Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease

Objective To determine whether the hypometabolism observed in PET images of patients with Alzheimer's disease (AD) is due entirely to brain atrophy. Background Reduced brain glucose metabolism in AD patients measured using PET has been reported by numerous authors. Actual glucose metabolic values in AD may be reduced artificially because of brain atrophy, which accentuates the partial volume effect (PVE) on data collected by PET. Methods Using segmented MR images, we corrected regional cerebral metabolic rates for glucose for PVEs to evaluate the effect of atrophy on uncorrected values for brain metabolism in AD patients and healthy control subjects. Results Global glucose metabolism was reduced significantly before and after correction in AD patients compared with controls. Before PVE correction, glucose metabolic values in patients were lower than in control subjects in the inferior parietal, frontal, and lateral temporal cortex; in the posterior cingulate; and in the precuneus. These reductions remained significantly lower after PVE correction, although in the posterior cingulate the difference in metabolism between AD patients and control subjects lessened. Regional glucose metabolism of these areas with PVE correction was lower in moderately-severely demented patients than in mildly demented patients. Conclusion Reduced glucose metabolism measured by PET in AD is not simply an artifact due to an increase in CSF space induced by atrophy, but reflects a true metabolic reduction per gram of tissue.

[1]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[2]  M. Reivich,et al.  THE [14C]DEOXYGLUCOSE METHOD FOR THE MEASUREMENT OF LOCAL CEREBRAL GLUCOSE UTILIZATION: THEORY, PROCEDURE, AND NORMAL VALUES IN THE CONSCIOUS AND ANESTHETIZED ALBINO RAT 1 , 1977, Journal of neurochemistry.

[3]  Louis Sokoloff,et al.  Activity‐dependent Energy Metabolism in Rat Posterior Pituitary Primarily Reflects Sodium Pump Activity , 1980, Journal of neurochemistry.

[4]  E. Hoffman,et al.  Noninvasive determination of local cerebral metabolic rate of glucose in man. , 1980, The American journal of physiology.

[5]  R. DeTeresa,et al.  Some morphometric aspects of the brain in senile dementia of the alzheimer type , 1981, Annals of neurology.

[6]  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.

[7]  R A Brooks,et al.  Alternative formula for glucose utilization using labeled deoxyglucose. , 1982, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  N. Foster,et al.  Wechsler Adult Intelligence Scale performance. Cortical localization by fluorodeoxyglucose F 18-positron emission tomography. , 1984, Archives of neurology.

[9]  J. Haxby,et al.  Relations between Neuropsychological and Cerebral Metabolic Asymmetries in Early Alzheimer's Disease , 1985, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  Peter Herscovitch,et al.  Correction of Positron Emission Tomography Data for Cerebral Atrophy , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[11]  J. Haxby,et al.  Positron emission tomography in Alzheimer's disease , 1986, Neurology.

[12]  B Horwitz,et al.  Relation of measured brain glucose utilisation and cerebral atrophy in man. , 1987, Journal of neurology, neurosurgery, and psychiatry.

[13]  R. DeTeresa,et al.  Neocortical cell counts in normal human adult aging , 1987, Annals of neurology.

[14]  C. Grady,et al.  Cerebral metabolism, anatomy, and cognition in monozygotic twins discordant for dementia of the Alzheimer type. , 1987, Journal of neurology, neurosurgery, and psychiatry.

[15]  D. Mann,et al.  A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease , 1987, Journal of the Neurological Sciences.

[16]  A. Alavi,et al.  Positron emission tomography in aging and dementia: effect of cerebral atrophy. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[17]  M E Raichle,et al.  Regional Correction of Positron Emission Tomography Data for the Effects of Cerebral Atrophy , 1988, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  B. Horwitz Neuroplasticity and the progression of Alzheimer's disease. , 1988, The International journal of neuroscience.

[19]  B Horwitz,et al.  Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type. , 1988, Journal of clinical and experimental neuropsychology.

[20]  A. Alavi,et al.  Comparison of CT, MR, and PET in Alzheimer's dementia and normal aging. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  W. Jagust,et al.  Regional cerebral glucose transport and utilization in Alzheimer's disease , 1989, Neurology.

[22]  M. Torrens Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[23]  H. Mayberg,et al.  Correction of PET Data for Partial Volume Effects in Human Cerebral Cortex by MR Imaging , 1990, Journal of computer assisted tomography.

[24]  Karl J. Friston,et al.  The Relationship between Global and Local Changes in PET Scans , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  Stephen W. Scheff,et al.  Quantitative assessment of cortical synaptic density in Alzheimer's disease , 1990, Neurobiology of Aging.

[26]  Gwenn S. Smith,et al.  Alzheimer disease: measuring loss of cerebral gray matter with MR imaging. , 1991, Radiology.

[27]  Karl J. Friston,et al.  Comparing Functional (PET) Images: The Assessment of Significant Change , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  K. Herholz,et al.  Abnormalities of Energy Metabolism in Alzheimer's Disease Studied with PET a , 1991, Annals of the New York Academy of Sciences.

[29]  H. Fukuyama,et al.  Coronal reconstruction images of glucose metabolism in Alzheimer's disease , 1991, Journal of the Neurological Sciences.

[30]  J V Haxby,et al.  High-resolution PET studies in Alzheimer's disease. , 1991, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[31]  J. Haxby,et al.  Longitudinal changes in lateral ventricular volume in Datients with dementia of the Alzheimer type , 1992, Neurology.

[32]  Jerry L Prince,et al.  Measurement of Radiotracer Concentration in Brain Gray Matter Using Positron Emission Tomography: MRI-Based Correction for Partial Volume Effects , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[33]  Alan C. Evans,et al.  A Three-Dimensional Statistical Analysis for CBF Activation Studies in Human Brain , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  J. Mazziotta,et al.  Rapid Automated Algorithm for Aligning and Reslicing PET Images , 1992, Journal of computer assisted tomography.

[35]  M. Albert,et al.  Temporal lobe regions on magnetic resonance imaging identify patients with early Alzheimer's disease. , 1993, Archives of neurology.

[36]  A. Alavi,et al.  Quantitative analysis of PET and MRI data in normal aging and Alzheimer's disease: atrophy weighted total brain metabolism and absolute whole brain metabolism as reliable discriminators. , 1993, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[37]  P. Lantos,et al.  Alzheimer's Disease Families with Amyloid Precursor Protein Mutations a , 1993, Annals of the New York Academy of Sciences.

[38]  C. Grady,et al.  Parametric in vivo brain imaging during activation to examine pathological mechanisms of functional failure in Alzheimer disease. , 1993, The International journal of neuroscience.

[39]  B. Horwitz,et al.  Volumetric magnetic resonance imaging in men with dementia of the Alzheimer type: Correlations with disease severity , 1993, Biological Psychiatry.

[40]  J. Mazziotta,et al.  MRI‐PET Registration with Automated Algorithm , 1993, Journal of computer assisted tomography.

[41]  Karl J. Friston,et al.  Assessing the significance of focal activations using their spatial extent , 1994, Human brain mapping.

[42]  Karl J. Friston,et al.  Functional neuroanatomy of the human brain: positron emission tomography--a new neuroanatomical technique. , 1994, Journal of anatomy.

[43]  M. Jüptner,et al.  Review: Does Measurement of Regional Cerebral Blood Flow Reflect Synaptic Activity?—Implications for PET and fMRI , 1995, NeuroImage.

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

[45]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[46]  W. Jagust,et al.  Functional Imaging Patterns in Alzheimer's Disease Relationships to Neurobiology a , 1996, Annals of the New York Academy of Sciences.

[47]  R. Frackowiak,et al.  Clinical and Neuroimaging Features of Familial Alzheimer's Disease a , 1996, Annals of the New York Academy of Sciences.

[48]  J. Brandt,et al.  Regional hypometabolism in Alzheimer's disease as measured by positron emission tomography after correction for effects of partial volume averaging , 1996, Neurology.

[49]  Jagath C. Rajapakse,et al.  Statistical approach to segmentation of single-channel cerebral MR images , 1997, IEEE Transactions on Medical Imaging.

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