Topographic Patterns of Brain Functional Impairment Progression According to Clinical Severity Staging in 116 Alzheimer Disease Patients: FDG-PET Study

The study aimed to explore topographic progression pattern of brain functional impairment according to clinical stage in Alzheimer disease (AD). One hundred and sixteen AD patients and 25 normal subjects underwent a [18F] fluorodeoxyglucose-positron emission tomography scan. Regional cerebral glucose metabolism was compared between severity groups based on the Clinical Dementia Rating through voxel-based analyses. As clinical severity progressed, hypometabolic areas gradually increased, involving initially posterior cingulate cortex, later temporoparietal, and finally frontal and some subcortical areas. The results indicate that progression patterns of hypometabolism in AD are close to that of typical neuropathology, but that they do not fully coincide with it.

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

[2]  L A Hansen,et al.  The importance of neuritic plaques and tangles to the development and evolution of AD , 2004, Neurology.

[3]  S. DeKosky,et al.  Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity , 1990, Annals of neurology.

[4]  A. Convit,et al.  Reduced hippocampal metabolism in MCI and AD , 2005, Neurology.

[5]  B. Landeau,et al.  Effects of Healthy Aging on the Regional Cerebral Metabolic Rate of Glucose Assessed with Statistical Parametric Mapping , 1996, NeuroImage.

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

[7]  S. Laureys,et al.  Comparison of Impaired Subcortico-Frontal Metabolic Networks in Normal Aging, Subcortico-Frontal Dementia, and Cortical Frontal Dementia , 1999, NeuroImage.

[8]  D. Y. Lee,et al.  Development of the Korean Version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K)Clinical and Neuropsychological Assessment Batteries , 2002 .

[9]  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.

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

[11]  E K Perry,et al.  Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. , 1978, British medical journal.

[12]  D. Bennett,et al.  MRI-derived entorhinal and hippocampal atrophy in incipient and very mild Alzheimer’s disease☆ ☆ This research was supported by grants P01 AG09466 and P30 AG10161 from the National Institute on Aging, National Institutes of Health. , 2001, Neurobiology of Aging.

[13]  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.

[14]  N. Foster,et al.  Preserved Pontine Glucose Metabolism in Alzheimer Disease: A Reference Region for Functional Brain Image (PET) Analysis , 1995, Journal of computer assisted tomography.

[15]  M Petrides,et al.  Architecture and connections of retrosplenial area 30 in the rhesus monkey (macaca mulatta). , 1999, The European journal of neuroscience.

[16]  G K Wilcock,et al.  Neurotransmitter dysfunction and atrophy of the caudate nucleus in Alzheimer's disease. , 1984, Neurochemical pathology.

[17]  Ki Woong Kim,et al.  A normative study of the CERAD neuropsychological assessment battery in the Korean elderly , 2004, Journal of the International Neuropsychological Society.

[18]  C. P. Hughes,et al.  A New Clinical Scale for the Staging of Dementia , 1982, British Journal of Psychiatry.

[19]  J. Hodges,et al.  Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment , 2003, Annals of neurology.

[20]  D Comar,et al.  Differential diagnosis of Alzheimer's disease with PET. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  J. Baron,et al.  Mild cognitive impairment , 2003, Neurology.

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

[23]  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.

[24]  Christian Degueldre,et al.  Voxel‐based analysis of confounding effects of age and dementia severity on cerebral metabolism in Alzheimer's disease , 2000, Human brain mapping.

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

[26]  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.

[27]  S S Furuie,et al.  Relation between medial temporal atrophy and functional brain activity during memory processing in Alzheimer’s disease: a combined MRI and SPECT study , 2002, Journal of neurology, neurosurgery, and psychiatry.

[28]  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.

[29]  K. Ishii,et al.  Glucose metabolic dysfunction in subjects with a Clinical Dementia Rating of 0.5 , 2003, Journal of the Neurological Sciences.

[30]  C. Grady,et al.  Heterogeneous anterior‐posterior metabolic patterns in dementia of the Alzheimer type , 1988, Neurology.

[31]  J. Morris,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease , 1989, Neurology.

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

[33]  G. Alexander,et al.  Association between brain functional failure and dementia severity in Alzheimer's disease: resting versus stimulation PET study. , 1999, The American journal of psychiatry.

[34]  P Pietrini,et al.  Increasing required neural response to expose abnormal brain function in mild versus moderate or severe Alzheimer's disease: PET study using parametric visual stimulation. , 1998, The American journal of psychiatry.

[35]  S. Black,et al.  Beyond the hippocampus , 2001, Neurology.

[36]  K. Herholz,et al.  Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type , 1992, Neurobiology of Aging.

[37]  J. Morris.  The Clinical Dementia Rating (CDR) , 1993, Neurology.

[38]  T. Tombaugh,et al.  The Mini‐Mental State Examination: A Comprehensive Review , 1992, Journal of the American Geriatrics Society.

[39]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[40]  L. Sokoloff,et al.  Relationships among local functional activity, energy metabolism, and blood flow in the central nervous system. , 1981, Federation proceedings.

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

[42]  G. Alexander,et al.  Regional glucose metabolic abnormalities are not the result of atrophy in Alzheimer's disease , 1998, Neurology.

[43]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[44]  Lars-Olof Wahlund,et al.  Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment , 2002, BMC neurology.