Age-related decline in white matter tract integrity and cognitive performance: A DTI tractography and structural equation modeling study

Age-related decline in microstructural integrity of certain white matter tracts may explain cognitive decline associated with normal aging. Whole brain tractography and a clustering segmentation in 48 healthy individuals across the adult lifespan were used to examine: interhemispheric (corpus callosum), intrahemispheric association (cingulum, uncinate, arcuate, inferior longitudinal, inferior occipitofrontal), and projection (corticospinal) fibers. Principal components analysis reduced cognitive tests into 6 meaningful factors: (1) memory and executive function; (2) visuomotor dexterity; (3) motor speed; (4) attention and working memory; (5) set-shifting/flexibility; and (6) visuospatial construction. Using theory-based structural equation modeling, relationships among age, white matter tract integrity, and cognitive performance were investigated. Parsimonious model fit demonstrated relationships where decline in white matter integrity may explain age-related decline in cognitive performance: inferior longitudinal fasciculus (ILF) with visuomotor dexterity; the inferior occipitofrontal fasciculus with visuospatial construction; and posterior fibers (i.e., splenium) of the corpus callosum with memory and executive function. Our findings suggest that decline in the microstructural integrity of white matter fibers can account for cognitive decline in normal aging.

[1]  J. Gold,et al.  Repeatable battery for the assessment of neuropsychological status as a screening test in schizophrenia I: sensitivity, reliability, and validity. , 1999, The American journal of psychiatry.

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

[3]  E. Ross,et al.  Sensory-specific and fractional disorders of recent memory in man , 1996 .

[4]  Carl-Fredrik Westin,et al.  Quantitative examination of a novel clustering method using magnetic resonance diffusion tensor tractography , 2008, NeuroImage.

[5]  B. Pakkenberg,et al.  Marked loss of myelinated nerve fibers in the human brain with age , 2003, The Journal of comparative neurology.

[6]  M. O’Sullivan,et al.  Damage within a network of white matter regions underlies executive dysfunction in CADASIL , 2005, Neurology.

[7]  P. Bentler,et al.  Comparative fit indexes in structural models. , 1990, Psychological bulletin.

[8]  R. Kikinis,et al.  A review of diffusion tensor imaging studies in schizophrenia. , 2007, Journal of psychiatric research.

[9]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. 1996. , 1996, Journal of magnetic resonance.

[10]  Adolf Pfefferbaum,et al.  Diffusion tensor imaging in normal aging and neuropsychiatric disorders. , 2003, European journal of radiology.

[11]  Randy L. Gollub,et al.  Reproducibility of quantitative tractography methods applied to cerebral white matter , 2007, NeuroImage.

[12]  H. Duffau,et al.  Does the left inferior longitudinal fasciculus play a role in language? A brain stimulation study. , 2007, Brain : a journal of neurology.

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

[14]  R. Killiany,et al.  Effects of age on the thickness of myelin sheaths in monkey primary visual cortex , 2001, The Journal of comparative neurology.

[15]  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.

[16]  Derek K. Jones,et al.  Virtual in Vivo Interactive Dissection of White Matter Fasciculi in the Human Brain , 2002, NeuroImage.

[17]  R. Cabeza,et al.  Que PASA? The posterior-anterior shift in aging. , 2008, Cerebral cortex.

[18]  B. Thompson,et al.  EFFECTS OF SAMPLE SIZE, ESTIMATION METHODS, AND MODEL SPECIFICATION ON STRUCTURAL EQUATION MODELING FIT INDEXES , 1999 .

[19]  T. Fritsch,et al.  Effects of Stimulus Properties and Age on Random-Array Letter Cancellation Tasks , 2000 .

[20]  P. Szeszko,et al.  MRI atlas of human white matter , 2006 .

[21]  W. C. Halstead Brain and intelligence , 1947 .

[22]  David Wechsler,et al.  Wechsler Memory scale. , 2005 .

[23]  C. A. Clark,et al.  A structural equation modeling investigation of age-related variance in executive function and DTI measured white matter damage , 2008, Neurobiology of Aging.

[24]  Marek Kubicki,et al.  Neuropsychological disturbance in schizophrenia: a diffusion tensor imaging study. , 2008, Neuropsychology.

[25]  P. Bentler,et al.  Cutoff criteria for fit indexes in covariance structure analysis : Conventional criteria versus new alternatives , 1999 .

[26]  Chris Rorden,et al.  Damage to white matter fiber tracts in acute spatial neglect. , 2009, Cerebral cortex.

[27]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[28]  M. Catani,et al.  A diffusion tensor imaging tractography atlas for virtual in vivo dissections , 2008, Cortex.

[29]  P Bartolomeo,et al.  Brain networks of spatial awareness: evidence from diffusion tensor imaging tractography , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[30]  D. Pandya,et al.  Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. , 2007, Brain : a journal of neurology.

[31]  A. Pfefferbaum,et al.  Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: Relations to timed performance , 2010, Neurobiology of Aging.

[32]  M. Mesulam Brain, Mind, and the Evolution of Connectivity , 2000, Brain and Cognition.

[33]  G. Bartzokis,et al.  Heterogeneous age-related breakdown of white matter structural integrity: implications for cortical “disconnection” in aging and Alzheimer’s disease , 2004, Neurobiology of Aging.

[34]  P. Basser,et al.  Water Diffusion Changes in Wallerian Degeneration and Their Dependence on White Matter Architecture , 2000 .

[35]  Derek K. Jones,et al.  Symmetries in human brain language pathways correlate with verbal recall , 2007, Proceedings of the National Academy of Sciences.

[36]  S. Wakana,et al.  MRI Atlas of Human White Matter , 2005 .

[37]  A. B. Hollingshead,et al.  Four factor index of social status , 1975 .

[38]  David H. Salat,et al.  Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness , 2010, Neurobiology of Aging.

[39]  Oliver Ganslandt,et al.  Quantitative diffusion tensor fiber tracking of age-related changes in the limbic system , 2007, European Radiology.

[40]  Susumu Mori,et al.  Fiber tracking: principles and strategies – a technical review , 2002, NMR in biomedicine.

[41]  K O Lim,et al.  In vivo detection and functional correlates of white matter microstructural disruption in chronic alcoholism. , 2000, Alcoholism, clinical and experimental research.

[42]  Dianne M. Finkelstein,et al.  A Beginner's Guide to Structural Equation Modeling , 2005, Technometrics.

[43]  Carl-Fredrik Westin,et al.  Automatic Tractography Segmentation Using a High-Dimensional White Matter Atlas , 2007, IEEE Transactions on Medical Imaging.

[44]  Michael I. Jordan,et al.  On Spectral Clustering: Analysis and an algorithm , 2001, NIPS.

[45]  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.

[46]  P. Basser,et al.  Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. , 1996, Journal of magnetic resonance. Series B.

[47]  Nathalie Tzourio-Mazoyer,et al.  New insights into the anatomo-functional connectivity of the semantic system: a study using cortico-subcortical electrostimulations. , 2005, Brain : a journal of neurology.

[48]  E. Ross Sensory-specific and fractional disorders of recent memory in man. I. Isolated loss of visual recent memory. , 1980, Archives of neurology.

[49]  Jitendra Malik,et al.  Normalized cuts and image segmentation , 1997, Proceedings of IEEE Computer Society Conference on Computer Vision and Pattern Recognition.

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

[51]  J. Klein,et al.  Human Motor Corpus Callosum: Topography, Somatotopy, and Link between Microstructure and Function , 2007, The Journal of Neuroscience.

[52]  G. Kindlmann,et al.  Orthogonal tensor invariants and the analysis of diffusion tensor magnetic resonance images , 2006, Magnetic resonance in medicine.

[53]  Sati Mazumdar,et al.  Rating chronic medical illness burden in geropsychiatric practice and research: Application of the Cumulative Illness Rating Scale , 1992, Psychiatry Research.

[54]  Frans A. J. Verstraten,et al.  Exploring the Anatomical Basis of Effective Connectivity Models with DTI-Based Fiber Tractography , 2008, Int. J. Biomed. Imaging.

[55]  R. Henson,et al.  The neural basis of episodic memory: evidence from functional neuroimaging. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[56]  M. Banich The Missing Link: The Role of Interhemispheric Interaction in Attentional Processing , 1998, Brain and Cognition.

[57]  Denis Le Bihan,et al.  Looking into the functional architecture of the brain with diffusion MRI , 2003, Nature Reviews Neuroscience.

[58]  A. Dale,et al.  Age-related alterations in white matter microstructure measured by diffusion tensor imaging , 2005, Neurobiology of Aging.

[59]  C. Westin,et al.  A method for clustering white matter fiber tracts. , 2006, AJNR. American journal of neuroradiology.

[60]  R. Bronen,et al.  MR imaging of the temporal stem: anatomic dissection tractography of the uncinate fasciculus, inferior occipitofrontal fasciculus, and Meyer's loop of the optic radiation. , 2004, AJNR. American journal of neuroradiology.

[61]  P. Reuter-Lorenz,et al.  Differential Effects of Aging on the Functions of the Corpus Callosum , 2000, Developmental neuropsychology.

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

[63]  Torsten Rohlfing,et al.  Problem Solving, Working Memory, and Motor Correlates of Association and Commissural Fiber Bundles in Normal Aging: a Quantitative Fiber Tracking Study , 2022 .

[64]  D. Royall,et al.  Bedside Assessment of Executive Cognitive Impairment: The Executive Interview , 1992, Journal of the American Geriatrics Society.

[65]  Roberto Cabeza,et al.  Aging Gracefully: Compensatory Brain Activity in High-Performing Older Adults , 2002, NeuroImage.

[66]  Derek K. Jones Studying connections in the living human brain with diffusion MRI , 2008, Cortex.

[67]  Jens Frahm,et al.  Topography of the human corpus callosum revisited—Comprehensive fiber tractography using diffusion tensor magnetic resonance imaging , 2006, NeuroImage.

[68]  Derek K. Jones,et al.  Occipito-temporal connections in the human brain. , 2003, Brain : a journal of neurology.

[69]  Jung-Lung Hsu,et al.  Gender differences and age-related white matter changes of the human brain: A diffusion tensor imaging study , 2008, NeuroImage.

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

[71]  R. Ruff,et al.  Selective Reminding Tests: a normative study of verbal learning in adults. , 1989, Journal of clinical and experimental neuropsychology.

[72]  Wei Wen,et al.  The topography of white matter hyperintensities on brain MRI in healthy 60- to 64-year-old individuals , 2004, NeuroImage.

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

[74]  R. Kikinis,et al.  Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study. , 2002, The American journal of psychiatry.

[75]  Raúl San José Estépar,et al.  Diffusion tractography of the fornix in schizophrenia , 2009, Schizophrenia Research.

[76]  Carl-Fredrik Westin,et al.  Processing and visualization for diffusion tensor MRI , 2002, Medical Image Anal..

[77]  J. Gold,et al.  Repeatable battery for the assessment of neuropsychological status as a screening test in schizophrenia, II: convergent/discriminant validity and diagnostic group comparisons. , 1999, The American journal of psychiatry.

[78]  J. Gabrieli,et al.  Insights into the ageing mind: a view from cognitive neuroscience , 2004, Nature Reviews Neuroscience.

[79]  R. Buckner,et al.  THE COGNITIVE NEUROSCIENCE OF REMEMBERING , 2001 .

[80]  G. Bartzokis Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer’s disease , 2004, Neurobiology of Aging.

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

[82]  M. Schlossberg The Halstead-Reitan Neuropsychological Test Battery: Theory and Clinical Interpretation. , 1986 .

[83]  M. Catani,et al.  Diffusion-based tractography in neurological disorders: concepts, applications, and future developments , 2008, The Lancet Neurology.

[84]  Alan Peters,et al.  Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey , 2002, The Journal of comparative neurology.

[85]  F. Aboitiz,et al.  The anatomy of language revisited. , 1997, Biological research.