Seminars in Nuclear Medicine
Volume 34, Issue 1 , Pages 70-82 , January 2004

Neurochemical imaging of dementias

  • Satoshi Minoshima

      Affiliations

    • Departments of Radiology and Bioengineering, University of Washington, Seattle, WA, USA
    • Corresponding Author InformationAddress reprint requests to Satoshi Minoshima, MD, PhD, Department of Radiology, University of Washington, Health Sciences Bldg., NW040J, 1959 N.E. Pacific St., Box 356004, Seattle, WA 98195-6004, USA
    • ,
  • Kirk A Frey

      Affiliations

    • Department of Radiology, University of Michigan, Ann Arbor, MI, USA
    • ,
  • Donna J Cross

      Affiliations

    • Washington National Primate Research Center, University of Washington, Seattle, WA, USA
    • ,
  • David E Kuhl

      Affiliations

    • Department of Radiology, University of Michigan, Ann Arbor, MI, USA

References 

  1. Folstein MF, Bassett SS, Anthony JC, et al.  Dementia (Case ascertainment in a community survey). J Gerontol. 1991;46:M132–M138
  2. Evans DA, Funkenstein HH, Albert MS, et al.  Prevalence of Alzheimer’s disease in a community population of older persons. Higher than previously reported. JAMA. 1989;262:2551–2556
  3. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998;88:1337–1342
  4. Hebert LE, Scherr PA, Bienias JL, et al.  Alzheimer disease in the US population (Prevalence estimates using the 2000 census). Arch Neurol. 2003;60:1119–1122
  5. Smith AL, Whitehouse PJ. Progress in the management of Alzheimer’s disease. Hosp Pract (Off Ed). 1998;33:151–154 157–166
  6. Ingvar D, Obrist W, Chivian E, et al.  General and regional abnormalities of cerebral blood flow in senile and “presenile” dementia. Scand J Clin Lab Invest Suppl. 1968;102: 12:B
  7. Simard D, Olesen J, Paulson OB, et al.  Regional cerebral blood flow and its regulation in dementia. Brain. 1971;94:273–288
  8. Sokoloff L, Reivich M, Kennedy C, et al.  The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization (Theory, procedure, and normal values in the conscious and anesthetized albino rat). J Neurochem. 1977;28:897–916
  9. Reivich M, Kuhl D, Wolf A, et al.  Measurement of local cerebral glucose metabolism in man with 18F-2-fluoro-2-deoxy-d-glucose. Acta Neurol Scand Suppl. 1977;64:190–191
  10. Reivich M, Alavi A, Wolf A, et al.  Use of 2-deoxy-D[1–11C]glucose for the determination of local cerebral glucose metabolism in humans (Variation within and between subjects). J Cereb Blood Flow Metab. 1982;2:307–319
  11. Farkas T, Ferris SH, Wolf AP, et al.  18F-2-deoxy-2-fluoro-D-glucose as a tracer in the positron emission tomographic study of senile dementia. Am J Psychiatry. 1982;139:352–353
  12. Kuhl DE, Phelps ME, Markham CH, et al.  Cerebral metabolism and atrophy in Huntington’s disease determined by 18FDG and computed tomographic scan. Ann Neurol. 1982;12:425–434
  13. Foster NL, Chase TN, Fedio P, et al.  Alzheimer’s disease (Focal cortical changes shown by positron emission tomography). Neurology. 1983;33:961–965
  14. 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;7:590–598
  15. Wagner HN, Burns HD, Dannals RF, et al.  Imaging dopamine receptors in the human brain by positron tomography. Science. 1983;221:1264–1266
  16. Garnett ES, Firnau G, Nahmias C. Dopamine visualized in the basal ganglia of living man. Nature. 1983;305:137–138
  17. Drayer B, Jaszczak R, Coleman E, et al.  Muscarinic cholinergic receptor binding (In vivo depiction using single photon emission computed tomography and radioiodinated quinuclidinyl benzilate). J Comput Assist Tomogr. 1982;6:536–543
  18. Eckelman WC, Reba RC, Rzeszotarski WJ, et al.  External imaging of cerebral muscarinic acetylcholine receptors. Science. 1984;223:291–293
  19. Klunk WE, Wang Y, Huang GF, et al.  Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain. Life Sci. 2001;69:1471–1484
  20. Mathis CA, Bacskai BJ, Kajdasz ST, et al.  A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain. Bioorg Med Chem Lett. 2002;12:295–298
  21. 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;10:24–35
  22. Phelps ME, Hoffman EJ, Raybaud C. Factors which affect cerebral uptake and retention of 13NH3. Stroke. 1977;8:694–702
  23. Oldendorf WH. Lipid solubility and drug penetration of the blood brain barrier. Proc Soc Exp Biol Med. 1974;147:813–815
  24. Alzheimer A. Uber einen eigenartigen schweren Erkrankungsprozeb der Hirnrinde. Neurologisches Centralblatt. Neurologisches Centralblatt. 1906;23:1129–1136
  25. Terry RD, Katzman R. Senile dementia of the Alzheimer type. Ann Neurol. 1983;14:497–506
  26. Fratiglioni L, Grut M, Forsell Y, et al.  Prevalence of Alzheimer’s disease and other dementias in an elderly urban population (relationship with age, sex, and education). Neurology. 1991;41:1886–1892
  27. Brun A. The pathology of presenile dementia related to cerebral blood flow. Lakartidningen. 1974;71:1290–1291
  28. Olesen J, Simard D, Paulson O, et al.  Focal cerebral blood flow, reactivity of cerebral blood vessels and cerebral oxydative metabolism in certain groups of patients with organic dementia. Acta Neurol Scand. 1970;46(suppl 43):76
  29. Drachman DA, Leavitt J. Human memory and the cholinergic system. A relationship to aging?. Arch Neurol. 1974;30:113–121
  30. Bowen DM, Smith CB, White P, et al.  Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain. 1976;99:459–496
  31. Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet. 1976;2:1403
  32. Kiyosawa M, Pappata S, Duverger D, et al.  Cortical hypometabolism and its recovery following nucleus basalis lesions in baboons (A PET study). J Cereb Blood Flow Metab. 1987;7:812–817
  33. Kiyosawa M, Baron JC, Hamel E, et al.  Time course of effects of unilateral lesions of the nucleus basalis of Meynert on glucose utilization by the cerebral cortex. Positron tomography in baboons. Brain. 1989;112:435–455
  34. Blin J, Piercey MF, Giuffra ME, et al.  Metabolic effects of scopolamine and physostigmine in human brain measured by positron emission tomography. J Neurol Sci. 1994;123:44–51
  35. Geaney DP, Soper N, Shepstone BJ, et al.  Effect of central cholinergic stimulation on regional cerebral blood flow in Alzheimer disease. Lancet. 1990;335:1484–1487
  36. Blin J, Ivanoiu A, Coppens A, et al.  Cholinergic neurotransmission has different effects on cerebral glucose consumption and blood flow in young normals, aged normals, and Alzheimer’s disease patients. Neuroimage. 1997;6:335–343
  37. Ebmeier KP, Hunter R, Curran SM, et al.  Effects of a single dose of the acetylcholinesterase inhibitor velnacrine on recognition memory and regional cerebral blood flow in Alzheimer’s disease. Psychopharmacology (Berl). 1992;108:103–109
  38. Holman BL, Gibson RE, Hill TC, et al.  Muscarinic acetylcholine receptors in Alzheimer’s disease. In vivo imaging with iodine 123-labeled 3-quinuclidinyl-4-iodobenzilate and emission tomography. JAMA. 1985;254:3063–3066
  39. Weinberger DR, Gibson R, Coppola R, et al.  The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia. A controlled study with 123IQNB and single photon emission computed tomography. Arch Neurol. 1991;48:169–176
  40. Weinberger DR, Jones D, Reba RC, et al.  A comparison of FDG PET and IQNB SPECT in normal subjects and in patients with dementia. J Neuropsychiatry Clin Neurosci. 1992;4:239–248
  41. Sunderland T, Esposito G, Molchan SE, et al.  Differential cholinergic regulation in Alzheimer’s patients compared to controls following chronic blockade with scopolamine (A SPECT study). Psychopharmacology (Berl). 1995;121:231–241
  42. Gibson RE, Moody T, Schneidau TA, et al.  The in vitro dissociation kinetics of (R, R)-[125I]4IQNB is reflected in the in vivo washout of the radioligand from rat brain. Life Sci. 1992;50:629–637
  43. Gibson RE, Weckstein DJ, Jagoda EM, et al.  The characteristics of I-125 4-IQNB and H-3 QNB in vivo and in vitro. J Nucl Med. 1984;25:214–222
  44. Sawada Y, Hiraga S, Francis B, et al.  Kinetic analysis of 3-quinuclidinyl 4-[125I]iodobenzilate transport and specific binding to muscarinic acetylcholine receptor in rat brain in vivo (Implications for human studies). J Cereb Blood Flow Metab. 1990;10:781–807
  45. Zubieta JK, Koeppe RA, Frey KA, et al.  Assessment of muscarinic receptor concentrations in aging and Alzheimer disease with [11C]NMPB and PET. Synapse. 2001;39:275–287
  46. Carson RE, Kiesewetter DO, Jagoda E, et al.  Muscarinic cholinergic receptor measurements with [18F]FP-TZTP (Control and competition studies). J Cereb Blood Flow Metab. 1998;18:1130–1142
  47. Nordberg A, Hartvig P, Lilja A, et al.  Nicotine receptors in the brain of patients with Alzheimer’s disease. Studies with 11C-nicotine and positron emission tomography. Acta Radiol Suppl. 1991;376:165–166
  48. Nordberg A, Lilja A, Lundqvist H, et al.  Tacrine restores cholinergic nicotinic receptors and glucose metabolism in Alzheimer patients as visualized by positron emission tomography. Neurobiol Aging. 1992;13:747–758
  49. Nordberg A. Effect of long-term treatment with tacrine (THA) in Alzheimer’s disease as visualized by PET. Acta Neurol Scand Suppl. 1993;149:62–65
  50. Olson L, Nordberg A, von Holst H, et al.  Nerve growth factor affects 11C-nicotine binding, blood flow, EEG, and verbal episodic memory in an Alzheimer patient (case report). J Neural Transm Park Dis Dement Sect. 1992;4:79–95
  51. Nordberg A, Lundqvist H, Hartvig P, et al.  Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains-In vivo assessment using positron emission tomography. Alzheimer Dis Assoc Disord. 1995;9:21–27
  52. Nordberg A, Lundqvist H, Hartvig P, et al.  Imaging of nicotinic and muscarinic receptors in Alzheimer’s disease (Effect of tacrine treatment). Dement Geriatr Cogn Disord. 1997;8:78–84
  53. Seiger A, Nordberg A, von Holst H, et al.  Intracranial infusion of purified nerve growth factor to an Alzheimer patient (the first attempt of a possible future treatment strategy). Behav Brain Res. 1993;57:255–261
  54. Sihver W, Langstrom B, Nordberg A. Ligands for in vivo imaging of nicotinic receptor subtypes in Alzheimer brain. Acta Neurol Scand Suppl. 2000;176:27–33
  55. Kuhl DE, Koeppe RA, Fessler JA, et al.  In vivo mapping of cholinergic neurons in the human brain using SPECT and IBVM. J Nucl Med. 1994;35:405–410
  56. Kuhl DE, Minoshima S, Fessler JA, et al.  In vivo mapping of cholinergic terminals in normal aging, Alzheimer’s disease, and Parkinson’s disease. Ann Neurol. 1996;40:399–410
  57. Frey KA, Minoshima S, Kuhl DE. Neurochemical imaging of Alzheimer’s disease and other degenerative dementias. Q J Nucl Med. 1998;42:166–178
  58. Namba H, Irie T, Fukushi K, et al.  In vivo measurement of acetylcholinesterase activity in the brain with a radioactive acetylcholine analog. Brain Res. 1994;667:278–282
  59. Irie T, Fukushi K, Namba H, et al.  Brain acetylcholinesterase activity (Validation of a PET tracer in a rat model of Alzheimer’s disease). J Nucl Med. 1996;37:649–655
  60. Kilbourn MR, Snyder SE, Sherman PS, et al.  In vivo studies of acetylcholinesterase activity using a labeled substrate, N-[11C]methylpiperdin-4-yl propionate ([11C]PMP). Synapse. 1996;22:123–131
  61. 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;349:1805–1809
  62. Kuhl DE, Koeppe RA, Minoshima S, et al.  In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer’s disease. Neurology. 1999;52:691–699
  63. Minoshima S, Cross DJ, Foster NL, et al.  Discordance between traditional pathologic and energy metabolic changes in very early Alzheimer’s disease. Pathophysiological implications. Ann N Y Acad Sci. 1999;893:350–352
  64. Minoshima S, Frey KA, Koeppe RA, et al.  A diagnostic approach in Alzheimer’s disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med. 1995;36:1238–1248
  65. Herholz K, Bauer B, Wienhard K, et al.  In-vivo measurements of regional acetylcholine esterase activity in degenerative dementia (Comparison with blood flow and glucose metabolism). J Neural Transm. 2000;107:1457–1468
  66. Namba H, Iyo M, Shinotoh H, et al.  Preserved acetylcholinesterase activity in aged cerebral cortex. Lancet. 1998;351:881–882
  67. 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;48:194–200
  68. Herholz K, Lercher M, Wienhard K, et al.  PET measurement of cerebral acetylcholine esterase activity without blood sampling. Eur J Nucl Med. 2001;28:472–477
  69. Tanaka N, Fukushi K, Shinotoh H, et al.  Positron emission tomographic measurement of brain acetylcholinesterase activity using N-[(11)C]methylpiperidin-4-yl acetate without arterial blood sampling (Methodology of shape analysis and its diagnostic power for Alzheimer’s disease). J Cereb Blood Flow Metab. 2001;21:295–306
  70. Kuhl DE, Minoshima S, Frey KA, et al.  Limited donepezil inhibition of acetylcholinesterase measured with PET in living Alzheimer cerebral cortex. Ann Neurol. 2000;48:391–395
  71. Perry EK, Haroutunian V, Davis KL, et al.  Neocortical cholinergic activities differentiate Lewy body dementia from classical Alzheimer’s disease. Neuroreport. 1994;5:747–749
  72. Garnett ES, Nahmias C, Firnau G. Central dopaminergic pathways in hemiparkinsonism examined by positron emission tomography. Can J Neurol Sci. 1984;11:174–179
  73. Leenders KL, Palmer AJ, Quinn N, et al.  Brain dopamine metabolism in patients with Parkinson’s disease measured with positron emission tomography. J Neurol Neurosurg Psychiatry. 1986;49:853–860
  74. Hagglund J, Aquilonius SM, Eckernas SA, et al.  Dopamine receptor properties in Parkinson’s disease and Huntington’s chorea evaluated by positron emission tomography using 11C-N-methyl-spiperone. Acta Neurol Scand. 1987;75:87–94
  75. Hagglund J, Aquilonius SM, Bergstrom K, et al.  Regional kinetics of [11C]methylspiperone in the brain studied by positron emission tomography in patients with Parkinson’s disease. Adv Neurol. 1987;45:99–101
  76. Sedvall G, Nyback H, Farde L, et al.  Neurotransmitter receptor imaging in Alzheimer’s disease. J Neural Transm Suppl. 1987;24:43–48
  77. Costa DC, Verhoeff NP, Cullum ID, et al.  In vivo characterisation of 3-iodo-6-methoxybenzamide 123I in humans. Eur J Nucl Med. 1990;16:813–816
  78. Snow BJ, Peppard RF, Guttman M, et al.  Positron emission tomographic scanning demonstrates a presynaptic dopaminergic lesion in Lytico-Bodig. The amyotrophic lateral sclerosis-parkinsonism-dementia complex of Guam. Arch Neurol. 1990;47:870–874
  79. Itoh M, Meguro K, Fujiwara T, et al.  Assessment of dopamine metabolism in brain of patients with dementia by means of 18F-fluorodopa and PET. Ann Nucl Med. 1994;8:245–251
  80. Liu Y, Stern Y, Chun MR, et al.  Pathological correlates of extrapyramidal signs in Alzheimer’s disease. Ann Neurol. 1997;41:368–374
  81. Tyrrell PJ, Sawle GV, Ibanez V, et al.  Clinical and positron emission tomographic studies in the ‘extrapyramidal syndrome’ of dementia of the Alzheimer type. Arch Neurol. 1990;47:1318–1323
  82. 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;47:1065–1068
  83. Rinne JO, Sahlberg N, Ruottinen H, et al.  Striatal uptake of the dopamine reuptake ligand [11C]beta-CFT is reduced in Alzheimer’s disease assessed by positron emission tomography. Neurology. 1998;50:152–156
  84. Kemppainen N, Ruottinen H, Nagren K, et al.  PET shows that striatal dopamine D1 and D2 receptors are differentially affected in AD. Neurology. 2000;55:205–209
  85. Lewy FH. Zur pathologischen Anatomie der Paralysis agitans. Dtsch Z Nervenheilk. 1913;50:50–55
  86. Lewy FH. Paralysis agitans: I. Pathologische anatomie. In:  Lewandowsky M editors. Handbuch der Neurologie. Berlin, Germany: Springer Verlag; 1912;p. 920–933
  87. Okazaki H, Lipkin LE, Aronson SM. Diffuse intracytoplasmic ganglionic inclusions (Lewy type) associated with progressive dementia and quadriparesis in flexion. J Neuropath Exp Neur. 1961;20:237–244
  88. Kosaka K, Oyanagi S, Matsushita M, et al.  Presenile dementia with Alzheimer-, Pick- and Lewy-body changes. Acta Neuropathol (Berl). 1976;36:221–233
  89. Kosaka K, Mehraein P. Dementia-Parkinsonism syndrome with numerous Lewy bodies and senile plaques in cerebral cortex. Arch Psychiatr Nervenkr. 1979;226:241–250
  90. McKeith LG, Galasko D, Kosaka K, et al.  Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) (Report of the consortium on DLB international workshop). Neurology. 1996;47:1113–1124
  91. Hansen LA, Masliah E, Galasko D, et al.  Plaque-only Alzheimer disease is usually the Lewy body variant, and vice versa. J Neuropathol Exp Neurol. 1993;52:648–654
  92. Donnemiller E, Heilmann J, Wenning GK, et al.  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. 1997;24:320–325
  93. Walker Z, Costa DC, Janssen AG, et al.  Dementia with lewy bodies (A study of post-synaptic dopaminergic receptors with iodine-123 iodobenzamide single-photon emission tomography). Eur J Nucl Med. 1997;24:609–614
  94. Walker Z, Costa DC, Ince P, et al.  In-vivo demonstration of dopaminergic degeneration in dementia with Lewy bodies. Lancet. 1999;354:646–647
  95. Hu XS, Okamura N, Arai H, et al.  18F-fluorodopa PET study of striatal dopamine uptake in the diagnosis of dementia with Lewy bodies. Neurology. 2000;55:1575–1577
  96. Hisanaga K, Suzuki H, Tanji H, et al.  Fluoro-DOPA and FDG positron emission tomography in a case of pathologically verified pure diffuse Lewy body disease. J Neurol. 2001;248:905–906
  97. Ransmayrl G, Seppi K, Donnemiller E, et al.  Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson’s disease. Eur J Nucl Med. 2001;28:1523–1528
  98. Walker Z, Costa DC, Walker RW, et al.  Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry. 2002;73:134–140
  99. Bhatt MH, Snow BJ, Martin WR, et al.  Positron emission tomography in progressive supranuclear palsy. Arch Neurol. 1991;48:389–391
  100. Frisoni GB, Pizzolato G, Bianchetti A, et al.  Single photon emission computed tomography with [99Tc]-HM-PAO and [123I]-IBZM in Alzheimer’s disease and dementia of frontal type (preliminary results). Acta Neurol Scand. 1994;89:199–203
  101. Rinne JO, Laine M, Kaasinen V, et al.  Striatal dopamine transporter and extrapyramidal symptoms in frontotemporal dementia. Neurology. 2002;58:1489–1493
  102. Brooks DJ, Ibanez V, Playford ED, et al.  Presynaptic and postsynaptic striatal dopaminergic function in neuroacanthocytosis (A positron emission tomographic study). Ann Neurol. 1991;30:166–171
  103. Backman L, Robins-Wahlin TB, Lundin A, et al.  Cognitive deficits in Huntington’s disease are predicted by dopaminergic PET markers and brain volumes. Brain. 1997;120:2207–2217
  104. Meyer M, Koeppe RA, Frey KA, et al.  Positron emission tomography measures of benzodiazepine binding in Alzheimer’s disease. Arch Neurol. 1995;52:314–317
  105. Schubiger PA, Hasler PH, Beer-Wohlfahrt H, et al.  Evaluation of a multicentre study with Iomazenil-A benzodiazepine receptor ligand. Nucl Med Commun. 1991;12:569–582
  106. 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;23:1323–1328
  107. 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;38:467–470
  108. Varrone A, Soricelli A, Postiglione A, et al.  Comparison between cortical distribution of I-123 iomazenil and Tc-99m HMPAO in patients with Alzheimer’s disease using SPECT. Clin Nucl Med. 1999;24:660–665
  109. Ohyama M, Senda M, Ishiwata K, et al.  Preserved benzodiazepine receptors in Alzheimer’s disease measured with C-11 flumazenil PET and I-123 iomazenil SPECT in comparison with CBF. Ann Nucl Med. 1999;13:309–315
  110. Lloyd GK, Lowenthal A, Javoy-Agid F, et al.  GABAA receptor complex function in frontal cortex membranes from control and neurological patients. Eur J Pharmacol. 1991;197:33–39
  111. Vogt BA, Plager MD, Crino PB, et al.  Laminar distributions of muscarinic acetylcholine, serotonin, GABA and opioid receptors in human posterior cingulate cortex. Neuroscience. 1990;36:165–174
  112. McGeer PL, Akiyama H, Itagaki S, et al.  Immune system response in Alzheimer’s disease. Can J Neurol Sci. 1989;16:516–527
  113. McGeer PL, Itagaki S, Tago H, et al.  Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett. 1987;79:195–200
  114. McGeer PL, Rogers J. Anti-inflammatory agents as a therapeutic approach to Alzheimer’s disease. Neurology. 1992;42:447–449
  115. Groom GN, Junck L, Foster NL, et al.  PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer’s disease. J Nucl Med. 1995;36:2207–2210
  116. Cagnin A, Brooks DJ, Kennedy AM, et al.  In-vivo measurement of activated microglia in dementia. Lancet. 2001;358:461–467
  117. 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;116:497–510
  118. Meltzer CC, Price JC, Mathis CA, et al.  PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Am J Psychiatry. 1999;156:1871–1878
  119. Meltzer CC, Smith G, DeKosky ST, et al.  Serotonin in aging, late-life depression, and Alzheimer’s disease (The emerging role of functional imaging). Neuropsychopharmacology. 1998;18:407–430
  120. Cohen RM, Andreason PJ, Doudet DJ, et al.  Opiate receptor avidity and cerebral blood flow in Alzheimer’s disease. J Neurol Sci. 1997;148:171–180
  121. Cohen RM, Carson RE, Sunderland T. Opiate receptor avidity in the thalamus is sexually dimorphic in the elderly. Synapse. 2000;38:226–229
  122. Davis KL, Mohs RC, Marin D, et al.  Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA. 1999;281:1401–1406
  123. Le Mestric C, Chavoix C, Chapon F, et al.  Effects of damage to the basal forebrain on brain glucose utilization (A reevaluation using positron emission tomography in baboons with extensive unilateral excitotoxic lesion). J Cereb Blood Flow Metab. 1998;18:476–490
  124. Meguro K, Blaizot X, Kondoh Y, et al.  Neocortical and hippocampal glucose hypometabolism following neurotoxic lesions of the entorhinal and perirhinal cortices in the non-human primate as shown by PET. Implications for Alzheimer’s disease. Brain. 1999;122:1519–1531
  125. Mohanakrishnan P, Fowler AH, Vonsattel JP, et al.  An in vitro 1H nuclear magnetic resonance study of the temporoparietal cortex of Alzheimer brains. Exp Brain Res. 1995;102:503–510
  126. Brown DR, Wyper DJ, Owens J, et al.  123Iodo-MK-801 (A spect agent for imaging the pattern and extent of glutamate (NMDA) receptor activation in Alzheimer’s disease). J Psychiatr Res. 1997;31:605–619
  127. Alavi A, Hirsch LJ. Studies of central nervous system disorders with single photon emission computed tomography and positron emission tomography (Evolution over the past 2 decades). Semin Nucl Med. 1991;21:58–81
  128. Minoshima S, Giordani B, Berent S, et al.  Metabolic reduction in the posterior cingulate cortex in very early Alzheimer’s disease. Ann Neurol. 1997;42:85–94
  129. 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;334:752–758
  130. Mielke R, Pietrzyk U, Jacobs A, et al.  HMPAO SPET and FDG PET in Alzheimer’s disease and vascular dementia (Comparison of perfusion and metabolic pattern). Eur J Nucl Med. 1994;21:1052–1060
  131. Salmon E, Sadzot B, Maquet P, et al.  Differential diagnosis of Alzheimer’s disease with PET. J Nucl Med. 1994;35:391–398
  132. Herholz K. FDG PET and differential diagnosis of dementia. Alzheimer Dis Assoc Disord. 1995;9:6–16
  133. Schenk D, Barbour R, Dunn W, et al.  Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999;400:173–177
  134. Tsai JY, Wolfe MS, Xia W. The search for gamma-secretase and development of inhibitors. Curr Med Chem. 2002;9:1087–1106
  135. Nordberg A. Clinical studies in Alzheimer patients with positron emission tomography. Behav Brain Res. 1993;57:215–224
  136. Mielke R, Moller HJ, Erkinjuntti T, et al.  Propentofylline in the treatment of vascular dementia and Alzheimer-type dementia (Overview of phase I and phase II clinical trials). Alzheimer Dis Assoc Disord. 1998;12(suppl 2):S29–S35
  137. Cutler NR, Sramek JJ. Review of the next generation of Alzheimer’s disease therapeutics (Challenges for drug development). Prog Neuropsychopharmacol Biol Psychiatry. 2001;25:27–57

☆ This work was supported by NIH grants RO1-NS24896, PO1-NS15655, and RO1 NS045254.

PII: S0001-2998(03)00074-6

doi: 10.1053/j.semnuclmed.2003.09.008

Seminars in Nuclear Medicine
Volume 34, Issue 1 , Pages 70-82 , January 2004

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