Glucose Metabolic Brain Networks in Early-Onset vs. Late-Onset Alzheimer's Disease

Objective: Early-onset Alzheimer's disease (EAD) shows distinct features from late-onset Alzheimer's disease (LAD). To explore the characteristics of EAD, clinical, neuropsychological, and functional imaging studies have been conducted. However, differences between EAD and LAD are not clear, especially in terms of brain connectivity and networks. In this study, we investigated the differences in metabolic connectivity between EAD and LAD by adopting graph theory measures. Methods: We analyzed 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images to investigate the distinct features of metabolic connectivity between EAD and LAD. Using metabolic connectivity and graph theory analysis, metabolic network differences between LAD and EAD were explored. Results: Results showed the decreased connectivity centered in the cingulate gyri and occipital regions in EAD, whereas decreased connectivity in the occipital and temporal regions as well as increased connectivity in the supplementary motor area were observed in LAD when compared with age-matched control groups. Global efficiency and clustering coefficients were decreased in EAD but not in LAD. EAD showed progressive network deterioration as a function of disease severity and clinical dementia rating (CDR) scores, mainly in terms of connectivity between the cingulate gyri and occipital regions. Global efficiency and clustering coefficients were also decreased along with disease severity. Conclusion: These results indicate that EAD and LAD have distinguished features in terms of metabolic connectivity, with EAD demonstrating more extensive and progressive deterioration.

[1]  Maja A. A. Binnewijzend,et al.  Widespread Disruption of Functional Brain Organization in Early-Onset Alzheimer’s Disease , 2014, PloS one.

[2]  Kwangsun Yoo,et al.  Progressive Changes in Hippocampal Resting-state Connectivity Across Cognitive Impairment: A Cross-sectional Study From Normal to Alzheimer Disease , 2014, Alzheimer disease and associated disorders.

[3]  J. Ranjeva,et al.  Functional connectivity changes differ in early and late‐onset alzheimer's disease , 2014, Human brain mapping.

[4]  P. Scheltens,et al.  Different patterns of gray matter atrophy in early- and late-onset Alzheimer’s disease , 2013, Neurobiology of Aging.

[5]  Yong He,et al.  BrainNet Viewer: A Network Visualization Tool for Human Brain Connectomics , 2013, PloS one.

[6]  Y. Pijnenburg,et al.  Prevalence of Neuropsychiatric Symptoms in Young-Onset Compared to Late-Onset Alzheimer’s Disease – Part 1: Findings of the Two-Year Longitudinal NeedYD-Study , 2012, Dementia and Geriatric Cognitive Disorders.

[7]  G. Frisoni,et al.  Early and late onset Alzheimer's disease patients have distinct patterns of white matter damage , 2012, Neurobiology of Aging.

[8]  A. Fleisher,et al.  Altered default mode network connectivity in alzheimer's disease—A resting functional MRI and bayesian network study , 2011, Human brain mapping.

[9]  H. Brodaty,et al.  Functional Alterations in Brain Activation and Deactivation in Mild Cognitive Impairment in Response to a Graded Working Memory Challenge , 2011, Dementia and Geriatric Cognitive Disorders.

[10]  S. Rombouts,et al.  Loss of ‘Small-World’ Networks in Alzheimer's Disease: Graph Analysis of fMRI Resting-State Functional Connectivity , 2010, PloS one.

[11]  Olaf Sporns,et al.  Complex network measures of brain connectivity: Uses and interpretations , 2010, NeuroImage.

[12]  G. Ridgway CLINICAL SYNDROMES ASSOCIATED WITH POSTERIOR ATROPHY: EARLY AGE AT ONSET AD SPECTRUM , 2010, Neurology.

[13]  Sang Won Seo,et al.  Comparison of Neuropsychological and FDG-PET Findings between Early- versus Late-Onset Mild Cognitive Impairment: A Five-Year Longitudinal Study , 2010, Dementia and Geriatric Cognitive Disorders.

[14]  M. Weiner,et al.  Increased metabolic vulnerability in early-onset Alzheimer's disease is not related to amyloid burden. , 2010, Brain : a journal of neurology.

[15]  S. Morikawa,et al.  Different Atrophic Patterns in Early- and Late-Onset Alzheimer’s Disease and Evaluation of Clinical Utility of a Method of Regional z-Score Analysis Using Voxel-Based Morphometry , 2008, Dementia and Geriatric Cognitive Disorders.

[16]  Jae Sung Lee,et al.  Metabolic connectivity by interregional correlation analysis using statistical parametric mapping (SPM) and FDG brain PET; methodological development and patterns of metabolic connectivity in adults , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[17]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[18]  Martin Klein,et al.  Precuneus atrophy in early-onset Alzheimer’s disease: a morphometric structural MRI study , 2007, Neuroradiology.

[19]  Kuncheng Li,et al.  Altered functional connectivity in early Alzheimer's disease: A resting‐state fMRI study , 2007, Human brain mapping.

[20]  Shunichiro Shinagawa,et al.  Frequency and Clinical Characteristics of Early-Onset Dementia in Consecutive Patients in a Memory Clinic , 2007, Dementia and Geriatric Cognitive Disorders.

[21]  Kiralee M. Hayashi,et al.  The topography of grey matter involvement in early and late onset Alzheimer's disease. , 2007, Brain : a journal of neurology.

[22]  Danielle Smith Bassett,et al.  Small-World Brain Networks , 2006, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[23]  Masayuki Matsuda,et al.  Four subgroups of Alzheimer's disease based on patterns of atrophy using VBM and a unique pattern for early onset disease , 2006, NeuroImage.

[24]  Karalyn Patterson,et al.  Evolution of Cognitive Deficits and Conversion to Dementia in Patients with Mild Cognitive Impairment: A Very-Long-Term Follow-Up Study , 2006, Dementia and Geriatric Cognitive Disorders.

[25]  M. Haan Therapy Insight: type 2 diabetes mellitus and the risk of late-onset Alzheimer's disease , 2006, Nature Clinical Practice Neurology.

[26]  C. Stam,et al.  Small-world networks and functional connectivity in Alzheimer's disease. , 2006, Cerebral cortex.

[27]  D. G. Clark,et al.  Early-Onset Dementia: Frequency and Causes Compared to Late-Onset Dementia , 2006, Dementia and Geriatric Cognitive Disorders.

[28]  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.

[29]  K. Ishii,et al.  Voxel-based morphometric comparison between early- and late-onset mild Alzheimer's disease and assessment of diagnostic performance of z score images. , 2005, AJNR. American journal of neuroradiology.

[30]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Tetsuya Mori,et al.  Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease , 2002, Journal of the Neurological Sciences.

[32]  Duncan J. Watts,et al.  Collective dynamics of ‘small-world’ networks , 1998, Nature.

[33]  M. Albert,et al.  Age at onset of Alzheimer's disease , 1994, Neurology.

[34]  K. Blennow,et al.  Neurologic Motor Signs in Early and Late Onset Alzheimer's Disease , 1992 .

[35]  L. Gwyther,et al.  Early‐onset Alzheimer's disease , 1987, Neurology.

[36]  W. Rocca,et al.  Origin of the distinction between Alzheimer's disease and senile dementia , 1986, Neurology.

[37]  S Tucek,et al.  Regulation of Acetylcholine Synthesis in the Brain , 1985, Journal of neurochemistry.

[38]  W. M. van der Flier,et al.  Early onset Alzheimer's disease is associated with a distinct neuropsychological profile. , 2012, Journal of Alzheimer's disease : JAD.

[39]  Wiesje M van der Flier,et al.  Early-versus late-onset Alzheimer's disease: more than age alone. , 2010, Journal of Alzheimer's disease : JAD.

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

[41]  W. Meier-Ruge,et al.  Changes in brain glucose metabolism as a key to the pathogenesis of Alzheimer's disease. , 1994, Gerontology.

[42]  T Gasser,et al.  Quantitative EEG analysis in early onset Alzheimer's disease: a controlled study. , 1993, Electroencephalography and clinical neurophysiology.