Structural MRI covariance patterns associated with normal aging and neuropsychological functioning

Structural magnetic resonance imaging (MRI) studies have shown dramatic age-associated changes in grey and white matter volume, but typically use univariate analyses that do not explicitly test the interrelationship among brain regions. The current study used a multivariate approach to identify covariance patterns of grey and white matter tissue density to distinguish older from younger adults. A second aim was to examine whether the expression of the age-associated covariance topographies is related to performance on cognitive tests affected by normal aging. Eighty-four young (mean age=24.0) and 29 older (mean age=73.1) participants were scanned with a 1.5T MRI machine and assessed with a cognitive battery. Images were spatially normalized and segmented to produce grey and white matter density maps. A multivariate technique, based on the subprofile scaling model, was used to capture sources of between- and within-group variation to produce a linear combination of principal components that represented a "pattern" or "network" that best discriminated between the two age groups. Univariate analyses were also conducted with statistical parametric maps. Grey and white matter covariance patterns were identified that reliably discriminated between the groups with greater than 0.90 sensitivity and specificity. The identified patterns were similar for the univariate and multivariate techniques, and involved widespread regions of the cortex and subcortex. Age and the expression of both patterns were significantly associated with performance on tests of attention, language, memory, and executive functioning. The results suggest that identifiable networks of grey and white matter regions systematically decline with age and that pattern expression is linked to age-related cognitive decline.

[1]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[2]  E. Plante,et al.  Memory and executive function in older adults: relationships with temporal and prefrontal gray matter volumes and white matter hyperintensities , 2004, Neuropsychologia.

[3]  M. Lezak,et al.  Neuropsychological assessment, 4th ed. , 2004 .

[4]  David R. Anderson,et al.  Model Selection and Multimodel Inference , 2003 .

[5]  Karl J. Friston,et al.  Why Voxel-Based Morphometry Should Be Used , 2001, NeuroImage.

[6]  Tom den Heijer,et al.  Hippocampal Head Size Associated with Verbal Memory Performance in Nondemented Elderly , 2002, NeuroImage.

[7]  K O Lim,et al.  Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: a quantitative MRI study. , 1992, Alcoholism, clinical and experimental research.

[8]  Faith M. Gunning-Dixon,et al.  Neuroanatomical correlates of selected executive functions in middle-aged and older adults: a prospective MRI study , 2003, Neuropsychologia.

[9]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[10]  Alan C. Evans,et al.  A voxel-based morphometric study to determine individual differences in gray matter density associated with age and cognitive change over time. , 2004, Cerebral cortex.

[11]  R. Reitan Validity of the Trail Making Test as an Indicator of Organic Brain Damage , 1958 .

[12]  R. Kikinis,et al.  White matter changes with normal aging , 1998, Neurology.

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

[14]  Yaakov Stern,et al.  Relation of cognitive reserve and task performance to expression of regional covariance networks in an event-related fMRI study of nonverbal memory☆ , 2003, NeuroImage.

[15]  Hiroshi Fukuda,et al.  Voxel-based morphometry of human brain with age and cerebrovascular risk factors , 2004, Neurobiology of Aging.

[16]  G. Alexander,et al.  The Metabolic Topography of Normal Aging , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  A. Dale,et al.  Effects of age on volumes of cortex, white matter and subcortical structures , 2005, Neurobiology of Aging.

[18]  John S. Allen,et al.  Normal neuroanatomical variation due to age: The major lobes and a parcellation of the temporal region , 2005, Neurobiology of Aging.

[19]  E. Gordon,et al.  Regional White Matter and Neuropsychological Functioning across the Adult Lifespan , 2006, Biological Psychiatry.

[20]  Karen J. Ferguson,et al.  Intracranial capacity and brain volumes are associated with cognition in healthy elderly men , 2002, Neurology.

[21]  V. Calhoun,et al.  Voxel-based morphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia , 2005, Schizophrenia Research.

[22]  Faith M. Gunning-Dixon,et al.  Neuroanatomical correlates of cognitive aging: evidence from structural magnetic resonance imaging. , 1998, Neuropsychology.

[23]  B. Tycko,et al.  Altered PET functional brain responses in cognitively intact elderly persons at risk for Alzheimer disease (carriers of the epsilon4 allele). , 2004, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[24]  S. Strother,et al.  Scaled Subprofile Model: A Statistical Approach to the Analysis of Functional Patterns in Positron Emission Tomographic Data , 1987, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  HERMAN BUSCHKE,et al.  Evaluating storage, retention, and retrieval in disordered memory and learning , 1974, Neurology.

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

[27]  G. Bartzokis,et al.  White matter structural integrity in healthy aging adults and patients with Alzheimer disease: a magnetic resonance imaging study. , 2003, Archives of neurology.

[28]  Yaakov Stern,et al.  Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance , 2004, NeuroImage.

[29]  Chao Zhao,et al.  Ageing and CNS remyelination , 2002, Neuroreport.

[30]  Vladimir V. Frolkis,et al.  Neurobiology of Aging , 2019, Psychobiology of Behaviour.

[31]  G. Press,et al.  Methods for measuring brain morphologic features on magnetic resonance images. Validation and normal aging. , 1990, Archives of neurology.

[32]  Y. Stern The Concept of Cognitive Reserve: A Catalyst for Research , 2003, Journal of clinical and experimental neuropsychology.

[33]  M. Sliwinski,et al.  Correlated and coupled cognitive change in older adults with and without preclinical dementia. , 2003, Psychology and aging.

[34]  M. D’Esposito,et al.  The Inferential Impact of Global Signal Covariates in Functional Neuroimaging Analyses , 1998, NeuroImage.

[35]  Yaakov Stern,et al.  Identification and differential vulnerability of a neural network in sleep deprivation. , 2004, Cerebral cortex.

[36]  Fred L. Bookstein,et al.  “Voxel-Based Morphometry” Should Not Be Used with Imperfectly Registered Images , 2001, NeuroImage.

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

[38]  W. Sturm,et al.  Neuropsychological assessment , 2007, Journal of Neurology.

[39]  R. V. Van Heertum,et al.  Brain networks associated with cognitive reserve in healthy young and old adults. , 2005, Cerebral cortex.

[40]  C. Fennema-Notestine,et al.  Effects of age on tissues and regions of the cerebrum and cerebellum , 2001, Neurobiology of Aging.

[41]  Y. Stern What is cognitive reserve? Theory and research application of the reserve concept , 2002, Journal of the International Neuropsychological Society.

[42]  Dc Washington Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. , 1994 .

[43]  T. Salthouse The processing-speed theory of adult age differences in cognition. , 1996, Psychological review.

[44]  D. Mathalon,et al.  A quantitative magnetic resonance imaging study of changes in brain morphology from infancy to late adulthood. , 1994, Archives of neurology.

[45]  Yaakov Stern,et al.  An event-related fMRI study of the neural networks underlying the encoding, maintenance, and retrieval phase in a delayed-match-to-sample task. , 2005, Brain research. Cognitive brain research.

[46]  S. Resnick,et al.  One-year age changes in MRI brain volumes in older adults. , 2000, Cerebral cortex.

[47]  Karl J. Friston,et al.  Automatic Differentiation of Anatomical Patterns in the Human Brain: Validation with Studies of Degenerative Dementias , 2002, NeuroImage.

[48]  M. Albert,et al.  Neuropsychological and neurophysiological changes in healthy adult humans across the age range , 1993, Neurobiology of Aging.

[49]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

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

[51]  H. Uylings,et al.  Thalamic volume predicts performance on tests of cognitive speed and decreases in healthy aging. A magnetic resonance imaging-based volumetric analysis. , 2001, Brain research. Cognitive brain research.

[52]  R. West,et al.  An application of prefrontal cortex function theory to cognitive aging. , 1996, Psychological bulletin.

[53]  J R Moeller,et al.  Individual differences in PET activation of object perception and attention systems predict face matching accuracy. , 1999, Neuroreport.

[54]  G. Bartzokis,et al.  Age-related changes in frontal and temporal lobe volumes in men: a magnetic resonance imaging study. , 2001, Archives of general psychiatry.

[55]  Jens C. Pruessner,et al.  Regional Frontal Cortical Volumes Decrease Differentially in Aging: An MRI Study to Compare Volumetric Approaches and Voxel-Based Morphometry , 2002, NeuroImage.