Neuroimaging of Alzheimer’s Disease, Mild Cognitive Impairment, and Other Dementias

  • Shannon L. Risacher
  • Andrew J. Saykin


The goal of the present chapter is to provide an overview of the major findings from studies of neuroimaging in dementia, particularly from patients with Alzheimer’s disease (AD). The major emphasis is on findings from a variety of imaging modalities and the use of these measures for early diagnosis and as biomarkers of disease progression. In this chapter, we first describe the basic neurobiological changes and clinical symptoms associated with AD and related cognitive decline. Next, we discuss results from studies in AD utilizing structural neuroimaging techniques, including computerized tomography (CT), traditional structural magnetic resonance imaging (MRI), and other MRI techniques [diffusion tensor imaging (DTI), perfusion MRI, magnetic resonance spectroscopy (MRS)]. Next, we explore findings from functional MRI studies, including task-related activation studies and resting and functional connectivity research. We, then, discuss results from the use of nuclear medicine techniques in AD, including single-photon emission computerized tomography (SPECT) and positron emission tomography (PET) studies. Neuroimaging in other dementias is also briefly discussed, with particular emphasis on differential diagnosis of dementia type. Finally, we explore future directions for neuroimaging of early AD and dementia.


Mild Cognitive Impairment Fractional Anisotropy Dementia With Lewy Body Default Mode Network Medial Temporal Lobe 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Preparation of this manuscript was supported in part by grants from the National Institutes of Health (NIA R01 AG19771 to AJS and P30 AG101133-18S1 Core Supplement to Bernardino Ghetti, MD and AJS; CTSI Training Grant, TL1 RR025759 to SLR; and NIBIB R03 EB008674 to Li Shen, PhD), the Indiana Economic Development Corporation (IEDC #87884 to AJS), and by the Alzheimer’s Disease Neuroimaging Initiative (PI: Michael Weiner, MD; NIH grant U01 AG024904 and RC2 AG036535-01). ADNI is funded by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and through generous contribution from the following: Pfizer Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck & Co. Inc., AstraZeneca AB, Novartis Pharmaceuticals Corporation, the Alzheimer’s Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories, and the Institute for the Study of Aging, with participation of the U.S. Food and Drug Administration. Industry partnerships are coordinated through the Foundation for the National Institutes of Health. The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles.


  1. 1.
    Wimo A, Winblad B, Aguero-Torres H, von Strauss E. The magnitude of dementia occurrence in the world. Alzheimer Dis Assoc Disord. 2003;17(2):63-67.PubMedCrossRefGoogle Scholar
  2. 2.
    Newcomer RJ, Fox PJ, Harrington CA. Health and long-term care for people with Alzheimer’s disease and related dementias: policy research issues. Aging Ment Health. 2001;5(Suppl 1):S124-S137.PubMedGoogle Scholar
  3. 3.
    Bertram L, Tanzi RE. Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci. 2008;9(10):768-778.PubMedCrossRefGoogle Scholar
  4. 4.
    Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261(5123):921-923.PubMedCrossRefGoogle Scholar
  5. 5.
    Mayeux R, Saunders AM, Shea S, et al. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. Alzheimer’s Disease Centers Consortium on Apolipoprotein E and Alzheimer’s Disease. N Engl J Med. 1998;338(8):506-511.PubMedCrossRefGoogle Scholar
  6. 6.
    Corder EH, Saunders AM, Risch NJ, et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet. 1994;7(2):180-184.PubMedCrossRefGoogle Scholar
  7. 7.
    Masters CL, Cappai R, Barnham KJ, Villemagne VL. Molecular mechanisms for Alzheimer’s disease: implications for neuroimaging and therapeutics. J Neurochem. 2006;97(6):1700-1725.PubMedCrossRefGoogle Scholar
  8. 8.
    Minati L, Edginton T, Bruzzone MG, Giaccone G. Current concepts in Alzheimer’s disease: a multidisciplinary review. Am J Alzheimers Dis Other Demen. 2009;24(2):95-121.PubMedCrossRefGoogle Scholar
  9. 9.
    Nathalie P, Jean-Noel O. Processing of amyloid precursor protein and amyloid peptide neurotoxicity. Curr Alzheimer Res. 2008;5(2):92-99.PubMedCrossRefGoogle Scholar
  10. 10.
    Brion JP. Neurofibrillary tangles and Alzheimer’s disease. Eur Neurol. 1998;40(3):130-140.PubMedCrossRefGoogle Scholar
  11. 11.
    Sorrentino G, Bonavita V. Neurodegeneration and Alzheimer’s disease: the lesson from tauopathies. Neurol Sci. 2007;28(2):63-71.PubMedCrossRefGoogle Scholar
  12. 12.
    Braak H, Braak E, Bohl J. Staging of Alzheimer-related cortical destruction. Eur Neurol. 1993;33(6):403-408.PubMedCrossRefGoogle Scholar
  13. 13.
    Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol. 1981;10(2):122-126.PubMedCrossRefGoogle Scholar
  14. 14.
    Braak H, Braak E. Evolution of the neuropathology of Alzheimer’s disease. Acta Neurol Scand Suppl. 1996;165:3-12.PubMedGoogle Scholar
  15. 15.
    Storey E, Kinsella GJ, Slavin MJ. The neuropsychological diagnosis of Alzheimer’s disease. J Alzheimers Dis. 2001;3(3):261-285.PubMedGoogle Scholar
  16. 16.
    Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183-194.PubMedCrossRefGoogle Scholar
  17. 17.
    Petersen RC. Mild cognitive impairment: current research and clinical implications. Semin Neurol. 2007;27:22-31.PubMedCrossRefGoogle Scholar
  18. 18.
    Petersen RC, Bennett D. Mild cognitive impairment: is it Alzheimer’s disease or not? J Alzheimers Dis. 2005;7(3):241-245. discussion 55-62.PubMedGoogle Scholar
  19. 19.
    Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56(3):303-308.PubMedCrossRefGoogle Scholar
  20. 20.
    Ahmed S, Mitchell J, Arnold R, Dawson K, Nestor PJ, Hodges JR. Memory complaints in mild cognitive impairment, worried well, and semantic dementia patients. Alzheimer Dis Assoc Disord. 2008;22(3):227-235.PubMedCrossRefGoogle Scholar
  21. 21.
    Dik MG, Jonker C, Comijs HC, et al. Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly. Neurology. 2001;57(12):2217-2222.PubMedGoogle Scholar
  22. 22.
    Kliegel M, Zimprich D, Eschen A. What do subjective cognitive complaints in persons with aging-associated cognitive decline reflect? Int Psychogeriatr. 2005;17(3):499-512.PubMedCrossRefGoogle Scholar
  23. 23.
    Nunes T, Fragata I, Ribeiro F, et al. The outcome of elderly patients with cognitive complaints but normal neuropsychological tests. J Alzheimers Dis. 2009 Sep 11.Google Scholar
  24. 24.
    Saykin AJ, Wishart HA, Rabin LA, et al. Older adults with cognitive complaints show brain atrophy similar to that of amnestic MCI. Neurology. 2006;67(5):834-842.PubMedCrossRefGoogle Scholar
  25. 25.
    Jack CR Jr, Bernstein MA, Fox NC, et al. The Alzheimer’s Disease Neuroimaging Initiative (ADNI): MRI methods. J Magn Reson Imaging. 2008;27(4):685-691.PubMedCrossRefGoogle Scholar
  26. 26.
    Mueller SG, Weiner MW, Thal LJ, et al. The Alzheimer’s disease neuroimaging initiative. Neuroimaging Clin N Am. 2005;15(4):869-877. xi-xii.PubMedCrossRefGoogle Scholar
  27. 27.
    Mueller SG, Weiner MW, Thal LJ, et al. Ways toward an early diagnosis in Alzheimer’s disease: the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Alzheimers Dement. 2005;1(1):55-66.PubMedCrossRefGoogle Scholar
  28. 28.
    Chang YL, Jacobson MW, Fennema-Notestine C, et al. Level of executive function influences verbal memory in amnestic mild cognitive impairment and predicts prefrontal and posterior cingulate thickness. Cereb Cortex. 2010;20(6):1305-1313.PubMedCrossRefGoogle Scholar
  29. 29.
    Chou YY, Lepore N, Avedissian C, et al. 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. 2009;46(2):394-410.PubMedCrossRefGoogle Scholar
  30. 30.
    Desikan RS, Cabral HJ, Hess CP, et al. Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer’s disease. Brain. 2009;132(Pt 8):2048-2057.PubMedCrossRefGoogle Scholar
  31. 31.
    Fan Y, Batmanghelich N, Clark CM, Davatzikos C. Spatial patterns of brain atrophy in MCI patients, identified via high-dimensional pattern classification, predict subsequent cognitive decline. Neuroimage. 2008;39(4):1731-1743.PubMedCrossRefGoogle Scholar
  32. 32.
    Fan Y, Resnick SM, Wu X, Davatzikos C. Structural and functional biomarkers of prodromal Alzheimer’s disease: a high-dimensional pattern classification study. Neuroimage. 2008;41(2):277-285.PubMedCrossRefGoogle Scholar
  33. 33.
    Fennema-Notestine C, Hagler DJ Jr, McEvoy LK, et al. Structural MRI biomarkers for preclinical and mild Alzheimer’s disease. Hum Brain Mapp. 2009;30(10):3238-3253.PubMedCrossRefGoogle Scholar
  34. 34.
    Gerardin E, Chetelat G, Chupin M, et al. Multidimensional classification of hippocampal shape features discriminates Alzheimer’s disease and mild cognitive impairment from normal aging. Neuroimage. 2009;47(4):1476-1486.PubMedCrossRefGoogle Scholar
  35. 35.
    Hinrichs C, Singh V, Mukherjee L, Xu G, Chung MK, Johnson SC. Spatially augmented LPboosting for AD classification with evaluations on the ADNI dataset. Neuroimage. 2009;48(1):138-149.PubMedCrossRefGoogle Scholar
  36. 36.
    Hua X, Leow AD, Parikshak N, et al. Tensor-based morphometry as a neuroimaging biomarker for Alzheimer’s disease: an MRI study of 676 AD, MCI, and normal subjects. Neuroimage. 2008;43(3):458-469.PubMedCrossRefGoogle Scholar
  37. 37.
    Jack CR Jr, Lowe VJ, Weigand SD, et al. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer’s disease: implications for sequence of pathological events in Alzheimer’s disease. Brain. 2009;132(Pt 5):1355-1365.PubMedCrossRefGoogle Scholar
  38. 38.
    Kovacevic S, Rafii MS, Brewer JB. High-throughput, fully automated volumetry for prediction of MMSE and CDR decline in mild cognitive impairment. Alzheimer Dis Assoc Disord. 2009;23(2):139-145.PubMedCrossRefGoogle Scholar
  39. 39.
    Leow AD, Yanovsky I, Parikshak N, et al. Alzheimer’s Disease Neuroimaging Initiative: A one-year follow up study using Tensor-Based Morphometry correlating degenerative rates, biomarkers and cognition. Neuroimage. 2009;45(3):644-655.Google Scholar
  40. 40.
    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. 2009;44(4):1415-1422.PubMedCrossRefGoogle Scholar
  41. 41.
    Morra JH, Tu Z, Apostolova LG, et al. Validation of a fully automated 3D hippocampal segmentation method using subjects with Alzheimer’s disease mild cognitive impairment, and elderly controls. Neuroimage. 2008;43(1):59-68.PubMedCrossRefGoogle Scholar
  42. 42.
    Risacher SL, Saykin AJ, West JD, et al. Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort. Curr Alzheimer Res. 2009;6:347-361.PubMedCrossRefGoogle Scholar
  43. 43.
    Vemuri P, Wiste HJ, Weigand SD, et al. MRI and CSF biomarkers in normal, MCI, and AD subjects: diagnostic discrimination and cognitive correlations. Neurology. 2009;73(4):287-293.PubMedCrossRefGoogle Scholar
  44. 44.
    Walhovd KB, Fjell AM, Dale AM, et al. Multi-modal imaging predicts memory performance in normal aging and cognitive decline. Neurobiol Aging. 2010;31(7):1107-1121.PubMedCrossRefGoogle Scholar
  45. 45.
    Risacher SL, Shen L, West JD, et al. Longitudinal MRI atrophy biomarkers: Relationship to conversion in the ADNI cohort. Neurobiol Aging. 2010;31(8):1401-1418.PubMedCrossRefGoogle Scholar
  46. 46.
    Morra JH, Tu Z, Apostolova LG, et al. 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. 2009;45(1 Suppl):S3-S15.PubMedCrossRefGoogle Scholar
  47. 47.
    Vemuri P, Wiste HJ, Weigand SD, et al. MRI and CSF biomarkers in normal, MCI, and AD subjects: predicting future clinical change. Neurology. 2009;73(4):294-301.PubMedCrossRefGoogle Scholar
  48. 48.
    Haense C, Herholz K, Jagust WJ, Heiss WD. Performance of FDG PET for detection of Alzheimer’s disease in two independent multicentre samples (NEST-DD and ADNI). Dement Geriatr Cogn Disord. 2009;28(3):259-266.PubMedCrossRefGoogle Scholar
  49. 49.
    Jagust WJ, Landau SM, Shaw LM, et al. Relationships between biomarkers in aging and dementia. Neurology. 2009;73(15):1193-1199.PubMedCrossRefGoogle Scholar
  50. 50.
    Landau SM, Harvey D, Madison CM, et al. Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging. 2009 Aug 4.Google Scholar
  51. 51.
    Langbaum JB, Chen K, Lee W, et al. Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neuroimage. 2009;45(4):1107-1116.PubMedCrossRefGoogle Scholar
  52. 52.
    Mormino EC, Kluth JT, Madison CM, et al. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain. 2009;132(Pt 5):1310-1323.PubMedCrossRefGoogle Scholar
  53. 53.
    Leow AD, Yanovsky I, Parikshak N, et al. Alzheimer’s disease neuroimaging initiative: a one-year follow up study using tensor-based morphometry correlating degenerative rates, biomarkers and cognition. Neuroimage. 2009;45(3):645-655.PubMedCrossRefGoogle Scholar
  54. 54.
    Schuff N, Woerner N, Boreta L, et al. MRI of hippocampal volume loss in early Alzheimer’s disease in relation to ApoE genotype and biomarkers. Brain. 2009;132(Pt 4):1067-1077.PubMedGoogle Scholar
  55. 55.
    Shaw LM, Vanderstichele H, Knapik-Czajka M, et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65(4):403-413.PubMedCrossRefGoogle Scholar
  56. 56.
    de Leon MJ, George AE, Reisberg B, et al. Alzheimer’s disease: longitudinal CT studies of ventricular change. AJR Am J Roentgenol. 1989;152(6):1257-1262.PubMedGoogle Scholar
  57. 57.
    Willmer J, Carruthers A, Guzman DA, Collins B, Pogue J, Stuss DT. The usefulness of CT scanning in diagnosing dementia of the Alzheimer type. Can J Neurol Sci. 1993;20(3):210-216.PubMedGoogle Scholar
  58. 58.
    LeMay M, Stafford JL, Sandor T, Albert M, Haykal H, Zamani A. Statistical assessment of perceptual CT scan ratings in patients with Alzheimer type dementia. J Comput Assist Tomogr. 1986;10(5):802-809.PubMedCrossRefGoogle Scholar
  59. 59.
    Kido DK, Caine ED, LeMay M, Ekholm S, Booth H, Panzer R. Temporal lobe atrophy in patients with Alzheimer disease: a CT study. AJNR Am J Neuroradiol. 1989;10(3):551-555.PubMedGoogle Scholar
  60. 60.
    DeCarli C, Kaye JA, Horwitz B, Rapoport SI. Critical analysis of the use of computer-assisted transverse axial tomography to study human brain in aging and dementia of the Alzheimer type. Neurology. 1990;40(6):872-883.PubMedGoogle Scholar
  61. 61.
    George AE, de Leon MJ, Stylopoulos LA, et al. CT diagnostic features of Alzheimer disease: importance of the choroidal/hippocampal fissure complex. AJNR Am J Neuroradiol. 1990;11(1):101-107.PubMedGoogle Scholar
  62. 62.
    de Leon MJ, George AE, Stylopoulos LA, Smith G, Miller DC. Early marker for Alzheimer’s disease: the atrophic hippocampus. Lancet. 1989;2(8664):672-673.PubMedGoogle Scholar
  63. 63.
    Ambrosetto P, Bacci A. CT diagnostic features of choroidal/hippocampal fissure complex in Alzheimer disease and progressive supranuclear palsy. AJNR Am J Neuroradiol. 1991;12(3):583-584.PubMedGoogle Scholar
  64. 64.
    Jack CR Jr, Petersen RC, O’Brien PC, Tangalos EG. MR-based hippocampal volumetry in the diagnosis of Alzheimer’s disease. Neurology. 1992;42(1):183-188.PubMedGoogle Scholar
  65. 65.
    Jack CR Jr, Petersen RC, Xu YC, et al. Medial temporal atrophy on MRI in normal aging and very mild Alzheimer’s disease. Neurology. 1997;49(3):786-794.PubMedGoogle Scholar
  66. 66.
    Korf ES, Wahlund LO, Visser PJ, Scheltens P. Medial temporal lobe atrophy on MRI predicts dementia in patients with mild cognitive impairment. Neurology. 2004;63(1):94-100.PubMedGoogle Scholar
  67. 67.
    Scheltens P, Pasquier F, Weerts JG, Barkhof F, Leys D. Qualitative assessment of cerebral atrophy on MRI: inter- and intra-observer reproducibility in dementia and normal aging. Eur Neurol. 1997;37(2):95-99.PubMedCrossRefGoogle Scholar
  68. 68.
    Dale A, Fischl B, Sereno M. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage. 1999;9(2):179-194.PubMedCrossRefGoogle Scholar
  69. 69.
    Fischl B, Dale AM. Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A. 2000;97(20):11050-11055.PubMedCrossRefGoogle Scholar
  70. 70.
    Fischl B, Salat D, Busa E, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron. 2002;33(3):341-355.PubMedCrossRefGoogle Scholar
  71. 71.
    Ashburner J, Friston KJ. Voxel-based morphometry – the methods. Neuroimage. 2000;11(6 Pt 1):805-821.PubMedCrossRefGoogle Scholar
  72. 72.
    Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage. 2001;14(1 Pt 1):21-36.PubMedCrossRefGoogle Scholar
  73. 73.
    Jack CR Jr, Dickson DW, Parisi JE, et al. Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology. 2002;58(5):750-757.PubMedGoogle Scholar
  74. 74.
    Henneman WJ, Sluimer JD, Barnes J, et al. Hippocampal atrophy rates in Alzheimer disease: added value over whole brain volume measures. Neurology. 2009;72(11):999-1007.PubMedCrossRefGoogle Scholar
  75. 75.
    Convit A, de Leon MJ, Golomb J, et al. Hippocampal atrophy in early Alzheimer’s disease: anatomic specificity and validation. Psychiatr Q. 1993;64(4):371-387.PubMedCrossRefGoogle Scholar
  76. 76.
    de Leon MJ, Convit A, DeSanti S, et al. The hippocampus in aging and Alzheimer’s disease. Neuroimaging Clin N Am. 1995;5(1):1-17.PubMedGoogle Scholar
  77. 77.
    Laakso MP, Lehtovirta M, Partanen K, Riekkinen PJ, Soininen H. Hippocampus in Alzheimer’s disease: a 3-year follow-up MRI study. Biol Psychiatry. 2000;47(6):557-561.PubMedCrossRefGoogle Scholar
  78. 78.
    Bobinski M, de Leon MJ, Convit A, et al. MRI of entorhinal cortex in mild Alzheimer’s disease. Lancet. 1999;353(9146):38-40.PubMedCrossRefGoogle Scholar
  79. 79.
    De Toledo-Morrell L, Goncharova I, Dickerson B, Wilson RS, Bennett DA. From healthy aging to early Alzheimer’s disease: in vivo detection of entorhinal cortex atrophy. Ann NY Acad Sci. 2000;911:240-253.PubMedCrossRefGoogle Scholar
  80. 80.
    Dickerson BC, Goncharova I, Sullivan MP, et al. MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer’s disease. Neurobiol Aging. 2001;22(5):747-754.PubMedCrossRefGoogle Scholar
  81. 81.
    Killiany RJ, Hyman BT, Gomez-Isla T, et al. MRI measures of entorhinal cortex vs hippocampus in preclinical AD. Neurology. 2002;58(8):1188-1196.PubMedGoogle Scholar
  82. 82.
    Laakso MP, Soininen H, Partanen K, et al. Volumes of hippocampus, amygdala and frontal lobes in the MRI-based diagnosis of early Alzheimer’s disease: correlation with memory functions. J Neural Transm Park Dis Dement Sect. 1995;9(1):73-86.PubMedCrossRefGoogle Scholar
  83. 83.
    Lehericy S, Baulac M, Chiras J, et al. Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease. AJNR Am J Neuroradiol. 1994;15(5):929-937.PubMedGoogle Scholar
  84. 84.
    Teipel SJ, Pruessner JC, Faltraco F, et al. Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI. J Neurol. 2006;253(6):794-800.PubMedCrossRefGoogle Scholar
  85. 85.
    Carmichael OT, Kuller LH, Lopez OL, et al. Ventricular volume and dementia progression in the Cardiovascular Health Study. Neurobiol Aging. 2007;28(3):389-397.PubMedCrossRefGoogle Scholar
  86. 86.
    Tanna NK, Kohn MI, Horwich DN, et al. Analysis of brain and cerebrospinal fluid volumes with MR imaging: impact on PET data correction for atrophy. Part II. Aging and Alzheimer dementia. Radiology. 1991;178(1):123-130.PubMedGoogle Scholar
  87. 87.
    Giesel FL, Hahn HK, Thomann PA, et al. Temporal horn index and volume of medial temporal lobe atrophy using a new semiautomated method for rapid and precise assessment. AJNR Am J Neuroradiol. 2006;27(7):1454-1458.PubMedGoogle Scholar
  88. 88.
    Bottino CM, Castro CC, Gomes RL, Buchpiguel CA, Marchetti RL, Neto MR. Volumetric MRI measurements can differentiate Alzheimer’s disease, mild cognitive impairment, and normal aging. Int Psychogeriatr. 2002;14(1):59-72.PubMedCrossRefGoogle Scholar
  89. 89.
    Convit A, De Leon MJ, Tarshish C, et al. Specific hippocampal volume reductions in individuals at risk for Alzheimer’s disease. Neurobiol Aging. 1997;18(2):131-138.PubMedCrossRefGoogle Scholar
  90. 90.
    Du AT, Schuff N, Amend D, et al. Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2001;71(4):441-447.PubMedCrossRefGoogle Scholar
  91. 91.
    Jack CR Jr, Petersen RC, Xu YC, et al. Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment. Neurology. 1999;52(7):1397-1403.PubMedGoogle Scholar
  92. 92.
    Killiany RJ, Gomez-Isla T, Moss M, et al. Use of structural magnetic resonance imaging to predict who will get Alzheimer’s disease. Ann Neurol. 2000;47(4):430-439.PubMedCrossRefGoogle Scholar
  93. 93.
    Pennanen C, Kivipelto M, Tuomainen S, et al. Hippocampus and entorhinal cortex in mild cognitive impairment and early AD. Neurobiol Aging. 2004;25(3):303-310.PubMedCrossRefGoogle Scholar
  94. 94.
    Xu Y, Jack CR Jr, O’Brien PC, et al. Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD. Neurology. 2000;54(9):1760-1767.PubMedGoogle Scholar
  95. 95.
    Apostolova LG, Dinov ID, Dutton RA, et al. 3D comparison of hippocampal atrophy in amnestic mild cognitive impairment and Alzheimer’s disease. Brain. 2006;129(Pt 11):2867-2873.PubMedCrossRefGoogle Scholar
  96. 96.
    Ballmaier M, O’Brien JT, Burton EJ, et al. Comparing gray matter loss profiles between dementia with Lewy bodies and Alzheimer’s disease using cortical pattern matching: diagnosis and gender effects. Neuroimage. 2004;23(1):325-335.PubMedCrossRefGoogle Scholar
  97. 97.
    Becker JT, Davis SW, Hayashi KM, et al. Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment. Arch Neurol. 2006;63(1):97-101.PubMedCrossRefGoogle Scholar
  98. 98.
    Kaye JA, Swihart T, Howieson D, et al. Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia. Neurology. 1997;48(5):1297-1304.PubMedGoogle Scholar
  99. 99.
    Thompson PM, Hayashi KM, de Zubicaray G, et al. Dynamics of gray matter loss in Alzheimer’s disease. J Neurosci. 2003;23(3):994-1005.PubMedGoogle Scholar
  100. 100.
    Du AT, Schuff N, Kramer JH, et al. Higher atrophy rate of entorhinal cortex than hippocampus in AD. Neurology. 2004;62(3):422-427.PubMedGoogle Scholar
  101. 101.
    Frisoni GB, Laakso MP, Beltramello A, et al. Hippocampal and entorhinal cortex atrophy in frontotemporal dementia and Alzheimer’s disease. Neurology. 1999;52(1):91-100.PubMedGoogle Scholar
  102. 102.
    Juottonen K, Laakso MP, Insausti R, et al. Volumes of the entorhinal and perirhinal cortices in Alzheimer’s disease. Neurobiol Aging. 1998;19(1):15-22.PubMedCrossRefGoogle Scholar
  103. 103.
    Juottonen K, Laakso MP, Partanen K, Soininen H. Comparative MR analysis of the entorhinal cortex and hippocampus in diagnosing Alzheimer disease. AJNR Am J Neuroradiol. 1999;20(1):139-144.PubMedGoogle Scholar
  104. 104.
    Convit A, de Leon MJ, Hoptman MJ, Tarshish C, De Santi S, Rusinek H. Age-related changes in brain: I. Magnetic resonance imaging measures of temporal lobe volumes in normal subjects. Psychiatr Q. 1995;66(4):343-355.PubMedCrossRefGoogle Scholar
  105. 105.
    De Santi S, de Leon MJ, Rusinek H, et al. Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging. 2001;22(4):529-539.PubMedCrossRefGoogle Scholar
  106. 106.
    Wolf H, Grunwald M, Kruggel F, et al. Hippocampal volume discriminates between normal cognition; questionable and mild dementia in the elderly. Neurobiol Aging. 2001;22(2):177-186.PubMedCrossRefGoogle Scholar
  107. 107.
    Baron JC, Chetelat G, Desgranges B, et al. In vivo mapping of gray matter loss with voxel-based morphometry in mild Alzheimer’s disease. Neuroimage. 2001;14(2):298-309.PubMedCrossRefGoogle Scholar
  108. 108.
    Bozzali M, Filippi M, Magnani G, et al. The contribution of voxel-based morphometry in staging patients with mild cognitive impairment. Neurology. 2006;67(3):453-460.PubMedCrossRefGoogle Scholar
  109. 109.
    Busatto GF, Garrido GE, Almeida OP, et al. A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer’s disease. Neurobiol Aging. 2003;24(2):221-231.PubMedCrossRefGoogle Scholar
  110. 110.
    Chetelat G, Desgranges B, De La Sayette V, Viader F, Eustache F, Baron JC. Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment. Neuroreport. 2002;13(15):1939-1943.PubMedCrossRefGoogle Scholar
  111. 111.
    Frisoni GB, Testa C, Zorzan A, et al. Detection of grey matter loss in mild Alzheimer’s disease with voxel based morphometry. J Neurol Neurosurg Psychiatry. 2002;73(6):657-664.PubMedCrossRefGoogle Scholar
  112. 112.
    Hirata Y, Matsuda H, Nemoto K, et al. Voxel-based morphometry to discriminate early Alzheimer’s disease from controls. Neurosci Lett. 2005;382(3):269-274.PubMedCrossRefGoogle Scholar
  113. 113.
    Jack CR Jr, Lowe VJ, Senjem ML, et al. 11C PiB and structural MRI provide complementary information in imaging of Alzheimer’s disease and amnestic mild cognitive impairment. Brain. 2008;131(Pt 3):665-680.PubMedCrossRefGoogle Scholar
  114. 114.
    Karas GB, Burton EJ, Rombouts SA, et al. A comprehensive study of gray matter loss in patients with Alzheimer’s disease using optimized voxel-based morphometry. Neuroimage. 2003;18(4):895-907.PubMedCrossRefGoogle Scholar
  115. 115.
    Karas GB, Scheltens P, Rombouts SA, et al. Global and local gray matter loss in mild cognitive impairment and Alzheimer’s disease. Neuroimage. 2004;23(2):708-716.PubMedCrossRefGoogle Scholar
  116. 116.
    Hamalainen A, Tervo S, Grau-Olivares M, et al. Voxel-based morphometry to detect brain atrophy in progressive mild cognitive impairment. Neuroimage. 2007;37(4):1122-1131.PubMedCrossRefGoogle Scholar
  117. 117.
    Trivedi MA, Wichmann AK, Torgerson BM, et al. Structural MRI discriminates individuals with Mild Cognitive Impairment from age-matched controls: a combined neuropsychological and voxel based morphometry study. Alzheimers Dement. 2006;2:296-302.PubMedCrossRefGoogle Scholar
  118. 118.
    Whitwell JL, Shiung MM, Przybelski SA, et al. MRI patterns of atrophy associated with progression to AD in amnestic mild cognitive impairment. Neurology. 2008;70(7):512-520.PubMedCrossRefGoogle Scholar
  119. 119.
    Whitwell JL, Przybelski SA, Weigand SD, et al. 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer’s disease. Brain. 2007;130(Pt 7):1777-1786.PubMedCrossRefGoogle Scholar
  120. 120.
    Cardenas VA, Du AT, Hardin D, et al. Comparison of methods for measuring longitudinal brain change in cognitive impairment and dementia. Neurobiol Aging. 2003;24(4):537-544.PubMedCrossRefGoogle Scholar
  121. 121.
    Fox NC, Freeborough PA. Brain atrophy progression measured from registered serial MRI: validation and application to Alzheimer’s disease. J Magn Reson Imaging. 1997;7(6):1069-1075.PubMedCrossRefGoogle Scholar
  122. 122.
    Jack CR Jr, Shiung MM, Gunter JL, et al. Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. Neurology. 2004;62(4):591-600.PubMedGoogle Scholar
  123. 123.
    Barnes J, Lewis EB, Scahill RI, et al. Automated measurement of hippocampal atrophy using fluid-registered serial MRI in AD and controls. J Comput Assist Tomogr. 2007;31(4):581-587.PubMedCrossRefGoogle Scholar
  124. 124.
    Mungas D, Harvey D, Reed BR, et al. Longitudinal volumetric MRI change and rate of cognitive decline. Neurology. 2005;65(4):565-571.PubMedCrossRefGoogle Scholar
  125. 125.
    Stoub TR, Rogalski EJ, Leurgans S, Bennett DA, Detoledo-Morrell L. Rate of entorhinal and hippocampal atrophy in incipient and mild AD: relation to memory function. Neurobiol Aging. 2010;31(7):1089-1098.PubMedCrossRefGoogle Scholar
  126. 126.
    Barnes J, Bartlett JW, van de Pol LA, et al. A meta-analysis of hippocampal atrophy rates in Alzheimer’s disease. Neurobiol Aging. 2009;30(11):1711-1723.PubMedCrossRefGoogle Scholar
  127. 127.
    Jack CR Jr, Petersen RC, Xu Y, et al. Rate of medial temporal lobe atrophy in typical aging and Alzheimer’s disease. Neurology. 1998;51(4):993-999.PubMedGoogle Scholar
  128. 128.
    Scahill RI, Schott JM, Stevens JM, Rossor MN, Fox NC. Mapping the evolution of regional atrophy in Alzheimer’s disease: unbiased analysis of fluid-registered serial MRI. Proc Natl Acad Sci U S A. 2002;99(7):4703-4707.PubMedCrossRefGoogle Scholar
  129. 129.
    Thompson PM, Hayashi KM, De Zubicaray GI, et al. Mapping hippocampal and ventricular change in Alzheimer disease. Neuroimage. 2004;22(4):1754-1766.PubMedCrossRefGoogle Scholar
  130. 130.
    Thompson PM, Hayashi KM, Sowell ER, et al. Mapping cortical change in Alzheimer’s disease, brain development, and schizophrenia. Neuroimage. 2004;23(Suppl 1):S2-S18.PubMedCrossRefGoogle Scholar
  131. 131.
    Whitwell JL, Jack CR Jr, Pankratz VS, et al. Rates of brain atrophy over time in autopsy-proven frontotemporal dementia and Alzheimer disease. Neuroimage. 2008;39(3):1034-1040.PubMedCrossRefGoogle Scholar
  132. 132.
    deToledo-Morrell L, Stoub TR, Bulgakova M, et al. MRI-derived entorhinal volume is a good predictor of conversion from MCI to AD. Neurobiol Aging. 2004;25(9):1197-1203.PubMedCrossRefGoogle Scholar
  133. 133.
    Devanand DP, Liu X, Tabert MH, et al. Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer’s disease. Biol Psychiatry. 2008;64(10):871-879.PubMedCrossRefGoogle Scholar
  134. 134.
    Devanand DP, Pradhaban G, Liu X, et al. Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer disease. Neurology. 2007;68(11):828-836.PubMedCrossRefGoogle Scholar
  135. 135.
    Eckerstrom C, Olsson E, Borga M, et al. Small baseline volume of left hippocampus is associated with subsequent conversion of MCI into dementia: the Goteborg MCI study. J Neurol Sci. 2008;272(1-2):48-59.PubMedCrossRefGoogle Scholar
  136. 136.
    Visser PJ, Verhey FR, Hofman PA, Scheltens P, Jolles J. Medial temporal lobe atrophy predicts Alzheimer’s disease in patients with minor cognitive impairment. J Neurol Neurosurg Psychiatry. 2002;72(4):491-497.PubMedGoogle Scholar
  137. 137.
    Convit A, de Asis J, de Leon MJ, Tarshish CY, De Santi S, Rusinek H. Atrophy of the medial occipitotemporal, inferior, and middle temporal gyri in non-demented elderly predict decline to Alzheimer’s disease. Neurobiol Aging. 2000;21(1):19-26.PubMedCrossRefGoogle Scholar
  138. 138.
    Teipel SJ, Born C, Ewers M, et al. Multivariate deformation-based analysis of brain atrophy to predict Alzheimer’s disease in mild cognitive impairment. Neuroimage. 2007;38(1):13-24.PubMedCrossRefGoogle Scholar
  139. 139.
    Wolf H, Grunwald M, Ecke GM, et al. The prognosis of mild cognitive impairment in the elderly. J Neural Transm Suppl. 1998;54:31-50.PubMedGoogle Scholar
  140. 140.
    Chetelat G, Landeau B, Eustache F, et al. Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage. 2005;27(4):934-946.PubMedCrossRefGoogle Scholar
  141. 141.
    Karas G, Sluimer J, Goekoop R, et al. Amnestic mild cognitive impairment: structural MR imaging findings predictive of conversion to Alzheimer disease. AJNR Am J Neuroradiol. 2008;29(5):944-949.PubMedCrossRefGoogle Scholar
  142. 142.
    Erten-Lyons D, Howieson D, Moore MM, et al. Brain volume loss in MCI predicts dementia. Neurology. 2006;66(2):233-235.PubMedCrossRefGoogle Scholar
  143. 143.
    Jack CR Jr, Petersen RC, Xu Y, et al. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology. 2000;55(4):484-489.PubMedGoogle Scholar
  144. 144.
    Jack CR Jr, Shiung MM, Weigand SD, et al. Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology. 2005;65(8):1227-1231.PubMedCrossRefGoogle Scholar
  145. 145.
    Sluimer JD, van der Flier WM, Karas GB, et al. Whole-brain atrophy rate and cognitive decline: longitudinal MR study of memory clinic patients. Radiology. 2008;248(2):590-598.PubMedCrossRefGoogle Scholar
  146. 146.
    Tapiola T, Pennanen C, Tapiola M, et al. MRI of hippocampus and entorhinal cortex in mild cognitive impairment: a follow-up study. Neurobiol Aging. 2008;29(1):31-38.PubMedCrossRefGoogle Scholar
  147. 147.
    Wang PN, Lirng JF, Lin KN, Chang FC, Liu HC. Prediction of Alzheimer’s disease in mild cognitive impairment: a prospective study in Taiwan. Neurobiol Aging. 2006;27(12):1797-1806.PubMedCrossRefGoogle Scholar
  148. 148.
    Bozzali M, Falini A, Franceschi M, et al. White matter damage in Alzheimer’s disease assessed in vivo using diffusion tensor magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 2002;72(6):742-746.PubMedCrossRefGoogle Scholar
  149. 149.
    Choi SJ, Lim KO, Monteiro I, Reisberg B. Diffusion tensor imaging of frontal white matter microstructure in early Alzheimer’s disease: a preliminary study. J Geriatr Psychiatry Neurol. 2005;18(1):12-19.PubMedCrossRefGoogle Scholar
  150. 150.
    Fellgiebel A, Wille P, Muller MJ, et al. Ultrastructural hippocampal and white matter alterations in mild cognitive impairment: a diffusion tensor imaging study. Dement Geriatr Cogn Disord. 2004;18(1):101-108.PubMedCrossRefGoogle Scholar
  151. 151.
    Ibrahim I, Horacek J, Bartos A, et al. Combination of voxel based morphometry and diffusion tensor imaging in patients with Alzheimer’s disease. Neuro Endocrinol Lett. 2009;30(1):39-45.PubMedGoogle Scholar
  152. 152.
    Kiuchi K, Morikawa M, Taoka T, et al. Abnormalities of the uncinate fasciculus and posterior cingulate fasciculus in mild cognitive impairment and early Alzheimer’s disease: a diffusion tensor tractography study. Brain Res. 2009;1287:184-191.PubMedCrossRefGoogle Scholar
  153. 153.
    Medina D, DeToledo-Morrell L, Urresta F, et al. White matter changes in mild cognitive impairment and AD: a diffusion tensor imaging study. Neurobiol Aging. 2006;27(5):663-672.PubMedCrossRefGoogle Scholar
  154. 154.
    Naggara O, Oppenheim C, Rieu D, et al. Diffusion tensor imaging in early Alzheimer’s disease. Psychiatry Res. 2006;146(3):243-249.PubMedCrossRefGoogle Scholar
  155. 155.
    Parente DB, Gasparetto EL, Da Cruz LC Jr, Domingues RC, Baptista AC, Carvalho AC. Potential role of diffusion tensor MRI in the differential diagnosis of mild cognitive impairment and Alzheimer’s disease. AJR Am J Roentgenol. 2008;190(5):1369-1374.PubMedCrossRefGoogle Scholar
  156. 156.
    Rose SE, Janke AL, Chalk JB. Gray and white matter changes in Alzheimer’s disease: a diffusion tensor imaging study. J Magn Reson Imaging. 2008;27(1):20-26.PubMedCrossRefGoogle Scholar
  157. 157.
    Stahl R, Dietrich O, Teipel S, Hampel H, Reiser MF, Schoenberg SO. Assessment of axonal degeneration on Alzheimer’s disease with diffusion tensor MRI. Radiologe. 2003;43(7):566-575.PubMedCrossRefGoogle Scholar
  158. 158.
    Stahl R, Dietrich O, Teipel SJ, Hampel H, Reiser MF, Schoenberg SO. White matter damage in Alzheimer disease and mild cognitive impairment: assessment with diffusion-tensor MR imaging and parallel imaging techniques. Radiology. 2007;243(2):483-492.PubMedCrossRefGoogle Scholar
  159. 159.
    Sugihara S, Kinoshita T, Matsusue E, Fujii S, Ogawa T. Usefulness of diffusion tensor imaging of white matter in Alzheimer disease and vascular dementia. Acta Radiol. 2004;45(6):658-663.PubMedCrossRefGoogle Scholar
  160. 160.
    Sydykova D, Stahl R, Dietrich O, et al. Fiber connections between the cerebral cortex and the corpus callosum in Alzheimer’s disease: a diffusion tensor imaging and voxel-based morphometry study. Cereb Cortex. 2007;17(10):2276-2282.PubMedCrossRefGoogle Scholar
  161. 161.
    Takahashi S, Yonezawa H, Takahashi J, Kudo M, Inoue T, Tohgi H. Selective reduction of diffusion anisotropy in white matter of Alzheimer disease brains measured by 3.0 Tesla magnetic resonance imaging. Neurosci Lett. 2002;332(1):45-48.PubMedCrossRefGoogle Scholar
  162. 162.
    Zhang Y, Schuff N, Jahng GH, et al. Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease. Neurology. 2007;68(1):13-19.PubMedCrossRefGoogle Scholar
  163. 163.
    Fellgiebel A, Muller MJ, Wille P, et al. Color-coded diffusion-tensor-imaging of posterior cingulate fiber tracts in mild cognitive impairment. Neurobiol Aging. 2005;26(8):1193-1198.PubMedCrossRefGoogle Scholar
  164. 164.
    Muller MJ, Greverus D, Weibrich C, et al. Diagnostic utility of hippocampal size and mean diffusivity in amnestic MCI. Neurobiol Aging. 2007;28(3):398-403.PubMedCrossRefGoogle Scholar
  165. 165.
    Rose SE, McMahon KL, Janke AL, et al. Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment. J Neurol Neurosurg Psychiatry. 2006;77(10):1122-1128.PubMedCrossRefGoogle Scholar
  166. 166.
    Kantarci K, Jack CR Jr, Xu YC, et al. Mild cognitive impairment and Alzheimer disease: regional diffusivity of water. Radiology. 2001;219(1):101-107.PubMedGoogle Scholar
  167. 167.
    Muller MJ, Greverus D, Dellani PR, et al. Functional implications of hippocampal volume and diffusivity in mild cognitive impairment. Neuroimage. 2005;28(4):1033-1042.PubMedCrossRefGoogle Scholar
  168. 168.
    Ray KM, Wang H, Chu Y, et al. Mild cognitive impairment: apparent diffusion coefficient in regional gray matter and white matter structures. Radiology. 2006;241(1):197-205.PubMedCrossRefGoogle Scholar
  169. 169.
    Sandson TA, Felician O, Edelman RR, Warach S. Diffusion-weighted magnetic resonance imaging in Alzheimer’s disease. Dement Geriatr Cogn Disord. 1999;10(2):166-171.PubMedCrossRefGoogle Scholar
  170. 170.
    Wang H, Su MY. Regional pattern of increased water diffusivity in hippocampus and corpus callosum in mild cognitive impairment. Dement Geriatr Cogn Disord. 2006;22(3):223-229.PubMedCrossRefGoogle Scholar
  171. 171.
    Kantarci K, Petersen RC, Boeve BF, et al. DWI predicts future progression to Alzheimer disease in amnestic mild cognitive impairment. Neurology. 2005;64(5):902-904.PubMedGoogle Scholar
  172. 172.
    D’Adamo AF Jr, Gidez LI, Yatsu FM. Acetyl transport mechanisms. Involvement of N-acetyl aspartic acid in de novo fatty acid biosynthesis in the developing rat brain. Exp Brain Res. 1968;5(4):267-273.PubMedGoogle Scholar
  173. 173.
    Simmons ML, Frondoza CG, Coyle JT. Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies. Neuroscience. 1991;45(1):37-45.PubMedCrossRefGoogle Scholar
  174. 174.
    Downes CP, Macphee CH. Myo-inositol metabolites as cellular signals. Eur J Biochem. 1990;193(1):1-18.PubMedCrossRefGoogle Scholar
  175. 175.
    Kanfer JN, Sorrentino G, Sitar DS. Phospholipases as mediators of amyloid beta peptide neurotoxicity: an early event contributing to neurodegeneration characteristic of Alzheimer’s disease. Neurosci Lett. 1998;257(2):93-96.PubMedCrossRefGoogle Scholar
  176. 176.
    Miller BL, Chang L, Booth R, et al. In vivo 1H MRS choline: correlation with in vitro chemistry/histology. Life Sci. 1996;58(22):1929-1935.PubMedCrossRefGoogle Scholar
  177. 177.
    Bartres-Faz D, Junque C, Clemente IC, et al. Relationship among (1)H-magnetic resonance spectroscopy, brain volumetry and genetic polymorphisms in humans with memory impairment. Neurosci Lett. 2002;327(3):177-180.PubMedCrossRefGoogle Scholar
  178. 178.
    Block W, Traber F, Flacke S, Jessen F, Pohl C, Schild H. In-vivo proton MR-spectroscopy of the human brain: assessment of N-acetylaspartate (NAA) reduction as a marker for neurodegeneration. Amino Acids. 2002;23(1-3):317-323.PubMedCrossRefGoogle Scholar
  179. 179.
    Chantal S, Braun CM, Bouchard RW, Labelle M, Boulanger Y. Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease. Brain Res. 2004;1003(1-2):26-35.PubMedCrossRefGoogle Scholar
  180. 180.
    Firbank MJ, Harrison RM, O’Brien JT. A comprehensive review of proton magnetic resonance spectroscopy studies in dementia and Parkinson’s disease. Dement Geriatr Cogn Disord. 2002;14(2):64-76.PubMedCrossRefGoogle Scholar
  181. 181.
    Parnetti L, Tarducci R, Presciutti O, et al. Proton magnetic resonance spectroscopy can differentiate Alzheimer’s disease from normal aging. Mech Ageing Dev. 1997;97(1):9-14.PubMedCrossRefGoogle Scholar
  182. 182.
    Schuff N, Capizzano AA, Du AT, et al. Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD. Neurology. 2002;58(6):928-935.PubMedGoogle Scholar
  183. 183.
    Catani M, Cherubini A, Howard R, et al. (1)H-MR spectroscopy differentiates mild cognitive impairment from normal brain aging. Neuroreport. 2001;12(11):2315-2317.PubMedCrossRefGoogle Scholar
  184. 184.
    Kantarci K, Jack CR Jr, Xu YC, et al. Regional metabolic patterns in mild cognitive impairment and Alzheimer’s disease: a 1H MRS study. Neurology. 2000;55(2):210-217.PubMedGoogle Scholar
  185. 185.
    Kantarci K, Reynolds G, Petersen RC, et al. Proton MR spectroscopy in mild cognitive impairment and Alzheimer disease: comparison of 1.5 and 3 T. AJNR Am J Neuroradiol. 2003;24(5):843-849.PubMedGoogle Scholar
  186. 186.
    Moats RA, Ernst T, Shonk TK, Ross BD. Abnormal cerebral metabolite concentrations in patients with probable Alzheimer disease. Magn Reson Med. 1994;32(1):110-115.PubMedCrossRefGoogle Scholar
  187. 187.
    Shonk TK, Moats RA, Gifford P, et al. Probable Alzheimer disease: diagnosis with proton MR spectroscopy. Radiology. 1995;195(1):65-72.PubMedGoogle Scholar
  188. 188.
    Antuono PG, Jones JL, Wang Y, Li SJ. Decreased glutamate + glutamine in Alzheimer’s disease detected in vivo with (1)H-MRS at 0.5 T. Neurology. 2001;56(6):737-742.PubMedGoogle Scholar
  189. 189.
    Chantal S, Labelle M, Bouchard RW, Braun CM, Boulanger Y. Correlation of regional proton magnetic resonance spectroscopic metabolic changes with cognitive deficits in mild Alzheimer disease. Arch Neurol. 2002;59(6):955-962.PubMedCrossRefGoogle Scholar
  190. 190.
    Miller BL, Moats RA, Shonk T, Ernst T, Woolley S, Ross BD. Alzheimer disease: depiction of increased cerebral myo-inositol with proton MR spectroscopy. Radiology. 1993;187(2):433-437.PubMedGoogle Scholar
  191. 191.
    Jessen F, Traeber F, Freymann N, et al. A comparative study of the different N-acetylaspartate measures of the medial temporal lobe in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2005;20(2-3):178-183.PubMedCrossRefGoogle Scholar
  192. 192.
    Schuff N, Amend D, Ezekiel F, et al. Changes of hippocampal N-acetyl aspartate and volume in Alzheimer’s disease. A proton MR spectroscopic imaging and MRI study. Neurology. 1997;49(6):1513-1521.PubMedGoogle Scholar
  193. 193.
    Jessen F, Block W, Traber F, et al. Proton MR spectroscopy detects a relative decrease of N-acetylaspartate in the medial temporal lobe of patients with AD. Neurology. 2000;55(5):684-688.PubMedGoogle Scholar
  194. 194.
    Pfefferbaum A, Adalsteinsson E, Spielman D, Sullivan EV, Lim KO. In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease. Arch Gen Psychiatry. 1999;56(2):185-192.PubMedCrossRefGoogle Scholar
  195. 195.
    Metastasio A, Rinaldi P, Tarducci R, et al. Conversion of MCI to dementia: role of proton magnetic resonance spectroscopy. Neurobiol Aging. 2006;27(7):926-932.PubMedCrossRefGoogle Scholar
  196. 196.
    Modrego PJ, Fayed N, Pina MA. Conversion from mild cognitive impairment to probable Alzheimer’s disease predicted by brain magnetic resonance spectroscopy. Am J Psychiatry. 2005;162(4):667-675.PubMedCrossRefGoogle Scholar
  197. 197.
    Bozzao A, Floris R, Baviera ME, Apruzzese A, Simonetti G. Diffusion and perfusion MR imaging in cases of Alzheimer’s disease: correlations with cortical atrophy and lesion load. AJNR Am J Neuroradiol. 2001;22(6):1030-1036.PubMedGoogle Scholar
  198. 198.
    Harris GJ, Lewis RF, Satlin A, et al. Dynamic susceptibility contrast MRI of regional cerebral blood volume in Alzheimer’s disease. Am J Psychiatry. 1996;153(5):721-724.PubMedGoogle Scholar
  199. 199.
    Harris GJ, Lewis RF, Satlin A, et al. Dynamic susceptibility contrast MR imaging of regional cerebral blood volume in Alzheimer disease: a promising alternative to nuclear medicine. AJNR Am J Neuroradiol. 1998;19(9):1727-1732.PubMedGoogle Scholar
  200. 200.
    Maas LC, Harris GJ, Satlin A, English CD, Lewis RF, Renshaw PF. Regional cerebral blood volume measured by dynamic susceptibility contrast MR imaging in Alzheimer’s disease: a principal components analysis. J Magn Reson Imaging. 1997;7(1):215-219.PubMedCrossRefGoogle Scholar
  201. 201.
    Mattia D, Babiloni F, Romigi A, et al. Quantitative EEG and dynamic susceptibility contrast MRI in Alzheimer’s disease: a correlative study. Clin Neurophysiol. 2003;114(7):1210-1216.PubMedCrossRefGoogle Scholar
  202. 202.
    Olazaran J, Alvarez-Linera J, de Santiago R, Escribano J, Benito-Leon J, Morales JM. Regional correlations between MR imaging perfusion and SPECT in Alzheimer’s disease. Neurologia. 2005;20(5):240-244.PubMedGoogle Scholar
  203. 203.
    Sandson TA, O’Connor M, Sperling RA, Edelman RR, Warach S. Noninvasive perfusion MRI in Alzheimer’s disease: a preliminary report. Neurology. 1996;47(5):1339-1342.PubMedGoogle Scholar
  204. 204.
    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(1):93-100.PubMedCrossRefGoogle Scholar
  205. 205.
    Johnson NA, Jahng GH, Weiner MW, et al. Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience. Radiology. 2005;234(3):851-859.PubMedCrossRefGoogle Scholar
  206. 206.
    Du AT, Jahng GH, Hayasaka S, et al. Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI. Neurology. 2006;67(7):1215-1220.PubMedCrossRefGoogle Scholar
  207. 207.
    Hayasaka S, Du AT, Duarte A, et al. A non-parametric approach for co-analysis of multi-modal brain imaging data: application to Alzheimer’s disease. Neuroimage. 2006;30(3):768-779.PubMedCrossRefGoogle Scholar
  208. 208.
    Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci U S A. 1990;87(24):9868-9872.PubMedCrossRefGoogle Scholar
  209. 209.
    Ogawa S, Tank DW, Menon R, et al. Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc Natl Acad Sci U S A. 1992;89(13):5951-5955.PubMedCrossRefGoogle Scholar
  210. 210.
    Buxton RB, Uludag K, Dubowitz DJ, Liu TT. Modeling the hemodynamic response to brain activation. Neuroimage. 2004;23(Suppl 1):S220-S233.PubMedCrossRefGoogle Scholar
  211. 211.
    Uludag K, Dubowitz DJ, Yoder EJ, Restom K, Liu TT, Buxton RB. Coupling of cerebral blood flow and oxygen consumption during physiological activation and deactivation measured with fMRI. Neuroimage. 2004;23(1):148-155.PubMedCrossRefGoogle Scholar
  212. 212.
    Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature. 2001;412(6843):150-157.PubMedCrossRefGoogle Scholar
  213. 213.
    Rombouts SA, Goekoop R, Stam CJ, Barkhof F, Scheltens P. Delayed rather than decreased BOLD response as a marker for early Alzheimer’s disease. Neuroimage. 2005;26(4):1078-1085.PubMedCrossRefGoogle Scholar
  214. 214.
    Buckner RL, Snyder AZ, Sanders AL, Raichle ME, Morris JC. Functional brain imaging of young, nondemented, and demented older adults. J Cogn Neurosci. 2000;12(Suppl 2):24-34.PubMedCrossRefGoogle Scholar
  215. 215.
    D’Esposito M, Deouell LY, Gazzaley A. Alterations in the BOLD fMRI signal with ageing and disease: a challenge for neuroimaging. Nat Rev Neurosci. 2003;4:863-872.PubMedCrossRefGoogle Scholar
  216. 216.
    Tekes A, Mohamed MA, Browner NM, Calhoun VD, Yousem DM. Effect of age on visuomotor functional MR imaging. Acad Radiol. 2005;12(6):739-745.PubMedCrossRefGoogle Scholar
  217. 217.
    Squire LR, Knowlton B, Musen G. The structure and organization of memory. Annu Rev Psychol. 1993;44:453-495.PubMedCrossRefGoogle Scholar
  218. 218.
    Celone KA, Calhoun VD, Dickerson BC, et al. Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis. J Neurosci. 2006;26(40):10222-10231.PubMedCrossRefGoogle Scholar
  219. 219.
    Daselaar SM, Veltman DJ, Rombouts SA, Raaijmakers JG, Jonker C. Neuroanatomical correlates of episodic encoding and retrieval in young and elderly subjects. Brain. 2003;126(Pt 1):43-56.PubMedCrossRefGoogle Scholar
  220. 220.
    Gron G, Bittner D, Schmitz B, Wunderlich AP, Riepe MW. Subjective memory complaints: objective neural markers in patients with Alzheimer’s disease and major depressive disorder. Ann Neurol. 2002;51(4):491-498.PubMedCrossRefGoogle Scholar
  221. 221.
    Remy F, Mirrashed F, Campbell B, Richter W. Verbal episodic memory impairment in Alzheimer’s disease: a combined structural and functional MRI study. Neuroimage. 2005;25(1):253-266.PubMedCrossRefGoogle Scholar
  222. 222.
    Yetkin FZ, Rosenberg RN, Weiner MF, Purdy PD, Cullum CM. FMRI of working memory in patients with mild cognitive impairment and probable Alzheimer’s disease. Eur Radiol. 2006;16(1):193-206.PubMedCrossRefGoogle Scholar
  223. 223.
    Dickerson BC, Salat DH, Greve DN, et al. Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology. 2005;65(3):404-411.PubMedCrossRefGoogle Scholar
  224. 224.
    Golby A, Silverberg G, Race E, et al. Memory encoding in Alzheimer’s disease: an fMRI study of explicit and implicit memory. Brain. 2005;128(Pt 4):773-787.PubMedCrossRefGoogle Scholar
  225. 225.
    Hamalainen A, Pihlajamaki M, Tanila H, et al. Increased fMRI responses during encoding in mild cognitive impairment. Neurobiol Aging. 2007;28(12):1889-1903.PubMedCrossRefGoogle Scholar
  226. 226.
    Kato T, Knopman D, Liu H. Dissociation of regional activation in mild AD during visual encoding: a functional MRI study. Neurology. 2001;57(5):812-816.PubMedGoogle Scholar
  227. 227.
    Machulda MM, Ward HA, Borowski B, et al. Comparison of memory fMRI response among normal, MCI, and Alzheimer’s patients. Neurology. 2003;61(4):500-506.PubMedGoogle Scholar
  228. 228.
    Rombouts SA, Barkhof F, Veltman DJ, et al. Functional MR imaging in Alzheimer’s disease during memory encoding. AJNR Am J Neuroradiol. 2000;21(10):1869-1875.PubMedGoogle Scholar
  229. 229.
    Small SA, Nava AS, Perera GM, Delapaz R, Stern Y. Evaluating the function of hippocampal subregions with high-resolution MRI in Alzheimer’s disease and aging. Microsc Res Tech. 2000;51(1):101-108.PubMedCrossRefGoogle Scholar
  230. 230.
    Sperling RA, Bates JF, Chua EF, et al. fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003;74(1):44-50.PubMedCrossRefGoogle Scholar
  231. 231.
    Pariente J, Cole S, Henson R, et al. Alzheimer’s patients engage an alternative network during a memory task. Ann Neurol. 2005;58(6):870-879.PubMedCrossRefGoogle Scholar
  232. 232.
    Petrella JR, Prince SE, Wang L, Hellegers C, Doraiswamy PM. Prognostic value of posteromedial cortex deactivation in mild cognitive impairment. PLoS ONE. 2007;2(10):e1104.PubMedCrossRefGoogle Scholar
  233. 233.
    Johnson SC, Baxter LC, Susskind-Wilder L, Connor DJ, Sabbagh MN, Caselli RJ. Hippocampal adaptation to face repetition in healthy elderly and mild cognitive impairment. Neuropsychologia. 2004;42(7):980-989.PubMedCrossRefGoogle Scholar
  234. 234.
    Johnson SC, Schmitz TW, Moritz CH, et al. Activation of brain regions vulnerable to Alzheimer’s disease: the effect of mild cognitive impairment. Neurobiol Aging. 2006;27(11):1604-1612.PubMedCrossRefGoogle Scholar
  235. 235.
    Mandzia JL, McAndrews MP, Grady CL, Graham SJ, Black SE. Neural correlates of incidental memory in mild cognitive impairment: an fMRI study. Neurobiol Aging. 2009;30(5):717-730.PubMedCrossRefGoogle Scholar
  236. 236.
    Trivedi MA, Murphy CM, Goetz C, et al. fMRI activation changes during successful episodic memory encoding and recognition in amnestic mild cognitive impairment relative to cognitively healthy older adults. Dement Geriatr Cogn Disord. 2008;26(2):123-137.PubMedCrossRefGoogle Scholar
  237. 237.
    Ries ML, Schmitz TW, Kawahara TN, Torgerson BM, Trivedi MA, Johnson SC. Task-dependent posterior cingulate activation in mild cognitive impairment. Neuroimage. 2006;29(2):485-492.PubMedCrossRefGoogle Scholar
  238. 238.
    O’Brien JL, O’Keefe KM, LaViolette PS, et al. Longitudinal fMRI in elderly reveals loss of hippocampal activation with clinical decline. Neurology. 2010;74(24):1969-1976.PubMedCrossRefGoogle Scholar
  239. 239.
    Kircher TT, Weis S, Freymann K, et al. Hippocampal activation in patients with mild cognitive impairment is necessary for successful memory encoding. J Neurol Neurosurg Psychiatry. 2007;78(8):812-818.PubMedCrossRefGoogle Scholar
  240. 240.
    Grossman M, Koenig P, DeVita C, et al. Neural basis for verb processing in Alzheimer’s disease: an fMRI study. Neuropsychology. 2003;17(4):658-674.PubMedCrossRefGoogle Scholar
  241. 241.
    Grossman M, Koenig P, Glosser G, et al. Neural basis for semantic memory difficulty in Alzheimer’s disease: an fMRI study. Brain. 2003;126(Pt 2):292-311.PubMedCrossRefGoogle Scholar
  242. 242.
    Saykin AJ, Flashman LA, Frutiger SA, et al. Neuroanatomic substrates of semantic memory impairment in Alzheimer’s disease: patterns of functional MRI activation. J Int Neuropsychol Soc. 1999;5(5):377-392.PubMedCrossRefGoogle Scholar
  243. 243.
    Miller SL, Fenstermacher E, Bates J, Blacker D, Sperling RA, Dickerson BC. Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline. J Neurol Neurosurg Psychiatry. 2008;79(6):630-635.PubMedCrossRefGoogle Scholar
  244. 244.
    Bassett SS, Yousem DM, Cristinzio C, et al. Familial risk for Alzheimer’s disease alters fMRI activation patterns. Brain. 2006;129(Pt 5):1229-1239.PubMedCrossRefGoogle Scholar
  245. 245.
    Bondi MW, Houston WS, Eyler LT, Brown GG. fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease. Neurology. 2005;64(3):501-508.PubMedGoogle Scholar
  246. 246.
    Bookheimer SY, Strojwas MH, Cohen MS, et al. Patterns of brain activation in people at risk for Alzheimer’s disease. N Engl J Med. 2000;343(7):450-456.PubMedCrossRefGoogle Scholar
  247. 247.
    Fleisher AS, Houston WS, Eyler LT, et al. Identification of Alzheimer disease risk by functional magnetic resonance imaging. Arch Neurol. 2005;62(12):1881-1888.PubMedCrossRefGoogle Scholar
  248. 248.
    Han SD, Houston WS, Jak AJ, et al. Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response. Neurobiol Aging. 2007;28(2):238-247.PubMedCrossRefGoogle Scholar
  249. 249.
    Johnson SC, Schmitz TW, Trivedi MA, et al. The influence of Alzheimer disease family history and apolipoprotein E epsilon4 on mesial temporal lobe activation. J Neurosci. 2006;26:6069-6076.PubMedCrossRefGoogle Scholar
  250. 250.
    Lind J, Ingvar M, Persson J, et al. Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon4 carriers. Neuroreport. 2006;17(16):1683-1686.PubMedCrossRefGoogle Scholar
  251. 251.
    Lind J, Persson J, Ingvar M, et al. Reduced functional brain activity response in cognitively intact apolipoprotein E epsilon4 carriers. Brain. 2006;129(Pt 5):1240-1248.PubMedCrossRefGoogle Scholar
  252. 252.
    Trivedi MA, Schmitz TW, Ries ML, et al. fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: risk factors for Alzheimer’s disease. Neuropsychologia. 2008;46(6):1667-1678.PubMedCrossRefGoogle Scholar
  253. 253.
    Trivedi MA, Schmitz TW, Ries ML, et al. Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer’s disease: a cross-sectional study. BMC Med. 2006;4:1.PubMedCrossRefGoogle Scholar
  254. 254.
    Xu G, McLaren DG, Ries ML, et al. The influence of parental history of Alzheimer’s disease and apolipoprotein E epsilon4 on the BOLD signal during recognition memory. Brain. 2009;132(Pt 2):383-391.PubMedGoogle Scholar
  255. 255.
    Filbey FM, Slack KJ, Sunderland TP, Cohen RM. Functional magnetic resonance imaging and magnetoencephalography differences associated with APOEepsilon4 in young healthy adults. Neuroreport. 2006;17(15):1585-1590.PubMedCrossRefGoogle Scholar
  256. 256.
    Smith CD, Andersen AH, Kryscio RJ, et al. Altered brain activation in cognitively intact individuals at high risk for Alzheimer’s disease. Neurology. 1999;53(7):1391-1396.PubMedGoogle Scholar
  257. 257.
    Smith CD, Andersen AH, Kryscio RJ, et al. Women at risk for AD show increased parietal activation during a fluency task. Neurology. 2002;58(8):1197-1202.PubMedGoogle Scholar
  258. 258.
    Smith CD, Kryscio RJ, Schmitt FA, et al. Longitudinal functional alterations in asymptomatic women at risk for Alzheimer’s disease. J Neuroimaging. 2005;15(3):271-277.PubMedGoogle Scholar
  259. 259.
    Wishart HA, Saykin AJ, Rabin LA, et al. Increased brain activation during working memory in cognitively intact adults with the APOE epsilon4 allele. Am J Psychiatry. 2006;163(9):1603-1610.PubMedCrossRefGoogle Scholar
  260. 260.
    Yassa MA, Verduzco G, Cristinzio C, Bassett SS. Altered fMRI activation during mental rotation in those at genetic risk for Alzheimer disease. Neurology. 2008;70(20):1898-1904.PubMedCrossRefGoogle Scholar
  261. 261.
    Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995;34(4):537-541.PubMedCrossRefGoogle Scholar
  262. 262.
    Cordes D, Haughton VM, Arfanakis K, et al. Mapping functionally related regions of brain with functional connectivity MR imaging. AJNR Am J Neuroradiol. 2000;21(9):1636-1644.PubMedGoogle Scholar
  263. 263.
    Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005;102(27):9673-9678.PubMedCrossRefGoogle Scholar
  264. 264.
    Friston K. Causal modelling and brain connectivity in functional magnetic resonance imaging. PLoS Biol. 2009;7(2):e33.PubMedCrossRefGoogle Scholar
  265. 265.
    Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003;100(1):253-258.PubMedCrossRefGoogle Scholar
  266. 266.
    Hampson M, Peterson BS, Skudlarski P, Gatenby JC, Gore JC. Detection of functional connectivity using temporal correlations in MR images. Hum Brain Mapp. 2002;15(4):247-262.PubMedCrossRefGoogle Scholar
  267. 267.
    Allen G, Barnard H, McColl R, et al. Reduced hippocampal functional connectivity in Alzheimer disease. Arch Neurol. 2007;64(10):1482-1487.PubMedCrossRefGoogle Scholar
  268. 268.
    Bai F, Zhang Z, Watson DR, et al. Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment. Biol Psychiatry. 2009;65(11):951-958.PubMedCrossRefGoogle Scholar
  269. 269.
    Bokde AL, Lopez-Bayo P, Meindl T, et al. Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment. Brain. 2006;129(Pt 5):1113-1124.PubMedCrossRefGoogle Scholar
  270. 270.
    Grady CL, McIntosh AR, Beig S, Keightley ML, Burian H, Black SE. Evidence from functional neuroimaging of a compensatory prefrontal network in Alzheimer’s disease. J Neurosci. 2003;23(3):986-993.PubMedGoogle Scholar
  271. 271.
    Petrella JR, Krishnan S, Slavin MJ, Tran TT, Murty L, Doraiswamy PM. Mild cognitive impairment: evaluation with 4-T functional MR imaging. Radiology. 2006;240(1):177-186.PubMedCrossRefGoogle Scholar
  272. 272.
    Pihlajamaki M, DePeau KM, Blacker D, Sperling RA. Impaired medial temporal repetition suppression is related to failure of parietal deactivation in Alzheimer disease. Am J Geriatr Psychiatry. 2008;16(4):283-292.PubMedCrossRefGoogle Scholar
  273. 273.
    Rombouts S, Scheltens P. Functional connectivity in elderly controls and AD patients using resting state fMRI: a pilot study. Curr Alzheimer Res. 2005;2(2):115-116.PubMedCrossRefGoogle Scholar
  274. 274.
    Zhou Y, Dougherty JH Jr, Hubner KF, Bai B, Cannon RL, Hutson RK. Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer’s disease and mild cognitive impairment. Alzheimers Dement. 2008;4(4):265-270.PubMedCrossRefGoogle Scholar
  275. 275.
    Wang K, Jiang T, Liang M, et al. Discriminative analysis of early Alzheimer’s disease based on two intrinsically anti-correlated networks with resting-state fMRI. Med Image Comput Comput Assist Interv. 2006;9(Pt 2):340-347.PubMedCrossRefGoogle Scholar
  276. 276.
    Bartres-Faz D, Serra-Grabulosa JM, Sun FT, et al. Functional connectivity of the hippocampus in elderly with mild memory dysfunction carrying the APOE epsilon4 allele. Neurobiol Aging. 2008;29(11):1644-1653.PubMedCrossRefGoogle Scholar
  277. 277.
    Beckmann CF, DeLuca M, Devlin JT, Smith SM. Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci. 2005;360(1457):1001-1013.PubMedCrossRefGoogle Scholar
  278. 278.
    Buckner RL, Snyder AZ, Shannon BJ, et al. Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25(34):7709-7717.PubMedCrossRefGoogle Scholar
  279. 279.
    Fransson P. Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the resting-state default mode of brain function hypothesis. Hum Brain Mapp. 2005;26(1):15-29.PubMedCrossRefGoogle Scholar
  280. 280.
    Greicius M. Resting-state functional connectivity in neuropsychiatric disorders. Curr Opin Neurol. 2008;21(4):424-430.PubMedCrossRefGoogle Scholar
  281. 281.
    Gusnard DA, Raichle ME. Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci. 2001;2(10):685-694.PubMedCrossRefGoogle Scholar
  282. 282.
    Guye M, Bartolomei F, Ranjeva JP. Imaging structural and functional connectivity: towards a unified definition of human brain organization? Curr Opin Neurol. 2008;21(4):393-403.PubMedCrossRefGoogle Scholar
  283. 283.
    Damoiseaux JS, Rombouts SA, Barkhof F, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci U S A. 2006;103(37):13848-13853.PubMedCrossRefGoogle Scholar
  284. 284.
    Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009;19(1):72-78.PubMedCrossRefGoogle Scholar
  285. 285.
    Lustig C, Snyder AZ, Bhakta M, et al. Functional deactivations: change with age and dementia of the Alzheimer type. Proc Natl Acad Sci U S A. 2003;100(24):14504-14509.PubMedCrossRefGoogle Scholar
  286. 286.
    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(2):676-682.PubMedCrossRefGoogle Scholar
  287. 287.
    Wagner AD, Shannon BJ, Kahn I, Buckner RL. Parietal lobe contributions to episodic memory retrieval. Trends Cogn Sci. 2005;9(9):445-453.PubMedCrossRefGoogle Scholar
  288. 288.
    Grady CL, Springer MV, Hongwanishkul D, McIntosh AR, Winocur G. Age-related changes in brain activity across the adult lifespan. J Cogn Neurosci. 2006;18(2):227-241.PubMedCrossRefGoogle Scholar
  289. 289.
    Greicius MD, Srivastava G, Reiss AL, Menon V. Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A. 2004;101(13):4637-4642.PubMedCrossRefGoogle Scholar
  290. 290.
    He Y, Wang L, Zang Y, et al. Regional coherence changes in the early stages of Alzheimer’s disease: a combined structural and resting-state functional MRI study. Neuroimage. 2007;35(2):488-500.PubMedCrossRefGoogle Scholar
  291. 291.
    Rombouts SA, Barkhof F, Goekoop R, Stam CJ, Scheltens P. Altered resting state networks in mild cognitive impairment and mild Alzheimer’s disease: an fMRI study. Hum Brain Mapp. 2005;26(4):231-239.PubMedCrossRefGoogle Scholar
  292. 292.
    Sorg C, Riedl V, Muhlau M, et al. Selective changes of resting-state networks in individuals at risk for Alzheimer’s disease. Proc Natl Acad Sci U S A. 2007;104(47):18760-18765.PubMedCrossRefGoogle Scholar
  293. 293.
    Wang K, Liang M, Wang L, et al. Altered functional connectivity in early Alzheimer’s disease: a resting-state fMRI study. Hum Brain Mapp. 2007;28(10):967-978.PubMedCrossRefGoogle Scholar
  294. 294.
    Wang L, Zang Y, He Y, et al. Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. Neuroimage. 2006;31(2):496-504.PubMedCrossRefGoogle Scholar
  295. 295.
    Bartenstein P, Minoshima S, Hirsch C, et al. Quantitative assessment of cerebral blood flow in patients with Alzheimer’s disease by SPECT. J Nucl Med. 1997;38(7):1095-1101.PubMedGoogle Scholar
  296. 296.
    Bradley KM, O’Sullivan VT, Soper ND, et al. Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer’s disease. Brain. 2002;125(Pt 8):1772-1781.PubMedCrossRefGoogle Scholar
  297. 297.
    Johnson KA, Jones K, Holman BL, et al. Preclinical prediction of Alzheimer’s disease using SPECT. Neurology. 1998;50:1563-1571.PubMedGoogle Scholar
  298. 298.
    Julin P, Lindqvist J, Svensson L, Slomka P, Wahlund LO. MRI-guided SPECT measurements of medial temporal lobe blood flow in Alzheimer’s disease. J Nucl Med. 1997;38:914-919.PubMedGoogle Scholar
  299. 299.
    Kogure D, Matsuda H, Ohnishi T, et al. Longitudinal evaluation of early Alzheimer’s disease using brain perfusion SPECT. J Nucl Med. 2000;41:1155-1162.PubMedGoogle Scholar
  300. 300.
    Scheltens P, Launer LJ, Barkhof F, Weinstein HC, Jonker C. The diagnostic value of magnetic resonance imaging and technetium 99m-HMPAO single-photon-emission computed tomography for the diagnosis of Alzheimer disease in a community-dwelling elderly population. Alzheimer Dis Assoc Disord. 1997;11(2):63-70.PubMedCrossRefGoogle Scholar
  301. 301.
    Silverman DH. Brain 18F-FDG PET in the diagnosis of neurodegenerative dementias: comparison with perfusion SPECT and with clinical evaluations lacking nuclear imaging. J Nucl Med. 2004;45(4):594-607.PubMedGoogle Scholar
  302. 302.
    Caroli A, Testa C, Geroldi C, et al. Cerebral perfusion correlates of conversion to Alzheimer’s disease in amnestic mild cognitive impairment. J Neurol. 2007;254(12):1698-1707.PubMedCrossRefGoogle Scholar
  303. 303.
    Phelps ME, Schelbert HR, Mazziotta JC. Positron computed tomography for studies of myocardial and cerebral function. Ann Intern Med. 1983;98(3):339-359.PubMedGoogle Scholar
  304. 304.
    Reivich M. Application of the deoxyglucose method to human cerebral dysfunction. The use of [2-18F] fluoro-2-deoxy-D-glucose in man. Neurosci Res Program Bull. 1976;14(4):502-504.PubMedGoogle Scholar
  305. 305.
    Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306-319.PubMedCrossRefGoogle Scholar
  306. 306.
    Kudo Y, Okamura N, Furumoto S, et al. 2-(2-[2-Dimethylaminothiazol-5-yl]ethenyl)-6- (2-[fluoro]ethoxy)benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer’s disease patients. J Nucl Med. 2007;48(4):553-561.PubMedCrossRefGoogle Scholar
  307. 307.
    Shoghi-Jadid K, Small GW, Agdeppa ED, et al. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002;10(1):24-35.PubMedGoogle Scholar
  308. 308.
    Small GW, Kepe V, Ercoli LM, et al. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006;355(25):2652-2663.PubMedCrossRefGoogle Scholar
  309. 309.
    Verhoeff NP, Wilson AA, Takeshita S, et al. In-vivo imaging of Alzheimer disease beta-amyloid with [11C]SB-13 PET. Am J Geriatr Psychiatry. 2004;12(6):584-595.PubMedGoogle Scholar
  310. 310.
    Pappata S, Salvatore E, Postiglione A. In vivo imaging of neurotransmission and brain receptors in dementia. J Neuroimaging. 2008;18(2):111-124.PubMedCrossRefGoogle Scholar
  311. 311.
    Banati RB, Newcombe J, Gunn RN, et al. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain. 2000;123(Pt 11):2321-2337.PubMedCrossRefGoogle Scholar
  312. 312.
    Chaki S, Funakoshi T, Yoshikawa R, et al. Binding characteristics of [3H]DAA1106, a novel and selective ligand for peripheral benzodiazepine receptors. Eur J Pharmacol. 1999;371(2-3):197-204.PubMedCrossRefGoogle Scholar
  313. 313.
    Choo IH, Lee DY, Youn JC, et al. Topographic patterns of brain functional impairment progression according to clinical severity staging in 116 Alzheimer disease patients: FDG-PET study. Alzheimer Dis Assoc Disord. 2007;21(2):77-84.PubMedCrossRefGoogle Scholar
  314. 314.
    Desgranges B, Baron JC, de la Sayette V, et al. The neural substrates of memory systems impairment in Alzheimer’s disease. A PET study of resting brain glucose utilization. Brain. 1998;121(Pt 4):611-631.PubMedCrossRefGoogle Scholar
  315. 315.
    Drzezga A, Riemenschneider M, Strassner B, et al. Cerebral glucose metabolism in patients with AD and different APOE genotypes. Neurology. 2005;64(1):102-107.PubMedGoogle Scholar
  316. 316.
    Foster NL, Chase TN, Mansi L, et al. Cortical abnormalities in Alzheimer’s disease. Ann Neurol. 1984;16(6):649-654.PubMedCrossRefGoogle Scholar
  317. 317.
    Friedland RP, Budinger TF, Ganz E, et al. Regional cerebral metabolic alterations in dementia of the Alzheimer type: positron emission tomography with [18F]fluorodeoxyglucose. J Comput Assist Tomogr. 1983;7(4):590-598.PubMedCrossRefGoogle Scholar
  318. 318.
    Heiss WD, Pawlik G, Holthoff V, Kessler J, Szelies B. PET correlates of normal and impaired memory functions. Cerebrovasc Brain Metab Rev. 1992;4(1):1-27.PubMedGoogle Scholar
  319. 319.
    Herholz K. FDG PET and differential diagnosis of dementia. Alzheimer Dis Assoc Disord. 1995;9(1):6-16.PubMedCrossRefGoogle Scholar
  320. 320.
    Hoffman JM, Welsh-Bohmer KA, Hanson M, et al. FDG PET imaging in patients with pathologically verified dementia. J Nucl Med. 2000;41(11):1920-1928.PubMedGoogle Scholar
  321. 321.
    Jagust WJ, Eberling JL, Richardson BC, et al. The cortical topography of temporal lobe hypometabolism in early Alzheimer’s disease. Brain Res. 1993;629(2):189-198.PubMedCrossRefGoogle Scholar
  322. 322.
    Jelic V, Nordberg A. Early diagnosis of Alzheimer disease with positron emission tomography. Alzheimer Dis Assoc Disord. 2000;14(Suppl 1):S109-S113.PubMedGoogle Scholar
  323. 323.
    Mielke R, Heiss WD. Positron emission tomography for diagnosis of Alzheimer’s disease and vascular dementia. J Neural Transm Suppl. 1998;53:237-250.PubMedGoogle Scholar
  324. 324.
    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(1):85-94.PubMedCrossRefGoogle Scholar
  325. 325.
    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(4):486-510.PubMedCrossRefGoogle Scholar
  326. 326.
    Mosconi L, Tsui WH, Herholz K, et al. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med. 2008;49(3):390-398.PubMedCrossRefGoogle Scholar
  327. 327.
    Nestor PJ, Fryer TD, Smielewski P, Hodges JR. Limbic hypometabolism in Alzheimer’s disease and mild cognitive impairment. Ann Neurol. 2003;54(3):343-351.PubMedCrossRefGoogle Scholar
  328. 328.
    Ouchi Y, Nobezawa S, Okada H, Yoshikawa E, Futatsubashi M, Kaneko M. Altered glucose metabolism in the hippocampal head in memory impairment. Neurology. 1998;51(1):136-142.PubMedGoogle Scholar
  329. 329.
    Sakamoto S, Ishii K, Sasaki M, et al. Differences in cerebral metabolic impairment between early and late onset types of Alzheimer’s disease. J Neurol Sci. 2002;200(1-2):27-32.PubMedCrossRefGoogle Scholar
  330. 330.
    Silverman DH, Small GW, Chang CY, et al. Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA. 2001;286(17):2120-2127.PubMedCrossRefGoogle Scholar
  331. 331.
    Herholz K, Nordberg A, Salmon E, et al. Impairment of neocortical metabolism predicts progression in Alzheimer’s disease. Dement Geriatr Cogn Disord. 1999;10(6):494-504.PubMedCrossRefGoogle Scholar
  332. 332.
    Jagust WJ, Haan MN, Eberling JL, Wolfe N, Reed BR. Functional imaging predicts cognitive decline in Alzheimer’s disease. J Neuroimaging. 1996;6(3):156-160.PubMedGoogle Scholar
  333. 333.
    Lee DY, Seo EH, Choo IH, et al. Neural correlates of the Clock Drawing Test performance in Alzheimer’s disease: a FDG-PET study. Dement Geriatr Cogn Disord. 2008;26(4):306-313.PubMedCrossRefGoogle Scholar
  334. 334.
    Fellgiebel A, Siessmeier T, Scheurich A, et al. Association of elevated phospho-tau levels with Alzheimer-typical 18F-fluoro-2-deoxy-D-glucose positron emission tomography findings in patients with mild cognitive impairment. Biol Psychiatry. 2004;56(4):279-283.PubMedCrossRefGoogle Scholar
  335. 335.
    Yamaguchi S, Meguro K, Itoh M, et al. Decreased cortical glucose metabolism correlates with hippocampal atrophy in Alzheimer’s disease as shown by MRI and PET. J Neurol Neurosurg Psychiatry. 1997;62(6):596-600.PubMedCrossRefGoogle Scholar
  336. 336.
    Azari NP, Pettigrew KD, Schapiro MB, et al. Early detection of Alzheimer’s disease: a statistical approach using positron emission tomographic data. J Cereb Blood Flow Metab. 1993;13(3):438-447.PubMedGoogle Scholar
  337. 337.
    Dobert N, Pantel J, Frolich L, Hamscho N, Menzel C, Grunwald F. Diagnostic value of FDG-PET and HMPAO-SPET in patients with mild dementia and mild cognitive impairment: metabolic index and perfusion index. Dement Geriatr Cogn Disord. 2005;20(2-3):63-70.PubMedCrossRefGoogle Scholar
  338. 338.
    Herholz K, Perani D, Salmon E, et al. Comparability of FDG PET studies in probable Alzheimer’s disease. J Nucl Med. 1993;34(9):1460-1466.PubMedGoogle Scholar
  339. 339.
    Herholz K, Salmon E, Perani D, et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage. 2002;17(1):302-316.PubMedCrossRefGoogle Scholar
  340. 340.
    Kippenhan JS, Barker WW, Nagel J, Grady C, Duara R. Neural-network classification of normal and Alzheimer’s disease subjects using high-resolution and low-resolution PET cameras. J Nucl Med. 1994;35(1):7-15.PubMedGoogle Scholar
  341. 341.
    Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med. 1995;36(7):1238-1248.PubMedGoogle Scholar
  342. 342.
    Herholz K. PET studies in dementia. Ann Nucl Med. 2003;17(2):79-89.PubMedCrossRefGoogle Scholar
  343. 343.
    Magistretti PJ, Pellerin L. The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies. Mol Psychiatry. 1996;1(6):445-452.PubMedGoogle Scholar
  344. 344.
    Rocher AB, Chapon F, Blaizot X, Baron JC, Chavoix C. Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons. Neuroimage. 2003;20(3):1894-1898.PubMedCrossRefGoogle Scholar
  345. 345.
    Alexander GE, Chen K, Pietrini P, Rapoport SI, Reiman EM. Longitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer’s disease treatment studies. Am J Psychiatry. 2002;159(5):738-745.PubMedCrossRefGoogle Scholar
  346. 346.
    Hirono N, Hashimoto M, Ishii K, Kazui H, Mori E. One-year change in cerebral glucose metabolism in patients with Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 2004;16(4):488-492.PubMedGoogle Scholar
  347. 347.
    Reiman EM, Caselli RJ, Chen K, Alexander GE, Bandy D, Frost J. Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: a foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer’s disease. Proc Natl Acad Sci U S A. 2001;98(6):3334-3339.PubMedCrossRefGoogle Scholar
  348. 348.
    Small GW, Ercoli LM, Silverman DH, et al. Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A. 2000;97(11):6037-6042.PubMedCrossRefGoogle Scholar
  349. 349.
    Smith GS, de Leon MJ, George AE, et al. Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer’s disease. Pathophysiologic implications. Arch Neurol. 1992;49(11):1142-1150.PubMedGoogle Scholar
  350. 350.
    de Leon MJ, Convit A, Wolf OT, et al. Prediction of cognitive decline in normal elderly subjects with 2-[(18)F]fluoro-2-deoxy-D-glucose/poitron-emission tomography (FDG/PET). Proc Natl Acad Sci U S A. 2001;98(19):10966-10971.PubMedCrossRefGoogle Scholar
  351. 351.
    Kennedy AM, Frackowiak RS, Newman SK, et al. Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer’s disease. Neurosci Lett. 1995;186(1):17-20.PubMedCrossRefGoogle Scholar
  352. 352.
    Mosconi L, Tsui WH, Pupi A, et al. (18)F-FDG PET database of longitudinally confirmed healthy elderly individuals improves detection of mild cognitive impairment and Alzheimer’s disease. J Nucl Med. 2007;48(7):1129-1134.PubMedCrossRefGoogle Scholar
  353. 353.
    Reiman EM, Caselli RJ, Yun LS, et al. Preclinical evidence of Alzheimer’s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996;334(12):752-758.PubMedCrossRefGoogle Scholar
  354. 354.
    Reiman EM, Chen K, Alexander GE, et al. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer’s dementia. Proc Natl Acad Sci U S A. 2004;101(1):284-289.PubMedCrossRefGoogle Scholar
  355. 355.
    Reiman EM, Chen K, Alexander GE, et al. Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proc Natl Acad Sci U S A. 2005;102(23):8299-8302.PubMedCrossRefGoogle Scholar
  356. 356.
    Rimajova M, Lenzo NP, Wu JS, et al. Fluoro-2-deoxy-D-glucose (FDG)-PET in APOEepsilon4 carriers in the Australian population. J Alzheimers Dis. 2008;13(2):137-146.PubMedGoogle Scholar
  357. 357.
    Small GW, Mazziotta JC, Collins MT, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA. 1995;273(12):942-947.PubMedCrossRefGoogle Scholar
  358. 358.
    Anchisi D, Borroni B, Franceschi M, et al. Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease. Arch Neurol. 2005;62(11):1728-1733.PubMedCrossRefGoogle Scholar
  359. 359.
    Arnaiz E, Jelic V, Almkvist O, et al. Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment. Neuroreport. 2001;12(4):851-855.PubMedCrossRefGoogle Scholar
  360. 360.
    Berent S, Giordani B, Foster N, et al. Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer’s disease. J Psychiatr Res. 1999;33(1):7-16.PubMedCrossRefGoogle Scholar
  361. 361.
    Caselli RJ, Chen K, Lee W, Alexander GE, Reiman EM. Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. Arch Neurol. 2008;65(9):1231-1236.PubMedCrossRefGoogle Scholar
  362. 362.
    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(8):1374-1377.PubMedGoogle Scholar
  363. 363.
    Chetelat G, Eustache F, Viader F, et al. FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment. Neurocase. 2005;11(1):14-25.PubMedCrossRefGoogle Scholar
  364. 364.
    Drzezga A, Grimmer T, Riemenschneider M, et al. Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. J Nucl Med. 2005;46(10):1625-1632.PubMedGoogle Scholar
  365. 365.
    Drzezga A, Lautenschlager N, Siebner H, et al. 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(8):1104-1113.PubMedCrossRefGoogle Scholar
  366. 366.
    Mosconi L, De Santi S, Li J, et al. Hippocampal hypometabolism predicts cognitive decline from normal aging. Neurobiol Aging. 2008;29(5):676-692.PubMedCrossRefGoogle Scholar
  367. 367.
    Mosconi L, Perani D, Sorbi S, et al. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology. 2004;63(12):2332-2340.PubMedGoogle Scholar
  368. 368.
    Heiss WD, Kessler J, Mielke R, Szelies B, Herholz K. Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer’s disease. A neuropsychological, EEG, and PET investigation. Dementia. 1994;5(2):88-98.PubMedGoogle Scholar
  369. 369.
    Kadir A, Darreh-Shori T, Almkvist O, et al. PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD. Neurobiol Aging. 2008;29(8):1204-1217.PubMedCrossRefGoogle Scholar
  370. 370.
    Mega MS, Cummings JL, O’Connor SM, et al. Cognitive and metabolic responses to metrifonate therapy in Alzheimer disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):63-68.PubMedGoogle Scholar
  371. 371.
    Potkin SG, Anand R, Fleming K, et al. Brain metabolic and clinical effects of rivastigmine in Alzheimer’s disease. Int J Neuropsychopharmacol. 2001;4(3):223-230.PubMedCrossRefGoogle Scholar
  372. 372.
    Teipel SJ, Drzezga A, Bartenstein P, Moller HJ, Schwaiger M, Hampel H. Effects of donepezil on cortical metabolic response to activation during (18)FDG-PET in Alzheimer’s disease: a double-blind cross-over trial. Psychopharmacology (Berl). 2006;187(1):86-94.CrossRefGoogle Scholar
  373. 373.
    Tune L, Tiseo PJ, Ieni J, et al. Donepezil HCl (E2020) maintains functional brain activity in patients with Alzheimer disease: results of a 24-week, double-blind, placebo-controlled study. Am J Geriatr Psychiatry. 2003;11(2):169-177.PubMedGoogle Scholar
  374. 374.
    Backman L, Andersson JL, Nyberg L, Winblad B, Nordberg A, Almkvist O. Brain regions associated with episodic retrieval in normal aging and Alzheimer’s disease. Neurology. 1999;52(9):1861-1870.PubMedGoogle Scholar
  375. 375.
    Kessler J, Herholz K, Grond M, Heiss WD. Impaired metabolic activation in Alzheimer’s disease: a PET study during continuous visual recognition. Neuropsychologia. 1991;29(3):229-243.PubMedCrossRefGoogle Scholar
  376. 376.
    Moulin CJ, Laine M, Rinne JO, et al. Brain function during multi-trial learning in mild cognitive impairment: a PET activation study. Brain Res. 2007;1136(1):132-141.PubMedCrossRefGoogle Scholar
  377. 377.
    Schroder J, Buchsbaum MS, Shihabuddin L, et al. Patterns of cortical activity and memory performance in Alzheimer’s disease. Biol Psychiatry. 2001;49(5):426-436.PubMedCrossRefGoogle Scholar
  378. 378.
    Woodard JL, Grafton ST, Votaw JR, Green RC, Dobraski ME, Hoffman JM. Compensatory recruitment of neural resources during overt rehearsal of word lists in Alzheimer’s disease. Neuropsychology. 1998;12(4):491-504.PubMedCrossRefGoogle Scholar
  379. 379.
    Klunk WE, Lopresti BJ, Ikonomovic MD, et al. Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer’s disease brain but not in transgenic mouse brain. J Neurosci. 2005;25(46):10598-10606.PubMedCrossRefGoogle Scholar
  380. 380.
    Lockhart A, Lamb JR, Osredkar T, et al. PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain. 2007;130(Pt 10):2607-2615.PubMedCrossRefGoogle Scholar
  381. 381.
    Johnson KA, Gregas M, Becker JA, et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol. 2007;62(3):229-234.PubMedCrossRefGoogle Scholar
  382. 382.
    Bacskai BJ, Frosch MP, Freeman SH, et al. Molecular imaging with Pittsburgh Compound B confirmed at autopsy: a case report. Arch Neurol. 2007;64(3):431-434.PubMedCrossRefGoogle Scholar
  383. 383.
    Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain. 2008;131(Pt 6):1630-1645.PubMedCrossRefGoogle Scholar
  384. 384.
    Leinonen V, Alafuzoff I, Aalto S, et al. Assessment of beta-amyloid in a frontal cortical brain biopsy specimen and by positron emission tomography with carbon 11-labeled Pittsburgh Compound B. Arch Neurol. 2008;65(10):1304-1309.PubMedCrossRefGoogle Scholar
  385. 385.
    Kemppainen NM, Aalto S, Wilson IA, et al. Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Neurology. 2006;67(9):1575-1580.PubMedCrossRefGoogle Scholar
  386. 386.
    Kemppainen NM, Aalto S, Wilson IA, et al. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology. 2007;68(19):1603-1606.PubMedCrossRefGoogle Scholar
  387. 387.
    Li Y, Rinne JO, Mosconi L, et al. Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2008;35(12):2169-2181.PubMedCrossRefGoogle Scholar
  388. 388.
    Lowe VJ, Kemp BJ, Jack CR Jr, et al. Comparison of 18F-FDG and PiB PET in cognitive impairment. J Nucl Med. 2009;50(6):878-886.PubMedCrossRefGoogle Scholar
  389. 389.
    Mintun MA, Larossa GN, Sheline YI, et al. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006;67(3):446-452.PubMedCrossRefGoogle Scholar
  390. 390.
    Ng S, Villemagne VL, Berlangieri S, et al. Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer’s disease. J Nucl Med. 2007;48(4):547-552.PubMedCrossRefGoogle Scholar
  391. 391.
    Pike KE, Savage G, Villemagne VL, et al. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease. Brain. 2007;130(Pt 11):2837-2844.PubMedCrossRefGoogle Scholar
  392. 392.
    Rabinovici GD, Furst AJ, O’Neil JP, et al. 11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Neurology. 2007;68(15):1205-1212.PubMedCrossRefGoogle Scholar
  393. 393.
    Rowe CC, Ng S, Ackermann U, et al. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007;68(20):1718-1725.PubMedCrossRefGoogle Scholar
  394. 394.
    Wiley CA, Lopresti BJ, Venneti S, et al. Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol. 2009;66(1):60-67.PubMedCrossRefGoogle Scholar
  395. 395.
    Ziolko SK, Weissfeld LA, Klunk WE, et al. Evaluation of voxel-based methods for the statistical analysis of PIB PET amyloid imaging studies in Alzheimer’s disease. Neuroimage. 2006;33(1):94-102.PubMedCrossRefGoogle Scholar
  396. 396.
    Edison P, Archer HA, Hinz R, et al. Amyloid, hypometabolism, and cognition in Alzheimer disease: an [11C]PIB and [18F]FDG PET study. Neurology. 2007;68(7):501-508.PubMedCrossRefGoogle Scholar
  397. 397.
    Engler H, Forsberg A, Almkvist O, et al. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain. 2006;129(Pt 11):2856-2866.PubMedCrossRefGoogle Scholar
  398. 398.
    Forsberg A, Engler H, Almkvist O, et al. PET imaging of amyloid deposition in patients with mild cognitive impairment. Neurobiol Aging. 2008;29(10):1456-1465.PubMedCrossRefGoogle Scholar
  399. 399.
    Grimmer T, Henriksen G, Wester HJ, et al. Clinical severity of Alzheimer’s disease is associated with PIB uptake in PET. Neurobiol Aging. 2009;30(12):1902-1909.PubMedCrossRefGoogle Scholar
  400. 400.
    Villemagne VL, Pike KE, Darby D, et al. Abeta deposits in older non-demented individuals with cognitive decline are indicative of preclinical Alzheimer’s disease. Neuropsychologia. 2008;46(6):1688-1697.PubMedCrossRefGoogle Scholar
  401. 401.
    Dickerson BC, Bakkour A, Salat DH, et al. The cortical signature of Alzheimer’s disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. Cereb Cortex. 2009;19(3):497-510.PubMedCrossRefGoogle Scholar
  402. 402.
    Kemppainen NM, Aalto S, Karrasch M, et al. Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer’s disease. Ann Neurol. 2008;63(1):112-118.PubMedCrossRefGoogle Scholar
  403. 403.
    Fagan AM, Mintun MA, Mach RH, et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006;59(3):512-519.PubMedCrossRefGoogle Scholar
  404. 404.
    Grimmer T, Riemenschneider M, Forstl H, et al. Beta amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry. 2009;65(11):927-934.PubMedCrossRefGoogle Scholar
  405. 405.
    Koivunen J, Pirttila T, Kemppainen N, et al. PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dement Geriatr Cogn Disord. 2008;26(4):378-383.PubMedCrossRefGoogle Scholar
  406. 406.
    Klunk WE, Mathis CA, Price JC, Lopresti BJ, DeKosky ST. Two-year follow-up of amyloid deposition in patients with Alzheimer’s disease. Brain. 2006;129(Pt 11):2805-2807.PubMedCrossRefGoogle Scholar
  407. 407.
    Price JC, Klunk WE, Lopresti BJ, et al. Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh Compound-B. J Cereb Blood Flow Metab. 2005;25(11):1528-1547.PubMedCrossRefGoogle Scholar
  408. 408.
    Wolk DA, Price JC, Saxton JA, et al. Amyloid imaging in mild cognitive impairment subtypes. Ann Neurol. 2009;65(5):557-568.PubMedCrossRefGoogle Scholar
  409. 409.
    Okello A, Koivunen J, Edison P, et al. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology. 2009;73(10):754-760.PubMedCrossRefGoogle Scholar
  410. 410.
    Aizenstein HJ, Nebes RD, Saxton JA, et al. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch Neurol. 2008;65(11):1509-1517.PubMedCrossRefGoogle Scholar
  411. 411.
    Reiman EM, Chen K, Liu X, et al. Fibrillar amyloid-beta burden in cognitively normal people at 3 levels of genetic risk for Alzheimer’s disease. Proc Natl Acad Sci U S A. 2009;106(16):6820-6825.PubMedCrossRefGoogle Scholar
  412. 412.
    Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet. 1976;2(8000):1403.PubMedCrossRefGoogle Scholar
  413. 413.
    Bohnen NI, Kaufer DI, Ivanco LS, et al. Cortical cholinergic function is more severely affected in parkinsonian dementia than in Alzheimer disease: an in vivo positron emission tomographic study. Arch Neurol. 2003;60(12):1745-1748.PubMedCrossRefGoogle Scholar
  414. 414.
    Davis KL, Mohs RC, Marin D, et al. Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA. 1999;281(15):1401-1406.PubMedCrossRefGoogle Scholar
  415. 415.
    Eggers C, Herholz K, Kalbe E, Heiss WD. Cortical acetylcholine esterase activity and ApoE4-genotype in Alzheimer disease. Neurosci Lett. 2006;408(1):46-50.PubMedCrossRefGoogle Scholar
  416. 416.
    Herholz K, Weisenbach S, Zundorf G, et al. In vivo study of acetylcholine esterase in basal forebrain, amygdala, and cortex in mild to moderate Alzheimer disease. Neuroimage. 2004;21(1):136-143.PubMedCrossRefGoogle Scholar
  417. 417.
    Iyo M, Namba H, Fukushi K, et al. Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer’s disease. Lancet. 1997;349(9068):1805-1809.PubMedCrossRefGoogle Scholar
  418. 418.
    Kuhl DE, Koeppe RA, Minoshima S, et al. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease. Neurology. 1999;52(4):691-699.PubMedGoogle Scholar
  419. 419.
    Poirier J, Delisle MC, Quirion R, et al. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc Natl Acad Sci U S A. 1995;92(26):12260-12264.PubMedCrossRefGoogle Scholar
  420. 420.
    Rinne JO, Kaasinen V, Jarvenpaa T, et al. Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2003;74(1):113-115.PubMedCrossRefGoogle Scholar
  421. 421.
    Shinotoh H, Namba H, Fukushi K, et al. Progressive loss of cortical acetylcholinesterase activity in association with cognitive decline in Alzheimer’s disease: a positron emission tomography study. Ann Neurol. 2000;48(2):194-200.PubMedCrossRefGoogle Scholar
  422. 422.
    Herholz K, Weisenbach S, Kalbe E, Diederich NJ, Heiss WD. Cerebral acetylcholine esterase activity in mild cognitive impairment. Neuroreport. 2005;16(13):1431-1434.PubMedCrossRefGoogle Scholar
  423. 423.
    Bohnen NI, Kaufer DI, Hendrickson R, et al. Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2005;76(3):315-319.PubMedCrossRefGoogle Scholar
  424. 424.
    Shinotoh H, Aotsuka A, Fukushi K, et al. Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET. Neurology. 2001;56(3):408-410.PubMedGoogle Scholar
  425. 425.
    O’Brien JT, Colloby SJ, Pakrasi S, et al. Alpha4beta2 nicotinic receptor status in Alzheimer’s disease using 123I-5IA-85380 single-photon-emission computed tomography. J Neurol Neurosurg Psychiatry. 2007;78(4):356-362.PubMedCrossRefGoogle Scholar
  426. 426.
    Sabri O, Kendziorra K, Wolf H, Gertz HJ, Brust P. Acetylcholine receptors in dementia and mild cognitive impairment. Eur J Nucl Med Mol Imaging. 2008;35(Suppl 1):S30-S45.PubMedCrossRefGoogle Scholar
  427. 427.
    Fukuchi K, Hashikawa K, Seike Y, et al. Comparison of iodine-123-iomazenil SPECT and technetium-99m-HMPAO-SPECT in Alzheimer’s disease. J Nucl Med. 1997;38(3):467-470.PubMedGoogle Scholar
  428. 428.
    Soricelli A, Postiglione A, Grivet-Fojaja MR, et al. Reduced cortical distribution volume of iodine-123 iomazenil in Alzheimer’s disease as a measure of loss of synapses. Eur J Nucl Med. 1996;23(10):1323-1328.PubMedCrossRefGoogle Scholar
  429. 429.
    Blin J, Baron JC, Dubois B, et al. Loss of brain 5-HT2 receptors in Alzheimer’s disease. In vivo assessment with positron emission tomography and [18F]setoperone. Brain. 1993;116(Pt 3):497-510.PubMedCrossRefGoogle Scholar
  430. 430.
    Hasselbalch SG, Madsen K, Svarer C, et al. Reduced 5-HT2A receptor binding in patients with mild cognitive impairment. Neurobiol Aging. 2008;29(12):1830-1838.PubMedCrossRefGoogle Scholar
  431. 431.
    Kepe V, Barrio JR, Huang SC, et al. Serotonin 1A receptors in the living brain of Alzheimer’s disease patients. Proc Natl Acad Sci U S A. 2006;103(3):702-707.PubMedCrossRefGoogle Scholar
  432. 432.
    Meltzer CC, Price JC, Mathis CA, et al. PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Am J Psychiatry. 1999;156(12):1871-1878.PubMedGoogle Scholar
  433. 433.
    Versijpt J, Van Laere KJ, Dumont F, et al. Imaging of the 5-HT2A system: age-, gender-, and Alzheimer’s disease-related findings. Neurobiol Aging. 2003;24(4):553-561.PubMedCrossRefGoogle Scholar
  434. 434.
    Kemppainen N, Laine M, Laakso MP, et al. Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer’s disease. Eur J Neurosci. 2003;18(1):149-154.PubMedCrossRefGoogle Scholar
  435. 435.
    Kemppainen N, Ruottinen H, Nagren K, Rinne JO. PET shows that striatal dopamine D1 and D2 receptors are differentially affected in AD. Neurology. 2000;55(2):205-209.PubMedGoogle Scholar
  436. 436.
    Meguro K, Yamaguchi S, Itoh M, Fujiwara T, Yamadori A. Striatal dopamine metabolism correlated with frontotemporal glucose utilization in Alzheimer’s disease: a double-tracer PET study. Neurology. 1997;49(4):941-945.PubMedGoogle Scholar
  437. 437.
    Pizzolato G, Chierichetti F, Fabbri M, et al. Reduced striatal dopamine receptors in Alzheimer’s disease: single photon emission tomography study with the D2 tracer [123I]-IBZM. Neurology. 1996;47(4):1065-1068.PubMedGoogle Scholar
  438. 438.
    Haga S, Akai K, Ishii T. Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. An immunohistochemical study using a novel monoclonal antibody. Acta Neuropathol. 1989;77(6):569-575.PubMedCrossRefGoogle Scholar
  439. 439.
    Venneti S, Wiley CA, Kofler J. Imaging microglial activation during neuroinflammation and Alzheimer’s disease. J Neuroimmune Pharmacol. 2009;4(2):227-243.PubMedCrossRefGoogle Scholar
  440. 440.
    Cagnin A, Brooks DJ, Kennedy AM, et al. In-vivo measurement of activated microglia in dementia. Lancet. 2001;358(9280):461-467.PubMedCrossRefGoogle Scholar
  441. 441.
    Edison P, Archer HA, Gerhard A, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32(3):412-419.PubMedCrossRefGoogle Scholar
  442. 442.
    Okello A, Edison P, Archer HA, et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology. 2009;72(1):56-62.PubMedCrossRefGoogle Scholar
  443. 443.
    Tomasi G, Edison P, Bertoldo A, et al. Novel reference region model reveals increased microglial and reduced vascular binding of 11C-(R)-PK11195 in patients with Alzheimer’s disease. J Nucl Med. 2008;49(8):1249-1256.PubMedCrossRefGoogle Scholar
  444. 444.
    Versijpt JJ, Dumont F, Van Laere KJ, et al. Assessment of neuroinflammation and microglial activation in Alzheimer’s disease with radiolabelled PK11195 and single photon emission computed tomography. A pilot study. Eur Neurol. 2003;50(1):39-47.PubMedCrossRefGoogle Scholar
  445. 445.
    Yasuno F, Ota M, Kosaka J, et al. Increased binding of peripheral benzodiazepine receptor in Alzheimer’s disease measured by positron emission tomography with [11C]DAA1106. Biol Psychiatry. 2008;64(10):835-841.PubMedCrossRefGoogle Scholar
  446. 446.
    Groom GN, Junck L, Foster NL, Frey KA, Kuhl DE. PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer’s disease. J Nucl Med. 1995;36(12):2207-2210.PubMedGoogle Scholar
  447. 447.
    O’Brien JT. Role of imaging techniques in the diagnosis of dementia. Br J Radiol. 2007;80(Spec No 2):S71-S77.PubMedCrossRefGoogle Scholar
  448. 448.
    Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993;43(2):250-260.PubMedGoogle Scholar
  449. 449.
    Kalaria RN. Small vessel disease and Alzheimer’s dementia: pathological considerations. Cerebrovasc Dis. 2002;13(Suppl 2):48-52.PubMedCrossRefGoogle Scholar
  450. 450.
    Kalaria RN. Vascular factors in Alzheimer’s disease. Int Psychogeriatr. 2003;15(Suppl 1):47-52.PubMedCrossRefGoogle Scholar
  451. 451.
    Mills S, Cain J, Purandare N, Jackson A. Biomarkers of cerebrovascular disease in dementia. Br J Radiol. 2007;80(Spec No 2):S128-S145.PubMedCrossRefGoogle Scholar
  452. 452.
    De Groot JC, De Leeuw FE, Oudkerk M, et al. Periventricular cerebral white matter lesions predict rate of cognitive decline. Ann Neurol. 2002;52(3):335-341.PubMedCrossRefGoogle Scholar
  453. 453.
    Meyer JS, Rauch GM, Crawford K, et al. Risk factors accelerating cerebral degenerative changes, cognitive decline and dementia. Int J Geriatr Psychiatry. 1999;14(12):1050-1061.PubMedCrossRefGoogle Scholar
  454. 454.
    McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005;65(12):1863-1872.PubMedCrossRefGoogle Scholar
  455. 455.
    Burton EJ, Karas G, Paling SM, et al. Patterns of cerebral atrophy in dementia with Lewy bodies using voxel-based morphometry. Neuroimage. 2002;17(2):618-630.PubMedCrossRefGoogle Scholar
  456. 456.
    Whitwell JL, Weigand SD, Shiung MM, et al. Focal atrophy in dementia with Lewy bodies on MRI: a distinct pattern from Alzheimer’s disease. Brain. 2007;130(Pt 3):708-719.PubMedCrossRefGoogle Scholar
  457. 457.
    Ishii K, Hosaka K, Mori T, Mori E. Comparison of FDG-PET and IMP-SPECT in patients with dementia with Lewy bodies. Ann Nucl Med. 2004;18(5):447-451.PubMedCrossRefGoogle Scholar
  458. 458.
    Lobotesis K, Fenwick JD, Phipps A, et al. Occipital hypoperfusion on SPECT in dementia with Lewy bodies but not AD. Neurology. 2001;56(5):643-649.PubMedGoogle Scholar
  459. 459.
    O’Brien JT, Colloby S, Fenwick J, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol. 2004;61(6):919-925.PubMedCrossRefGoogle Scholar
  460. 460.
    Colloby SJ, Williams ED, Burn DJ, Lloyd JJ, McKeith IG, O’Brien JT. Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson’s disease with and without dementia assessed using 123I-FP-CIT SPECT. Eur J Nucl Med Mol Imaging. 2005;32(10):1176-1185.PubMedCrossRefGoogle Scholar
  461. 461.
    McKeith I, O’Brien J, Walker Z, et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol. 2007;6(4):305-313.PubMedCrossRefGoogle Scholar
  462. 462.
    Boxer AL, Miller BL. Clinical features of frontotemporal dementia. Alzheimer Dis Assoc Disord. 2005;19(Suppl 1):S3-S6.PubMedCrossRefGoogle Scholar
  463. 463.
    Du AT, Schuff N, Kramer JH, et al. Different regional patterns of cortical thinning in Alzheimer’s disease and frontotemporal dementia. Brain. 2007;130(Pt 4):1159-1166.PubMedGoogle Scholar
  464. 464.
    Good CD, Scahill RI, Fox NC, et al. Automatic differentiation of anatomical patterns in the human brain: validation with studies of degenerative dementias. Neuroimage. 2002;17(1):29-46.PubMedCrossRefGoogle Scholar
  465. 465.
    Laakso MP, Frisoni GB, Kononen M, et al. Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer’s disease: a morphometric MRI study. Biol Psychiatry. 2000;47(12):1056-1063.PubMedCrossRefGoogle Scholar
  466. 466.
    Whitwell JL, Jack CR Jr, Baker M, et al. Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutations. Arch Neurol. 2007;64(3):371-376.PubMedCrossRefGoogle Scholar
  467. 467.
    Whitwell JL, Jack CR Jr, Parisi JE, et al. Rates of cerebral atrophy differ in different degenerative pathologies. Brain. 2007;130(Pt 4):1148-1158.PubMedGoogle Scholar
  468. 468.
    Whitwell JL, Jack CR Jr, Senjem ML, Josephs KA. Patterns of atrophy in pathologically confirmed FTLD with and without motor neuron degeneration. Neurology. 2006;66(1):102-104.PubMedCrossRefGoogle Scholar
  469. 469.
    Galton CJ, Patterson K, Graham K, et al. Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia. Neurology. 2001;57(2):216-225.PubMedGoogle Scholar
  470. 470.
    Foster NL, Heidebrink JL, Clark CM, et al. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer’s disease. Brain. 2007;130(Pt 10):2616-2635.PubMedCrossRefGoogle Scholar
  471. 471.
    McNeill R, Sare GM, Manoharan M, et al. Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2007;78(4):350-355.PubMedCrossRefGoogle Scholar
  472. 472.
    Gatz M, Reynolds CA, Fratiglioni L, et al. Role of genes and environments for explaining Alzheimer disease. Arch Gen Psychiatry. 2006;63(2):168-174.PubMedCrossRefGoogle Scholar
  473. 473.
    Potkin SG, Turner JA, Guffanti G, et al. Genome-wide strategies for discovering genetic influences on cognition and cognitive disorders: methodological considerations. Cogn Neuropsychiatry. 2009;14(4-5):391-418.PubMedCrossRefGoogle Scholar
  474. 474.
    Shen L, Kim S, Risacher SL, et al. 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. 2010 Jan 25; in press, doi:10.1016/j.neuroimage.2010.01.042.PubMedCrossRefGoogle Scholar
  475. 475.
    Storandt M, Grant EA, Miller JP, Morris JC. Longitudinal course and neuropathologic outcomes in original vs revised MCI and in pre-MCI. Neurology. 2006;67(3):467-473.PubMedCrossRefGoogle Scholar
  476. 476.
    Caselli RJ, Reiman EM, Locke DE, et al. Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Arch Neurol. 2007;64(9):1306-1311.PubMedCrossRefGoogle Scholar
  477. 477.
    Jack CR Jr, Petersen RC, Grundman M, et al. Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI. Neurobiol Aging. 2008;29(9):1285-1295.PubMedCrossRefGoogle Scholar
  478. 478.
    Fox NC, Black RS, Gilman S, et al. Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology. 2005;64(9):1563-1572.PubMedCrossRefGoogle Scholar
  479. 479.
    Fox NC, Cousens S, Scahill R, Harvey RJ, Rossor MN. Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects. Arch Neurol. 2000;57(3):339-344.PubMedCrossRefGoogle Scholar
  480. 480.
    Mechelli A, Price CJ, Friston KJ, Ashburner J. Voxel-based morphometry of the human brain: methods and applications. Curr Med Imaging Rev. 2005;1(1):1-9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.IU Center for Neuroimaging, Department of Radiology and Imaging SciencesIndiana University School of MedicineIndianapolisUSA
  2. 2.Indiana Alzheimer Disease CenterIndiana University School of MedicineIndianapolisUSA
  3. 3.Medical Neuroscience Program, Stark Neurosciences Research InstituteIndiana University School of MedicineIndianapolisUSA

Personalised recommendations