Background: Recent studies have demonstrated that arterial spin labeling magnetic resonance imaging (ASL-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) identify similar regional abnormalities and have comparable diagnostic accuracy in Alzheimer's disease (AD). The agreement between these modalities in the AD continuum, which is an important concept for early detection and disease monitoring, is yet unclear. Objective: We aimed to assess the ability of the cerebral blood flow (CBF) measures from ASL-MRI and cerebral metabolic rate for glucose (CMRgl) measures from FDG-PET to distinguish amyloid-β-positive (Aβ+) subjects in the AD continuum from healthy controls. Methods: The study included asymptomatic, cognitively normal (CN) controls and patients with early mild cognitive impairment (MCI), late MCI, and AD, all with significant levels of cortical Aβ based on their florbetapir PET scans to restrict the study to patients truly in the AD continuum. The discrimination power of each modality was based on the whole-brain patterns of CBF and CMRgl changes identified by partial least squares logistic regression, a multivariate analysis technique. Results: While CBF changes in the posterior inferior aspects of the brain and a pattern of CMRgl changes in the superior aspects of the brain including frontal and parietal regions best discriminated the Aβ+ subjects in the early disease stages from the Aβ- CN subjects, there was a greater agreement in the whole-brain patterns of CBF and CMRgl changes that best discriminated the Aβ+ subjects from the Aβ- CN subjects in the later disease stages. Despite the differences in the whole-brain patterns of CBF and CMRgl changes, the discriminative powers of both modalities were similar with statistically nonsignificant performance differences in sensitivity and specificity. Conclusion: The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum.

1.
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: 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. Alzheimers Dementia 2011;7:280-292.
2.
Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ: Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 2013;12:207-216.
3.
Fox PT, Raichle ME, Mintun MA, Dence C: Nonoxidative glucose consumption during focal physiologic neural activity. Science 1988;241:462-464.
4.
Magistretti PJ, Pellerin L: Astrocytes couple synaptic activity to glucose utilization in the brain. News Physiol Sci 1999;14:177-182.
5.
Attwell D, Laughlin SB: An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 2001;21:1133-1145.
6.
Silverman DH, Small GW, Chang CY, Lu CS, Kung De Aburto MA, Chen W, Czernin J, Rapoport SI, Pietrini P, Alexander GE, Schapiro MB, Jagust WJ, Hoffman JM, Welsh-Bohmer KA, Alavi A, Clark CM, Salmon E, de Leon MJ, Mielke R, Cummings JL, Kowell AP, Gambhir SS, Hoh CK, Phelps ME: Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA 2001;286:2120-2127.
7.
Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE: Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol 1997;42:85-94.
8.
Mosconi L: Brain glucose metabolism in the early and specific diagnosis of Alzheimer's disease. FDG-PET studies in MCI and AD. Eur J Nucl Med Mol Imaging 2005;32:486-510.
9.
Herholz K, Salmon E, Perani D, Baron JC, Holthoff V, Frolich L, Schonknecht P, Ito K, Mielke R, Kalbe E, Zundorf G, Delbeuck X, Pelati O, Anchisi D, Fazio F, Kerrouche N, Desgranges B, Eustache F, Beuthien-Baumann B, Menzel C, Schroder J, Kato T, Arahata Y, Henze M, Heiss WD: Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage 2002;17:302-316.
10.
Mosconi L, Tsui WH, Herholz K, Pupi A, Drzezga A, Lucignani G, Reiman EM, Holthoff V, Kalbe E, Sorbi S, Diehl-Schmid J, Perneczky R, Clerici F, Caselli R, Beuthien-Baumann B, Kurz A, Minoshima S, de Leon MJ: Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias. J Nucl Med 2008;49:390-398.
11.
De Leon MJ, Convit A, Wolf OT, Tarshish CY, DeSanti S, Rusinek H, Tsui W, Kandil E, Scherer AJ, Roche A, Imossi A, Thorn E, Bobinski M, Caraos C, Lesbre P, Schlyer D, Poirier J, Reisberg B, Fowler J: Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET). Proc Natl Acad Sci USA 2001;98:10966-10971.
12.
Mosconi L, De Santi S, Li J, Tsui WH, Li Y, Boppana M, Laska E, Rusinek H, de Leon MJ: Hippocampal hypometabolism predicts cognitive decline from normal aging. Neurobiol Aging 2008;29:676-692.
13.
Jagust W, Gitcho A, Sun F, Kuczynski B, Mungas D, Haan M: Brain imaging evidence of preclinical Alzheimer's disease in normal aging. Ann Neurol 2006;59:673-681.
14.
Mosconi L, Mistur R, Switalski R, Tsui WH, Glodzik L, Li Y, Pirraglia E, De Santi S, Reisberg B, Wisniewski T, de Leon MJ: FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer's disease. Eur J Nucl Med Mol Imaging 2009;36:811-822.
15.
Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D: Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 1996;334:752-758.
16.
Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY, Lavretsky H, Miller K, Siddarth P, Rasgon NL, Mazziotta JC, Saxena S, Wu HM, Mega MS, Cummings JL, Saunders AM, Pericak-Vance MA, Roses AD, Barrio JR, Phelps ME: Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. Proc Natl Acad Sci USA 2000;97:6037-6042.
17.
Mosconi L, Perani D, Sorbi S, Herholz K, Nacmias B, Holthoff V, Salmon E, Baron JC, De Cristofaro MT, Padovani A, Borroni B, Franceschi M, Bracco L, Pupi A: MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 2004;63:2332-2340.
18.
Chetelat G, Desgranges B, de la Sayette V, Viader F, Eustache F, Baron JC: Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer's disease? Neurology 2003;60:1374-1377.
19.
Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M, Willoch F, Minoshima S, Schwaiger M, Kurz A: Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 2003;30:1104-1113.
20.
Baron JC, Lebrun-Grandie P, Collard P, Crouzel C, Mestelan G, Bousser MG: Noninvasive measurement of blood flow, oxygen consumption, and glucose utilization in the same brain regions in man by positron emission tomography: concise communication. J Nucl Med 1982;23:391-399.
21.
Furlow TW Jr, Martin RM, Harrison LE: Simultaneous measurement of local glucose utilization and blood flow in the rat brain: an autoradiographic method using two tracers labeled with carbon-14. J Cereb Blood Flow Metab 1983;3:62-66.
22.
Detre JA, Rao H, Wang DJ, Chen YF, Wang Z: Applications of arterial spin labeled MRI in the brain. J Magn Reson Imaging 2012;35:1026-1037.
23.
Detre JA, Alsop DC: Perfusion magnetic resonance imaging with continuous arterial spin labeling: methods and clinical applications in the central nervous system. Eur J Radiol 1999;30:115-124.
24.
Alsop DC, Detre JA, Grossman M: Assessment of cerebral blood flow in Alzheimer's disease by spin-labeled magnetic resonance imaging. Ann Neurol 2000;47:93-100.
25.
Johnson NA, Jahng GH, Weiner MW, Miller BL, Chui HC, Jagust WJ, Gorno-Tempini ML, Schuff N: Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology 2005;234:851-859.
26.
Musiek ES, Chen Y, Korczykowski M, Saboury B, Martinez PM, Reddin JS, Alavi A, Kimberg DY, Wolk DA, Julin P, Newberg AB, Arnold SE, Detre JA: Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's disease. Alzheimers Dement 2012;8:51-59.
27.
Chen Y, Wolk DA, Reddin JS, Korczykowski M, Martinez PM, Musiek ES, Newberg AB, Julin P, Arnold SE, Greenberg JH, Detre JA: Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease. Neurology 2011;77:1977-1985.
28.
Cha YH, Jog MA, Kim YC, Chakrapani S, Kraman SM, Wang DJ: Regional correlation between resting state FDG PET and pCASL perfusion MRI. J Cereb Blood Flow Metab 2013;33:1909-1914.
29.
Zlokovic BV: Neurovascular mechanisms of Alzheimer's neurodegeneration. Trends Neurosci 2005;28:202-208.
30.
Landau SM, Breault C, Joshi AD, Pontecorvo M, Mathis CA, Jagust WJ, Mintun MA: Amyloid-beta imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med 2013;54:70-77.
31.
Joshi A, Koeppe RA, Fessler JA: Reducing between scanner differences in multi-center PET studies. Neuroimage 2009;46:154-159.
32.
Wold S, Geladi P, Esbensen K, Öhman J: Multi-way principal components- and PLS-analysis. J Chemometr 1987;1:41-56.
33.
Gray KRG, Aljabar P, Heckemann RA, Hammers A, Rueckert D; Alzheimer's Disease Neuroimaging Initiative: Random forest-based similarity measures for multi-modal classification of Alzheimer's disease. Neuroimage 2013;65C:167-175.
34.
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, Siuciak JA, Soares H, Toga AW, Trojanowski JQ: The Alzheimer's Disease Neuroimaging Initiative: a review of papers published since its inception. Alzheimers Dement 2012;8(suppl):S1-S68.
35.
Xekardaki A, Rodriguez C, Montandon M-L, Toma S, Tombeur E, Herrmann FR, Zekry D, Lovblad K-O, Barkhof F, Giannakopoulos P, Haller S: Arterial spin labeling may contribute to the prediction of cognitive deterioration in healthy elderly individuals. Radiology 2015;274:490-499.
36.
Muller-Gartner HW, Links JM, Prince JL, Bryan RN, McVeigh E, Leal JP, Davatzikos C, Frost JJ: Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. J Cereb Blood Flow Metab 1992;12:571-583.
37.
Raichle ME: Behind the scenes of functional brain imaging: a historical and physiological perspective. Proc Natl Acad Sci USA 1998;95:765-772.
38.
Jueptner M, Weiller C: Review: does measurement of regional cerebral blood flow reflect synaptic activity? Implications for PET and fMRI. Neuroimage 1995;2:148-156.
39.
Niwa K, Kazama K, Younkin SG, Carlson GA, Iadecola C: Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein. Neurobiol Dis 2002;9:61-68.
40.
Ruitenberg A, den Heijer T, Bakker SL, van Swieten JC, Koudstaal PJ, Hofman A, Breteler MM: Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 2005;57:789-794.
41.
Knopman DS, Roberts R: Vascular risk factors: imaging and neuropathologic correlates. J Alzheimers Dis 2010;20:699-709.
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