FDG- and amyloid-PET in Alzheimer's disease: is the whole greater than the sum of the parts?

The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring prior to the onset of clinical symptoms, when the potential for preservation of function is at the greatest. In vivo brain imaging is a promising tool for the early detection of AD through visualization of abnormalities in brain structure, function and histopathology. Currently, positron emission tomography (PET) imaging with amyloid-beta (Aβ) tracers and 2-[(18)F]fluoro-2-Deoxy-D-glucose (FDG) is largely utilized in the diagnosis of AD. This paper reviews brain Aβ- and FDG-PET studies in AD patients as well as in non-demented individuals at risk for AD. We then discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Aβ-PET to improve the early detection of AD.

[1]  Amity E. Green,et al.  Effects of ApoE4 and maternal history of dementia on hippocampal atrophy , 2012, Neurobiology of Aging.

[2]  M. Folstein,et al.  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 , 2011, Neurology.

[3]  D. Bennett,et al.  Neuropathological Associates of Multiple Cognitive Functions in Two Community-Based Cohorts of Older Adults , 2010, Journal of the International Neuropsychological Society.

[4]  Sterling C. Johnson,et al.  White matter is altered with parental family history of Alzheimer's disease , 2010, Alzheimer's & Dementia.

[5]  Wendy R. Sanhai,et al.  Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives , 2010, Nature Reviews Drug Discovery.

[6]  D. Bennett,et al.  Intermediate Phenotypes Identify Divergent Pathways to Alzheimer's Disease , 2010, PloS one.

[7]  Ranjan Duara,et al.  Reliability and validity of an algorithm for the diagnosis of normal cognition, mild cognitive impairment, and dementia: implications for multicenter research studies. , 2010, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[8]  S. de Santi,et al.  Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer’s , 2010, Proceedings of the National Academy of Sciences.

[9]  G. Grossberg,et al.  Dementia risk prediction: are we there yet? , 2010, Clinics in geriatric medicine.

[10]  C. Jack,et al.  Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade , 2010, The Lancet Neurology.

[11]  R. Honea,et al.  Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease , 2010, Neurology.

[12]  M. D. de Leon,et al.  Maternal transmission of Alzheimer's disease: Prodromal metabolic phenotype and the search for genes , 2010, Human Genomics.

[13]  A. Fagan,et al.  Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. , 2009, Archives of neurology.

[14]  J. Morris,et al.  Longitudinal study of the transition from healthy aging to Alzheimer disease. , 2009, Archives of neurology.

[15]  Nick C Fox,et al.  Conversion of amyloid positive and negative MCI to AD over 3 years , 2009, Neurology.

[16]  M. Sarazin,et al.  Faculty Opinions recommendation of Conversion of amyloid positive and negative MCI to AD over 3 years: an 11C-PIB PET study. , 2009 .

[17]  C. Jack,et al.  Comparison of 18F-FDG and PiB PET in Cognitive Impairment , 2009, Journal of Nuclear Medicine.

[18]  Jeffrey A. James,et al.  Amyloid imaging in mild cognitive impairment subtypes , 2009, Annals of neurology.

[19]  Rachel L. Mistur,et al.  Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease , 2009, Neurology.

[20]  Rachel L. Mistur,et al.  FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s disease , 2009, European Journal of Nuclear Medicine and Molecular Imaging.

[21]  H. Engler,et al.  PET imaging of amyloid deposition in patients with mild cognitive impairment , 2008, Neurobiology of Aging.

[22]  A. Paetau,et al.  PET amyloid ligand [11C]PIB uptake shows predominantly striatal increase in variant Alzheimer's disease. , 2008, Brain : a journal of neurology.

[23]  H. Rusinek,et al.  Regional analysis of FDG and PIB-PET images in normal aging, mild cognitive impairment, and Alzheimer’s disease , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[24]  S. Santi,et al.  Hippocampal hypometabolism predicts cognitive decline from normal aging , 2008, Neurobiology of Aging.

[25]  S. Aalto,et al.  Carbon 11-labeled pittsburgh compound B positron emission tomographic amyloid imaging in patients with APP locus duplication. , 2008, Archives of neurology.

[26]  C. Jack,et al.  11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment. , 2008, Brain : a journal of neurology.

[27]  C. Rowe,et al.  Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism , 2008, The Lancet Neurology.

[28]  H. Engler,et al.  [(11)C]-PIB imaging in patients with Parkinson's disease: preliminary results. , 2008, Parkinsonism & related disorders.

[29]  Rachel L. Mistur,et al.  Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism , 2007, Proceedings of the National Academy of Sciences.

[30]  V. Libri,et al.  PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. , 2007, Brain : a journal of neurology.

[31]  Keith A. Johnson,et al.  Imaging of amyloid burden and distribution in cerebral amyloid angiopathy , 2007, Annals of neurology.

[32]  Kathryn Ziegler-Graham,et al.  Forecasting the global burden of Alzheimer’s disease , 2007, Alzheimer's & Dementia.

[33]  M. Viitanen,et al.  PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment , 2007, Neurology.

[34]  V. Haroutunian,et al.  Correlation of the clinical severity of alzheimer’s disease with an aberration in mitochondrial DNA (mtDNA) , 2001, Journal of Molecular Neuroscience.

[35]  T. J. Grabowski,et al.  Two-year followup of amyloid deposition in patients with Alzheimer's disease , 2007 .

[36]  Paul Maruff,et al.  Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. , 2007, Brain : a journal of neurology.

[37]  P. Thompson,et al.  PET of brain amyloid and tau in mild cognitive impairment. , 2006, The New England journal of medicine.

[38]  M. Viitanen,et al.  Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease , 2006, Neurology.

[39]  M. D. de Leon,et al.  Hypometabolism exceeds atrophy in presymptomatic early-onset familial Alzheimer's disease. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[40]  H. Engler,et al.  Two-year follow-up of amyloid deposition in patients with Alzheimer's disease. , 2006, Brain : a journal of neurology.

[41]  Keith A. Johnson,et al.  P2-366 Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees , 2006, Alzheimer's & Dementia.

[42]  R. Petersen,et al.  Cognitive measures predict pathologic Alzheimer disease. , 2006, Archives of neurology.

[43]  Felice Sun,et al.  Brain imaging evidence of preclinical Alzheimer's disease in normal aging , 2006, Annals of neurology.

[44]  V. Kepe,et al.  Exploring a Mathematical Model for the Kinetics of β-Amyloid Molecular Imaging Probes through a Critical Analysis of Plaque Pathology , 2006, Molecular Imaging and Biology.

[45]  K. Davis,et al.  Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease , 2006, Neurology.

[46]  Yvette I. Sheline,et al.  Potential antecedent marker of Alzheimer disease , 2006 .

[47]  S. DeKosky,et al.  Simplified quantification of Pittsburgh Compound B amyloid imaging PET studies: a comparative analysis. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[48]  D. Perani,et al.  Heterogeneity of brain glucose metabolism in mild cognitive impairment and clinical progression to Alzheimer disease. , 2005, Archives of neurology.

[49]  Sue J. Kang,et al.  Glucose metabolism in early onset versus late onset Alzheimer's disease: an SPM analysis of 120 patients. , 2005, Brain : a journal of neurology.

[50]  S. DeKosky,et al.  Kinetic Modeling of Amyloid Binding in Humans using PET Imaging and Pittsburgh Compound-B , 2005, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[51]  G. Small,et al.  Imaging beta-amyloid fibrils in Alzheimer's disease: a critical analysis through simulation of amyloid fibril polymerization. , 2005, Nuclear medicine and biology.

[52]  D. Marin,et al.  Variability of familial risk of Alzheimer disease across the late life span. , 2005, Archives of general psychiatry.

[53]  L. Mosconi,et al.  Brain glucose metabolism in the early and specific diagnosis of Alzheimer’s disease , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[54]  D. Perani,et al.  MCI conversion to dementia and the APOE genotype , 2004, Neurology.

[55]  R. Green,et al.  Estimating risk curves for first-degree relatives of patients with Alzheimer’s disease: The REVEAL study , 2004, Genetics in Medicine.

[56]  D A Bennett,et al.  State-specific projections through 2025 of Alzheimer disease prevalence , 2004, Neurology.

[57]  W. Klunk,et al.  Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B , 2004, Annals of neurology.

[58]  P. Hof,et al.  Neuropathological changes in the cerebral cortex of 1258 cases from a geriatric hospital: retrospective clinicopathological evaluation of a 10-year autopsy population , 1994, Acta Neuropathologica.

[59]  W. Klunk,et al.  Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain. , 2004, Current pharmaceutical design.

[60]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[61]  G. Alexander,et al.  Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[62]  G. Small,et al.  Prognostic value of regional cerebral metabolism in patients undergoing dementia evaluation: comparison to a quantifying parameter of subsequent cognitive performance and to prognostic assessment without PET. , 2003, Molecular Genetics and Metabolism.

[63]  Alan A. Wilson,et al.  11C-labeled stilbene derivatives as Abeta-aggregate-specific PET imaging agents for Alzheimer's disease. , 2003, Nuclear medicine and biology.

[64]  D. Bennett,et al.  Alzheimer disease in the US population: prevalence estimates using the 2000 census. , 2003, Archives of neurology.

[65]  A. Drzezga,et al.  Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[66]  Simon M Laws,et al.  Expanding the association between the APOE gene and the risk of Alzheimer's disease: possible roles for APOE promoter polymorphisms and alterations in APOE transcription , 2003, Journal of neurochemistry.

[67]  J. Blass,et al.  Alzheimer’s disease and Alzheimer’s dementia: distinct but overlapping entities , 2002, Neurobiology of Aging.

[68]  G. Schellenberg,et al.  Dementia and Alzheimer disease incidence: a prospective cohort study. , 2002, Archives of neurology.

[69]  et al.,et al.  Discrimination between Alzheimer Dementia and Controls by Automated Analysis of Multicenter FDG PET , 2002, NeuroImage.

[70]  G. Alexander,et al.  Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies. , 2002, The American journal of psychiatry.

[71]  A. Granholm,et al.  Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh , 2002, Trends in Neurosciences.

[72]  R. Green,et al.  Risk of dementia among white and African American relatives of patients with Alzheimer disease. , 2002, JAMA.

[73]  G. Small,et al.  Binding Characteristics of Radiofluorinated 6-Dialkylamino-2-Naphthylethylidene Derivatives as Positron Emission Tomography Imaging Probes for β-Amyloid Plaques in Alzheimer's Disease , 2001, The Journal of Neuroscience.

[74]  J. Morris,et al.  Current concepts in mild cognitive impairment. , 2001, Archives of neurology.

[75]  G. Alexander,et al.  Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome. , 2001, JAMA.

[76]  Lars Bertram,et al.  New Frontiers in Alzheimer's Disease Genetics , 2001, Neuron.

[77]  M. J. Wade,et al.  Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. , 2001, Archives of neurology.

[78]  M. Bobinski,et al.  Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET) , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[79]  G. Alexander,et al.  Declining brain activity in cognitively normal apolipoprotein E ɛ4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[80]  J. Mazziotta,et al.  Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[81]  R. Lipton,et al.  The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians. , 2000, Archives of neurology.

[82]  K. Davis,et al.  Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline. , 2000, JAMA.

[83]  Mayo Clinic,et al.  PRECLINICAL EVIDENCE OF ALZHEIMER’S DISEASE IN PERSONS HOMOZYGOUS FOR THE , 2000 .

[84]  F. Fazio,et al.  Impairment of Neocortical Metabolism Predicts Progression in Alzheimer’s Disease , 1999, Dementia and Geriatric Cognitive Disorders.

[85]  M. Mesulam.  Neuroplasticity Failure in Alzheimer's Disease Bridging the Gap between Plaques and Tangles , 1999, Neuron.

[86]  Michael E. Phelps,et al.  Clinical Value of Neuroimaging in the Diagnosis of Dementia. Sensitivity and Specificity of Regional Cerebral Metabolic and Other Parameters for Early Identification of Alzheimer's Disease. , 1999, Clinical positron imaging : official journal of the Institute for Clinical P.E.T.

[87]  A. Delacourte,et al.  The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease , 1999, Neurology.

[88]  E. Tangalos,et al.  Mild Cognitive Impairment Clinical Characterization and Outcome , 1999 .

[89]  J. Morris,et al.  Tangles and plaques in nondemented aging and “preclinical” Alzheimer's disease , 1999, Annals of neurology.

[90]  L. Lue,et al.  Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer's disease. , 1999, The American journal of pathology.

[91]  T. Morgan,et al.  Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[92]  N. Robakis,et al.  Alzheimer's disease: a re-examination of the amyloid hypothesis , 1998, Trends in Neurosciences.

[93]  K. Jobst,et al.  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 , 1997, International Psychogeriatrics.

[94]  J. Morrison,et al.  Life and death of neurons in the aging brain. , 1997, Science.

[95]  N. Foster,et al.  Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease , 1997, Annals of neurology.

[96]  D. Perani,et al.  PET study in subjects from two Italian FAD families with APP717 Val to Ileu mutation , 1997 .

[97]  D. Selkoe,et al.  Alzheimer's Disease--Genotypes, Phenotype, and Treatments , 1997, Science.

[98]  N. Volkow,et al.  Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[99]  H. Braak,et al.  Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis , 1996, Acta Neuropathologica.

[100]  J. Price,et al.  Cerebral amyloid deposition and diffuse plaques in ``normal'' aging , 1996, Neurology.

[101]  R. Mohs,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). , 1995, Neurology.

[102]  J C Mazziotta,et al.  Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. , 1995, JAMA.

[103]  Richard S. J. Frackowiak,et al.  Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer's disease , 1995, Neuroscience Letters.

[104]  R. Frackowiak,et al.  Chromosome 14 linked familial Alzheimer's disease. A clinico-pathological study of a single pedigree. , 1995, Brain : a journal of neurology.

[105]  K. Herholz,et al.  Quantitative topographical EEG compared to FDG PET for classification of vascular and degenerative dementia. , 1994, Electroencephalography and clinical neurophysiology.

[106]  Bradley T. Hyman,et al.  Distribution of Alzheimer‐type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease , 1992, Neurology.

[107]  D. Salmon,et al.  Physical basis of cognitive alterations in alzheimer's disease: Synapse loss is the major correlate of cognitive impairment , 1991, Annals of neurology.

[108]  R. Martins,et al.  A4 amyloid protein deposition and the diagnosis of Alzheimer's disease , 1988, Neurology.

[109]  C. L. Grady,et al.  Stability of metabolic and neuropsychological asymmetries in dementia of the Alzheimer type , 1986, Neurology.

[110]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[111]  J. Ulrich,et al.  Alzheimer changes in nondemented patients younger than sixty‐five: Possible early stages of Alzheimer's disease and senile dementia of Alzheimer type , 1985, Annals of neurology.

[112]  A. Nappi,et al.  Alzheimer ' s Disease : Cell-Specific Pathology Isolates the Hippocampal Formation , 2022 .