Seeing is believing: neuroimaging adds to our understanding of cerebral pathology

Purpose of review Recent technological developments in neuroimaging have led to new technologies that provide measures of the cerebral pathology of neurodegeneration in living humans. The purpose of this review is to provide background behind these developments and update readers on new findings. Recent findings Several imaging methods using positron emission tomography have provided measures of amyloid senile plaques in the brain of demented patients and patients with early memory symptoms. ([F-18]FDDNP)-positron emission tomography provides measures of both amyloid plaques and neurofibrillary tangles. Initial results indicate that the pattern of binding values in Alzheimer's disease is consistent with the known neuropathology from autopsy studies, and patients with mild cognitive impairment, who are at risk of Alzheimer's disease, show binding values intermediate between Alzheimer's disease and normal aging. 2-(1-{6-[(2-[F-18]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) positron emission tomography also shows a pattern of neuropathology distribution for frontotemporal dementia that differs from that of Alzheimer's disease. Summary In-vivo imaging of cerebral pathology offers the potential for more effective and earlier diagnosis and use of these technologies as surrogate markers to test novel treatments aimed at preventing or eliminating cerebral plaque and tangle accumulation.

[1]  W Vaalburg,et al.  On the quantification of [18F]MPPF binding to 5-HT1A receptors in the human brain. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

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

[3]  C. Jack,et al.  Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment , 1999, Neurology.

[4]  M. Pangalos,et al.  Neurotransmitter receptors of rat cortical pyramidal neurones: implications for in vivo imaging and therapy. , 1993, Journal of reproduction and fertility. Supplement.

[5]  Sung-Cheng Huang,et al.  Serotonin 1A receptors in the living brain of Alzheimer's disease patients. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

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

[7]  G. Small Neuroimaging as a Diagnostic Tool in Dementia with Lewy Bodies , 2003, Dementia and Geriatric Cognitive Disorders.

[8]  A. Drzezga,et al.  Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

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

[10]  Brigitte Landeau,et al.  Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: A longitudinal MRI study , 2005, NeuroImage.

[11]  Nick C Fox,et al.  A Volumetric Magnetic Resonance Imaging Study of the Amygdala in Frontotemporal Lobar Degeneration and Alzheimer’s Disease , 2005, Dementia and Geriatric Cognitive Disorders.

[12]  Ellen Frank,et al.  Anatomical MRI study of corpus callosum in unipolar depression. , 2005, Journal of psychiatric research.

[13]  William E. Klunk,et al.  The Binding of 2-(4′-Methylaminophenyl)Benzothiazole to Postmortem Brain Homogenates Is Dominated by the Amyloid Component , 2003, The Journal of Neuroscience.

[14]  H. Akiyama,et al.  A high incidence of apolipoprotein E ε4 allele in middle-aged non-demented subjects with cerebral amyloid β protein deposits , 1999, Acta Neuropathologica.

[15]  E. Tangalos,et al.  CME Practice parameter: , 2022 .

[16]  H. Soininen,et al.  MRI of the Hippocampus in Alzheimer’s Disease: Sensitivity, Specificity, and Analysis of the Incorrectly Classified Subjects , 1998, Neurobiology of Aging.

[17]  Paul M. Grasby,et al.  A positron emission tomography (PET) investigation of the role of striatal dopamine (D2) receptor availability in spatial cognition , 2005, NeuroImage.

[18]  M. Pangalos,et al.  5-Hydroxytryptamine1A but not 5-hydroxytryptamine2 receptors are enriched on neocortical pyramidal neurones destroyed by intrastriatal volkensin. , 1992, The Journal of pharmacology and experimental therapeutics.

[19]  Daniel L. Schacter,et al.  Retrieving accurate and distorted memories: Neuroimaging evidence for effects of emotion , 2005, NeuroImage.

[20]  V. Kepe,et al.  In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer’s brain using the positron emission tomography molecular imaging probe 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile , 2003, Neuroscience.

[21]  D R Wekstein,et al.  Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study. , 1996, JAMA.

[22]  J. Cummings,et al.  A potential role of the curry spice curcumin in Alzheimer's disease. , 2005, Current Alzheimer research.

[23]  G. Small,et al.  In vivo [F-18]FDDNP microPET imaging of brain B-amyloid in a transgenic rat model of Alzheimer’s disease , 2005, Alzheimer's & Dementia.

[24]  L. Frölich,et al.  The clinical utility of structural neuroimaging with MRI for diagnosis and differential diagnosis of dementia: a memory clinic study , 2005, International journal of geriatric psychiatry.

[25]  G. Small,et al.  Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. , 2002, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

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

[27]  K. Ishii,et al.  Cerebral glucose metabolism in patients with frontotemporal dementia. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  F Barkhof,et al.  Progression of cerebral white matter lesions in Alzheimer’s disease: a new window for therapy? , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[29]  P. Van Bogaert,et al.  Comparative study of hippocampal neuronal loss and in vivo binding of 5-HT1a receptors in the KA model of limbic epilepsy in the rat , 2001, Epilepsy Research.

[30]  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.

[31]  R. Albin,et al.  Cerebral metabolic differences in Parkinson's and Alzheimer's diseases matched for dementia severity. , 1997, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  J. Trojanowski,et al.  Iodinated tracers for imaging amyloid plaques in the brain. , 2003, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[33]  Richard Hollister,et al.  Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease , 1997, Annals of neurology.

[34]  Mark S. Cohen,et al.  Patterns of brain activation in people at risk for Alzheimer's disease. , 2000, The New England journal of medicine.

[35]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[36]  M. Mendez,et al.  Loss of insight and functional neuroimaging in frontotemporal dementia. , 2005, The Journal of neuropsychiatry and clinical neurosciences.