Skip to main content
×
Home
    • Aa
    • Aa

The diagnosis and evaluation of dementia and mild cognitive impairment with emphasis on SPECT perfusion neuroimaging

  • Theodore A. Henderson (a1)
Abstract

As the world population ages, the incidence of dementing illnesses will dramatically increase. The number of people afflicted with dementia is expected to quadruple in the next 50 years. Since the neuropathology of the dementias precedes clinical symptoms often by several years, earlier detection and intervention could be key steps to mitigating the progression and burden of these diseases. This review will explore methods of evaluating, differentiating, and diagnosing the multiple forms of dementia. Particular emphasis will be placed on the diagnosis of mild cognitive impairment—the precursor to dementia. Anatomical imaging; cerebrospinal fluid markers; functional neuroimaging, such as positron emission tomography and single photon emission tomography; and molecular imaging, such as amyloid marker imaging, will be assessed in terms of sensitivity and specificity. Cost will also be a consideration, as the growing population afflicted with dementia represents an increasingly large financial encumbrance to the healthcare systems of every nation. In the face of expensive new markers and limited availability of cyclotrons, single photon emission computer tomography (SPECT) provides relatively high sensitivity and specificity at a comparatively low overall cost.

Copyright
Corresponding author
*Address for correspondence: Theodore A. Henderson, MD, PhD, The Synaptic Space, 3979 E. Arapahoe Road, Suite 200, Centennial, CO 80112. (Email Drted2u@drted2u.cnc.net)
References
Hide All
1.Cummings JL. The Neuropsychiatry of Alzheimer's Disease and Related Dementias. London: Martin Dunitz, Ltd; 2003.
2.Ferri CP, Prince M, Brayne C, etal. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005; 366(9503): 21122117.
3.Jorm AF. Cross-national comparisons of the occurrence of Alzheimer's and vascular dementias. Eur Arch Psychiatry Clin Neurosci. 1991; 240(4–5): 218222.
4.Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol. 2003; 60(8): 11191122.
5.Small GW. What does imaging add to the management of Alzheimer's disease? CNS Spectr. 2004; 9(7 Suppl 5): 2023.
6.Silverman DH, Small GW, Chang CY, etal. Positron emission tomography in evaluation of dementia: regional brain metabolism and long-term outcome. JAMA. 2001; 286(17): 21202127.
7. Kantarci K, Kemp BJ, Lowe VL. Glucose metabolic patterns in amnestic mild cognitive impairment and Alzheimer's disease: an FDG-PET study. 9th International Conference on Alzheimer's Disease and Related Disorders; July 17, 2004; Philadelphia, PA.
8.Bonte FJ, Weiner MF, Bigio EH, White CL III. Brain blood flow in the dementias: SPECT with histopathologic correlation in 54 patients. Radiology. 1997; 202(3): 793797.
9.Camargo EE. Brain SPECT in neurology and psychiatry. J Nucl Med. 2001; 42(4): 611623.
10.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): 594607.
11.Villemagne VL, Ong K, Mulligan RS, etal. Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias. J Nucl Med. 2011; 52(8): 12101217.
12.Bohnen NI, Djang DS, Herholz K, Anzai Y, Minoshima S. Effectiveness and safety of 18F-FDG PET in the evaluation of dementia: a review of the recent literature. J Nucl Med. 2012; 53(1): 5971.
13. Pavel D, Devore-Best S, Craita I. Routine use of high resolution brain SPECT and multiple display modes for dementia differential and follow-up. 9th International Conference on Alzheimer's Disease and Related Disorders; July 17, 2004; Philadelphia, PA.
14.Foster NL, Heidebrink JL, Clark CM, etal. FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. Brain. 2007; 130(Pt 10): 26162635.
15.Lim SM, Katsifis A, Villemagne VL, etal. The 18F-FDG PET cingulate island sign and comparison to 123I-beta-CIT SPECT for diagnosis of dementia with Lewy bodies. J Nucl Med. 2009; 50(10): 16381645.
16.Nobili F, Frisoni GB, Portet F, etal. Brain SPECT in subtypes of mild cognitive impairment: findings from the DESCRIPA multicenter study. J Neurol. 2008; 255(9): 13441353.
17.Rowe CC, Villemagne VL. Brain amyloid imaging. J Nucl Med. 2011; 52(11): 17331740.
18.Pickut BA, Saerens J, Marien P, etal. Discriminative use of SPECT in frontal lobe-type dementia versus (senile) dementia of the Alzheimer's type. J Nucl Med. 1997; 38(6): 929934.
19.Van Heertum RL, Drocea C, Ichise M, Lobotesis K, Fawwaz RA. Single photon emission CT and positron emission tomography in the evaluation of neurologic disease. Radiol Clin North Am. 2001; 39(5): 10071033.
20.Miller BL, Cummings JL, Villanueva-Meyer J, etal. Frontal lobe degeneration: clinical, neuropsychological, and SPECT characteristics. Neurology. 1991; 41(9): 13741382.
21.Villemagne VL, Pike KE, Chetelat G, etal. Longitudinal assessment of Abeta and cognition in aging and Alzheimer disease. Ann Neurol. 2011; 69(1): 181192.
22.Jack CR Jr; Wiste HJ, Vemuri P, etal. Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease. Brain. 2010; 133(11): 33363348.
23.Kantarci K, Jack CR Jr. Neuroimaging in Alzheimer disease: an evidence-based review. Neuroimaging Clin N Am. 2003; 13(2): 197209.
24.Mistur R, Mosconi L, Santi SD, etal. Current challenges for the early detection of Alzheimer's disease: brain imaging and CSF studies. J Clin Neurol. 2009; 5(4): 153166.
25.Jagust W, Thisted R, Devous MD Sr., etal. SPECT perfusion imaging in the diagnosis of Alzheimer's disease: a clinical-pathologic study. Neurology. 2001; 56(7): 950956.
26.Samuels SC, Grossman H. Emerging therapeutics for Alzheimer's disease: an avenue of hope. CNS Spectr. 2003; 8(11): 834845.
27.Jellinger KA, Bancher C. Neuropathology of Alzheimer's disease: a critical update. J Neural Transm Suppl. 1998; 54: 7795.
28.Price JL, Davis PB, Morris JC, White DL. The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol Aging. 1991; 12(4): 295312.
29.Mirra SS, Heyman A, McKeel D, etal. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II: standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991; 41(4): 479486.
30.Rozemuller JM, Stam FC, Eikelenboom P. Acute phase proteins are present in amorphous plaques in the cerebral but not in the cerebellar cortex of patients with Alzheimer's disease. Neurosci Lett. 1990; 119(1): 7578.
31.Le TV, Crook R, Hardy J, Dickson DW. Cotton wool plaques in non-familial late-onset Alzheimer disease. J Neuropathol Exp Neurol. 2001; 60(11): 10511061.
32.McKhann G, Drachman D, Folstein M, etal. 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. 1984; 34(7): 939944.
33.Dubois B, Feldman HH, Jacova C, etal. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007; 6(8): 734746.
34.Knopman DS, DeKosky ST, Cummings JL, etal. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001; 56(9): 11431153.
35.Jagust W, Reed B, Mungas D, Ellis W, DeCarli C. What does fluorodeoxyglucose PET imaging add to a clinical diagnosis of dementia? Neurology. 2007; 69(9): 871877.
36.Hardy J. Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci. 1997; 20(4): 154159.
37.Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer's disease. Neuron. 2009; 63(3): 287303.
38.Ravona-Springer R, Davidson M, Noy S. The role of cardiovascular risk factors in Alzheimer's disease. CNS Spectr. 2003; 8(11): 824833.
39.Wu CC, Mungas D, Eberling JL, Reed BR, Jagust WJ. Imaging Interactions between Alzheimer's disease and cerebrovascular disease. Ann N Y Acad Sci. 2002; 977: 403410.
40.Hanyu H, Shimuzu S, Tanaka Y, etal. Cerebral blood flow patterns in Binswanger's disease: a SPECT study using three-dimensional stereotactic surface projections. J Neurol Sci. 2004; 220(1–2): 7984.
41.Talbot PR, Goulding PJ, Lloyd JJ, etal. Inter-relation between “classic” motor neuron disease and frontotemporal dementia: neuropsychological and single photon emission computed tomography study. J Neurol Neurosurg Psychiatry. 1995; 58(5): 541547.
42.Tranfaglia C, Palumbo B, Siepi D, Sinzinger H, Parnetti L. Semi-quantitative analysis of perfusion of Brodmann areas in the differential diagnosis of cognitive impairment in Alzheimer's disease, fronto-temporal dementia and mild cognitive impairment. Hell J Nucl Med. 2009; 12(2): 110114.
43.Pickering-Brown SM, Baker M, Nonaka T, etal. Frontotemporal dementia with Pick-type histology associated with Q336R mutation in the tau gene. Brain. 2004; 127(Pt 6): 14151426.
44.Bronner IF, ter Meulen BC, Azmani A, etal. Hereditary Pick's disease with the G272 V tau mutation shows predominant three-repeat tau pathology. Brain. 2005; 128(Pt 11): 26452653.
45.Tateno M, Kobayashi S, Saito T. Imaging improves diagnosis of dementia with Lewy bodies. Psychiatry Investigation. 2009; 6(4): 233240.
46.Tateno M, Kobayashi S, Shirasaka T, etal. Comparison of the usefulness of brain perfusion SPECT and MIBG myocardial scintigraphy for the diagnosis of dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2008; 26(5): 453457.
47.Yoshita M, Taki J, Yokoyama K, etal. Value of 123I-MIBG radioactivity in the differential diagnosis of DLB from AD. Neurology. 2006; 66(12): 18501854.
48.Tateno F, Sakakibara R, Kishi M, etal. Sensitivity and specificity of metaiodobenzylguanidine (MIBG) myocardial accumulation in the diagnosis of Lewy body diseases in a movement disorder clinic. Parkinsonism Relat Disord. 2011; 17(5): 395397.
49.Fann JR, Burington B, Leonetti A, etal. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry. 2004; 61(1): 5361.
50.Guskiewicz KM, Marshall SW, Bailes J, etal. Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc. 2007; 39(6): 903909.
51.Guskiewicz KM, Marshall SW, Bailes J, etal. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005; 57(4): 719726.
52.McKee AC, Cantu RC, Nowinski CJ, etal. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 2009; 68(7): 709735.
53.Omalu BI, Hamilton RL, Kamboh MI, DeKosky ST, Bailes J. Chronic traumatic encephalopathy (CTE) in a National Football League Player: case report and emerging medicolegal practice questions. J Forensic Nurs. 2010; 6(1): 4046.
54.Omalu BI, DeKosky ST, Hamilton RL, etal. Chronic traumatic encephalopathy in a National Football League player: part II. Neurosurgery. 2006; 59(5): 10861092.
55.Omalu BI, DeKosky ST, Minster RL, etal. Chronic traumatic encephalopathy in a National Football League player. Neurosurgery. 2005; 57(1): 128134.
56. Schwarz A. Dementia risk seen in players in NFL study. The New York Times. 2009, Sep. 30.
57. Henderson TA. Traumatic brain injury in professional American football players. 2012. Unpublished work.
58.Amen DG, Newberg A, Thatcher R, etal. Impact of playing American professional football on long-term brain function. J Neuropsychiatry Clin Neurosci. 2011; 23(1): 98106.
59.Lopez OL, Jagust WJ, DeKosky ST, etal. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Arch Neurol. 2003; 60(10): 13851389.
60.Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004; 256(3): 183194.
61.Bennett DA, Wilson RS, Schneider JA, etal. Natural history of mild cognitive impairment in older persons. Neurology. 2002; 59(2): 198205.
62.Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology. 2006; 67(3): 441445.
63.Trojanowski JQ, Vandeerstichele H, Korecka M, etal. Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects. Alzheimers Dement. 2010; 6(3): 230238.
64. Henderson TA. Neuroimaging updates on dementias and parkinsonian syndromes. Society of Nuclear Medicine Webinar, April 19, 2012. http://interactive.snm.org/index.cfm?PageID=9162.
65.Jack CR Jr., Knopman DS, Jagust WJ, etal. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010; 9(1): 119128.
66.Fagan AM, Holtzman DM. Cerebrospinal fluid biomarkers of Alzheimer's disease. Biomark Med. 2010; 4(1): 5163.
67.Mattsson N, Blennow K, Zetterberg H. CSF biomarkers: pinpointing Alzheimer pathogenesis. Ann N Y Acad Sci. 2009; 1180: 2835.
68.Aluise CD, Sowell RA, Butterfield DA. Peptides and proteins in plasma and cerebrospinal fluid as biomarkers for the prediction, diagnosis, and monitoring of therapeutic efficacy of Alzheimer's disease. Biochim Biophys Acta. 2008; 1782(10): 549558.
69.Blennow K. Cerebrospinal fluid protein biomarkers for Alzheimer's disease. NeuroRx. 2004; 1(2): 213225.
70.Blennow K, de Leon MJ, Zetterberg H. Alzheimer's disease. Lancet. 2006; 368(9533): 387403.
71.Blennow K, Hampel H. CSF markers for incipient Alzheimer's disease. Lancet Neurol. 2003; 2(10): 605613.
72.Hertze J, Minthon L, Zetterberg H, Vanmechelen E, Blennow K, Hansson O. Evaluation of CSF biomarkers as predictors of Alzheimer's disease: a clinical follow-up study of 4.7 years. J Alzheimers Dis. 2010; 21(4): 11191128.
73.Humpel C. Identifying and validating biomarkers for Alzheimer's disease. Trends Biotechnol. 2011; 29(1): 2632.
74.Mollenhauer B, Bibl M, Trenkwalder C, etal. Follow-up investigations in cerebrospinal fluid of patients with dementia with Lewy bodies and Alzheimer's disease. J Neural Transm. 2005; 112(7): 933948.
75.Arai H, Morikawa Y, Higuchi M, etal. Cerebrospinal fluid tau levels in neurodegenerative diseases with distinct tau-related pathology. Biochem Biophys Res Commun. 1997; 236(2): 262264.
76.Hesse C, Rosengren L, Andreasen N, etal. Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke. Neurosci Lett. 2001; 297(3): 187190.
77.Andreasen N, Vanmechelen E, Van d V, etal. Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease: a community based follow up study. J Neurol Neurosurg Psychiatry. 1998; 64(3): 298305.
78.Parnetti L, Lanari A, Amici S, etal. CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies. Phospho-Tau International Study Group. Neurol Sci. 2001; 22(1): 7778.
79.Buerger K, Zinkowski R, Teipel SJ, etal. Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol. 2002; 59(8): 12671272.
80.Buerger K, Zinkowski R, Teipel SJ, etal. Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. Am J Psychiatry. 2003; 160(2): 376379.
81.Buerger K, Ewers M, Pirttila T, etal. CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer's disease. Brain. 2006; 129(Pt 11): 30353041.
82.Hampel H, Buerger K, Zinkowski R, etal. Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheimer disease: a comparative cerebrospinal fluid study. Arch Gen Psychiatry. 2004; 61(1): 95102.
83.de Leon MJ, DeSanti S, Zinkowski R, etal. Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Neurobiol Aging. 2006; 27(3): 394401.
84.Strozyk D, Blennow K, White LR, Launer LJ. CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology. 2003; 60(4): 652656.
85.Andreasen N, Minthon L, Vanmechelen E, etal. Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment. Neurosci Lett. 1999; 273(1): 58.
86.Hansson O, Zetterberg H, Buchhave P, etal. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006; 5(3): 228234.
87.Okonkwo OC, Mielke MM, Griffith HR, etal. Cerebrospinal fluid profiles and prospective course and outcome in patients with amnestic mild cognitive impairment. Arch Neurol. 2011; 68(1): 113119.
88.Tapiola T, Pirttila T, Mikkonen M, etal. Three-year follow-up of cerebrospinal fluid tau, beta-amyloid 42 and 40 concentrations in Alzheimer's disease. Neurosci Lett. 2000; 280(2): 119122.
89.Mollenhauer B, Cepek L, Bibl M, etal. Tau protein, Abeta42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2005; 19(2–3): 164170.
90.Andreasen N, Minthon L, Davidsson P, etal. Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice. Arch Neurol. 2001; 58(3): 373379.
91.Kapaki E, Paraskevas GP, Papageorgiou SG, etal. Diagnostic value of CSF biomarker profile in frontotemporal lobar degeneration. Alzheimer Dis Assoc Disord. 2008; 22(1): 4753.
92.Clifford DB, Fagan AM, Holtzman DM, etal. CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease. Neurology. 2009; 73(23): 19821987.
93.Fagan AM, Mintun MA, Mach RH, etal. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006; 59(3): 512519.
94.Pratico D. F(2)-isoprostanes: sensitive and specific non-invasive indices of lipid peroxidation in vivo. Atherosclerosis. 1999; 147(1): 110.
95.Montine TJ, Markesbery WR, Zackert W, etal. The magnitude of brain lipid peroxidation correlates with the extent of degeneration but not with density of neuritic plaques or neurofibrillary tangles or with APOE genotype in Alzheimer's disease patients. Am J Pathol. 1999; 155(3): 863868.
96.Pratico D, Clark CM, Liun F, etal. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol. 2002; 59(6): 972976.
97.Montine TJ, Kaye JA, Montine KS, etal. Cerebrospinal fluid abeta42, tau, and f2-isoprostane concentrations in patients with Alzheimer disease, other dementias, and in age-matched controls. Arch Pathol Lab Med. 2001; 125(4): 510512.
98.Grossman M, Farmer J, Leight S, etal. Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease. Ann Neurol. 2005; 57(5): 721729.
99.Yao Y, Zhukareva V, Sung S, etal. Enhanced brain levels of 8, 12-iso-iPF2alpha-VI differentiate AD from frontotemporal dementia. Neurology. 2003; 61(4): 475478.
100.Johansson P, Mattsson N, Hansson O, etal. Cerebrospinal fluid biomarkers for Alzheimer's disease: diagnostic performance in a homogeneous mono-center population. J Alzheimers Dis. 2011; 24(3): 537546.
101.Maddalena A, Papassotiropoulos A, Muller-Tillmanns B, etal. Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42. Arch Neurol. 2003; 60(9): 12021206.
102.Forlenza OV, Diniz BS, Gattaz WF. Diagnosis and biomarkers of predementia in Alzheimer's disease. BMC Med. 2010; 8: 89.
103.Li G, Sokal I, Quinn JF, etal. CSF tau/Abeta42 ratio for increased risk of mild cognitive impairment: a follow-up study. Neurology. 2007; 69(7): 631639.
104.Atiya M, Hyman BT, Albert MS, Killiany R. Structural magnetic resonance imaging in established and prodromal Alzheimer disease: a review. Alzheimer Dis Assoc Disord. 2003; 17(3): 177195.
105.Rusinek H, De SS, Frid D, etal. Regional brain atrophy rate predicts future cognitive decline: 6-year longitudinal MR imaging study of normal aging. Radiology. 2003; 229(3): 691696.
106.Fox NC, Warrington EK, Rossor MN. Serial magnetic resonance imaging of cerebral atrophy in preclinical Alzheimer's disease. Lancet. 1999; 353(9170): 2125.
107.Capizzano AA, Acion L, Bekinschtein T, etal. White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2004; 75(6): 822827.
108. Fennema-Notestine C, Archibald SL, Gamst AC, et al. Regional distribution of white matter changes in Alzheimer's disease. 9th International Conference on Alzheimer's Disease and Related Disorders; July 17, 2004; Philadelphia, PA.
109.Bonte FJ, Harris TS, Roney CA, Hynan LS. Differential diagnosis between Alzheimer's and frontotemporal disease by the posterior cingulate sign. J Nucl Med. 2004; 45(5): 771774.
110.Du AT, Schuff N, Amend D, etal. Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2001; 71(4): 441447.
111.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): 139145.
112.Duara R, Loewenstein DA, Potter E, etal. Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease. Neurology. 2008; 71(24): 19861992.
113.DeCarli C, Frisoni GB, Clark CM, etal. Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia. Arch Neurol. 2007; 64(1): 108115.
114.Whitwell JL, Przybelski SA, Weigand SD, etal. 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): 17771786.
115.Nagy Z, Hindley NJ, Braak H, etal. Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by “stages”: a prospective study. Dement Geriatr Cogn Disord. 1999; 10(2): 109114.
116.Du AT, Schuff N, Zhu XP, etal. Atrophy rates of entorhinal cortex in AD and normal aging. Neurology. 2003; 60(3): 481486.
117.Ferreira LK, Diniz BS, Forlenza OV, Busatto GF, Zanetti MV. Neurostructural predictors of Alzheimer's disease: a meta-analysis of VBM studies. Neurobiol Aging. 2011; 32(10): 17331741.
118.Hanggi J, Streffer J, Jancke L, Hock C. Volumes of lateral temporal and parietal structures distinguish between healthy aging, mild cognitive impairment, and Alzheimer's disease. J Alzheimers Dis. 2011; 26(4): 719734.
119.Thompson PM, Hayashi KM, Dutton RA, etal. Tracking Alzheimer's disease. Ann N Y Acad Sci. 2007; 1097: 183214.
120.Colliot O, Chetelat G, Chupin M, etal. Discrimination between Alzheimer disease, mild cognitive impairment, and normal aging by using automated segmentation of the hippocampus. Radiology. 2008; 248(1): 194201.
121.Chetelat G, Landeau B, Eustache F, etal. Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: a longitudinal MRI study. Neuroimage. 2005; 27(4): 934946.
122.Desikan RS, Sabuncu MR, Schmansky NJ, etal. Selective disruption of the cerebral neocortex in Alzheimer's disease. PLoS One. 2010; 5(9): e12853.
123.Thurfjell L, Lotjonen J, Lundqvist R, etal. Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment. Neurodegener Dis. 2012; 10(1–4): 246249.
124.McKinnon MC, Yucel K, Nazarov A, MacQueen GM. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci. 2009; 34(1): 4154.
125.Bremner JD. The relationship between cognitive and brain changes in posttraumatic stress disorder. Ann N Y Acad Sci. 2006; 1071: 8086.
126.Hedges DW, Woon FL. Alcohol use and hippocampal volume deficits in adults with posttraumatic stress disorder: a meta-analysis. Biol Psychol. 2010; 84(2): 163168.
127.Woon FL, Sood S, Hedges DW. Hippocampal volume deficits associated with exposure to psychological trauma and posttraumatic stress disorder in adults: a meta-analysis. Prog Neuropsychopharmacol Biol Psychiatry. 2010; 34(7): 11811188.
128.Agartz I, Momenan R, Rawlings RR, Kerich MJ, Hommer DW. Hippocampal volume in patients with alcohol dependence. Arch Gen Psychiatry. 1999; 56(4): 356363.
129.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): 28052807.
130.Klunk WE, Engler H, Nordberg A, etal. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004; 55(3): 306319.
131.Pike KE, Savage G, Villemagne VL, etal. Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain. 2007; 130(Pt 11): 28372844.
132.Cairns NJ, Ikonomovic MD, Benzinger T, etal. Absence of Pittsburgh compound B detection of cerebral amyloid beta in a patient with clinical, cognitive, and cerebrospinal fluid markers of Alzheimer disease: a case report. Arch Neurol. 2009; 66(12): 15571562.
133.Mintun MA, LaRossa GN, Sheline YI, etal. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006; 67(3): 446452.
134.Rowe CC, Ng S, Ackermann U, etal. Imaging beta-amyloid burden in aging and dementia. Neurology. 2007; 68(20): 17181725.
135.Villemagne VL, Chetelat G, Pike K, Rowe CC. Comparison of biomarkers for the prediction of cognitive decline. Alzheimers Dement. 2010; 6(4): S139.
136.Lockhart A, Lamb JR, Osredkar T, etal. PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. Brain. 2007; 130(Pt 10): 26072615.
137.Mok V, Leung EY, Chu W, etal. Pittsburgh compound B binding in poststroke dementia. J Neurol Sci. 2010; 290(1–2): 135137.
138.Gomperts SN, Rentz DM, Moran E, etal. Imaging amyloid deposition in Lewy body diseases. Neurology. 2008; 71(12): 903910.
139.Masters CL, Villemagne V, McLean C. 11C-PiB-postmortem: a plaque load correlation. Alzheimers Dement. 2010; 6(4): S234.
140.Villemagne VL, Rowe CC. Amyloid imaging. Int Psychogeriatr. 2011; 23 Suppl 2: S41S49.
141.Okello A, Koivunen J, Edison P, etal. Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. Neurology. 2009; 73(10): 754760.
142.Mintun MA, Vlasenko A, Sheline YI, Morris JC. Longitudinal PIB PET imaging of the appearance and accumulation of beta-amyloid in cognitively normal middle and late life adults. Alzheimers Dement. 2010; 6(4): S2.
143.Rowe CC. Standardization of amyloid imaging. Alzheimers Dement. 2010; 6(4): S87.
144.Chetelat G, Villemagne V, Bourgeat P, etal. Relationship between atrophy and beta-amyloid deposition in normal elderly, mild cognitive impairment and Alzheimer's disease. Alzheimers Dement. 2010; 6(4): S45.
145. Leung K. 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile. Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004–2011. 2005 Jul 25 [updated 2011 Jun 26].
146.Small GW, Kepe V, Ercoli LM, etal. PET of brain amyloid and tau in mild cognitive impairment. N Engl J Med. 2006; 355(25): 26522663.
147.Agdeppa ED, Kepe V, Liu J, etal. 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. 2001; 21(24): RC189.
148.Shoghi-Jadid K, Small GW, Agdeppa ED, etal. Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry. 2002; 10(1): 2435.
149.Ossenkoppele R, Tolboom N, Foster-Dingley J, etal. First ever longitudinal C-11-PIB and F18-FDDNP PET studies in patients with Alzheimer's disease or mild cognitive impairment and healthy controls. Alzheimers Dement. 2010; 6(4): S72.
150.Villemagne VL, Mulligan RS, Pejoska S, etal. Comparison of (11)C-PiB and (18)F-florbetaben for Abeta imaging in ageing and Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2012; 39(6): 983989.
151.Villemagne VL, Chetelat G, Pike K, etal. Comparison of biomarkers for the prediction of cognitive decline. Alzheimers Dement. 2010; 6(4): S139.
152.Rowe CC, Ackerman U, Browne W, etal. Imaging of amyloid beta in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol. 2008; 7(2): 129135.
153.Sabri O, Gertz HJ, Dresel S, etal. Florbetaben for beta-amyloid brain PET in Alzheimer's disease: results of a multicenter phase 2 trial. Alzheimers Dement. 2010; 6(4): S70.
154.Ong K, Villemagne V, Langdon N, etal. Assessment of a deposition in mild cognitive impairment with 18F-florbetaben. Alzheimers Dement. 2010; 6(4): S26.
155.Braak H, Braak E. Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol Aging. 1995; 16(3): 271278.
156.Seibyl J, Barret O, Zubal G. Objective SUVR determination using MRI segmentation maps in florbetaben beta-amyloid brain PET improves discrimination of Alzhemer's and controls. Alzheimers Dement. 2010; 6(4): S50.
157.Villemagne V, Ong K, Langdon N, etal. 18F-Florbetaben-pet imaging in the differential diagnosis of dementia. Alzheimers Dement. 2010; 6(4): S70S71.
158.Barthel H, Gertz HJ, Dresel S, etal. Cerebral amyloid-beta PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Lancet Neurol. 2011; 10(5): 424435.
159.Kukull WA, Larson EB, Reifler BV, etal. The validity of 3 clinical diagnostic criteria for Alzheimer's disease. Neurology. 1990; 40(9): 13641369.
160.Barthel H, Luthardt J, Becker G, etal. Individualized quantification of brain beta-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer's disease and healthy controls. Eur J Nucl Med Mol Imaging. 2011; 38(9): 17021714.
161. Rowe, CC. Clinical use of amyloid neuroimaging. Paper presented at: Society of Nuclear Medicine Annual Meeting; June 9, 2012; Miami Beach, FL.
162.Barthel H, Sabri O. Florbetaben to trace amyloid-β in the Alzheimer brain by means of PET. J. Alzheimers Dis. 2011; 26(S3): 117121.
163. Sabri O. Multicentre phase 3 trial on florbetaben for beta-amyloid brain PET in Alzheimer disease. Paper presented at: Society of Nuclear Medicine Annual Meeting; June 10, 2012; Miami Beach, FL.
164.Buckley CJ, Thurfjell L, Farrar G, etal. Visual read performance and related metrics of the amyloid imaging agent F18-flutemetamol: results from the phase II multicenter trial. Alzheimers Dement. 2010; 6(4): S49.
165.Jureus A, Swahn BM, Sandell J, etal. Characterization of AZD4694, a novel fluorinated Abeta plaque neuroimaging PET radioligand. J Neurochem. 2010; 114(3): 784794.
166.Cselenyi Z, Jonhagen ME, Forsberg A, etal. Clinical validation of 18F-AZD4694, an amyloid-beta-specific PET radioligand. J Nucl Med. 2012; 53(3): 415424.
167.Clark CM, Schneider JA, Mintun MA, etal. Phase III trial results for the amyoid PET imaging agent florbetapir F 18 (18F-AV-45): imaging to histopathologic correlations in an end-of-life human subject study. Alzheimers Dement. 2010; 6(4): S71.
168.Wong DF, Rosenberg PB, Zhou Y, etal. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F 18). J Nucl Med. 2010; 51(6): 913920.
169.Joshi AD, Pontecorvo MJ, Clark CM, etal. Performance characteristics of amyloid PET with florbetapir F 18 in patients with Alzheimer's disease and cognitively normal subjects. J Nucl Med. 2012; 53(3): 378384.
170.Newberg AB, Arnold SE, Wintering N, Rovner BW, Alavi A. Initial clinical comparison of 18F-florbetapir and 18F-FDG PET in patients with Alzheimer disease and controls. J Nucl Med. 2012; 53(6): 902907.
171.Sperling RA, Doraiswamy PM, Johnson K, etal. Florbetapir F 18 (18F-AV-45) PET amyloid imaging predicts progression of cognitive impairment: a longitudinal clinical follow up study. Alzheimers Dement. 2010; 6(4): S71.
172.Clark CM, Schneider JA, Bedell BJ, etal. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011; 305(3): 275283.
173.Camus V, Payoux P, Barre L, etal. Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment. Eur J Nucl Med Mol Imaging. 2012; 39(4): 621631.
174.Jobst KA, Barnetson LP, Shepstone BJ. Accurate prediction of histologically confirmed Alzheimer's disease and the differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford Project to Investigate Memory and Aging. Int Psychogeriatr. 1998; 10(3): 271302.
175.Herholz K, Carter SF, Jones M. Positron emission tomography imaging in dementia. Br J Radiol. 2007; 80(Spec No. 2): S160S167.
176.McMurtray AM, Licht E, Yeo T, etal. Positron emission tomography facilitates diagnosis of early-onset Alzheimer's disease. Eur Neurol. 2008; 59(1–2): 3137.
177.de Leon MJ, Convit A, Wolf OT, etal. 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): 1096610971.
178.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): 486510.
179.Mosconi L, Tsui WH, Herholz K, etal. Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias. J Nucl Med. 2008; 49(3): 390398.
180.Jagust W. Molecular neuroimaging in Alzheimer's disease. NeuroRx. 2004; 1(2): 206212.
181.Minoshima S, Giordani B, Berent S, etal. Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease. Ann Neurol. 1997; 42(1): 8594.
182.Minoshima S, Foster NL, Kuhl DE. Posterior cingulate cortex in Alzheimer's disease. Lancet. 1994; 344(8926): 895.
183.Patwardhan MB, McCrory DC, Matchar DB, Samsa GP, Rutschmann OT. Alzheimer disease: operating characteristics of PET—a meta-analysis. Radiology. 2004; 231(1): 7380.
184.Panegyres PK, Rogers JM, McCarthy M, Campbell A, Wu JS. Fluorodeoxyglucose-positron emission tomography in the differential diagnosis of early-onset dementia: a prospective, community-based study. BMC Neurol. 2009; 9: 4150.
185.Minoshima S, Foster NL, Sima AA, etal. Alzheimer's disease versus dementia with Lewy bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol. 2001; 50(3): 358365.
186.Mosconi L, De SS, Li Y, etal. Visual rating of medial temporal lobe metabolism in mild cognitive impairment and Alzheimer's disease using FDG-PET. Eur J Nucl Med Mol Imaging. 2006; 33(2): 210221.
187.Dobert N, Pantel J, Frolich L, etal. 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): 6370.
188.Drzezga A, Lautenschlager N, Siebner H, etal. 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): 11041113.
189.Pagani M, Dessi B, Morbelli S, etal. MCI patients declining and not-declining at mid-term follow-up: FDG-PET findings. Curr Alzheimer Res. 2010; 7(4): 287294.
190.Yuan Y, Gu ZX, Wei WS. Fluorodeoxyglucose-positron-emission tomography, single-photon emission tomography, and structural MR imaging for prediction of rapid conversion to Alzheimer disease in patients with mild cognitive impairment: a meta-analysis. AJNR Am J Neuroradiol. 2009; 30(2): 404410.
191.Devous MD. SPECT functional brain imaging. In: Toga AW, Mazziotta JC, editors. Brain Mapping: The Methods, 2nd ed. London: Academic Press; 2002: 513536.
192.Devous MD. SPECT functional brain imaging: instrumentation, radiopharmaceuticals and technical factors. In: Van Heertum RL, Tikofsky RS, Ichise M, editors. Functional Cerebral SPECT and PET Imaging, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2010: 322.
193.Darcourt J, Mena I, Cauvin J-C, Miller BL. Absolute calibration of HMPAO SPECT using (133)Xe rCBF values. Alasbimn J. 1999; 2(5). http://www.alasbimnjournal.cl/revistas/5/darcourt.htm.
194.Payne JK, Trivedi MH, Devous MD Sr. Comparison of technetium-99m-HMPAO and xenon-133 measurements of regional cerebral blood flow by SPECT. J Nucl Med. 1996; 37(10): 17351740.
195.Pimlott SL, Ebmeier KP. SPECT imaging in dementia. Br J Radiol. 2007; 80(Spec No 2): S153S159.
196.Matsuda H. Role of neuroimaging in Alzheimer's disease, with emphasis on brain perfusion SPECT. J Nucl Med. 2007; 48(8): 12891300.
197.Cherry S, Phelps ME. Positron emission tomography: methods and instrumentation. In: Sandler M, Coleman RE, Patton J, Wacker F J T, Gottschalk A, editors. Diagnostic Nuclear Medicine, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2003: 6183.
198. Harkness LJ, Boston AJ, Boston HC. Prospectus: development of a compton camera for medical imaging. In: Dosse O, Schegel WC, editors. IFMBE Proceedings 2009: World Congress on Medical Physics and Biomedical Engineering: 2009 Sept 7–12. Munich: Springer; 2012: 102–105.
199.Ducassou D, Brendel A, Lacroix F, Brothier JP. Clinical value of single photon emission computerized tomography in encephalic exploration. Int J Nucl Med Biol. 1980; 7(1): 2531.
200.Lassen NA. Regional cerebral blod flow studied by xenon-133: intra-arterial injection studies and inhalation studies using emission tomography. Bull Schweiz Akad Med Wiss. 1980; 36(1–3): 93100.
201.Hill TC, Costello P, Gramm HF, Lovett R, McNeill BJ, Treves S. Early clinical experience with a radionuclide emission computed tomographic brain imaging system. Radiology. 1978; 128(3): 803806.
202.Bonte FJ, Ross ED, Chehabi HH, Devous MD Sr. SPECT study of regional cerebral blood flow in Alzheimer disease. J Comput Assist Tomogr. 1986; 10(4): 579583.
203.Battistin L, Pizzolato G, Dam M, etal. Regional cerebral blood flow study with 99mTc-hexamethyl-propyleneamine oxime single photon emission computed tomography in Alzheimer's and multi-infarct dementia. Eur Neurol. 1990; 30(5): 296301.
204.Knapp WH, Dannenberg C, Marschall B, etal. Changes in local cerebral blood flow by neuroactivation and vasoactivation in patients with impaired cognitive function. Eur J Nucl Med. 1996; 23(8): 878888.
205.Mattman A, Feldman H, Forster B, etal. Regional HmPAO SPECT and CT measurements in the diagnosis of Alzheimer's disease. Can J Neurol Sci. 1997; 24(1): 2228.
206.Varma AR, Adams W, Lloyd JJ, etal. Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer's disease, frontotemporal dementia and vascular dementia. Acta Neurol Scand. 2002; 105(4): 261269.
207.Hellman RS, Tikofsky RS, Van HR, etal. A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO). Eur J Nucl Med. 1994; 21(4): 306313.
208.Talbot PR, Lloyd JJ, Snowden JS, Neary D, Testa HJ. A clinical role for 99mTc-HMPAO-SPECT in the investigation of dementia? J Neurol Neurosurg Psychiatry. 1998; 64(3): 306313.
209.Dougall NJ, Bruggink S, Ebmeier KP. Systematic review of the diagnostic accuracy of 99mTc-HMPAO-SPECT in dementia. Am J Geriatr Psychiatry. 2004; 12(6): 554570.
210.Van Heertum RL. Dementia: diagnosis of dementia. In: Van Heertum RL, Tikofsky RS, Ichise M, editors. Functional Cerebral SPECT and PET Imaging, 4th ed. Philadephia: Lippincott Williams & Wilkins; 2010: 8195.
211.Bloudek LM, Spackman DE, Blankenburg M, Sullivan SD. Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer's disease. J Alzheimers Dis. 2011; 26(4): 627645.
212.Bonte FJ, Harris TS, Hynan LS, Bigio EH, White CL III. Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmation. Clin Nucl Med. 2006; 31(7): 376378.
213.Hanyu H, Abe S, Arai H, etal. Diagnostic accuracy of single photon emission computed tomography in Alzheimer's disease. Gerontology. 1993; 39(5): 260266.
214.Perani D, Di Piero V, Vallar G, etal. Technetium-99m HM-PAO-SPECT study of regional cerebral perfusion in early Alzheimer's disease. J Nucl Med. 1988; 29(9): 15071514.
215.Leys D, Steinling M, Petit H, etal. [Alzheimer's disease: study by single photon emission tomography (Hm PAO Tc99m)]. Rev Neurol (Paris). 1989; 145(6–7): 443450.
216.Hurwitz TA, Ammann W, Chu D, etal. Single photon emission computed tomography using 99mTc-HM-PAO in the routine evaluation of Alzheimer's disease. Can J Neurol Sci. 1991; 18(1): 5962.
217.O'Brien JT, Eagger S, Syed GM, Sahakian BJ, Levy R. A study of regional cerebral blood flow and cognitive performance in Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1992; 55(12): 11821187.
218.Claus JJ, van HF, Breteler MM, etal. Assessment of cerebral perfusion with single-photon emission tomography in normal subjects and in patients with Alzheimer's disease: effects of region of interest selection. Eur J Nucl Med. 1994; 21(10): 10441051.
219.Sloan EP, Fenton GW, Kennedy NS, MacLennan JM. Electroencephalography and single photon emission computed tomography in dementia: a comparative study. Psychol Med. 1995; 25(3): 631638.
220.O'Mahony D, Coffey J, Murphy J, etal. The discriminant value of semiquantitative SPECT data in mild Alzheimer's disease. J Nucl Med. 1994; 35(9): 14501455.
221.O'Brien JT, Ames D, Desmond P, etal. Combined magnetic resonance imaging and single-photon emission tomography scanning in the discrimination of Alzheimer's disease from age-matched controls. Int Psychogeriatr. 2001; 13(2): 149161.
222.Honda N, Machida K, Hosono M, etal. Interobserver variation in diagnosis of dementia by brain perfusion SPECT. Radiat Med. 2002; 20(6): 281289.
223.Soonawala D, Amin T, Ebmeier KP, etal. Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake. Neuroimage. 2002; 17(3): 11931202.
224.Johnson KA, Kijewski MF, Becker JA, etal. Quantitative brain SPECT in Alzheimer's disease and normal aging. J Nucl Med. 1993; 34(11): 20442048.
225.Waldemar G, Bruhn P, Kristensen M, etal. Heterogeneity of neocortical cerebral blood flow deficits in dementia of the Alzheimer type: a [99mTc]-d,l-HMPAO SPECT study. J Neurol Neurosurg Psychiatry. 1994; 57(3): 285295.
226.Karbe H, Kertesz A, Davis J, etal. Quantification of functional deficit in Alzheimer's disease using a computer-assisted mapping program for 99mTc-HMPAO SPECT. Neuroradiology. 1994; 36(1): 16.
227.Messa C, Perani D, Lucignani G, etal. High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's disease: comparison with fluorine-18-FDG PET. J Nucl Med. 1994; 35(2): 210216.
228.Ichise M, Crisp S, Ganguli N, Tsai S, Gray BG. A method of two-dimensional mapping of cortical perfusion by cylindrical transformation of HMPAO SPET data. Nucl Med Commun. 1995; 16(5): 386394.
229.Hashikawa K, Matsumoto M, Moriwaki H, etal. Three-dimensional display of surface cortical perfusion by SPECT: application in assessing Alzheimer's disease. J Nucl Med. 1995; 36(4): 690696.
230.deFigueiredo RJ, Shankle WR, Maccato A, etal. Neural-network-based classification of cognitively normal, demented, Alzheimer disease and vascular dementia from single photon emission with computed tomography image data from brain. Proc Natl Acad Sci U S A. 1995; 92(12): 55305534.
231.van Dyck CH, Lin CH, Smith EO, etal. Comparison of technetium-99m-HMPAO and technetium-99m-ECD cerebral SPECT images in Alzheimer's disease. J Nucl Med. 1996; 37(11): 17491755.
232.Bartenstein P, Minoshima S, Hirsch C, etal. Quantitative assessment of cerebral blood flow in patients with Alzheimer's disease by SPECT. J Nucl Med. 1997; 38(7): 10951101.
233.Johnson KA, Jones K, Holman BL, etal. Preclinical prediction of Alzheimer's disease using SPECT. Neurology. 1998; 50(6): 15631571.
234.Honda N, Machida K, Matsumoto T, etal. Three-dimensional stereotactic surface projection of brain perfusion SPECT improves diagnosis of Alzheimer's disease. Ann Nucl Med. 2003; 17(8): 641648.
235.Elgh E, Sundstrom T, Nasman B, Ahlstrom R, Nyberg L. Memory functions and rCBF (99m)Tc-HMPAO SPET: developing diagnostics in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2002; 29(9): 11401148.
236.Kubota T, Ushijima Y, Yamada K, etal. Diagnosis of Alzheimer's disease using brain perfusion SPECT and MR imaging: which modality achieves better diagnostic accuracy? Eur J Nucl Med Mol Imaging. 2005; 32(4): 414421.
237.Kemp PM, Hoffmann SA, Holmes C, etal. The contribution of statistical parametric mapping in the assessment of precuneal and medial temporal lobe perfusion by 99mTc-HMPAO SPECT in mild Alzheimer's and Lewy body dementia. Nucl Med Commun. 2005; 26(12): 10991106.
238.Chaves R, Ramirez J, Gorriz JM, etal. SVM-based computer-aided diagnosis of the Alzheimer's disease using t-test NMSE feature selection with feature correlation weighting. Neurosci Lett. 2009; 461(3): 293297.
239.Pagani M, Salmaso D, Rodriguez G, Nardo D, Nobili F. Principal component analysis in mild and moderate Alzheimer's disease—a novel approach to clinical diagnosis. Psychiatry Res. 2009; 173(1): 814.
240.Ishii S, Shishido F, Miyajima M, etal. Comparison of Alzheimer's disease with vascular dementia and non-dementia using specific voxel-based Z score maps. Ann Nucl Med. 2009; 23(1): 2531.
241.Rusina R, Kukal J, Belicek T, Buncova M, Matej R. Use of fuzzy edge single-photon emission computed tomography analysis in definite Alzheimer's disease—a retrospective study. BMC Med Imaging. 2010; 10: 20.
242.Starkstein SE, Sabe L, Vazquez S, etal. Neuropsychological, psychiatric, and cerebral blood flow findings in vascular dementia and Alzheimer's disease. Stroke. 1996; 27(3): 408414.
243.Yoshikawa T, Murase K, Oku N, etal. Heterogeneity of cerebral blood flow in Alzheimer disease and vascular dementia. AJNR Am J Neuroradiol. 2003; 24(7): 13411347.
244.Jagust WJ, Budinger TF, Reed BR. The diagnosis of dementia with single photon emission computed tomography. Arch Neurol. 1987; 44(3): 258262.
245.Yoshikawa T, Murase K, Oku N, etal. Statistical image analysis of cerebral blood flow in vascular dementia with small-vessel disease. J Nucl Med. 2003; 44(4): 505511.
246.Butler RE, Costa DC, Greco A, etal. Differentiation between Alzheimer's disease and multi-infarct dementia: SPECT vs. MR imaging. Int J Geriatr Psychiatry. 1995; 10: 121128.
247.Uchida Y, Minoshima S, Okada S, Kawata T, Ito H. Diagnosis of dementia using perfusion SPECT imaging at the patient's initial visit to a cognitive disorder clinic. Clin Nucl Med. 2006; 31(12): 764773.
248.Pavics L, Grunwald F, Reichmann K, etal. Regional cerebral blood flow single-photon emission tomography with 99mTc-HMPAO and the acetazolamide test in the evaluation of vascular and Alzheimer's dementia. Eur J Nucl Med. 1999; 26(3): 239245.
249.Bergman H, Chertkow H, Wolfson C, etal. HM-PAO (CERETEC) SPECT brain scanning in the diagnosis of Alzheimer's disease. J Am Geriatr Soc. 1997; 45(1): 1520.
250.Mielke R, Pietrzyk U, Jacobs A, etal. HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern. Eur J Nucl Med. 1994; 21(10): 10521060.
251.Houston AS, Kemp PM, Macleod MA. A method for assessing the significance of abnormalities in HMPO brain SPECT images. J Nucl Med. 1994; 35(2): 239244.
252.Launes J, Sulkava R, Erkinjuntti T, etal. 99Tcm-HMPAO SPECT in suspected dementia. Nucl Med Commun. 1991; 12(9): 757765.
253.Kato H, Yoshikawa T, Oku N, etal. Statistical parametric analysis of cerebral blood flow in vascular dementia with small-vessel disease using Tc-HMPAO SPECT. Cerebrovasc Dis. 2008; 26(5): 556562.
254.Shim YS, Yang DW, Kim BS, Shon YM, Chung YA. Comparison of regional cerebral blood flow in two subsets of subcortical ischemic vascular dementia: statistical parametric mapping analysis of SPECT. J Neurol Sci. 2006; 250(1–2): 8591.
255.Vorstrup S, Henriksen L, Paulson OB. Effect of acetazolamide on cerebral blood flow and cerebral metabolic rate for oxygen. J Clin Invest. 1984; 74(5): 16341639.
256.Takasawa M, Murase K, Oku N, etal. Assessment of acetazolamide reactivity in cerebral blood flow using spectral analysis and technetium-99m hexamethylpropylene amine oxime. J Cereb Blood Flow Metab. 2002; 22(8): 10041009.
257.Vorstrup S. Tomographic cerebral blood flow measurements in patients with ischemic cerebrovascular disease and evaluation of the vasodilatory capacity by the acetazolamide test. Acta Neurol Scand Suppl. 1988; 114: 148.
258.Devous MD Sr. Functional brain imaging in the dementias: role in early detection, differential diagnosis, and longitudinal studies. Eur J Nucl Med Mol Imaging. 2002; 29(12): 16851696.
259.Bonte FJ, Tintner R, Weiner MF, Bigio EH, White CL III. Brain blood flow in the dementias: SPECT with histopathologic correlation. Radiology. 1993; 186(2): 361365.
260.Matsuda H, Mizumura S, Nagao T, etal. Automated discrimination between very early Alzheimer disease and controls using an easy Z-score imaging system for multicenter brain perfusion single-photon emission tomography. AJNR Am J Neuroradiol. 2007; 28(4): 731736.
261.Neary D, Snowden JS, Shields RA, etal. Single photon emission tomography using 99mTc-HM-PAO in the investigation of dementia. J Neurol Neurosurg Psychiatry. 1987; 50(9): 11011109.
262.Testa HJ, Snowden JS, Neary D, etal. The use of [99mTc]-HM-PAO in the diagnosis of primary degenerative dementia. J Cereb Blood Flow Metab. 1988; 8(6): S123S126.
263.McNeill R, Sare GM, Manoharan M, etal. Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2007; 78(4): 350355.
264.Charpentier P, Lavenu I, Defebvre L, etal. Alzheimer's disease and frontotemporal dementia are differentiated by discriminant analysis applied to (99m)Tc HmPAO SPECT data. J Neurol Neurosurg Psychiatry. 2000; 69(5): 661663.
265.Boutoleau-Bretonniere C, Lebouvier T, Delaroche O, etal. Value of neuropsychological testing, imaging, and CSF biomarkers for the differential diagnosis and prognosis of clinically ambiguous dementia. J Alzheimers Dis. 2012; 28(2): 323336.
266.Horn JF, Habert MO, Kas A, etal. Differential automatic diagnosis between Alzheimer's disease and frontotemporal dementia based on perfusion SPECT images. Artif Intell Med. 2009; 47(2): 147158.
267.Shimizu S, Hanyu H, Kanetaka H, etal. Differentiation of dementia with Lewy bodies from Alzheimer's disease using brain SPECT. Dement Geriatr Cogn Disord. 2005; 20(1): 2530.
268.Goto H, Ishii K, Uemura T, etal. Differential diagnosis of dementia with Lewy bodies and Alzheimer disease using combined MR imaging and brain perfusion single-photon emission tomography. AJNR Am J Neuroradiol. 2010; 31(4): 720725.
269.Johnson KA, Moran EK, Becker JA, etal. Single photon emission computed tomography perfusion differences in mild cognitive impairment. J Neurol Neurosurg Psychiatry. 2007; 78(3): 240247.
270.Edman A, Edenbrandt L, Freden-Lindqvist J, Nilsson M, Wallin A. Asymmetric cerebral blood flow in patients with mild cognitive impairment: possible relationship to further cognitive deterioration. Dement Geriatr Cogn Dis Extra. 2011; 1(1): 228236.
271.Habert MO, Horn JF, Sarazin M, etal. Brain perfusion SPECT with an automated quantitative tool can identify prodromal Alzheimer's disease among patients with mild cognitive impairment. Neurobiol Aging. 2011; 32(1): 1523.
272.Encinas M, De JR, Marcos A, etal. Regional cerebral blood flow assessed with 99mTc-ECD SPET as a marker of progression of mild cognitive impairment to Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2003; 30(11): 14731480.
273.Caroli A, Testa C, Geroldi C, etal. Cerebral perfusion correlates of conversion to Alzheimer's disease in amnestic mild cognitive impairment. J Neurol. 2007; 254(12): 16981707.
274.Nobili F, De CF, Frisoni GB, etal. SPECT predictors of cognitive decline and Alzheimer's disease in mild cognitive impairment. J Alzheimers Dis. 2009; 17(4): 761772.
275.Kogure D, Matsuda H, Ohnishi T, etal. Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT. J Nucl Med. 2000; 41(7): 11551162.
276.Huang C, Wahlund LO, Svensson L, Winblad B, Julin P. Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment. BMC Neurol. 2002; 2: 915.
277.Ishiwata A, Sakayori O, Minoshima S, etal. Preclinical evidence of Alzheimer changes in progressive mild cognitive impairment: a qualitative and quantitative SPECT study. Acta Neurol Scand. 2006; 114(2): 9196.
278.Borroni B, Anchisi D, Paghera B, etal. Combined 99mTc-ECD SPECT and neuropsychological studies in MCI for the assessment of conversion to AD. Neurobiol Aging. 2006; 27(1): 2431.
279.Wolfe N, Reed BR, Eberling JL, Jagust WJ. Temporal lobe perfusion on single photon emission computed tomography predicts the rate of cognitive decline in Alzheimer's disease. Arch Neurol. 1995; 52(3): 257262.
280.Desgranges B, Baron JC, de la Sayette V, etal. The neural substrates of memory systems impairment in Alzheimer's disease: a PET study of resting brain glucose utilization. Brain. 1998; 121(4): 611631.
281.Hirao K, Ohnishi T, Matsuda H, etal. Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer's disease using brain perfusion single-photon emission computed tomography. Nucl Med Commun. 2006; 27(2): 151156.
282.Mosconi L, Pupi A, De Cristofaro MT, etal. Functional interactions of the entorhinal cortex: an 18F-FDG PET study on normal aging and Alzheimer's disease. J Nucl Med. 2004; 45(3): 382392.
283.Matsuda H. The role of neuroimaging in mild cognitive impairment. Neuropathology. 2007; 27(6): 570577.
284.Gomez-Isla T, Price JL, McKeel DW Jr, etal. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J Neurosci. 1996; 16(14): 44914500.
285.Price JL, Ko AI, Wade MJ, etal. Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol. 2001; 58(9): 13951402.
286.Minoshima S, Cross DJ, Foster NL, Henry TR, Kuhl DE. Discordance between traditional pathologic and energy metabolic changes in very early Alzheimer's disease: pathophysiological implications. Ann N Y Acad Sci. 1999; 893: 350352.
287.Matsuda H. The role of neuroimaging in mild cognitive impairment. Neuropathology. 2007; 27(6): 570577.
288.Petersen RC, Stevens JC, Ganguli M, etal. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001; 56(9): 11331142.
289. Consensus report of the Working Group on: “Molecular and Biochemical Markers of Alzheimer's Disease”, The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group. Neurobiol Aging. 1998; 19(2): 109–116.
290.Herholz K. Perfusion SPECT and FDG-PET. Int Psychogeriatr. 2011; 23(Suppl 2): S25S31.
291.Weih M, Degirmenci U, Kreil S, etal. Perfusion imaging with SPECT in the era of pathophysiology-based biomarkers for Alzheimer's disease. Int J Alzheimers Dis. 2010; 2010: 109618.
292.Herholz K, Schopphoff H, Schmidt M, etal. Direct comparison of spatially normalized PET and SPECT scans in Alzheimer's disease. J Nucl Med. 2002; 43(1): 2126.
293.Shipley S, Kluger B, Filley C. Accuracy of community-acquired PET scans in the diagnosis of dementia. Paper presented at: American Acemdey of Neurology 64th Annual Meeting; April 23, 2012; New Orleans, LA.
294.Clark CM, Schneider JA, Mintun MA, etal. Phase III trial results for the amyoid PET imaging agent Florbetapir F 18 (18F-AV-45): imaging to histopathologic correlations in an end-of-life human subject study. Alzheimers Dement. 2010; 6(4): S71.
295.Joshi A, Koeppe RA, Fessler JA. Reducing between scanner differences in multi-center PET studies. Neuroimage. 2009; 46(1): 154159.
296.Ng S, Villemagne VL, Berlangieri S, etal. 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): 547552.
297.Hort J, O'Brien JT, Gainotti G, etal. EFNS guidelines for the diagnosis and management of Alzheimer's disease. Eur J Neurol. 2010; 17(10): 12361248.
298.Rollin-Sillaire A, Bombois S, Deramecourt V, etal. Contribution of single photon emission computed tomography to the differential diagnosis of dementia in a memory clinic. J Alzheimers Dis. 2012; 30(4): 833845.
299.Read SL, Miller BL, Mena I, etal. SPECT in dementia: clinical and pathological correlation. J Am Geriatr Soc. 1995; 43(11): 12431247.
300.Borghesani PR, DeMers SM, Manchanda V, etal. Neuroimaging in the clinical diagnosis of dementia: observations from a memory disorders clinic. J Am Geriatr Soc. 2010; 58(8): 14531458.
301.Burns A, Rossor M, Hecker J, etal. The effects of donepezil in Alzheimer's disease—results from a multinational trial. Dement Geriatr Cogn Disord. 1999; 10(3): 237244.
302.Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology. 1998; 50(1): 136145.
303.Tariot PN, Farlow MR, Grossberg GT, etal. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004; 291(3): 317324.
304.Ceravolo R, Volterrani D, Frosini D, etal. Brain perfusion effects of cholinesterase inhibitors in Parkinson's disease with dementia. J Neural Transm. 2006; 113(11): 17871790.
305.Shimizu S, Hanyu H, Iwamoto T, Koizumi K, Abe K. SPECT follow-up study of cerebral blood flow changes during Donepezil therapy in patients with Alzheimer's disease. J Neuroimaging. 2006; 16(1): 1623.
306.Nakano S, Asada T, Matsuda H, Uno M, Takasaki M. Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease. J Nucl Med. 2001; 42(10): 14411445.
307.Nobili F, Vitali P, Canfora M, etal. Effects of long-term Donepezil therapy on rCBF of Alzheimer's patients. Clin Neurophysiol. 2002; 113(8): 12411248.
308.Raskind MA, Peskind ER, Truyen L, Kershaw P, Damaraju CV. The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial. Arch Neurol. 2004; 61(2): 252256.
309.Raskind MA, Peskind ER, Wessel T, Yuan W. Galantamine in AD: a 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology. 2000; 54(12): 22612268.
310.Heneka MT, O'Banion MK, Terwel D, Kummer MP. Neuroinflammatory processes in Alzheimer's disease. J Neural Transm. 2010; 117(8): 919947.
311.Wilson D. Lilly stops Alzheimer's drug trials. The New York Times. 2010 Aug 17.
312.Hirao K, Ohnishi T, Hirata Y, etal. The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT. Neuroimage. 2005; 28(4): 10141021.
313.Hampel H, Burger K, Teipel SJ, etal. Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. Alzheimers Dement. 2008; 4(1): 3848.
314.Waldemar G. Diagnostic markers: when and how? Alzheimers Dement. 2010; 6(4): S87.
315.Hyman BT, Phelps CH, Beach TG, etal. National Institute on Aging–Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012; 8(1): 113.
316.Bateman RJ, Xiong C, Benzinger TL, etal. Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease. N Engl J Med. 2012 Jul 11. http://www.nejm.org/doi/full/10.1056/NEJMoa1202753#t=articleTop
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

CNS Spectrums
  • ISSN: 1092-8529
  • EISSN: 2165-6509
  • URL: /core/journals/cns-spectrums
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 3
Total number of PDF views: 39 *
Loading metrics...

Abstract views

Total abstract views: 290 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 21st October 2017. This data will be updated every 24 hours.