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Dementia Due to Neurodegenerative Disease: Molecular Imaging Findings

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PET and SPECT in Neurology

Abstract

This chapter focuses on molecular imaging in dementia using PET and SPECT. The performance of FDG-PET, PIB-PET, and DAT SPECT in the differential and early diagnosis of dementia will be evaluated. Finally, more experimental PET tracers will be discussed.

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References

  • Agdeppa E, Kepe V, Liu J, Flores-Torres S et al (2001) Binding characteristics of radiofluorinated 6-dialkylamino-2-naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer’s disease. J Neurosci 15:RC189

    Google Scholar 

  • Aisen PS, Schmeidler J, Pasinetti GM (2002) Randomized pilot study of nimesulide treatment in Alzheimer’s disease. Neurology 58:1050–1054

    CAS  PubMed  Google Scholar 

  • Aisen PS, Schafer KA, Grundman M, Pfeiffer E et al (2003) Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA 289: 2819–2826

    CAS  PubMed  Google Scholar 

  • Albert MS, DeKosky ST, Dickson D, Dubois B et al (2011) The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:270–279

    PubMed Central  PubMed  Google Scholar 

  • Alexander GE, Chen K, Pietrini P, Rapoport SI, Reiman EM (2002) Longitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer’s disease treatment studies. Am J Psychiatry 159:738–745

    PubMed  Google Scholar 

  • Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133–1145

    CAS  PubMed  Google Scholar 

  • Auning E, Rongve A, Fladby T, Booij J et al (2011) Early and presenting symptoms of dementia with Lewy bodies. Dement Geriatr Cogn Disord 32:202–208

    PubMed  Google Scholar 

  • Barthel H, Gertz HJ, Dresel S, Peters O et al (2011) Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer’s disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol 10:424–435

    CAS  PubMed  Google Scholar 

  • Becker JA, Hedden T, Carmasin J, Maye J et al (2011) Amyloid-β associated cortical thinning in clinically normal elderly. Ann Neurol 69:1032–1042

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bergfield KL, Hanson KD, Chen K, Teipel SJ et al (2010) Age-related networks of regional covariance in MRI gray matter: reproducible multivariate patterns in healthy aging. Neuroimage 49:1750–1759

    PubMed Central  PubMed  Google Scholar 

  • Blennow K, Hampel H (2003) CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2:605–613

    CAS  PubMed  Google Scholar 

  • Bohnen N, Kaufer D, Hendrickson R, Ivanco L et al (2005) Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 76:315–319

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bohnen NI, Djang DS, Herholz K, Anzai Y, Minoshima S (2012) Effectiveness and safety of 18F-FDG PET in the evaluation of dementia: a review of the recent literature. J Nucl Med 53:59–71

    CAS  PubMed  Google Scholar 

  • Booij J, Teune LK, Verberne HJ (2012) The role of molecular imaging in the differential diagnosis of parkinsonism. Q J Nucl Med Mol Imaging 56:17–26

    CAS  PubMed  Google Scholar 

  • Boutin H, Chauveau F, Thominiaux C, Kuhnast B et al (2007) In vivo imaging of brain lesions with [(11)C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors. Glia 55:1459–1468

    PubMed  Google Scholar 

  • Briard E, Zoghbi SS, Imaizumi M, Gourley JP et al (2008) Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo. J Med Chem 51:17–30

    CAS  PubMed  Google Scholar 

  • Brix G, Zaers J, Adam LE, Bellemann ME et al (1997) Performance evaluation of a whole-body PET scanner using the NEMA protocol. National Electrical Manufacturers Association. J Nucl Med 38:1614–1623

    CAS  PubMed  Google Scholar 

  • Buchsbaum MS, Haier RJ, Potkin SG, Nuechterlein K et al (1992) Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenics. Arch Gen Psychiatry 49:935–942

    CAS  PubMed  Google Scholar 

  • Burack MA, Hartlein J, Flores HP, Taylor-Reinwald L et al (2010) In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia. Neurology 74:77–84

    CAS  PubMed Central  PubMed  Google Scholar 

  • Burke JF, Albin RL, Koeppe RA, Giordani B et al (2011) Assessment of mild dementia with amyloid and dopamine terminal positron emission tomography. Brain 134:1647–1657

    PubMed Central  PubMed  Google Scholar 

  • Cabeza R, Anderson ND, Locantore JK, McIntosh AR (2002) Aging gracefully: compensatory brain activity in high-performing older adults. Neuroimage 17:1394–1402

    PubMed  Google Scholar 

  • Cagnin A, Brooks DJ, Kennedy AM, Gunn RN et al (2001) In-vivo measurement of activated microglia in dementia. Lancet 358:461–467

    CAS  PubMed  Google Scholar 

  • Camacho V, Marquié M, Lleó A, Alvés L et al (2011) Cardiac sympathetic impairment parallels nigrostriatal degeneration in probable Dementia with Lewy bodies. Q J Nucl Med Mol Imaging 55:476–483

    CAS  PubMed  Google Scholar 

  • Carter S, Schöll M, Almkvist O, Wall A et al (2012) Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med 53:37–46

    CAS  PubMed  Google Scholar 

  • Caso F, Gesierich B, Henry M, Sidhu M et al (2012) Nonfluent/agrammatic PPA with in-vivo cortical amyloidosis and Pick’s disease pathology. Behav Neurol 26(1–2):95–106

    Google Scholar 

  • Chen MK, Guilarte TR (2006) Imaging the peripheral benzodiazepine receptor response in central nervous system demyelination and remyelination. Toxicol Sci 91:532–539

    CAS  PubMed  Google Scholar 

  • Chen WP, Samuraki M, Yanase D, Shima K et al (2008) Effect of sample size for normal database on diagnostic performance of brain FDG PET for the detection of Alzheimer’s disease using automated image analysis. Nucl Med Commun 29:270–276

    PubMed  Google Scholar 

  • Chételat G, Desgranges B, de la Sayette V, Viader F et al (2003) Mild cognitive impairment: can FDG-PET predict who is to rapidly convert to Alzheimer’s disease? Neurology 60:1374–1377

    PubMed  Google Scholar 

  • Chételat G, Villemagne VL, Bourgeat P, Pike KE et al (2010) Relationship between atrophy and beta-amyloid deposition in Alzheimer disease. Ann Neurol 67:317–324

    PubMed  Google Scholar 

  • Clark CM, Schneider JA, Bedell BJ, Beach TG et al (2011) Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 305:275–283

    CAS  PubMed  Google Scholar 

  • Cohen AD, Price JC, Weissfeld LA, James J et al (2009) Basal cerebral metabolism may modulate the cognitive effects of Abeta in mild cognitive impairment: an example of brain reserve. J Neurosci 29:14770–14778

    CAS  PubMed Central  PubMed  Google Scholar 

  • DeCarli C (2003) Mild cognitive impairment: prevalence, prognosis, aetiology, and treatment. Lancet Neurol 2:15–21

    PubMed  Google Scholar 

  • Dickerson BC, Bakkour A, Salat DH, Feczko E et al (2009) 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 19:497–510

    PubMed Central  PubMed  Google Scholar 

  • Diehl-Schmid J, Grimmer T, Drzezga A, Bornschein S et al (2007) Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study. Neurobiol Aging 28:42–50

    CAS  PubMed  Google Scholar 

  • DiPatre PL, Gelman BB (1997) Microglial cell activation in aging and Alzheimer disease: partial linkage with neurofibrillary tangle burden in the hippocampus. J Neuropathol Exp Neurol 56:143–149

    CAS  PubMed  Google Scholar 

  • Donnemiller E, Heilmann J, Wenning GK, Berger W et al (1997) Brain perfusion scintigraphy with 99mTc-HMPAO or 99mTc-ECD and 123I-beta-CIT single-photon emission tomography in dementia of the Alzheimer-type and diffuse Lewy body disease. Eur J Nucl Med 24:320–325

    CAS  PubMed  Google Scholar 

  • Doorduin J, Klein HC, Dierckx RA, James M et al (2009) [11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis. Mol Imaging Biol 11:386–398

    PubMed Central  PubMed  Google Scholar 

  • Drzezga A, Lautenschlager N, Siebner H, Riemenschneider M et al (2003) Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer’s disease: a PET follow-up study. Eur J Nucl Med Mol Imaging 30:1104–1113

    PubMed  Google Scholar 

  • Dubois B, Feldman HH, Jacova C, Dekosky ST et al (2007) Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 6:734–746

    PubMed  Google Scholar 

  • Engler H, Santillo AF, Wang SX, Lindau M et al (2008) In vivo amyloid imaging with PET in frontotemporal dementia. Eur J Nucl Med Mol Imaging 35:100–106

    PubMed  Google Scholar 

  • Fagan AM, Mintun MA, Mach RH, Lee SY et al (2006) Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol 59:512–519

    CAS  PubMed  Google Scholar 

  • Farias ST, Mungas D, Reed BR, Harvey D, DeCarli C (2009) Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts. Arch Neurol 66:1151–1157

    PubMed Central  PubMed  Google Scholar 

  • Fleisher AS, Chen K, Liu X, Ayutyanont N et al (2012) Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiol Aging 34(1):1–12

    PubMed  Google Scholar 

  • Foster NL, Chase TN, Mansi L, Brooks R et al (1984) Cortical abnormalities in Alzheimer’s disease. Ann Neurol 16:649–654

    CAS  PubMed  Google Scholar 

  • Foster NL, Heidebrink JL, Clark CM, Jagust WJ et al (2007) FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer’s disease. Brain 130:2616–2635

    PubMed  Google Scholar 

  • Fowler J, MacGregor R, Wolf A, Arnett C et al (1987) Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET. Science 23:481–485

    Google Scholar 

  • Galton CJ, Patterson K, Xuereb JH, Hodges JR (2000) Atypical and typical presentations of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 123:484–498

    PubMed  Google Scholar 

  • Gavish M, Bachman I, Shoukrun R, Katz Y et al (1999) Enigma of the peripheral benzodiazepine receptor. Pharmacol Rev 51:629–650

    CAS  PubMed  Google Scholar 

  • Gilman S, Koeppe RA, Little R, An H et al (2004) Striatal monoamine terminals in Lewy body dementia and Alzheimer’s disease. Ann Neurol 55:774–780

    PubMed  Google Scholar 

  • Giulian D, Haverkamp LJ, Yu JH, Karshin W et al (1996) Specific domains of beta-amyloid from Alzheimer plaque elicit neuron killing in human microglia. J Neurosci 16:6021–6037

    CAS  PubMed  Google Scholar 

  • Goldstein DS, Holmes C, Cannon RO, Eisenhofer G, Kopin IJ (1997) Sympathetic cardioneuropathy in dysautonomias. N Engl J Med 336:696–702

    CAS  PubMed  Google Scholar 

  • Gomperts SN, Rentz DM, Moran E, Becker JA et al (2008) Imaging amyloid deposition in Lewy body diseases. Neurology 71:903–910

    CAS  PubMed Central  PubMed  Google Scholar 

  • Harding AJ, Halliday GM (2001) Cortical Lewy body pathology in the diagnosis of dementia. Acta Neuropathol 102:355–363

    CAS  PubMed  Google Scholar 

  • Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185

    CAS  PubMed  Google Scholar 

  • Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356

    CAS  PubMed  Google Scholar 

  • Herholz K, Bauer B, Wienhard K, Kracht L et al (2000) In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia: comparison with blood flow and glucose metabolism. J Neural Transm 107:1457–1468

    CAS  PubMed  Google Scholar 

  • Herholz K, Salmon E, Perani D, Baron JC et al (2002) Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. Neuroimage 17:302–316

    CAS  PubMed  Google Scholar 

  • Herholz K, Carter S, Jones M (2007) Positron emission tomography imaging in dementia. Br J Radiol 80:2S160–2S167

    Google Scholar 

  • Holthoff VA, Beuthien-Baumann B, Zündorf G, Triemer A et al (2004) Changes in brain metabolism associated with remission in unipolar major depression. Acta Psychiatr Scand 110:184–194

    CAS  PubMed  Google Scholar 

  • Hosaka K, Ishii K, Sakamoto S, Mori T et al (2002) Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration. J Neurol Sci 199:67–71

    CAS  PubMed  Google Scholar 

  • Hu XS, Okamura N, Arai H, Higuchi M et al (2000) 18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with Lewy bodies. Neurology 55:1575–1577

    CAS  PubMed  Google Scholar 

  • Ikonomovic MD, Klunk WE, Abrahamson EE, Mathis CA et al (2008) Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer’s disease. Brain 131:1630–1645

    PubMed Central  PubMed  Google Scholar 

  • Ikonomovic MD, Abrahamson EE, Price JC, Hamilton RL et al (2012) Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study. Acta Neuropathol 123:433–447

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iranzo A, Lomeña F, Stockner H, Valldeoriola F et al (2010) Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol 9:1070–1077

    CAS  PubMed  Google Scholar 

  • Ishii K, Imamura T, Sasaki M, Yamaji S et al (1998a) Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer’s disease. Neurology 51:125–130

    CAS  PubMed  Google Scholar 

  • Ishii K, Sakamoto S, Sasaki M, Kitagaki H et al (1998b) Cerebral glucose metabolism in patients with frontotemporal dementia. J Nucl Med 39:1875–1878

    CAS  PubMed  Google Scholar 

  • Ishii K, Soma T, Kono AK, Sofue K et al (2007) Comparison of regional brain volume and glucose metabolism between patients with mild dementia with Lewy bodies and those with mild Alzheimer’s disease. J Nucl Med 48:704–711

    PubMed  Google Scholar 

  • Iyo M, Namba H, Fukushi K, Shinotoh H et al (1997) Measurement of acetylcholinesterase by positron emission tomography in the brains of healthy controls and patients with Alzheimer’s disease. Lancet 21:1805–1809

    Google Scholar 

  • Jagust W, Reed B, Mungas D, Ellis W, Decarli C (2007) What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? Neurology 69:871–877

    CAS  PubMed  Google Scholar 

  • Jagust WJ, Landau SM, Shaw LM, Trojanowski JQ et al (2009) Relationships between biomarkers in aging and dementia. Neurology 73:1193–1199

    CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson KA, Gregas M, Becker JA, Kinnecom C et al (2007) Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol 62:229–234

    PubMed  Google Scholar 

  • Juh R, Pae CU, Kim TS, Lee CU et al (2005) Cerebral glucose metabolism in corticobasal degeneration comparison with progressive supranuclear palsy using statistical mapping analysis. Neurosci Lett 383:22–27

    CAS  PubMed  Google Scholar 

  • Kaasinen V, Någren K, Järvenpää T, Roivainen A et al (2002) Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer’s disease. J Clin Psychopharmacol 22:615–620

    CAS  PubMed  Google Scholar 

  • Kadir A, Darreh-Shori T, Almkvist O, Wall A et al (2008) PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD. Neurobiol Aging 29:1204–1217

    CAS  PubMed  Google Scholar 

  • Kasanuki K, Iseki E, Fujishiro H, Yamamoto R et al (2012) Neuropathological investigation of the hypometabolic regions on positron emission tomography with [18F] fluorodeoxyglucose in patients with dementia with Lewy bodies. J Neurol Sci 314:111–119

    CAS  PubMed  Google Scholar 

  • Kashihara K, Ohno M, Kawada S, Okumura Y (2006) Reduced cardiac uptake and enhanced washout of 123I-MIBG in pure autonomic failure occurs conjointly with Parkinson’s disease and dementia with Lewy bodies. J Nucl Med 47:1099–1101

    CAS  PubMed  Google Scholar 

  • King AE, Mintz J, Royall DR (2011) Meta-analysis of 123I-MIBG cardiac scintigraphy for the diagnosis of Lewy body-related disorders. Mov Disord 26:1218–1224

    PubMed  Google Scholar 

  • Klunk WE (2011) Amyloid imaging as a biomarker for cerebral β-amyloidosis and risk prediction for Alzheimer dementia. Neurobiol Aging 32(Suppl 1):S20–S36

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klunk WE, Wang Y, Huang GF, Debnath ML et al (2003) The binding of 2-(4'-methylaminophenyl)benzothiazole to postmortem brain homogenates is dominated by the amyloid component. J Neurosci 23:2086–2092

    CAS  PubMed  Google Scholar 

  • Klunk WE, Engler H, Nordberg A, Wang Y et al (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319

    CAS  PubMed  Google Scholar 

  • Knopman DS, DeKosky ST, Cummings JL, Chui H et al (2001) Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56:1143–1153

    CAS  PubMed  Google Scholar 

  • Koeppe RA, Gilman S, Junck L, Wernette K, Frey KA (2008) Differentiating Alzheimer’s disease from dementia with Lewy bodies and Parkinson’s disease with (+)-[11C]dihydrotetrabenazine positron emission tomography. Alzheimers Dement 4:S67–S76

    PubMed  Google Scholar 

  • Koivunen J, Pirttilä T, Kemppainen N, Aalto S et al (2008) PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment. Dement Geriatr Cogn Disord 26:378–383

    CAS  PubMed  Google Scholar 

  • Koivunen J, Scheinin N, Virta JR, Aalto S et al (2011) Amyloid PET imaging in patients with mild cognitive impairment: a 2-year follow-up study. Neurology 22:1085–1090

    Google Scholar 

  • Kreisl WC, Fujita M, Fujimura Y, Kimura N et al (2010) Comparison of [(11)C]-(R)-PK 11195 and [(11)C]PBR28, two radioligands for translocator protein (18kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker. Neuroimage 49:2924–2932

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318

    CAS  PubMed  Google Scholar 

  • Kuhl D, Koeppe R, Minoshima S, Snyder S et al (1999) In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease. Neurology 10:691–699

    Google Scholar 

  • Landau SM, Harvey D, Madison CM, Reiman EM et al (2010) Comparing predictors of conversion and decline in mild cognitive impairment. Neurology 75:230–238

    CAS  PubMed Central  PubMed  Google Scholar 

  • Landau SM, Harvey D, Madison CM, Koeppe RA et al (2011) Associations between cognitive, functional, and FDG-PET measures of decline in AD and MCI. Neurobiol Aging 32:1207–1218

    PubMed Central  PubMed  Google Scholar 

  • Lee JH, Kim SH, Kim GH, Seo SW et al (2011) Identification of pure subcortical vascular dementia using 11C-Pittsburgh compound B. Neurology 77:18–25

    CAS  PubMed  Google Scholar 

  • Leinonen V, Alafuzoff I, Aalto S, Suotunen T et al (2008) 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 65:1304–1309

    PubMed  Google Scholar 

  • Lim SM, Katsifis A, Villemagne VL, Best R et al (2009) The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies. J Nucl Med 50:1638–1645

    CAS  PubMed  Google Scholar 

  • Maeda J, Suhara T, Zhang MR, Okauchi T et al (2004) Novel peripheral benzodiazepine receptor ligand [11C]DAA1106 for PET: an imaging tool for glial cells in the brain. Synapse 52:283–291

    CAS  PubMed  Google Scholar 

  • McGeer PL, Itagaki S, McGeer EG (1988) Expression of the histocompatibility glycoprotein HLA-DR in neurological disease. Acta Neuropathol 76:550–557

    CAS  PubMed  Google Scholar 

  • McKeith IG, Galasko D, Kosaka K, Perry EK et al (1996) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 47:1113–1124

    CAS  PubMed  Google Scholar 

  • McKeith IG, Dickson DW, Lowe J, Emre M et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872

    CAS  PubMed  Google Scholar 

  • McKeith I, O’Brien J, Walker Z, Tatsch K et al (2007) Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 6:305–313

    PubMed  Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34:939–944

    CAS  PubMed  Google Scholar 

  • McKhann GM, Knopman DS, Chertkow H, Hyman BT et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269

    PubMed Central  PubMed  Google Scholar 

  • McMurtray AM, Licht E, Yeo T, Krisztal E et al (2008) Positron emission tomography facilitates diagnosis of early-onset alzheimer’s disease. Eur Neurol 59:31–37

    PubMed  Google Scholar 

  • Minoshima S, Foster NL, Kuhl DE (1994) Posterior cingulate cortex in Alzheimer’s disease. Lancet 24:895

    Google Scholar 

  • Minoshima S, Foster NL, Sima AA, Frey KA et al (2001) Alzheimer’s disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol 50:358–365

    CAS  PubMed  Google Scholar 

  • Mizukami K, Homma T, Aonuma K, Kinoshita T et al (2009) Decreased ventilatory response to hypercapnia in dementia with Lewy bodies. Ann Neurol 65:614–617

    PubMed  Google Scholar 

  • Moeller JR, Ishikawa T, Dhawan V, Spetsieris P et al (1996) The metabolic topography of normal aging. J Cereb Blood Flow Metab 16:385–398

    CAS  PubMed  Google Scholar 

  • Moreno-López L, Stamatakis EA, Fernández-Serrano MJ, Gómez-Río M et al (2012) Neural correlates of the severity of cocaine, heroin, alcohol, MDMA and cannabis use in polysubstance abusers: a resting-PET brain metabolism study. PLoS One 7:e39830

    PubMed Central  PubMed  Google Scholar 

  • Morgan S, Kemp P, Booij J, Costa DC et al (2012) Differentiation of frontotemporal dementia from dementia with Lewy bodies using FP-CIT SPECT. J Neurol Neurosurg Psychiatry 83:1063–1070

    PubMed  Google Scholar 

  • Mormino EC, Kluth JT, Madison CM, Rabinovici GD et al (2009) Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain 132:1310–1323

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mormino EC, Brandel MG, Madison CM, Marks S et al (2012) Aβ deposition in aging is associated with increases in brain activation during successful memory encoding. Cereb Cortex 22:1813–1823

    PubMed Central  PubMed  Google Scholar 

  • Morris JC, Roe CM, Grant EA, Head D et al (2009) Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. Arch Neurol 66:1469–1475

    PubMed Central  PubMed  Google Scholar 

  • Mosconi L, Tsui WH, Pupi A, De Santi S et al (2007) (18)F-FDG PET database of longitudinally confirmed healthy elderly individuals improves detection of mild cognitive impairment and Alzheimer’s disease. J Nucl Med 48:1129–1134

    PubMed  Google Scholar 

  • Mosconi L, Tsui WH, Herholz K, Pupi A et al (2008) Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer’s disease, and other dementias. J Nucl Med 49:390–398

    PubMed Central  PubMed  Google Scholar 

  • Mourik JE, Lubberink M, van Velden FH, Kloet RW et al (2010) In vivo validation of reconstruction-based resolution recovery for human brain studies. J Cereb Blood Flow Metab 30:381–389

    PubMed Central  PubMed  Google Scholar 

  • Neary D, Snowden JS, Gustafson L, Passant U et al (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51:1546–1554

    CAS  PubMed  Google Scholar 

  • Ng S, Villemagne VL, Berlangieri S, Lee ST et al (2007) Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer’s disease. J Nucl Med 48:547–552

    CAS  PubMed  Google Scholar 

  • O’Brien JT, Colloby S, Fenwick J, Williams ED et al (2004) Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol 61:919–925

    PubMed  Google Scholar 

  • O’Brien JT, McKeith IG, Walker Z, Tatsch K et al (2009) Diagnostic accuracy of 123I-FP-CIT SPECT in possible dementia with Lewy bodies. Br J Psychiatry 194:34–39

    PubMed  Google Scholar 

  • Oh H, Mormino EC, Madison C, Hayenga A et al (2011) β-Amyloid affects frontal and posterior brain networks in normal aging. Neuroimage 54:1887–1895

    CAS  PubMed Central  PubMed  Google Scholar 

  • Okello A, Edison P, Archer HA, Turkheimer FE et al (2009) Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 72:56–62

    CAS  PubMed Central  PubMed  Google Scholar 

  • Orimo S, Uchihara T, Nakamura A, Mori F et al (2008) Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson’s disease. Brain 131:642–650

    PubMed  Google Scholar 

  • Ossenkoppele R, van Berckel BN, Prins ND (2011) Amyloid imaging in prodromal Alzheimer’s disease. Alzheimers Res Ther 3:26–28

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ossenkoppele R, Prins ND, Pijnenburg YA, Lemstra AW et al (2012a) Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement 9(4):414–421

    PubMed  Google Scholar 

  • Ossenkoppele R, Tolboom N, Foster-Dingley JC, Adriaanse SF et al (2012b) Longitudinal imaging of Alzheimer pathology using [(11)C]PIB, [(18)F]FDDNP and [(18)F]FDG PET. Eur J Nucl Med Mol Imaging 39(6):990–1000

    CAS  PubMed  Google Scholar 

  • Owen DR, Howell OW, Tang SP, Wells LA et al (2010) Two binding sites for [3H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation. J Cereb Blood Flow Metab 30:1608–1618

    PubMed Central  PubMed  Google Scholar 

  • Owen DR, Gunn RN, Rabiner EA, Bennacef I et al (2011) Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med 52:24–32

    CAS  PubMed Central  PubMed  Google Scholar 

  • Panegyres PK, Rogers JM, McCarthy M, Campbell A, Wu JS (2009) Fluorodeoxyglucose-positron emission tomography in the differential diagnosis of early-onset dementia: a prospective, community-based study. BMC Neurol 9:41

    PubMed Central  PubMed  Google Scholar 

  • Papathanasiou ND, Boutsiadis A, Dickson J, Bomanji JB (2012) Diagnostic accuracy of 123I-FP-CIT (DaTSCAN) in dementia with Lewy bodies: a meta-analysis of published studies. Parkinsonism Relat Disord 18:225–229

    PubMed  Google Scholar 

  • Park DC, Reuter-Lorenz P (2009) The adaptive brain: aging and neurocognitive scaffolding. Annu Rev Psychol 60:173–196

    PubMed Central  PubMed  Google Scholar 

  • Perry E, Court J, Goodchild R, Griffiths M et al (1998) Clinical neurochemistry: developments in dementia research based on brain bank material. J Neural Transm 105:915–933

    CAS  PubMed  Google Scholar 

  • Petersen RC, Smith GE, Waring SC, Ivnik RJ et al (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308

    CAS  PubMed  Google Scholar 

  • Piggott MA, Marshall EF, Thomas N, Lloyd S et al (1999) Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer’s and Parkinson’s diseases: rostrocaudal distribution. Brain 122(Pt 8):1449–1468

    PubMed  Google Scholar 

  • Rabinovici GD, Rosen HJ, Alkalay A, Kornak J et al (2011) Amyloid vs FDG-PET in the differential diagnosis of AD and FTLD. Neurology 77:2034–2042

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rascovsky K, Hodges JR, Knopman D, Mendez MF et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–2477

    PubMed Central  PubMed  Google Scholar 

  • Reischle E, Sturm K, Schuierer G, Ibach B (2003) A case of schizophreniform disorder in frontotemporal dementia (FTD). Psychiatr Prax 30(Suppl 2):S78–S82

    PubMed  Google Scholar 

  • Resnick SM, Sojkova J, Zhou Y, An Y et al (2010) Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB. Neurology 74:807–815

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rinne J, Kaasinen V, Järvenpää T, Någren K et al (2003) Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease. J Neurol Neurosurg Psychiatry 74:113–115

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rocher AB, Chapon F, Blaizot X, Baron JC, Chavoix C (2003) Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons. Neuroimage 20:1894–1898

    PubMed  Google Scholar 

  • Román GC, Tatemichi TK, Erkinjuntti T, Cummings JL et al (1993) Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43:250–260

    PubMed  Google Scholar 

  • Roselli F, Pisciotta NM, Perneczky R, Pennelli M et al (2009) Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: a 123I-FP-CIT SPECT study. Mov Disord 24:2097–2103

    PubMed  Google Scholar 

  • Rosen AC, Prull MW, O’Hara R, Race EA et al (2002) Variable effects of aging on frontal lobe contributions to memory. Neuroreport 13:2425–2428

    PubMed  Google Scholar 

  • Rowe CC, Ellis KA, Rimajova M, Bourgeat P et al (2010) Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging 31:1275–1283

    PubMed  Google Scholar 

  • Rozemuller JM, Eikelenboom P, Pals ST, Stam FC (1989) Microglial cells around amyloid plaques in Alzheimer’s disease express leucocyte adhesion molecules of the LFA-1 family. Neurosci Lett 101:288–292

    CAS  PubMed  Google Scholar 

  • Salmon E, Garraux G, Delbeuck X, Collette F et al (2003) Predominant ventromedial frontopolar metabolic impairment in frontotemporal dementia. Neuroimage 20:435–440

    PubMed  Google Scholar 

  • Salmon E, Kerrouche N, Herholz K, Perani D et al (2006) Decomposition of metabolic brain clusters in the frontal variant of frontotemporal dementia. Neuroimage 30:871–878

    PubMed  Google Scholar 

  • Sánchez-Pernaute R, Ferree A, Cooper O, Yu M et al (2004) Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson’s disease. J Neuroinflammation 1:6

    PubMed Central  PubMed  Google Scholar 

  • Scheltens P, Leys D, Barkhof F, Huglo D et al (1992) Atrophy of medial temporal lobes on MRI in “probable” Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry 55:967–972

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schöll M, Wall A, Thordardottir S, Ferreira D et al (2012) Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers. Neurology 79:229–236

    PubMed  Google Scholar 

  • Schuitemaker A, Kropholler MA, Boellaard R, van der Flier WM et al (2012) Microglial activation in Alzheimer’s disease: an (R)-[(11)C]PK11195 positron emission tomography study. Neurobiol Aging 34:128–136

    PubMed  Google Scholar 

  • Silverman DH, Small GW, Chang CY, Lu CS et al (2001) Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA 286:2120–2127

    CAS  PubMed  Google Scholar 

  • Small G, Kepe V, Ercoli L, Siddarth P et al (2006) PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med 21:2652–2663

    Google Scholar 

  • Sperling RA, Aisen PS, Beckett LA, Bennett DA et al (2011) Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:280–292

    PubMed Central  PubMed  Google Scholar 

  • Storandt M, Mintun MA, Head D, Morris JC (2009) Cognitive decline and brain volume loss as signatures of cerebral amyloid-beta peptide deposition identified with Pittsburgh compound B: cognitive decline associated with Abeta deposition. Arch Neurol 66:1476–1481

    PubMed Central  PubMed  Google Scholar 

  • Streit WJ, Graeber MB, Kreutzberg GW (1988) Functional plasticity of microglia: a review. Glia 1:301–307

    CAS  PubMed  Google Scholar 

  • Streit WJ, Braak H, Xue QS, Bechmann I (2009) Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease. Acta Neuropathol 118:475–485

    PubMed Central  PubMed  Google Scholar 

  • Stubendorff K, Aarsland D, Minthon L, Londos E (2012) The impact of autonomic dysfunction on survival in patients with dementia with Lewy bodies and Parkinson’s disease with dementia. PLoS One 7:e45451

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suzuki M, Kurita A, Hashimoto M, Fukumitsu N et al (2006) Impaired myocardial 123I-metaiodobenzylguanidine uptake in Lewy body disease: comparison between dementia with Lewy bodies and Parkinson’s disease. J Neurol Sci 240:15–19

    CAS  PubMed  Google Scholar 

  • Taki J, Yoshita M, Yamada M, Tonami N (2004) Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson’s disease and related disorders: it can be a specific marker for Lewy body disease. Ann Nucl Med 18:453–461

    PubMed  Google Scholar 

  • Teune LK, Bartels AL, de Jong BM, Willemsen AT et al (2010) Typical cerebral metabolic patterns in neurodegenerative brain diseases. Mov Disord 25:2395–2404

    PubMed  Google Scholar 

  • Thaisetthawatkul P, Boeve BF, Benarroch EE, Sandroni P et al (2004) Autonomic dysfunction in dementia with Lewy bodies. Neurology 62:1804–1809

    CAS  PubMed  Google Scholar 

  • Thal DR, Rüb U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800

    PubMed  Google Scholar 

  • Tolboom N, van der Flier WM, Yaqub M, Boellaard R et al (2009a) Relationship of cerebrospinal fluid markers to 11C-PiB and 18F-FDDNP binding. J Nucl Med 50:1464–1470

    CAS  PubMed  Google Scholar 

  • Tolboom N, Yaqub M, van der Flier W, Boellaard R et al (2009b) Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET. J Nucl Med 50:191–197

    PubMed  Google Scholar 

  • Tolboom N, van der Flier WM, Boverhoff J, Yaqub M et al (2010) Molecular imaging in the diagnosis of Alzheimer’s disease: visual assessment of [11C]PIB and [18F]FDDNP PET images. J Neurol Neurosurg Psychiatry 81:882–884

    PubMed  Google Scholar 

  • Toru S, Uchihara T, Takahashi M, Ichihara K et al (2010) Depletion or preservation of cardiac sympathetic nerve – an autopsy-verified contrast in two cases of Alzheimer’s disease with or without Lewy bodies. Eur Neurol 64:129–133

    PubMed  Google Scholar 

  • Van Gool WA, Weinstein HC, Scheltens P, Walstra GJ, Scheltens PK (2001) Effect of hydroxychloroquine on progression of dementia in early Alzheimer’s disease: an 18-month randomised, double-blind, placebo-controlled study. Lancet 358:455–460

    PubMed  Google Scholar 

  • Van Laere K, Casteels C, De Ceuninck L, Vanbilloen B et al (2006) Dual-tracer dopamine transporter and perfusion SPECT in differential diagnosis of parkinsonism using template-based discriminant analysis. J Nucl Med 47:384–392

    PubMed  Google Scholar 

  • Vandenberghe R, Van Laere K, Ivanoiu A, Salmon E et al (2010) 18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial. Ann Neurol 68:319–329

    PubMed  Google Scholar 

  • Veerhuis R, Van Breemen MJ, Hoozemans JM, Morbin M et al (2003) Amyloid beta plaque-associated proteins C1q and SAP enhance the Abeta1-42 peptide-induced cytokine secretion by adult human microglia in vitro. Acta Neuropathol 105:135–144

    CAS  PubMed  Google Scholar 

  • Verwey NA, van der Flier WM, Blennow K, Clark C et al (2009) A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer’s disease. Ann Clin Biochem 46:235–240

    CAS  PubMed  Google Scholar 

  • Villemagne VL, McLean CA, Reardon K, Boyd A et al (2009) 11C-PiB PET studies in typical sporadic Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry 80:998–1001

    CAS  PubMed  Google Scholar 

  • Villemagne VL, Okamura N, Pejoska S, Drago J et al (2011a) In vivo assessment of vesicular monoamine transporter type 2 in dementia with Lewy bodies and Alzheimer disease. Arch Neurol 68:905–912

    PubMed  Google Scholar 

  • Villemagne VL, Pike KE, Chételat G, Ellis KA et al (2011b) Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease. Ann Neurol 69:181–192

    CAS  PubMed Central  PubMed  Google Scholar 

  • Villemagne VL, Okamura N, Pejoska S, Drago J et al (2012) Differential diagnosis in Alzheimer’s disease and dementia with Lewy bodies via VMAT2 and amyloid imaging. Neurodegener Dis 10:161–165

    CAS  PubMed  Google Scholar 

  • Vlassenko AG, Mintun MA, Xiong C, Sheline YI et al (2011) Amyloid-beta plaque growth in cognitively normal adults: longitudinal [11C]Pittsburgh compound B data. Ann Neurol 70:857–861

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walker Z, Costa P, Ince I, McKeith C et al (1999) In-vivo demonstration of dopaminergic degeneration in dementia with Lewy bodies. Lancet 354:646–647

    CAS  PubMed  Google Scholar 

  • Walker Z, Costa DC, Walker RW, Shaw K et al (2002) Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry 73:134–140

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walker Z, Jaros E, Walker RW, Lee L et al (2007) Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J Neurol Neurosurg Psychiatry 78:1176–1181

    PubMed Central  PubMed  Google Scholar 

  • Yaqub M, van Berckel BN, Schuitemaker A, Hinz R et al (2012) Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[(11)C]PK11195 brain PET studies. J Cereb Blood Flow Metab 32:1600–1608

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yoshita M, Taki J, Yokoyama K, Noguchi-Shinohara M et al (2006) Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD. Neurology 66:1850–1854

    CAS  PubMed  Google Scholar 

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Ossenkoppele, R., Booij, J., Scheltens, P., van Berckel, B.N.M. (2014). Dementia Due to Neurodegenerative Disease: Molecular Imaging Findings. In: Dierckx, R., Otte, A., de Vries, E., van Waarde, A., Leenders, K. (eds) PET and SPECT in Neurology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54307-4_9

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