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Preclinical prediction of Alzheimer's disease using SPECT
Abstract
BACKGROUND: Regional cerebral perfusion measured by single photon emission computed tomography (SPECT) was examined as a preclinical predictor of the development of Alzheimer's disease (AD). METHODS: Singular value decomposition was used to produce 20 SPECT factors (known as vectors) (n=152). Vector scores were then computed for four groups (n=136), differing in cognitive status: Group 1--normal controls at both baseline and follow-up; Group 2--subjects with "questionable" AD at both baseline and follow-up; Group 3--subjects with questionable AD at baseline who converted to AD on follow-up (Converters); Group 4--subjects with AD at baseline. All SPECT data in the analyses were gathered at baseline. RESULTS: The four groups could be distinguished on the basis of their baseline SPECT data (p < or = 0.00005; hit rate=83%). Regional decreases in perfusion were most prominent among Converters in the hippocampal-amygdaloid complex, the posterior cingulate, the anterior thalamus, and the anterior cingulate. Inclusion of apolipoprotein E status did not significantly improve the discrimination. CONCLUSIONS: SPECT data gathered and analyzed in this manner may be useful as one aspect of the preclinical prediction of AD. Three of the four brain regions important for discriminating Converters from normal controls involve a distributed brain network pertaining to memory, suggesting that this network may be selectively affected in the earliest stages of AD.
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“Reduced size or glucose metabolism (METglu) in the EC (10), Hip (11–16), temporal neocortex (17–20), and posterior cingulate gyrus (16) have been shown to predict the MCI conversion to AD.”
From Prediction of cognitive decline in normal elderly subjects with 2-[ 18 F]fluoro-2-deoxy- d -glucose/positron-emission tomography (FDG/PET) (2001) · cites this paper as [16]
In the citing paper
“The recent SPECT study by Johnson et al. (16) demonstrated that reduced perfusion of the Hip and posterior cingulate gyrus predicted AD.”
From Prediction of cognitive decline in normal elderly subjects with 2-[ 18 F]fluoro-2-deoxy- d -glucose/positron-emission tomography (FDG/PET) (2001) · cites this paper as [16]
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“For instance, SPECT showed that individuals with MCI who subsequently converted to AD had hypoperfusion in the posterior cingulate corte”
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“Authors of another study (81), using a quantitative singular-value decomposition analysis of SPECT images in patients with MCI, demonstrated regional decreases in uptake in the medial temporal lobe and cingulate regions that were most prominent among patients with MCI who subsequently converted to AD over the 1- to 2-…”
ResultSOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid precursor protein
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“Although the CBF alterations in Alzheimer's dementia could be secondary to neuronal degeneration or to morphological alterations in cerebral blood vessels, these factors are less likely to be involved in the cerebrovascular changes occurring early in the disease when pathological changes have not yet occurre”
BackgroundThe inter-relationship between delirium and dementia: the importance of delirium prevention
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Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry
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Predicting Conversion to Alzheimer Disease Using Standardized Clinical Information
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MethodSelf-citationMCI conversion to dementia and the APOE genotype
Mosconi, L., Perani, D., Sorbi, S., Herholz, K., Nacmias, B., Holthoff‐Detto, V., Salmon, É., Baron, J., Cristofaro, M. T. D., Padovani, A., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000147469.18313.3b · Cited by 347
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Evidence that Alzheimer’s disease is a microvascular disorder: the role of constitutive nitric oxide
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“and hippocampus in MCI subjects, which were associated with a higher risk of progressive cognitive decline (Arnaiz et al., 2001; Huang et al., 2002; Johnson et al., 1998; Kitayama et al., 2001; Minoshima et al., 1994; Okamura et al., 2002; Rodriguez et al., 2000).”
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Cummings, J. L., Doody, R. S., & Clark, C. (2007) · Neurology · doi:10.1212/01.wnl.0000295996.54210.69 · Cited by 284
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“It was shown that prior to clinical AD onset, hypoperfusion in the hippocampus, amygdala, posterior cingulate gyrus and left anterior thalamus precedes deficits in the temporoparietal cortex [75].”
BackgroundResultDissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment
Chetelat, G. (2003) · Brain · doi:10.1093/brain/awg196 · Cited by 264
“reported in two SPECT (single photon emission computed tomography) studies (Johnson et al., 1998; Kogure et al., 2000), as well as in non-demented subjects at risk of”
ResultStaging disease severity in pathologically confirmed cases of frontotemporal dementia
Broe, M., Hodges, J. R., Schofield, E. C., Shepherd, C. E., Kril, J. J., & Halliday, G. M. (2003) · Neurology · doi:10.1212/01.wnl.0000052685.09194.39 · Cited by 248
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Vascular Basis of Alzheimer's Pathogenesis
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“…been shown to exist very early in the course of AD (Minoshima et al., 1994, 1997; Reiman et al., 1996), and longitudinal studies show PCC dysfunction as a clinical predictor for later AD (Johnson et al., 1998; Kogure et al., 2000) that is correlated with severity of symptoms (Alsop et al., 2000).”
BackgroundCerebral blood flow and metabolic abnormalities in Alzheimer’s disease
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Neuroimaging in Alzheimer disease: an evidence-based review
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“PET [70] and SPECT [71] have also been shown to predict subsequent development of MCI and AD in clinically determined healthy elderly individuals and in individuals with questionable AD.”
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Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment
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“Johnson et al. demonstrated that SPECT was a promising method for the diagnosis of PMCI, in which the combination of the cingulate gyrus, hippocampal-amygdaloid complex and thalamus identified more than 80% of the subjects who would progress to AD after a 16.7 month follow-up [ 9 ].”
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“The specific task used in our study has previously been reported to distinguish AD and MCI from normal controls (Dickerson et al., 2005; Sperling et al., 2003b), as well as identify cognitively normal individuals at increased risk for AD (Fleisher et al., 2008).”
InfluentialA critical discussion of the role of neuroimaging in mild cognitive impairment*
Wolf, H., Jelić, V., Gertz, H., Nordberg, A. K., Julin, P., & Wahlund, L. (2003) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.107.s179.10.x · Cited by 213
“5) who progressed to AD during the 2-year follow-up (94).”
BackgroundMethodAlzheimer disease: new concepts on its neurobiology and the clinical role imaging will play
Jack, C. R. (2012) · Radiology · doi:10.1148/radiol.12110433 · Cited by 211
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“Using PET and single-photon emission computerized tomography, reduced activity in PCC, parietal, temporal, and prefrontal cortices has been observed consistently [Johnson et al., 1998; Matsuda, 2001; Minoshima et al., 1997].”
MethodYuan, Y., Gu, Z.-X., & Wei, W.-S. (2008) · American Journal of Neuroradiology · doi:10.3174/ajnr.a1357 · Cited by 212
“Eligible Studies Tables 2– 4 summarize the included studies, classified according to technique.(10-33) Our search strategy identified 326 artiTable 1: Diagnostic criteria of synonyms of MCI in eligible studies”
BackgroundMethodImaging the progression of Alzheimer pathology through the brain
Smith, A. D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.082107399 · Cited by 202
Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease
Bradley, K. M. (2002) · Brain · doi:10.1093/brain/awf185 · Cited by 203
“First, Johnson et al. (1998) described a small region of signi®cantly reduced perfusion in the caudal portion of the anterior cingulate.”
BackgroundInfluentialHippocampal hyperperfusion in Alzheimer's disease
Alsop, D. C., Casement, M. D., de BAZELAIRE, C., Fong, T. G., & Press, D. Z. (2008) · NeuroImage · doi:10.1016/j.neuroimage.2008.06.006 · Cited by 203
“Metabolic imaging with Positron Emission Tomography (PET) (Friedland et al., 1983; Reiman et al., 1996; Small et al., 1995) and blood flow imaging with PET and Single Photon Emission Computed Tomography (SPECT) (Bonte et al., 2001; Johnson et al., 1998) have highlighted loss of activity in temporal, parietal, and fron…”
BackgroundInfluentialImaging and CSF Studies in the Preclinical Diagnosis of Alzheimer's Disease
de Leon, M. J., Mosconi, L., Blennow, K., DeSanti, S., Zinkowski, R. P., Mehta, P. D., Praticò, D., Tsui, W., Louis, L. A. S., Sobanska, L., et al. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1379.012 · Cited by 198
Cerebral perfusion and oxygenation differences in Alzheimer's disease risk
Fleisher, A., Podraza, K. M., Bangen, K. J., Taylor, C., Sherzai, A. Z., Sidhar, K., Liu, T. T., Dale, A. M., & Buxton, R. B. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.01.012 · Cited by 183
Blood pressure and the risk for dementia—A double edged sword
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“Brain hypoperfusion therefore may be a critical factor in the development of both VaD (Roman et al., 2002; Roman, 2004) and AD (Johnson et al., 1998).”
BackgroundChua, E. F., Schacter, D. L., Rand-Giovannetti, E., & Sperling, R. A. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.09.058 · Cited by 174
“Furthermore, AD patients have shown abnormalities on resting PET (Herholz et al., 2002; K. A. Johnson et al., 1998) and fMRI (Greicius et al., 2004; Lustig et al., 2003) studies in the lateral and medial parietal regions and in the posterior cingulate.”
BackgroundVascular oxidative stress in Alzheimer disease
Zhu, X., Smith, M. A., Honda, K., Aliev, G., Moreira, P. I., Nunomura, A., Casadesús, G., Harris, P. L. R., Siedlak, S. L., & Perry, G. L. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2007.01.039 · Cited by 175
“Neuroimaging studies supports the notion that in MCI patients who later converted to AD, the presence of temporoparietal (including hippocampal) hypoperfusion, hippocampal-parahippocampal hypoperfusion, and posteriorcingulate hypoperfusion distinguish this population group from other groups suggesting that hypoperfusi…”
BackgroundSystematic Review of the Diagnostic Accuracy of 99mTc-HMPAO-SPECT in Dementia
Dougall, N. J., Bruggink, S., & Ebmeier, K. P. (2004) · American Journal of Geriatric Psychiatry · doi:10.1176/appi.ajgp.12.6.554 · Cited by 210
Cognitive impairment in chronic obstructive pulmonary disease
Antonelli Incalzi, R., Marra, C., Giordano, A., Calcagni, M. L., Cappa, A., Basso, S., Pagliari, G., & Fuso, L. (2003) · Journal of Neurology · doi:10.1007/s00415-003-1005-4 · Cited by 172
“Indeed, a perfusion deficit of select subcortical structures has been reported even in the earliest and preclinical stages of AD, whereas in H patients both blood gas derangement and smoke might be responsible for subcortical hypoperfusion [24, 29, 40].”
BackgroundAsllani, I., Habeck, C., Scarmeas, N., Borogovac, A., Brown, T. R., & Stern, Y. (2008) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600570 · Cited by 172
Chételat, G., Eustache, F., Viader, F., Sayette, V. D. L., Pèlerin, A., Mézenge, F., Hannequin, D., Dupuy, B., Baron, J., & Desgranges, B. (2005) · Neurocase · doi:10.1080/13554790490896938 · Cited by 164
“Previous studies report a significant hypometabolism in this area when comparing converters to nonconverters ( Drzezga et al , 2003 ; Chetelat et al , 2003a ; Huang et al , 2002 ), or to controls ( Minoshima et al , 1997; Johnson et al , 1998 ; 2001 ; Kogure et al , 2000 ).”
ResultAlzheimer's disease is a vasocognopathy: a new term to describe its nature
de la Torre, J. C. (2004) · Neurological Research · doi:10.1179/016164104225016254 · Cited by 168
Mild cognitive impairment: an epidemiological perspective
Ritchie, K. A. (2004) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2004.6.4/kritchie · Cited by 167
Synaptic Change in the Posterior Cingulate Gyrus in the Progression of Alzheimer's Disease
Scheff, S. W., PRICE, D. A., Ansari, M. A., Roberts, K. N., Schmitt, F. A., Ikonomović, M. D., & Mufson, E. J. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-141518 · Cited by 169
“The PostC has been shown to have decreased perfusion in patients that convert to AD from MCI [35].”
Age-related cognitive decline, mild cognitive impairment or preclinical Alzheimer's disease?
Celsis, P. (2000) · Annals of Medicine · doi:10.3109/07853890008995904 · Cited by 173
Kalback, W. M., Esh, C. L., Castaño, E. M., Rahman, A., Kokjohn, T. A., Luehrs, D. C., Sue, L. I., Cisneros, R., Gerber, F., Richardson, C., et al. (2004) · Neurological Research · doi:10.1179/016164104225017668 · Cited by 165
Borroni, B., Anchisi, D., Paghera, B., Vicini, B., Kerrouche, N., Garibotto, V., Terzi, A., Vignolo, L. A., Luca, M. D., Giubbini, R., et al. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.12.010 · Cited by 156
Matsuda, H., Kitayama, N., Ohnishi, T., Asada, T., Nakano, S., Sakamoto, S., Imabayashi, E., & Katoh, A. (2002) · PubMed · Cited by 157
Gefen, T. D., Peterson, M., Papastefan, S. T., Martersteck, A., Whitney, K. R., RADEMAKER, A. W., Bigio, E. H., Weıntraub, S., Rogalski, E. J., Mesulam, M. M., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.2998-14.2015 · Cited by 165
“, 2002), hypoperfusion (Johnson et al., 1998; Huang et al., 2002), amyloid load, and neurofibrillary degeneration (Braak and Braak, 1991; Chu et al.”
BackgroundMatsuda, H., Mizumura, S., Nagao, T., Ota, T., Iizuka, T., Nemoto, K., Takemura, N., Arai, H., & Homma, A. (2007) · PubMed Central · Cited by 153
Exercise, cognition and Alzheimer's disease: More is not necessarily better
Eggermont, L. H. P., Swaab, D. F., Luiten, P. G. M., & Scherder, E. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.10.004 · Cited by 156
“More specifically, participants who developed AD late showed decreased perfusion in the hippocampal-amygdaloı̈d complex, the anterior and posterior cingulate and the anterior thalamus (Johnson et al., 1998; Matsuda, 2001).”
BackgroundReduced cerebral glucose metabolism in patients at risk for Alzheimer's disease
Hunt, A., Schönknecht, P., Henze, M., Seidl, U., Haberkorn, U., & Schröder, J. (2007) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2006.12.003 · Cited by 146
Neuroimaging biomarkers for clinical trials of disease-modifying therapies in Alzheimer’s disease
Dickerson, B. C., & Sperling, R. A. (2005) · Neurotherapeutics · doi:10.1602/neurorx.2.2.348 · Cited by 159
“Recent animal studies have suggested that antiamyloid strategies may result in acute changes in synaptic function and behavior, in addition to altering amyloid plaque formation.108,109 FMRI studies have demonstrated significant alterations in memory-related activation with the administration of pharmacologic agents kn…”
BackgroundChertkow, H. M., Massoud, F., Nasreddine, Z. S., Belleville, S., Joanette, Y., Bocti, C., Drolet, V., Kirk, J., Freedman, M., & Bergman, H. (2008) · Canadian Medical Association Journal · doi:10.1503/cmaj.070797 · Cited by 147
Zhang, Y. S., Zhou, N., Knoll, B., Samra, S., Ward, M., Weıntraub, S., & Fawzi, A. A. (2019) · PLoS ONE · doi:10.1371/journal.pone.0214685 · Cited by 146
Cholinergic modulation of the cortical microvascular bed
Hamel, É. (2004) · Progress in brain research · doi:10.1016/s0079-6123(03)45012-7 · Cited by 140
How do heart disease and stroke become risk factors for Alzheimer's disease?
de la Torre, J. C. (2006) · Neurological Research · doi:10.1179/016164106x130362 · Cited by 139
Modrego, P. J., Fayed, N., & Pina, M. A. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.4.667 · Cited by 135
Sun, S., Dong, L.-X., Cao, Y., Sun, H., & Yan, X. (2013) · Analytical Chemistry · doi:10.1021/ac401879y · Cited by 137
Pathophysiology of Neuronal Energy Crisis in Alzheimer’s Disease
de la Torre, J. C. (2008) · Neurodegenerative Diseases · doi:10.1159/000113681 · Cited by 134
Brain imaging in the study of Alzheimer's disease
Reiman, E. M., & Jagust, W. J. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.11.075 · Cited by 139
“shown to predict decline in MCI (Johnson et al., 1998) and are related to autopsy findings (Bonte et al.”
ResultResting-State Multi-Spectrum Functional Connectivity Networks for Identification of MCI Patients
Chong-yaw Wee, A., Yap, P., Denny, K., Browndyke, J. N., Potter, G. G., Welsh-Bohmer, K. A., Wang, L., & Shen, D. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037828 · Cited by 125
“Our findings of relative asymmetric pattern, i.e., more regions in the left hemisphere were selected in training stage, is in line with some previous studies using SPECT and PET data [53,54].”
ResultHippocampal Shape Analysis of Alzheimer Disease Based on Machine Learning Methods
Li, S., Shi, F., Pu, F., Li, X., Jiang, T., Xie, S., & Wang, Y. (2007) · American Journal of Neuroradiology · doi:10.3174/ajnr.a0620 · Cited by 127
“Moreover, several VBM studies, 16,46 sulcal-warping studies, 47,48 and single-photon emission CT and positron-emission tomography studies 49,50 supported a laterality trend of the atrophic process and left more than right hemispheric involvement in AD.”
BackgroundCritical threshold cerebral hypoperfusion causes Alzheimer's disease?
de la Torre, J. C. (1999) · Acta Neuropathologica · doi:10.1007/s004010051044 · Cited by 124
“Second, a recent longitudinal study using SPECT measurements of rCBF in elderly individuals with ‘questionable’ AD (i.e., subjects with memory trouble who did not meet NINDS/ADRDA criteria for ‘probable’ AD), revealed that only those subjects with significant cerebral hypoperfusion in the amygdaloid-hippocampal region…”
BackgroundResultInfluential
Metadata
- Authors
- Johnson, K. A., Jones, K., Holman, B. L., Becker, J. A., Spiers, P. A., Satlin, A., & Albert, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Neurology
- Published
- 1998-06
- Volume
- 50
- Issue
- 6
- Pages
- 1563-1571
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W1964965688
- Cited by
- 471
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 11 · 2016: 12 · 2015: 17 · 2014: 13 · 2013: 15 · 2012: 12
- FWCI
- 15.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag009301-08)
- National Institute on Aging (R01-AG09301, P01AG004953)
- National Center for Research Resources (M01RR000088)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- Alzheimer's disease, single photon emission computed tomography, regional cerebral blood flow, singular value decomposition, posterior cingulate cortex, anterior thalamic nuclei, anterior cingulate cortex, apolipoprotein E, memory networks, cognitive decline
- MeSH terms
- Aged, Alzheimer Disease, Brain, Cerebrovascular Circulation, Female, Forecasting, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Tomography, Emission-Computed, Single-Photon, Discriminant Analysis, Disease Progression
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