Cited by 471Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

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Preclinical prediction of Alzheimer's disease using SPECT

Johnson, K. A., Jones, K., Holman, B. L., Becker, J. A., Spiers, P. A., Satlin, A., Albert, M. S.·1998·Neurology

DOI 10.1212/wnl.50.6.1563

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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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ResultSelf-citation
Chapter 3 Cerebrovascular and Cardiovascular Pathology in Alzheimer's Disease
de la Torre, J. C. (2009) · International review of neurobiology · doi:10.1016/s0074-7742(09)00403-6 · Cited by 71
Preclinical AD Workgroup staging: Pathological correlates and potential challenges
Jicha, G. A., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Riley, K. P., Cooper, G. E., Stiles, N., Mendiondo, M. S., Smith, C. D., Van Eldik, L. J., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.018 · Cited by 71
Longitudinal Cerebral Blood Flow and Amyloid Deposition: An Emerging Pattern?
Sojkova, J., Beason‐Held, L. L., Zhou, Y., An, Y., Kraut, M. A., Ye, W., Ferrucci, L., Mathis, C. A., Klunk, W. E., Wong, D. F., et al. (2008) · Journal of Nuclear Medicine · doi:10.2967/jnumed.108.051946 · Cited by 74
“in the anterior cingulate gyrus on SPECT of individuals who converted to AD (22), and deficits in executive function, in which the anterior cingulate has been reported to play a role, are among those exhibited early in the course of AD (23).”
Background
Regional Cerebral Blood Flow in Mild Cognitive Impairment and Alzheimer’s Disease Measured with Arterial Spin Labeling Magnetic Resonance Imaging
Sierra‐Marcos, A. (2017) · International Journal of Alzheimer s Disease · doi:10.1155/2017/5479597 · Cited by 75
Effects of partial volume correction on discrimination between very early Alzheimer?s dementia and controls using brain perfusion SPECT
Kanetaka, H., Matsuda, H., Asada, T., Ohnishi, T., Yamashita, F., Imabayashi, E., Tanaka, F., Nakano, S., & Takasaki, M. (2004) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-004-1491-3 · Cited by 69
“[27] revealed a decrease in rCBF in the anterior thalamus in subjects with very early AD.”
Pathological Aging of the Brain
de Bastos-Leite, A. J., Scheltens, P., & Barkhof, F. (2004) · Topics in Magnetic Resonance Imaging · doi:10.1097/01.rmr.0000168070.90113.dc · Cited by 67
Molecular imaging: design mechanism and bioapplications
Chen, L., Lyu, Y., Zhang, X., Zheng, L., Li, Q., Ding, D., Chen, F., Li, W., Li, W., Zhang, Y., et al. (2023) · Science China Chemistry · doi:10.1007/s11426-022-1461-3 · Cited by 69
Mild cognitive impairment: historical development and summary of research
Golomb, J. B., Kluger, A., & Ferris, S. H. (2004) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2004.6.4/jgolomb · Cited by 69
“Why some persons with medial temporal AD pathology are unimpaired (CDR=0), while others exhibit MCI is at present uncertain, although the explanation may, in part, reflect the emergence of neuronal loss within the entorhinal cortex,68,69 a more widespread neocortical localization of plaques and tangles,66 and, perhaps…”
MethodInfluential
Hypertension and Cognitive Function
Obisesan, T. O. (2009) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2009.03.002 · Cited by 71
“Late-onset AD patients demonstrating significant brain hypometabolism have attenuated perfusion in the hippocampal-amygdaloid complex, the anterior and posterior cingulate, and the anterior thalamus.(101,102) Regardless of the directionality of the association, collectively, the evidence mostly suggests that reduced C…”
Alzheimer's disease-related synapse loss in the cingulate cortex
Scheff, S. W., & PRICE, D. A. (2001) · Journal of Alzheimer s Disease · doi:10.3233/jad-2001-3509 · Cited by 68
“SPECT measurements of the caudal portion of the anterior cingulate appear to be a sensitive marker in individuals who “convert” to AD [36,37].”
Mild Cognitive Impairment and Dementia
Albert, M., & Blacker, D. (2006) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.144039 · Cited by 65
Self-citation
Circadian dysfunction and Alzheimer's disease – An updated review
Ahmad, F., Sachdeva, P., Sarkar, J., & Izhaar, R. (2022) · Aging Medicine · doi:10.1002/agm2.12221 · Cited by 70
The diffeomorphometry of regional shape change rates and its relevance to cognitive deterioration in mild cognitive impairment and A lzheimer's disease
Tang, X., Holland, D., Dale, A. M., Laurent Younes, B., Miller, M. I., & Initiative, A. D. N. (2015) · Human Brain Mapping · doi:10.1002/hbm.22758 · Cited by 67
“The observation that the left hemisphere is more severely affected in AD has also been reported in other literature, both metabolically and structurally [Janke et al., 2001; Johnson et al., 1998; Loewenstein et al., 1989; Thompson et al., 2001, 2003].”
Result
Single photon emission computed tomography perfusion differences in mild cognitive impairment
Johnson, K. A., Moran, E. K., Becker, J. A., Blacker, D., Fischman, A. J., & Albert, M. (2006) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.096800 · Cited by 67
Self-citation
Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers
Michels, L., Warnock, G., Buck, A., Macauda, G., Leh, S. E., Kaelin, A. M., Riese, F., Meyer, R., Tuura, R., Höck, C., et al. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15605847 · Cited by 63
“Alterations in regional cerebral blood flow (CBF) in subjects with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) have been consistently described.(1,2) These changes largely overlap with abnormalities in cerebral metabolism measured by 18-fluorodeoxyglucose positron emission tomography (FDG-PET).”
Background
Dissociation between top‐down attentional control and the time course of visual attention as measured by attentional dwell time in patients with mild cognitive impairment
Perry, R. J., & Hodges, J. R. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02754.x · Cited by 65
Mild Cognitive Impairment: Apparent Diffusion Coefficient in Regional Gray Matter and White Matter Structures
Ray, K. M., Wang, H., Chu, Y., Chen, Y., Bert, A., Hasso, A. N., & Su, M. (2006) · Radiology · doi:10.1148/radiol.2411051051 · Cited by 64
Amyloid-driven disruption of default mode network connectivity in cognitively healthy individuals
Ingala, S., Tomassen, J., Collij, L. E., Prent, N., Ent, D. V. ‘., ten Kate, M., Konijnenberg, E., Yaqub, M. M., Scheltens, P., de Geus, E. J. C., et al. (2021) · Brain Communications · doi:10.1093/braincomms/fcab201 · Cited by 65
“10,75,84,89,90 Our results confirm the central role of the PCC in Alzheimer’s disease, further extending the concept to the earliest phases of A b accumulation in cognitively healthy individuals, 8 as we show both early A b deposition and aberrant connectivity in this area.”
Result
Pathophysiology underlying diminished attention to novel events in patients with early AD
Daffner, K. R., Rentz, D. M., Scinto, L. F. M., Faust, R. R., Budson, A. E., & Holcomb, P. J. (2001) · Neurology · doi:10.1212/wnl.56.10.1377 · Cited by 60
Cognitive Impairment, No Dementia: Concepts and Issues
Tuokko, H. A., Frerichs, R. J., & Kristjansson, B. (2001) · International Psychogeriatrics · doi:10.1017/s104161020200813x · Cited by 62
On the multivariate nature of brain metabolic impairment in Alzheimer's disease
Salmon, É., Kerrouche, N., Perani, D., Lekeu, F., Holthoff‐Detto, V., Beuthien‐Baumann, B., Sorbi, S., Lemaire, C. F., Collette, F., & Herholz, K. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.06.010 · Cited by 58
Molecular neuroimaging in Alzheimer’s disease
Jagust, W. (2004) · Neurotherapeutics · doi:10.1602/neurorx.1.2.206 · Cited by 60
“fusion study found that individuals who subsequently converted to AD from MCI differed from normal controls in posterior and anterior cingulate, hippocampalamygdaloid complex, and anterior thalamus.(11) Although these studies in general used retrospective approaches in small samples, they suggest that molecular imagin…”
Ferulic Acid Ameliorates Alzheimer's Disease-like Pathology and Repairs Cognitive Decline by Preventing Capillary Hypofunction in APP/PS1 Mice
Wang, N.-Y., Li, J., Liu, W., Huang, Q., Li, W., Tan, Y., Liu, F., Song, Z., Wang, M.-Y., Xie, N., et al. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01024-7 · Cited by 59
Frequency Diffeomorphisms for Efficient Image Registration
Zhang, M., Liao, R., Dalca, A. V., et al. (2017) · Lecture notes in computer science · doi:10.1007/978-3-319-59050-9_44 · Cited by 56
“We evaluate the method on 3D brain MRI scans [9] and 4D in-utero MRI time series [11].”
Method
Inclusion of Neuropsychological Scores in Atrophy Models Improves Diagnostic Classification of Alzheimer’s Disease and Mild Cognitive Impairment
Goryawala, M., Zhou, Q., Barker, W., Loewenstein, D., Duara, R., & Adjouadi, M. (2015) · Computational Intelligence and Neuroscience · doi:10.1155/2015/865265 · Cited by 53
Long-term memory in Alzheimer’s disease
Fleischman, D. A., & Gabrieli, J. D. E. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)80034-8 · Cited by 52
Assessment of Suspected Dementia
Chertkow, H. M., Bergman, H., Schipper, H. M., Clarfield, A. M., Gauthier, S. G., Fontaine, S., & Bouchard, R. W. (2001) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100001189 · Cited by 52
Imaginem oblivionis: the prospects of neuroimaging for early detection of Alzheimer's disease
Villemagne, V. L., Rowe, C. C., Macfarlane, S., Novakovic, K. E., & Masters, C. L. (2005) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2004.03.011 · Cited by 50
A Two-Year Follow-Up of Cognitive Deficits and Brain Perfusion in Mild Cognitive Impairment and Mild Alzheimer's Disease
Alegret, M., Cuberas‐Borrós, G., Vinyes‐Junque, G., et al. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111850 · Cited by 49
Self-citation
Diagnostic Value of FDG-PET and HMPAO-SPET in Patients with Mild Dementia and Mild Cognitive Impairment: Metabolic Index and Perfusion Index
Döbert, N., Pantel, J., Frölich, L., Hamscho, N., Menzel, C., & Grünwald, F. (2005) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000085857 · Cited by 50
Age and ApoE genotype interaction in Alzheimer's disease: an FDG-PET study
Mosconi, L., Sorbi, S., Nacmias, B., Cristofaro, M. T. D., Fayyaz, M., Bracco, L., Herholz, K., & Pupi, A. (2004) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2003.12.005 · Cited by 50
“, 1990) and in the conversion from mild cognitive impairment to AD (Johnson et al., 1998; Matsuda et al., 2002), though irrespective of the ApoE genotype.”
Background
Limbic system perfusion in Alzheimer's disease measured by MRI-coregistered HMPAO SPET
Callen, D. J. A., Black, S. E., & Caldwell, C. B. (2002) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-002-0816-3 · Cited by 48
“Previous studies using SPM have found significant hypoperfusion or hypometabolism in some limbic regions in AD patients [28, 29 ].”
Result
Menopausal Hormone Therapy
Bhavnani, B. R., & Strickler, R. C. (2005) · Journal of Obstetrics and Gynaecology Canada · doi:10.1016/s1701-2163(16)30186-4 · Cited by 49
Deficits in Inhibition and Flexibility are Associated with the APOE-E4 Allele in Nondemented Older Adults
Wetter, S., Delis, D. C., Houston, W. S., Jacobson, M. W., Lansing, A. E., Cobell, K., Salmon, D. P., & Bondi, M. W. (2005) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/13803390490919001 · Cited by 47
Cerebral perfusion (HMPAO-SPECT) in patients with depression with cognitive impairment versus those with mild cognitive impairment and dementia of Alzheimer’s type: a semiquantitative and automated evaluation
Staffen, W., Bergmann, J., Huber-Schönauer, U., Zauner, H., Kronbichler, M., Golaszewski, S. M., & Ladurner, G. (2009) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-008-1028-2 · Cited by 49
Event Perception
Zacks, J. M., & Sargent, J. Q. (2010) · The Psychology of learning and motivation/The psychology of learning and motivation · doi:10.1016/s0079-7421(10)53007-x · Cited by 44
“Although the neurophysiological correlates of changes in attention in AD are not currently well understood (Hirao et al., 2005; Johnson et al., 1998), the literature does indicate that changes in attention and the precuneus, as well changes in memory and the MTL, may characterize early and even…”
Background
Classification of SPECT Images of Normal Subjects versus Images of Alzheimer’s Disease Patients
Stoeckel, J., Malandain, G., Migneco, O., et al. (2001) · Lecture notes in computer science · doi:10.1007/3-540-45468-3_80 · Cited by 47
“The majority of these results were obtained using techniques based on statistical parametric mapping (SPM) [3] or on principal component analysis (PCA)/singular value decomposition (SVD) [4,5,6].”
Method
Prediction of Preclinical Alzheimer's Disease: Longitudinal Rates of Change in Cognition
Riley, K. P., Jicha, G. A., Davis, D. G., Abner, E. L., Cooper, G. E., Stiles, N. J., Smith, C. D., Kryscio, R. J., Nelson, P. T., Eldik, L. J. V., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102133 · Cited by 55

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)
ORCID: Johnson, K. A.
Jones, K.
Becker, J. A.
Satlin, A.
Albert, M. S.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 1998-06
Volume: 50
Issue: 6
Pages: 1563-1571
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.50.6.1563
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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Preclinical prediction of Alzheimer's disease using SPECT

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