Brain 18F-FDG PET in the diagnosis of neurodegenerative dementias: comparison with perfusion SPECT and with clinical evaluations lacking nuclear imaging.

The clinical identification and differential diagnosis of dementias is especially challenging in the early stages, but the need for early, accurate diagnosis has become more important, now that several medications for the treatment of mild to moderate Alzheimer's disease (AD) are available. Many neurodegenerative diseases produce significant brain-function alterations detectable with PET or SPECT even when structural images with CT or MRI reveal no specific abnormalities. (18)F-FDG PET images of AD demonstrate focally decreased cerebral metabolism involving especially the posterior cingulate and neocortical association cortices, while largely sparing the basal ganglia, thalamus, cerebellum, and cortex mediating primary sensory and motor functions. Assessment of the precise diagnostic accuracy of PET had until recently been hindered by the paucity of data on diagnoses made using PET and confirmed by definitive histopathologic examination. In the past few years, however, studies comparing neuropathologic examination with PET have established reliable and consistent accuracy for diagnostic evaluations using PET-accuracies substantially exceeding those of comparable studies of the diagnostic value of SPECT or of both modalities assessed side by side, or of clinical evaluations done without nuclear imaging. Similar data are emerging concerning the prognostic value of (18)F-FDG PET. Improvements in the ability of PET to identify very early changes associated with AD and other neurodegenerative dementias are currently outpacing improvements in therapeutic options, but with advances in potential preventive and disease-modifying treatments appearing imminent, early detection and diagnosis will play an increasing role in the management of dementing illness.

[1]  S H Ferris,et al.  A family intervention to delay nursing home placement of patients with Alzheimer disease. A randomized controlled trial. , 1996, JAMA.

[2]  K Herholz,et al.  FDG PET and Differential Diagnosis of Dementia , 1995, Alzheimer disease and associated disorders.

[3]  A. Alavi,et al.  18F-2-deoxy-2-fluoro-D-glucose as a tracer in the positron emission tomographic study of senile dementia. , 1982, The American journal of psychiatry.

[4]  B. Gordon,et al.  Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. , 2001, Archives of neurology.

[5]  M. Wittekind,et al.  Comparative studies of active site-ligand interactions among various recombinant constructs of human beta-amyloid precursor protein cleaving enzyme. , 2003, Archives of biochemistry and biophysics.

[6]  M. Spieth,et al.  A tabulated summary of the FDG PET literature. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[7]  Dementia: Causes, Evaluation, and Management , 2001, Hospital practice.

[8]  J. Price,et al.  Mild cognitive impairment represents early-stage Alzheimer disease. , 2001, Archives of neurology.

[9]  B. Miller,et al.  CME Practice parameter : Diagnosis of dementia ( an evidence-based review ) Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2001 .

[10]  J. Haxby Resting state regional cerebral metabolism in dementia of the Alzheimer type , 1990 .

[11]  A. Convit,et al.  Hippocampal formation glucose metabolism and volume losses in MCI and AD , 2001, Neurobiology of Aging.

[12]  D. Benson,et al.  Positron emission computed tomography in the diagnosis of dementia. , 1981, Transactions of the American Neurological Association.

[13]  E. Peskind,et al.  Galantamine in AD , 2000, Neurology.

[14]  M H Buonocore,et al.  Brain structure and cognition in a community sample of elderly Latinos , 2002, Neurology.

[15]  H. Chui,et al.  Multicenter clinicopathological correlation in dementia. , 1995, The American journal of psychiatry.

[16]  P. Tariot,et al.  A 5-month, randomized, placebo-controlled trial of galantamine in AD , 2000, Neurology.

[17]  R. Hoffman Diagnostic errors in the evaluation of behavioral disorders. , 1982, JAMA.

[18]  William J Jagust,et al.  Brain function and cognition in a community sample of elderly Latinos , 2002, Neurology.

[19]  S H Ferris,et al.  Diagnosis and treatment of Alzheimer disease and related disorders. Consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society. , 1997, JAMA.

[20]  G. Waldemar,et al.  Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus. , 1995, Journal of neurology, neurosurgery, and psychiatry.

[21]  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.

[22]  O Almkvist,et al.  Impaired cerebral glucose metabolism and cognitive functioning predict deterioration in mild cognitive impairment , 2001, Neuroreport.

[23]  B. Reisberg,et al.  Positron emission tomography in dementia. , 1983, Advances in neurology.

[24]  S S Gambhir,et al.  A tabulated summary of the FDG PET literature. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  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.

[26]  J. Coyle,et al.  Galantamine, a cholinesterase inhibitor that allosterically modulates nicotinic receptors: effects on the course of Alzheimer’s disease , 2001, Biological Psychiatry.

[27]  Richard S. J. Frackowiak,et al.  The use of positron emission tomography in the clinical assessment of dementia. , 1992, Seminars in nuclear medicine.

[28]  K. Någren,et al.  Brain acetylcholinesterase activity in mild cognitive impairment and early Alzheimer’s disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[29]  B J Shepstone,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 , 1998, International Psychogeriatrics.

[30]  Karl J. Friston,et al.  Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions , 1993, Psychological Medicine.

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

[32]  Michael D. Devous,et al.  Functional brain imaging in the dementias: role in early detection, differential diagnosis, and longitudinal studies , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[33]  F Zito,et al.  High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's disease: comparison with fluorine-18-FDG PET. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[34]  Klemens Scheidhauer,et al.  Direct comparison of spatially normalized PET and SPECT scans in Alzheimer's disease. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[35]  W M Tierney,et al.  Documentation and Evaluation of Cognitive Impairment in Elderly Primary Care Patients , 1995, Annals of Internal Medicine.

[36]  G. Alexander,et al.  The neurometabolic landscape of cognitive decline: in vivo studies with positron emission tomography in Alzheimer's disease. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[37]  L. Friedhoff,et al.  The efficacy and safety of donepezil in patients with Alzheimer's disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial , 1996 .

[38]  L. Wilkins Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension , 2000, Neurology.

[39]  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.

[40]  R. Coleman,et al.  Interpretation variability of 18FDG-positron emission tomography studies in dementia. , 1996, Investigative radiology.

[41]  Functional Cerebral SPECT and PET Imaging , 2000 .

[42]  Jeffrey L. Cummings,et al.  Practice parameter: Diagnosis of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology , 2001 .

[43]  R B D'Agostino,et al.  Incidence of dementia and probable Alzheimer's disease in a general population , 1993, Neurology.

[44]  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.

[45]  T Jones,et al.  Regional cerebral oxygen supply and utilization in dementia. A clinical and physiological study with oxygen-15 and positron tomography. , 1981, Brain : a journal of neurology.

[46]  J. Hoffman,et al.  FDG PET imaging in patients with pathologically verified dementia. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[47]  Positron and single photon emission tomography in the differential diagnosis of dementia , 1990 .

[48]  Peter J. Ell,et al.  Nuclear medicine in clinical diagnosis and treatment , 2004 .

[49]  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.

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

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

[52]  Gereon R. Fink,et al.  HMPAO SPET and FDG PET in Alzheimer's disease and vascular dementia: comparison of perfusion and metabolic pattern , 1994, European Journal of Nuclear Medicine.