The role of diffusion tensor imaging in the study of cognitive aging.

This chapter gives an overview of the role that diffusion tensor MRI (DTI) can play in the study of cognitive decline that is associated with advancing age. A brief overview of biological injury processes that impinge on the aging brain is provided, and their overall effect on the integrity of neural architecture is described. Cognitive decline associated with aging, and white matter connectivity degradation as a biological substrate for that decline, is then described. We then briefly describe the technology of DTI as a means for in vivo, non-invasive interrogation of white matter connectivity, and relate it to FLAIR, a more traditional MRI method for assessing white matter injury. We then survey the existing findings on relationships between aging-associated neuropathological processes and DTI measurements on one hand; and relationships between DTI measurements and late-life cognitive function on the other. We conclude with a summary of current research directions in relation to DTI studies of cognitive aging.

[1]  Roland Bammer,et al.  New methods in diffusion-weighted and diffusion tensor imaging. , 2009, Magnetic resonance imaging clinics of North America.

[2]  M. Mesulam,et al.  From sensation to cognition. , 1998, Brain : a journal of neurology.

[3]  R. Cabeza Hemispheric asymmetry reduction in older adults: the HAROLD model. , 2002, Psychology and aging.

[4]  J. Miller,et al.  A prospective study of cognitive function and onset of dementia in cognitively healthy elders. , 1998, Archives of neurology.

[5]  D. Harvey,et al.  Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD , 2006, Neurology.

[6]  A. Auchus,et al.  Diffusion Tensor Imaging of Normal-Appearing White Matter in Mild Cognitive Impairment and Early Alzheimer Disease: Preliminary Evidence of Axonal Degeneration in the Temporal Lobe , 2007, American Journal of Neuroradiology.

[7]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[8]  Owen Carmichael,et al.  Update on the Magnetic Resonance Imaging core of the Alzheimer's Disease Neuroimaging Initiative , 2010, Alzheimer's & Dementia.

[9]  David J. Madden,et al.  Aging and Visual Attention , 2007, Current directions in psychological science.

[10]  Charles DeCarli,et al.  Heterogeneity of cognitive trajectories in diverse older persons. , 2010, Psychology and aging.

[11]  Scott A. Huettel,et al.  Diffusion tensor imaging of adult age differences in cerebral white matter: relation to response time , 2004, NeuroImage.

[12]  J. Bisley The neural basis of visual attention , 2011, The Journal of physiology.

[13]  E. Ringelstein,et al.  Serum C-reactive protein is linked to cerebral microstructural integrity and cognitive function , 2010, Neurology.

[14]  Vladimir Koltchinskii,et al.  Integral curves of noisy vector fields and statistical problems in diffusion tensor imaging: nonparametric kernel estimation and hypotheses testing , 2007, 0710.3509.

[15]  John S. Duncan,et al.  Identical, but not the same: Intra-site and inter-site reproducibility of fractional anisotropy measures on two 3.0 T scanners , 2010, NeuroImage.

[16]  Daniel Bandy,et al.  Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease , 1998, Annals of neurology.

[17]  Fanny Cazettes,et al.  Obesity-mediated inflammation may damage the brain circuit that regulates food intake , 2011, Brain Research.

[18]  Torsten Rohlfing,et al.  Longitudinal Study of Callosal Microstructure in the Normal Adult Aging Brain Using Quantitative DTI Fiber Tracking , 2010, Developmental neuropsychology.

[19]  W. Strittmatter,et al.  Molecular biology of apolipoprotein E , 2002, Current opinion in lipidology.

[20]  J. Schneider,et al.  Individual differences in rates of change in cognitive abilities of older persons. , 2002, Psychology and aging.

[21]  Tong Zhu,et al.  An optimized wild bootstrap method for evaluation of measurement uncertainties of DTI-derived parameters in human brain , 2008, NeuroImage.

[22]  David A. Bennett,et al.  Mixed brain pathologies account for most dementia cases in community-dwelling older persons , 2007, Neurology.

[23]  Evan Fletcher,et al.  White Matter Changes Compromise Prefrontal Cortex Function in Healthy Elderly Individuals , 2006 .

[24]  D. Harvey,et al.  Anatomical Mapping of White Matter Hyperintensities (WMH): Exploring the Relationships Between Periventricular WMH, Deep WMH, and Total WMH Burden , 2005, Stroke.

[25]  Bruce M Psaty,et al.  Biomarkers of Inflammation and MRI-Defined Small Vessel Disease of the Brain: The Cardiovascular Health Study , 2008, Stroke.

[26]  Owen Carmichael,et al.  White Matter Hyperintensity Penumbra , 2011, Stroke.

[27]  M. Bar A Cortical Mechanism for Triggering Top-Down Facilitation in Visual Object Recognition , 2003, Journal of Cognitive Neuroscience.

[28]  J. MacFall,et al.  Classification of White Matter Lesions on Magnetic Resonance Imaging in Elderly Persons , 2008, Biological Psychiatry.

[29]  Naoto Hayashi,et al.  Effect of scanner in asymmetry studies using diffusion tensor imaging , 2011, NeuroImage.

[30]  J. Illes,et al.  Diffusion-tensor imaging of cognitive performance , 2002, Brain and Cognition.

[31]  R B Wallace,et al.  Longitudinal application of cognitive function measures in a defined population of community-dwelling elders. , 1991, Annals of epidemiology.

[32]  Takayuki Itoh,et al.  Amyloid β1–42 oligomer inhibits myelin sheet formation in vitro , 2012, Neurobiology of Aging.

[33]  Edith V. Sullivan,et al.  Equivalent disruption of regional white matter microstructure in ageing healthy men and women , 2001, Neuroreport.

[34]  Keith A. Johnson,et al.  Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia , 2009, Neuron.

[35]  Nils Peters,et al.  Diffusion Magnetic Resonance Histograms as a Surrogate Marker and Predictor of Disease Progression in CADASIL: A Two-Year Follow-Up Study , 2005, Stroke.

[36]  Norbert Schuff,et al.  White matter damage in frontotemporal dementia and Alzheimer's disease measured by diffusion MRI , 2009, Brain : a journal of neurology.

[37]  S. Kiechl,et al.  The natural course of atherosclerosis. Part II: vascular remodeling. Bruneck Study Group. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[38]  O. Sporns,et al.  Complex brain networks: graph theoretical analysis of structural and functional systems , 2009, Nature Reviews Neuroscience.

[39]  F. Howe,et al.  Diffusion tensor imaging and MR spectroscopy in hypertension and presumed cerebral small vessel disease , 2008, Magnetic resonance in medicine.

[40]  J. O'Brien,et al.  Changes in DWI and MRS associated with white matter hyperintensities in elderly subjects , 2003, Neurology.

[41]  Jeffrey A. James,et al.  Frequent amyloid deposition without significant cognitive impairment among the elderly. , 2008, Archives of neurology.

[42]  Eric E. Smith,et al.  Tissue Microstructural Changes Are Independently Associated With Cognitive Impairment in Cerebral Amyloid Angiopathy , 2008, Stroke.

[43]  Chris A Clark,et al.  Multimodal MRI in Cerebral Small Vessel Disease: Its Relationship With Cognition and Sensitivity to Change Over Time , 2008, Stroke.

[44]  Carlo Pierpaoli,et al.  Variance of estimated DTI‐derived parameters via first‐order perturbation methods , 2007, Magnetic resonance in medicine.

[45]  L. Mucke,et al.  A network dysfunction perspective on neurodegenerative diseases , 2006, Nature.

[46]  F. Aboitiz,et al.  Age-related changes in fibre composition of the human corpus callosum: sex differences. , 1996, Neuroreport.

[47]  R. Califf,et al.  Metabolic syndrome: definition, pathophysiology, and mechanisms. , 2005, American heart journal.

[48]  A. Pfefferbaum,et al.  Diffusion tensor imaging and aging , 2006, Neuroscience & Biobehavioral Reviews.

[49]  C. Beaulieu,et al.  The basis of anisotropic water diffusion in the nervous system – a technical review , 2002, NMR in biomedicine.

[50]  R. Morris,et al.  Diffusion tensor imaging detects age related white matter change over a 2 year follow-up which is associated with working memory decline , 2009, Journal of Neurology, Neurosurgery & Psychiatry.

[51]  Bill Seeley,et al.  Neurodegenerative diseases target large-scale human brain networks , 2010, Alzheimer's & Dementia.

[52]  K. Schaie,et al.  Individual differences in cross-sectional and 3-year longitudinal memory performance across the adult life span. , 1993, Psychology and aging.

[53]  D. Head,et al.  Selective aging of the human cerebral cortex observed in vivo: differential vulnerability of the prefrontal gray matter. , 1997, Cerebral cortex.

[54]  Leslie G. Ungerleider,et al.  Mechanisms of visual attention in the human cortex. , 2000, Annual review of neuroscience.

[55]  Roberto Cabeza,et al.  Adult Age Differences in Functional Connectivity during Executive Control Nih Public Access Materials and Methods Cue-related Activation Functional Connectivity of Switch-related Activation on Cue-only Trials , 2022 .

[56]  A D Roses,et al.  Apolipoprotein E and Alzheimer disease. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Stephen Correia,et al.  Neuroimaging of White Matter in Aging and Dementia , 2007, The Clinical neuropsychologist.

[58]  Shengdi Chen,et al.  Diffusion Tensor Imaging Changes Correlate with Cognition Better than Conventional MRI Findings in Patients with Subcortical Ischemic Vascular Disease , 2010, Dementia and Geriatric Cognitive Disorders.

[59]  Klaus P. Ebmeier,et al.  The APOE ɛ4 allele modulates brain white matter integrity in healthy adults , 2011, Molecular Psychiatry.

[60]  Roberto Cabeza,et al.  Assessing the effects of age on long white matter tracts using diffusion tensor tractography , 2009, NeuroImage.

[61]  Shu-Wei Sun,et al.  Detection of age-dependent brain injury in a mouse model of brain amyloidosis associated with Alzheimer's disease using magnetic resonance diffusion tensor imaging , 2005, Experimental Neurology.

[62]  Wolfgang M. Pauli,et al.  Computational models of cognitive control , 2010, Current Opinion in Neurobiology.

[63]  M. Christiansen,et al.  The association between apolipoprotein E and multiple sclerosis , 2006, European journal of neurology.

[64]  Danielle J. Tisserand,et al.  On the Involvement of Prefrontal Networks in Cognitive Ageing , 2003, Cortex.

[65]  A. Fagan,et al.  Decreased cerebrospinal fluid Aβ42 correlates with brain atrophy in cognitively normal elderly , 2009, Annals of neurology.

[66]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[67]  Frederik Barkhof,et al.  Imaging of White Matter Lesions , 2002, Cerebrovascular Diseases.

[68]  H S Markus,et al.  Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI. , 1999, Stroke.

[69]  A. Kontush,et al.  Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis , 2006, Pharmacological Reviews.

[70]  C. Sudlow,et al.  Effects of apolipoprotein E genotype on outcome after ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[71]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[72]  Eric E. Smith,et al.  &bgr;-Amyloid, Blood Vessels, and Brain Function , 2009, Stroke.

[73]  Wang Zhan,et al.  Characterization of white matter degeneration in elderly subjects by magnetic resonance diffusion and FLAIR imaging correlation , 2009, NeuroImage.

[74]  E. Bizzi,et al.  The Cognitive Neurosciences , 1996 .

[75]  Roberto Cabeza,et al.  Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance , 2009, Journal of Cognitive Neuroscience.

[76]  H. Eichenbaum,et al.  The medial temporal lobe and recognition memory. , 2007, Annual review of neuroscience.

[77]  A. Pfefferbaum,et al.  MR Diffusion Tensor Imaging: A Window into White Matter Integrity of the Working Brain , 2010, Neuropsychology Review.

[78]  V. Hachinski,et al.  Progressive Increase in Infarct Size, Neuroinflammation, and Cognitive Deficits in the Presence of High Levels of Amyloid , 2007, Stroke.

[79]  J. Jia,et al.  Meta-analysis of APOE4 allele and outcome after traumatic brain injury. , 2008, Journal of neurotrauma.

[80]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[81]  L Nyberg,et al.  Altered brain white matter integrity in healthy carriers of the APOE ε4 allele , 2006, Neurology.

[82]  A. Song,et al.  Cerebral White Matter Integrity and Cognitive Aging: Contributions from Diffusion Tensor Imaging , 2009, Neuropsychology Review.

[83]  Owen Carmichael,et al.  Regional pattern of white matter microstructural changes in normal aging, MCI, and AD , 2009, Neurology.

[84]  C R Jack,et al.  Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia , 2010, Neurology.

[85]  M. O’Sullivan,et al.  Activate your online subscription , 2001, Neurology.

[86]  G. Zubicaray,et al.  Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment , 2006, Journal of Neurology, Neurosurgery & Psychiatry.

[87]  D. Bennett,et al.  Where Vascular Meets Neurodegenerative Disease , 2010, Stroke.

[88]  Timothy Edward John Behrens,et al.  Characterization and propagation of uncertainty in diffusion‐weighted MR imaging , 2003, Magnetic resonance in medicine.

[89]  S. D. Preston,et al.  Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid β from the human brain , 2003, Neuropathology and applied neurobiology.

[90]  M. Albert,et al.  Predictors of cognitive change in older persons: MacArthur studies of successful aging. , 1995, Psychology and aging.

[91]  Mark D'Esposito,et al.  Imaging the aging brain , 2009 .

[92]  A. Pfefferbaum,et al.  Replicability of diffusion tensor imaging measurements of fractional anisotropy and trace in brain , 2003, Journal of magnetic resonance imaging : JMRI.

[93]  Faith M. Gunning-Dixon,et al.  Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume , 2004, Neurobiology of Aging.

[94]  Michael P Vitek,et al.  Apolipoprotein E and neurological disease: therapeutic potential and pharmacogenomic interactions. , 2007, Pharmacogenomics.

[95]  L Nyberg,et al.  Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: a risk for AD? , 2006, Neurology.

[96]  R. Honea,et al.  Impact of APOE on the healthy aging brain: a voxel-based MRI and DTI study. , 2009, Journal of Alzheimer's disease : JAD.

[97]  R. Henry,et al.  Diffusion Tensor MR Imaging and Fiber Tractography: Technical Considerations , 2008, American Journal of Neuroradiology.

[98]  L. White,et al.  Adult age differences in the functional neuroanatomy of visual attention: A combined fMRI and DTI study , 2007, Neurobiology of Aging.

[99]  F. Lazeyras,et al.  Magnetic Resonance Imaging Techniques in White Matter Disease: Potentials and Limitations , 2009, Topics in magnetic resonance imaging : TMRI.

[100]  D. Medina,et al.  Diffusion tensor imaging investigations in Alzheimer’s disease: the resurgence of white matter compromise in the cortical dysfunction of the aging brain , 2008, Neuropsychiatric disease and treatment.

[101]  Anders H. Andersen,et al.  White matter diffusion alterations in normal women at risk of Alzheimer's disease , 2010, Neurobiology of Aging.

[102]  A. Fagan,et al.  Pittsburgh compound B imaging and prediction of progression from cognitive normality to symptomatic Alzheimer disease. , 2009, Archives of neurology.

[103]  Paul Maruff,et al.  β-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease , 2007 .

[104]  A. Pfefferbaum,et al.  Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking. , 2006, Cerebral cortex.

[105]  J. Janowsky,et al.  The role of androgens in cognition and brain aging in men , 2006, Neuroscience.

[106]  M. Corbetta,et al.  The Reorienting System of the Human Brain: From Environment to Theory of Mind , 2008, Neuron.

[107]  K. Blennow,et al.  Is it time for biomarker-based diagnostic criteria for prodromal Alzheimer's disease? , 2010, Alzheimer's Research & Therapy.

[108]  A. Dale,et al.  Functional Parcellation of Attentional Control Regions of the Brain , 2004, Journal of Cognitive Neuroscience.

[109]  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.

[110]  Charles DeCarli,et al.  Different mechanisms of episodic memory failure in mild cognitive impairment , 2005, Neuropsychologia.

[111]  C. DeCarli,et al.  When two are worse than one , 2006, Neurology.

[112]  H. Christensen,et al.  An analysis of diversity in the cognitive performance of elderly community dwellers: individual differences in change scores as a function of age. , 1999, Psychology and aging.

[113]  L. Bronge,et al.  Magnetic resonance imaging in dementia: a study of brain white matter changes , 2002 .

[114]  Cheryl L. Dahle,et al.  Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. , 2005, Cerebral cortex.

[115]  Bram Stieltjes,et al.  Longitudinal changes in fiber tract integrity in healthy aging and mild cognitive impairment: a DTI follow-up study. , 2010, Journal of Alzheimer's disease : JAD.

[116]  Alan Connelly,et al.  Direct estimation of the fiber orientation density function from diffusion-weighted MRI data using spherical deconvolution , 2004, NeuroImage.

[117]  D. Selkoe Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[118]  P. Greenwood,et al.  The frontal aging hypothesis evaluated , 2000, Journal of the International Neuropsychological Society.

[119]  M. Moseley,et al.  Magnetic Resonance in Medicine 51:924–937 (2004) Characterizing Non-Gaussian Diffusion by Using Generalized Diffusion Tensors , 2022 .

[120]  M. Fisher Injuries to the vascular endothelium: vascular wall and endothelial dysfunction. , 2008, Reviews in neurological diseases.

[121]  K. Schaie,et al.  Variability in cognitive function in the elderly: implications for societal participation. , 1988, Basic life sciences.

[122]  Yanjun Zeng,et al.  Evaluating ischemic stroke with diffusion tensor imaging , 2008, Neurological research.

[123]  I. Rosenberg,et al.  B vitamins, homocysteine, and neurocognitive function in the elderly. , 2000, The American journal of clinical nutrition.

[124]  M. Moseley Diffusion tensor imaging and aging – a review , 2002, NMR in biomedicine.

[125]  Stephen José Hanson,et al.  Foundational issues in human brain mapping , 2010 .

[126]  John J Sidtis,et al.  Abnormal white matter integrity in healthy apolipoprotein E epsilon4 carriers , 2005, Neuroreport.

[127]  White Matter Hyperintensities in Aging and Dementia , 2010 .

[128]  G. Mangun,et al.  The neural mechanisms of top-down attentional control , 2000, Nature Neuroscience.

[129]  T. Hendler,et al.  High b value q-space-analyzed diffusion MRI in vascular dementia: A preliminary study , 2002, Journal of the Neurological Sciences.

[130]  B. Mueller,et al.  Diffusion Tensor Imaging Identifies Deficits in White Matter Microstructure in Subjects With Type 1 Diabetes That Correlate With Reduced Neurocognitive Function , 2008, Diabetes.

[131]  H S Markus,et al.  Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[132]  G. Alexander,et al.  Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease , 2009, Proceedings of the National Academy of Sciences.

[133]  R. Henry,et al.  Diffusion Tensor MR Imaging and Fiber Tractography: Theoretic Underpinnings , 2008, American Journal of Neuroradiology.

[134]  Eric E. Smith,et al.  White Matter Alterations in Cerebral Amyloid Angiopathy Measured by Diffusion Tensor Imaging , 2006, Stroke.

[135]  L. Frank Characterization of anisotropy in high angular resolution diffusion‐weighted MRI , 2002, Magnetic resonance in medicine.

[136]  Paul Maruff,et al.  Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. , 2007, Brain : a journal of neurology.

[137]  Norbert Schuff,et al.  Neuropathological basis of magnetic resonance images in aging and dementia , 2008, Annals of neurology.

[138]  Christian Enzinger,et al.  Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study , 2003, The Lancet.

[139]  M. O’Sullivan,et al.  White matter damage on diffusion tensor imaging correlates with age-related cognitive decline , 2006, Neurology.

[140]  Atle Bjørnerud,et al.  Error-related negativity is mediated by fractional anisotropy in the posterior cingulate gyrus--a study combining diffusion tensor imaging and electrophysiology in healthy adults. , 2009, Cerebral cortex.

[141]  K. Lim,et al.  Advances in white matter imaging: A review of in vivo magnetic resonance methodologies and their applicability to the study of development and aging , 2006, Neuroscience & Biobehavioral Reviews.

[142]  M. Moseley,et al.  Atrophy and dysfunction of parahippocampal white matter in mild Alzheimer's disease , 2012, Neurobiology of Aging.

[143]  R. Buckner Memory and Executive Function in Aging and AD Multiple Factors that Cause Decline and Reserve Factors that Compensate , 2004, Neuron.

[144]  F. Laun,et al.  On the Reliability of Quantitative Volumetric and Structural Neuroimaging , 2008 .

[145]  S. Rose,et al.  Loss of connectivity in Alzheimer's disease: an evaluation of white matter tract integrity with colour coded MR diffusion tensor imaging , 2000, Journal of neurology, neurosurgery, and psychiatry.

[146]  Adam Gazzaley,et al.  Measuring functional connectivity during distinct stages of a cognitive task , 2004, NeuroImage.

[147]  Michael P. Harms,et al.  Evaluation of white matter integrity in ex vivo brains of amyloid plaque-bearing APPsw transgenic mice using magnetic resonance diffusion tensor imaging , 2006, Experimental Neurology.

[148]  A Hofman,et al.  C-Reactive Protein and Cerebral Small-Vessel Disease: The Rotterdam Scan Study , 2005, Circulation.