Suppl 3): S19-S31.PubMedCentralPubMed
22.
go back to reference Müller HP, Grön G, Sprengelmeyer R, Kassubek J, Ludolph AC, Hobbs N, Cole J, Roos RA, Duerr A, Tabrizi SJ, Landwehrmeyer GB, Süssmuth SD: Evaluating multicenter DTI data in Huntington’s disease on site specific effects: an ex post facto approach. NeuroImage Clinical. 2013, 2: 161-167.PubMedCentralCrossRefPubMed Müller HP, Grön G, Sprengelmeyer R, Kassubek J, Ludolph AC, Hobbs N, Cole J, Roos RA, Duerr A, Tabrizi SJ, Landwehrmeyer GB, Süssmuth SD: Evaluating multicenter DTI data in Huntington’s disease on site specific effects: an ex post facto approach. NeuroImage Clinical. 2013, 2: 161-167.PubMedCentralCrossRefPubMed
23.
go back to reference Dyrba M, Ewers M, Wegrzyn M, Kilimann I, Plant C, Oswald A, Meindl T, Pievani M, Bokde AL, Fellgiebel A, Filippi M, Hampel H, Klöppel S, Hauenstein K, Kirste T, Teipel SJ, EDSD study group: Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data. PLoS One. 2013, 8: e64925-10.1371/journal.pone.0064925. Dyrba M, Ewers M, Wegrzyn M, Kilimann I, Plant C, Oswald A, Meindl T, Pievani M, Bokde AL, Fellgiebel A, Filippi M, Hampel H, Klöppel S, Hauenstein K, Kirste T, Teipel SJ, EDSD study group: Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data. PLoS One. 2013, 8: e64925-10.1371/journal.pone.0064925.
24.
go back to reference Filippini N, MacIntosh BJ, Hough MG, Goodwin GM, Frisoni GB, Smith SM, Matthews PM, Beckmann CF, Mackay CE: Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci U S A. 2009, 106: 7209-7214. 10.1073/pnas.0811879106.PubMedCentralCrossRefPubMed Filippini N, MacIntosh BJ, Hough MG, Goodwin GM, Frisoni GB, Smith SM, Matthews PM, Beckmann CF, Mackay CE: Distinct patterns of brain activity in young carriers of the APOE-epsilon4 allele. Proc Natl Acad Sci U S A. 2009, 106: 7209-7214. 10.1073/pnas.0811879106.PubMedCentralCrossRefPubMed
25.
go back to reference Li W, Antuono PG, Xie C, Chen G, Jones JL, Ward BD, Franczak MB, Goveas JS, Li SJ: Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer’s disease after 12-week donepezil treatment. Neuroimage. 2012, 60: 1083-1091. 10.1016/j.neuroimage.2011.12.077.PubMedCentralCrossRefPubMed Li W, Antuono PG, Xie C, Chen G, Jones JL, Ward BD, Franczak MB, Goveas JS, Li SJ: Changes in regional cerebral blood flow and functional connectivity in the cholinergic pathway associated with cognitive performance in subjects with mild Alzheimer’s disease after 12-week donepezil treatment. Neuroimage. 2012, 60: 1083-1091. 10.1016/j.neuroimage.2011.12.077.PubMedCentralCrossRefPubMed
26.
go back to reference Chhatwal JP, Schultz AP, Johnson K, Benzinger TL, Jack C, Ances BM, Sullivan CA, Salloway SP, Ringman JM, Koeppe RA, Marcus DS, Thompson P, Saykin AJ, Correia S, Schofield PR, Rowe CC, Fox NC, Brickman AM, Mayeux R, McDade E, Bateman R, Fagan AM, Goate AM, Xiong C, Buckles VD, Morris JC, Sperling RA: Impaired default network functional connectivity in autosomal dominant Alzheimer disease. Neurology. 2013, 81: 736-744. 10.1212/WNL.0b013e3182a1aafe.PubMedCentralCrossRefPubMed Chhatwal JP, Schultz AP, Johnson K, Benzinger TL, Jack C, Ances BM, Sullivan CA, Salloway SP, Ringman JM, Koeppe RA, Marcus DS, Thompson P, Saykin AJ, Correia S, Schofield PR, Rowe CC, Fox NC, Brickman AM, Mayeux R, McDade E, Bateman R, Fagan AM, Goate AM, Xiong C, Buckles VD, Morris JC, Sperling RA: Impaired default network functional connectivity in autosomal dominant Alzheimer disease. Neurology. 2013, 81: 736-744. 10.1212/WNL.0b013e3182a1aafe.PubMedCentralCrossRefPubMed
27.
go back to reference Fleisher AS, Sherzai A, Taylor C, Langbaum JB, Chen K, Buxton RB: Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer’s disease risk groups. Neuroimage. 2009, 47: 1678-1690. 10.1016/j.neuroimage.2009.06.021.PubMedCentralCrossRefPubMed Fleisher AS, Sherzai A, Taylor C, Langbaum JB, Chen K, Buxton RB: Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer’s disease risk groups. Neuroimage. 2009, 47: 1678-1690. 10.1016/j.neuroimage.2009.06.021.PubMedCentralCrossRefPubMed
28.
go back to reference Wolk DA, Detre JA: Arterial spin labeling MRI: an emerging biomarker for Alzheimer’s disease and other neurodegenerative conditions. Curr Opin Neurol. 2012, 25: 421-428. 10.1097/WCO.0b013e328354ff0a.PubMedCentralCrossRefPubMed Wolk DA, Detre JA: Arterial spin labeling MRI: an emerging biomarker for Alzheimer’s disease and other neurodegenerative conditions. Curr Opin Neurol. 2012, 25: 421-428. 10.1097/WCO.0b013e328354ff0a.PubMedCentralCrossRefPubMed
29.
go back to reference Filippi M, Agosta F: Structural and functional network connectivity breakdown in Alzheimer’s disease studied with magnetic resonance imaging techniques. J Alzheimers Dis. 2011, 24: 455-474.PubMed Filippi M, Agosta F: Structural and functional network connectivity breakdown in Alzheimer’s disease studied with magnetic resonance imaging techniques. J Alzheimers Dis. 2011, 24: 455-474.PubMed
30.
go back to reference Sperling RA, Bates JF, Chua EF, Cocchiarella AJ, Rentz DM, Rosen BR, Schacter DL, Albert MS: fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003, 74: 44-50. 10.1136/jnnp.74.1.44.PubMedCentralCrossRefPubMed Sperling RA, Bates JF, Chua EF, Cocchiarella AJ, Rentz DM, Rosen BR, Schacter DL, Albert MS: fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003, 74: 44-50. 10.1136/jnnp.74.1.44.PubMedCentralCrossRefPubMed
31.
go back to reference Solé-Padullés C, Bartrés-Faz D, Junqué C, Vendrell P, Rami L, Clemente IC, Bosch B, Villar A, Bargalló N, Jurado MA, Barrios M, Molinuevo JL: Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging. 2009, 30: 1114-1124. 10.1016/j.neurobiolaging.2007.10.008.CrossRefPubMed Solé-Padullés C, Bartrés-Faz D, Junqué C, Vendrell P, Rami L, Clemente IC, Bosch B, Villar A, Bargalló N, Jurado MA, Barrios M, Molinuevo JL: Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging. 2009, 30: 1114-1124. 10.1016/j.neurobiolaging.2007.10.008.CrossRefPubMed
32.
go back to reference Celone KA, Calhoun VD, Dickerson BC, Atri A, Chua EF, Miller SL, DePeau K, Rentz DM, Selkoe DJ, Blacker D, Albert MS, Sperling RA: Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis. J Neurosci. 2006, 26: 10222-10231. 10.1523/JNEUROSCI.2250-06.2006.CrossRefPubMed Celone KA, Calhoun VD, Dickerson BC, Atri A, Chua EF, Miller SL, DePeau K, Rentz DM, Selkoe DJ, Blacker D, Albert MS, Sperling RA: Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis. J Neurosci. 2006, 26: 10222-10231. 10.1523/JNEUROSCI.2250-06.2006.CrossRefPubMed
33.
go back to reference Atri A, O’Brien JL, Sreenivasan A, Rastegar S, Salisbury S, DeLuca AN, O’Keefe KM, LaViolette PS, Rentz DM, Locascio JJ, Sperling RA: Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials. Arch Neurol. 2011, 68: 599-606.PubMedCentralCrossRefPubMed Atri A, O’Brien JL, Sreenivasan A, Rastegar S, Salisbury S, DeLuca AN, O’Keefe KM, LaViolette PS, Rentz DM, Locascio JJ, Sperling RA: Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials. Arch Neurol. 2011, 68: 599-606.PubMedCentralCrossRefPubMed
34.
go back to reference Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL: A default mode of brain function. Proc Natl Acad Sci U S A. 2001, 98: 676-682. 10.1073/pnas.98.2.676.PubMedCentralCrossRefPubMed Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL: A default mode of brain function. Proc Natl Acad Sci U S A. 2001, 98: 676-682. 10.1073/pnas.98.2.676.PubMedCentralCrossRefPubMed
35.
go back to reference Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC: [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006, 67: 446-452. 10.1212/01.wnl.0000228230.26044.a4.CrossRefPubMed Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC: [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006, 67: 446-452. 10.1212/01.wnl.0000228230.26044.a4.CrossRefPubMed
36.
go back to reference Dukart J, Kherif F, Mueller K, Adaszewski S, Schroeter ML, Frackowiak RS, Draganski B, Alzheimer’s Disease Neuroimaging I: Generative FDG-PET and MRI model of aging and disease progression in Alzheimer’s disease. PLoS Comput Biol. 2013, 9: e1002987-10.1371/journal.pcbi.1002987.PubMedCentralCrossRefPubMed Dukart J, Kherif F, Mueller K, Adaszewski S, Schroeter ML, Frackowiak RS, Draganski B, Alzheimer’s Disease Neuroimaging I: Generative FDG-PET and MRI model of aging and disease progression in Alzheimer’s disease. PLoS Comput Biol. 2013, 9: e1002987-10.1371/journal.pcbi.1002987.PubMedCentralCrossRefPubMed
37.
go back to reference Zeng F, Goodman MM: Fluorine-18 radiolabeled heterocycles as PET tracers for imaging beta-amyloid plaques in Alzheimer’s disease. Curr Top Med Chem. 2013, 13: 909-919. 10.2174/1568026611313080004.CrossRefPubMed Zeng F, Goodman MM: Fluorine-18 radiolabeled heterocycles as PET tracers for imaging beta-amyloid plaques in Alzheimer’s disease. Curr Top Med Chem. 2013, 13: 909-919. 10.2174/1568026611313080004.CrossRefPubMed
38.
go back to reference Wood H: Alzheimer disease: [C]PBB3 - a new PET ligand that identifies tau pathology in the brains of patients with AD. Nat Rev Neurol. 2013, 9: 599-10.1038/nrneurol.2013.216.CrossRefPubMed Wood H: Alzheimer disease: [C]PBB3 - a new PET ligand that identifies tau pathology in the brains of patients with AD. Nat Rev Neurol. 2013, 9: 599-10.1038/nrneurol.2013.216.CrossRefPubMed
39.
go back to reference Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC: Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013, 34: 457-468.PubMed Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC: Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013, 34: 457-468.PubMed
40.
go back to reference Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM: Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007, 64: 343-349. 10.1001/archneur.64.3.noc60123.CrossRefPubMed Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM: Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007, 64: 343-349. 10.1001/archneur.64.3.noc60123.CrossRefPubMed
41.
go back to reference Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR, Bapineuzumab 301 and 302 Clinical Trial Investigators: Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014, 370: 322-333. 10.1056/NEJMoa1304839.PubMedCentralCrossRefPubMed Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, Sabbagh M, Honig LS, Porsteinsson AP, Ferris S, Reichert M, Ketter N, Nejadnik B, Guenzler V, Miloslavsky M, Wang D, Lu Y, Lull J, Tudor IC, Liu E, Grundman M, Yuen E, Black R, Brashear HR, Bapineuzumab 301 and 302 Clinical Trial Investigators: Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med. 2014, 370: 322-333. 10.1056/NEJMoa1304839.PubMedCentralCrossRefPubMed
42.
go back to reference Jack CR, Dickson DW, Parisi JE, Xu YC, Cha RH, O’Brien PC, Edland SD, Smith GE, Boeve BF, Tangalos EG, Kokmen E, Petersen RC: Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology. 2002, 58: 750-757. 10.1212/WNL.58.5.750.PubMedCentralCrossRefPubMed Jack CR, Dickson DW, Parisi JE, Xu YC, Cha RH, O’Brien PC, Edland SD, Smith GE, Boeve BF, Tangalos EG, Kokmen E, Petersen RC: Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology. 2002, 58: 750-757. 10.1212/WNL.58.5.750.PubMedCentralCrossRefPubMed
43.
go back to reference Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM, AN1792(QS-21)-201 Study Team: Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005, 64: 1553-1562. 10.1212/01.WNL.0000159740.16984.3C.CrossRefPubMed Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM, AN1792(QS-21)-201 Study Team: Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005, 64: 1553-1562. 10.1212/01.WNL.0000159740.16984.3C.CrossRefPubMed
44.
go back to reference Boccardi M, Bocchetta M, Ganzola R, Robitaille N, Redolfi A, Duchesne S, Jack CR, Frisoni GB: EADC-ADNI Working Group on The Harmonized Protocol for Hippocampal Volumetry and for the Alzheimer’s Disease Neuroimaging Initiative: Operationalizing protocol differences for EADC-ADNI manual hippocampal segmentation. Alzheimers Dement. 2013, May 21. doi: 10.1016/j.jalz.2013.03.0013, Boccardi M, Bocchetta M, Ganzola R, Robitaille N, Redolfi A, Duchesne S, Jack CR, Frisoni GB: EADC-ADNI Working Group on The Harmonized Protocol for Hippocampal Volumetry and for the Alzheimer’s Disease Neuroimaging Initiative: Operationalizing protocol differences for EADC-ADNI manual hippocampal segmentation. Alzheimers Dement. 2013, May 21. doi: 10.1016/j.jalz.2013.03.0013,
45.
go back to reference Holland D, McEvoy LK, Dale AM, Alzheimer’s Disease Neuroimaging Initiative: Unbiased comparison of sample size estimates from longitudinal structural measures in ADNI. Hum Brain Mapp. 2012, 33: 2586-2602. 10.1002/hbm.21386.PubMedCentralCrossRefPubMed Holland D, McEvoy LK, Dale AM, Alzheimer’s Disease Neuroimaging Initiative: Unbiased comparison of sample size estimates from longitudinal structural measures in ADNI. Hum Brain Mapp. 2012, 33: 2586-2602. 10.1002/hbm.21386.PubMedCentralCrossRefPubMed
46.
go back to reference Barkhof F, Daams M, Scheltens P, Brashear HR, Arrighi HM, Bechten A, Morris K, McGovern M, Wattjes MP: An MRI rating scale for amyloid-related imaging abnormalities with edema or effusion. AJNR Am J Neuroradiol. 2013, 34: 1550-1555. 10.3174/ajnr.A3475.CrossRefPubMed Barkhof F, Daams M, Scheltens P, Brashear HR, Arrighi HM, Bechten A, Morris K, McGovern M, Wattjes MP: An MRI rating scale for amyloid-related imaging abnormalities with edema or effusion. AJNR Am J Neuroradiol. 2013, 34: 1550-1555. 10.3174/ajnr.A3475.CrossRefPubMed
47.
go back to reference Moseley M: Diffusion tensor imaging and aging - a review. NMR Biomed. 2002, 15: 553-560. 10.1002/nbm.785.CrossRefPubMed Moseley M: Diffusion tensor imaging and aging - a review. NMR Biomed. 2002, 15: 553-560. 10.1002/nbm.785.CrossRefPubMed
48.
go back to reference Johnson SC, Schmitz TW, Moritz CH, Meyerand ME, Rowley HA, Alexander AL, Hansen KW, Gleason CE, Carlsson CM, Ries ML, Asthana S, Chen K, Reiman EM, Alexander GE: Activation of brain regions vulnerable to Alzheimer’s disease: the effect of mild cognitive impairment. Neurobiol Aging. 2006, 27: 1604-1612. 10.1016/j.neurobiolaging.2005.09.017.PubMedCentralCrossRefPubMed Johnson SC, Schmitz TW, Moritz CH, Meyerand ME, Rowley HA, Alexander AL, Hansen KW, Gleason CE, Carlsson CM, Ries ML, Asthana S, Chen K, Reiman EM, Alexander GE: Activation of brain regions vulnerable to Alzheimer’s disease: the effect of mild cognitive impairment. Neurobiol Aging. 2006, 27: 1604-1612. 10.1016/j.neurobiolaging.2005.09.017.PubMedCentralCrossRefPubMed
49.
go back to reference Lorenzi M, Beltramello A, Mercuri NB, Canu E, Zoccatelli G, Pizzini FB, Alessandrini F, Cotelli M, Rosini S, Costardi D, Caltagirone C, Frisoni GB: Effect of memantine on resting state default mode network activity in Alzheimer’s disease. Drugs Aging. 2011, 28: 205-217. 10.2165/11586440-000000000-00000.CrossRefPubMed Lorenzi M, Beltramello A, Mercuri NB, Canu E, Zoccatelli G, Pizzini FB, Alessandrini F, Cotelli M, Rosini S, Costardi D, Caltagirone C, Frisoni GB: Effect of memantine on resting state default mode network activity in Alzheimer’s disease. Drugs Aging. 2011, 28: 205-217. 10.2165/11586440-000000000-00000.CrossRefPubMed
50.
go back to reference Hu WT, Wang Z, Lee VM, Trojanowski JQ, Detre JA, Grossman M: Distinct cerebral perfusion patterns in FTLD and AD. Neurology. 2010, 75: 881-888. 10.1212/WNL.0b013e3181f11e35.PubMedCentralCrossRefPubMed Hu WT, Wang Z, Lee VM, Trojanowski JQ, Detre JA, Grossman M: Distinct cerebral perfusion patterns in FTLD and AD. Neurology. 2010, 75: 881-888. 10.1212/WNL.0b013e3181f11e35.PubMedCentralCrossRefPubMed
Metadata
Title
Imaging as a biomarker in drug discovery for Alzheimer’s disease: is MRI a suitable technology?
Authors
Emilio Merlo Pich
Andreas Jeromin
Giovanni B Frisoni
Derek Hill
Andrew Lockhart
Mark E Schmidt
Martin R Turner
Stefania Mondello
William Z Potter
Publication date
01-08-2014
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 4/2014
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/alzrt276

Other articles of this Issue 4/2014

Alzheimer's Research & Therapy 4/2014 Go to the issue