Multimodal MRI Neuroimaging Biomarkers for Cognitive Normal Adults, Amnestic Mild Cognitive Impairment, and Alzheimer's Disease

Multimodal magnetic resonance imaging (MRI) techniques have been developed to noninvasively measure structural, metabolic, hemodynamic and functional changes of the brain. These advantages have made MRI an important tool to investigate neurodegenerative disorders, including diagnosis, disease progression monitoring, and treatment efficacy evaluation. This paper discusses recent findings of the multimodal MRI in the context of surrogate biomarkers for identifying the risk for AD in normal cognitive (NC) adults, brain anatomical and functional alterations in amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) patients. Further developments of these techniques and the establishment of promising neuroimaging biomarkers will enhance our ability to diagnose aMCI and AD in their early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

[1]  Jack L. Lancaster,et al.  Loss of cerebral white matter structural integrity tracks the gray matter metabolic decline in normal aging , 2009, NeuroImage.

[2]  Mojtaba Zarei,et al.  White matter tract integrity in aging and Alzheimer's disease , 2009, Human brain mapping.

[3]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[4]  C. Caltagirone,et al.  Regional brain atrophy and functional disconnection across Alzheimer's disease evolution , 2010, Journal of Neurology, Neurosurgery & Psychiatry.

[5]  M. Weiner,et al.  Automated MRI measures predict progression to Alzheimer's disease , 2010, Neurobiology of Aging.

[6]  Hilkka Soininen,et al.  Hippocampus in Alzheimer’s disease: a 3-year follow-up MRI study , 2000, Biological Psychiatry.

[7]  Paul M. Thompson,et al.  Relationship between white matter fractional anisotropy and other indices of cerebral health in normal aging: Tract-based spatial statistics study of aging , 2007, NeuroImage.

[8]  Paul M. Matthews,et al.  Differential effects of the APOE genotype on brain function across the lifespan , 2011, NeuroImage.

[9]  M. Weiner,et al.  Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer's disease* , 2009, Brain : a journal of neurology.

[10]  Jianfeng Gao,et al.  Cerebral blood flow measurement by dynamic contrast MRI using singular value decomposition with an adaptive threshold , 1999, Magnetic resonance in medicine.

[11]  Giovanni B. Frisoni,et al.  Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE ϵ4 carriers , 2009, Journal of magnetic resonance imaging : JMRI.

[12]  Aapo Hyvärinen,et al.  Independent component analysis of nondeterministic fMRI signal sources , 2003, NeuroImage.

[13]  N. Schuff,et al.  Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease , 2001, Journal of neurology, neurosurgery, and psychiatry.

[14]  J. Mazziotta,et al.  Age‐related morphology trends of cortical sulci , 2005, Human brain mapping.

[15]  C. DeCarli,et al.  Association of parental dementia with cognitive and brain MRI measures in middle-aged adults , 2009, Neurology.

[16]  L. Parsons,et al.  Interregional connectivity to primary motor cortex revealed using MRI resting state images , 1999, Human brain mapping.

[17]  D. Yablonskiy,et al.  Validation of oxygen extraction fraction measurement by qBOLD technique , 2008, Magnetic resonance in medicine.

[18]  Paul M. Thompson,et al.  Mapping hippocampal and ventricular change in Alzheimer disease , 2004, NeuroImage.

[19]  J. Kaye,et al.  Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia , 1997, Neurology.

[20]  A. Toga,et al.  Three-dimensional patterns of hippocampal atrophy in mild cognitive impairment. , 2006, Archives of neurology.

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

[22]  R. Honea,et al.  Reduced gray matter volume in normal adults with a maternal family history of Alzheimer disease , 2010, Neurology.

[23]  A. Toga,et al.  Tracking Alzheimer's Disease , 2007, Annals of the New York Academy of Sciences.

[24]  S. Resnick,et al.  Longitudinal pattern of regional brain volume change differentiates normal aging from MCI , 2009, Neurology.

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

[26]  Stephen M. Smith,et al.  Investigations into resting-state connectivity using independent component analysis , 2005, Philosophical Transactions of the Royal Society B: Biological Sciences.

[27]  C. Jack,et al.  Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease , 1998, Neurology.

[28]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[29]  G. Waldemar.  Functional brain imaging with SPECT in normal aging and dementia. Methodological, pathophysiological, and diagnostic aspects. , 1995, Cerebrovascular and brain metabolism reviews.

[30]  M. Barquero,et al.  Variability of age at onset in siblings with familial Alzheimer disease. , 2007, Archives of neurology.

[31]  Norbert Schuff,et al.  ASL Perfusion MRI Predicts Cognitive Decline and Conversion From MCI to Dementia , 2010, Alzheimer disease and associated disorders.

[32]  Hanzhang Lu,et al.  Quantitative evaluation of oxygenation in venous vessels using T2‐Relaxation‐Under‐Spin‐Tagging MRI , 2008, Magnetic resonance in medicine.

[33]  D. Yablonskiy,et al.  Quantitative BOLD: Mapping of human cerebral deoxygenated blood volume and oxygen extraction fraction: Default state , 2007, Magnetic resonance in medicine.

[34]  Jianfeng Gao,et al.  Insular Alzheimer's disease pathology as a cause of "age-related" autonomic dysfunction and mortality in the non-demented elderly. , 2006, Medical hypotheses.

[35]  R. Honea,et al.  Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease , 2011, Neurology.

[36]  C. Jack,et al.  Mild cognitive impairment – beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment , 2004, Journal of internal medicine.

[37]  Kiralee M. Hayashi,et al.  Three-dimensional gray matter atrophy mapping in mild cognitive impairment and mild Alzheimer disease. , 2007, Archives of neurology.

[38]  V. Haughton,et al.  Mapping functionally related regions of brain with functional connectivity MR imaging. , 2000, AJNR. American journal of neuroradiology.

[39]  C. Jack,et al.  Usefulness of MRI measures of entorhinal cortex versus hippocampus in AD , 2000, Neurology.

[40]  Donald S. Williams,et al.  Perfusion imaging , 1992, Magnetic resonance in medicine.

[41]  M. Albert,et al.  Surface-Based Analysis on Shape and Fractional Anisotropy of White Matter Tracts in Alzheimer's Disease , 2010, PloS one.

[42]  Weili Lin,et al.  Quantitative Measurements of Cerebral Blood Oxygen Saturation Using Magnetic Resonance Imaging , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[43]  Yasushi Kondoh,et al.  Vascular and metabolic reserve in Alzheimer’s disease , 2000, Neurobiology of Aging.

[44]  J. Coyle,et al.  Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies , 1991, Neuroscience.

[45]  M. Kopelman,et al.  The Memory Deficits in Alzheimer-Type Dementia: A Review , 1986, The Quarterly journal of experimental psychology. A, Human experimental psychology.

[46]  G. Frisoni,et al.  Structural imaging in the clinical diagnosis of Alzheimer's disease: problems and tools , 2001, Journal of neurology, neurosurgery, and psychiatry.

[47]  Rachel L. Mistur,et al.  Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease , 2009, Neurology.

[48]  C. Jack,et al.  MRI as a biomarker of disease progression in a therapeutic trial of milameline for AD , 2003, Neurology.

[49]  A. Convit,et al.  Specific Hippocampal Volume Reductions in Individuals at Risk for Alzheimer’s Disease , 1997, Neurobiology of Aging.

[50]  D. Glahn,et al.  Fractional anisotropy of water diffusion in cerebral white matter across the lifespan , 2012, Neurobiology of Aging.

[51]  Nick C Fox,et al.  Imaging cerebral atrophy: normal ageing to Alzheimer's disease , 2004, The Lancet.

[52]  S. Rapoport.  Coupled reductions in brain oxidative phosphorylation and synaptic function can be quantified and staged in the course of Alzheimer disease , 2009, Neurotoxicity Research.

[53]  C. Jack,et al.  Ways toward an early diagnosis in Alzheimer’s disease: The Alzheimer’s Disease Neuroimaging Initiative (ADNI) , 2005, Alzheimer's & Dementia.

[54]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[55]  C. Jack,et al.  Medial temporal atrophy on MRI in normal aging and very mild Alzheimer's disease , 1997, Neurology.

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

[57]  Matthias L. Schroeter,et al.  Neural correlates of Alzheimer's disease and mild cognitive impairment: A systematic and quantitative meta-analysis involving 1351 patients , 2009, NeuroImage.

[58]  Nick C Fox,et al.  Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects. , 2000, Archives of neurology.

[59]  R. Nathan Spreng,et al.  The Common Neural Basis of Autobiographical Memory, Prospection, Navigation, Theory of Mind, and the Default Mode: A Quantitative Meta-analysis , 2009, Journal of Cognitive Neuroscience.

[60]  J. Molinuevo,et al.  Multiple DTI index analysis in normal aging, amnestic MCI and AD. Relationship with neuropsychological performance , 2012, Neurobiology of Aging.

[61]  D. Yablonskiy,et al.  Quantitation of intrinsic magnetic susceptibility‐related effects in a tissue matrix. Phantom study , 1998, Magnetic resonance in medicine.

[62]  Jianfeng Gao,et al.  Asymmetric insular function predicts positional blood pressure in nondemented elderly. , 2009, The Journal of neuropsychiatry and clinical neurosciences.

[63]  K O Lim,et al.  In vivo brain concentrations of N-acetyl compounds, creatine, and choline in Alzheimer disease. , 1999, Archives of general psychiatry.

[64]  C R Jack,et al.  Serial MRI and CSF biomarkers in normal aging, MCI, and AD , 2010, Neurology.

[65]  Kiralee M. Hayashi,et al.  Dynamics of Gray Matter Loss in Alzheimer's Disease , 2003, The Journal of Neuroscience.

[66]  S. de Santi,et al.  Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer’s , 2010, Proceedings of the National Academy of Sciences.

[67]  Caroline Hayward,et al.  Ageing: Cognitive change and the APOE ɛ4 allele , 2002, Nature.

[68]  N. Schuff,et al.  Higher atrophy rate of entorhinal cortex than hippocampus in AD , 2004, Neurology.

[69]  H Rusinek,et al.  Hippocampal formation size in normal human aging: a correlate of delayed secondary memory performance. , 1994, Learning & memory.

[70]  Stephen M. Smith,et al.  DTI measures in crossing-fibre areas: Increased diffusion anisotropy reveals early white matter alteration in MCI and mild Alzheimer's disease , 2011, NeuroImage.

[71]  G. Alexander,et al.  Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect. , 2009, The New England journal of medicine.

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

[73]  Bruce Fischl,et al.  Regional white matter volume differences in nondemented aging and Alzheimer's disease , 2009, NeuroImage.

[74]  D. Bennett,et al.  Alzheimer disease in the US population: prevalence estimates using the 2000 census. , 2003, Archives of neurology.

[75]  Norbert Schuff,et al.  Joint analysis of structural and perfusion MRI for cognitive assessment and classification of Alzheimer's disease and normal aging , 2010, NeuroImage.

[76]  Armando Manduca,et al.  Methodological considerations for measuring rates of brain atrophy , 2003, Journal of magnetic resonance imaging : JMRI.

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

[78]  Carole Dufouil,et al.  Effects of ApoE-ɛ4 allele load and age on the rates of grey matter and hippocampal volumes loss in a longitudinal cohort of 1186 healthy elderly persons , 2010, NeuroImage.

[79]  Zhi-jun Zhang,et al.  Resting brain connectivity: changes during the progress of Alzheimer disease. , 2010, Radiology.

[80]  B. L. Miller,et al.  Reduced medial temporal lobe N-acetylaspartate in cognitively impaired but nondemented patients , 2005, Neurology.

[81]  B. Reisberg,et al.  MRI and CSF studies in the early diagnosis of Alzheimer's disease , 2004, Journal of internal medicine.

[82]  G. Alexander,et al.  Declining brain activity in cognitively normal apolipoprotein E ɛ4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[83]  Alan C. Evans,et al.  Focal decline of cortical thickness in Alzheimer's disease identified by computational neuroanatomy. , 2004, Cerebral cortex.

[84]  N. Filippini,et al.  Distinct patterns of brain activity in young carriers of the APOE e4 allele , 2009, NeuroImage.

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

[86]  E G Tangalos,et al.  1H MR spectroscopy in common dementias , 2004, Neurology.

[87]  S. Resnick,et al.  Longitudinal Magnetic Resonance Imaging Studies of Older Adults: A Shrinking Brain , 2003, The Journal of Neuroscience.

[88]  Jing He,et al.  Differences in brain volume, hippocampal volume, cerebrovascular risk factors, and apolipoprotein E4 among mild cognitive impairment subtypes. , 2009, Archives of neurology.

[89]  Sachin Dixit,et al.  APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF Aβ42 , 2010, The Journal of Neuroscience.

[90]  C. Jack,et al.  Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD , 2004, Neurology.

[91]  T. Chan,et al.  Independent component analysis-based classification of Alzheimer's disease MRI data. , 2011, Journal of Alzheimer's disease : JAD.

[92]  Jared Stokes,et al.  Temporal lobe functional activity and connectivity in young adult APOE ɛ4 carriers , 2010, Alzheimer's & Dementia.