Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging

With age, the brain undergoes both structural and functional alterations, probably resulting in reported cognitive declines. Relatively few investigations have sought to identify those areas that remain intact with aging, or undergo the least deterioration, which might underlie cognitive preservations. Our aim here was to establish a comprehensive profile of both structural and functional changes in the aging brain, using up-to-date voxel-based methodology (i.e. optimized voxel-based morphometry (VBM) procedure; resting-state (18)FDG-PET with correction for partial volume effects (PVE)) in 45 optimally healthy subjects aged 20-83 years. Negative and positive correlations between age and both gray matter (GM) volume and (18)FDG uptake were assessed. The frontal cortex manifested the greatest deterioration, both structurally and functionally, whereas the anterior hippocampus, the thalamus and (functionally) the posterior cingulate cortex were the least affected. Our results support the developmental theory which postulates that the first regions to emerge phylogenetically and ontogenetically are the most resistant to age effects, and the last ones the most vulnerable. Furthermore, the lesser affected anterior hippocampal region, together with the lesser functional alteration of the posterior cingulate cortex, appear to mark the parting of the ways between normal aging and Alzheimer's disease, which is characterized by early and prominent deterioration of both structures.

[1]  B. Desgranges,et al.  L'évaluation clinique de la mémoire , 1998 .

[2]  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.

[3]  Kazuyoshi Yajima,et al.  Brain FDG PET study of normal aging in Japanese: effect of atrophy correction , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[4]  F. Craik,et al.  Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[5]  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.

[6]  E. Tulving,et al.  Hippocampal PET activations of memory encoding and retrieval: The HIPER model , 1998, Hippocampus.

[7]  J R Hodges,et al.  Retrosplenial cortex (BA 29/30) hypometabolism in mild cognitive impairment (prodromal Alzheimer's disease) , 2003, The European journal of neuroscience.

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

[9]  Denise C. Park,et al.  Aging, cognition, and culture: a neuroscientific perspective , 2002, Neuroscience & Biobehavioral Reviews.

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

[11]  J. Baron,et al.  Neural correlates of age-related verbal episodic memory decline: A PET study with combined subtraction/correlation analysis , 2007, Neurobiology of Aging.

[12]  J. Baron,et al.  Entorhinal cortex disruption causes memory deficit in early Alzheimer's disease as shown by PET , 2001, Neuroreport.

[13]  H. Chugani A critical period of brain development: studies of cerebral glucose utilization with PET. , 1998, Preventive medicine.

[14]  Pietro Pietrini,et al.  Resting state brain glucose metabolism is not reduced in normotensive healthy men during aging, after correction for brain atrophy , 2004, Brain Research Bulletin.

[15]  Nick C Fox,et al.  A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. , 2003, Archives of neurology.

[16]  Terry L. Jernigan,et al.  Changes in volume with age—consistency and interpretation of observed effects , 2005, Neurobiology of Aging.

[17]  K. Meguro,et al.  Atrophy of the corpus callosum correlates with white matter lesions in patients with cerebral ischaemia , 2000, Neuroradiology.

[18]  Jerry L Prince,et al.  Cross-sectional and longitudinal analyses of anatomical sulcal changes associated with aging. , 2005, Cerebral cortex.

[19]  Gregor Kasprian,et al.  MRI of normal fetal brain development. , 2006, European journal of radiology.

[20]  Milos Judas,et al.  In vitro MRI of brain development. , 2006, European journal of radiology.

[21]  A. Delacourte,et al.  The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease , 1999, Neurology.

[22]  K. Van Laere,et al.  Brain perfusion SPECT: age- and sex-related effects correlated with voxel-based morphometric findings in healthy adults. , 2001, Radiology.

[23]  R. Peters,et al.  Ageing and the brain , 2006, Postgraduate Medical Journal.

[24]  Habib Zaidi,et al.  Comparative assessment of statistical brain MR image segmentation algorithms and their impact on partial volume correction in PET , 2006, NeuroImage.

[25]  Peter Delves,et al.  Encyclopedia of life sciences , 2009 .

[26]  Edith V. Sullivan,et al.  Preservation of hippocampal volume throughout adulthood in healthy men and women , 2005, Neurobiology of Aging.

[27]  K O Lim,et al.  A controlled study of cortical gray matter and ventricular changes in alcoholic men over a 5-year interval. , 1998, Archives of general psychiatry.

[28]  Peter Herscovitch,et al.  Age, sex and laterality effects on cerebral glucose metabolism in healthy adults , 2002, Psychiatry Research: Neuroimaging.

[29]  Richard S. J. Frackowiak,et al.  Alzheimer's patients engage an alternative network during a memory task , 2005, Annals of neurology.

[30]  Guy Marchal,et al.  Automated multi-modality image registration based on information theory , 1995 .

[31]  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.

[32]  Jens C. Pruessner,et al.  Hippocampal volume is as variable in young as in older adults: Implications for the notion of hippocampal atrophy in humans , 2007, NeuroImage.

[33]  C. Grady Functional brain imaging and age-related changes in cognition , 2000, Biological Psychology.

[34]  Habib Zaidi,et al.  Correction for Partial Volume Effects in Emission Tomography , 2006 .

[35]  Jerry L Prince,et al.  Measurement of Radiotracer Concentration in Brain Gray Matter Using Positron Emission Tomography: MRI-Based Correction for Partial Volume Effects , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

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

[37]  Alan C. Evans,et al.  Pixel- versus Region-Based Partial Volume Correction in PET 1 1Transcripts of the BRAINPET97 discussion of this chapter can be found in Section VIII. , 1998 .

[38]  J. Mazziotta,et al.  Brain mapping : the systems , 2000 .

[39]  M. Albert,et al.  Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD , 2005, Neurology.

[40]  Takashi Asada,et al.  Correction for partial-volume effects on brain perfusion SPECT in healthy men. , 2003, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

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

[42]  Osamu Abe,et al.  Aging in the CNS: Comparison of gray/white matter volume and diffusion tensor data , 2008, Neurobiology of Aging.

[43]  R. Buckner,et al.  Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD , 2005, Neurology.

[44]  M N Cantwell,et al.  Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[45]  J. Baron,et al.  Dissociating atrophy and hypometabolism impact on episodic memory in mild cognitive impairment. , 2003, Brain : a journal of neurology.

[46]  et al.,et al.  Discrimination between Alzheimer Dementia and Controls by Automated Analysis of Multicenter FDG PET , 2002, NeuroImage.

[47]  C. Calautti,et al.  Effects of Age on Brain Activation During Auditory-Cued Thumb-to-Index Opposition: A Positron Emission Tomography Study , 2001, Stroke.

[48]  P. Wahle,et al.  Neuronal activity and neurotrophic factors regulate GAD‐65/67 mRNA and protein expression in organotypic cultures of rat visual cortex , 2003, The European journal of neuroscience.

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

[50]  Karl J. Friston,et al.  Decreases in Regional Cerebral Blood Flow with Normal Aging , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[51]  S. Laureys,et al.  Comparison of Impaired Subcortico-Frontal Metabolic Networks in Normal Aging, Subcortico-Frontal Dementia, and Cortical Frontal Dementia , 1999, NeuroImage.

[52]  Guy Marchal,et al.  Automated multi-moda lity image registration based on information theory , 1995 .

[53]  J. Baron,et al.  Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment , 2002, Neuroreport.

[54]  A. Dale,et al.  Thinning of the cerebral cortex in aging. , 2004, Cerebral cortex.

[55]  J. Baron,et al.  The neural substrates of episodic memory impairment in Alzheimer's disease as revealed by FDG-PET: relationship to degree of deterioration. , 2002, Brain : a journal of neurology.

[56]  Daniel L. Schacter,et al.  The role of hippocampus and frontal cortex in age‐ related memory changes: a PET study , 1996, Neuroreport.

[57]  John S. Duncan,et al.  A longitudinal study of brain morphometrics using quantitative magnetic resonance imaging and difference image analysis , 2003, NeuroImage.

[58]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[59]  T. Sunderland,et al.  Hippocampal atrophy in the healthy is initially linear and independent of age , 2006, Neurobiology of Aging.

[60]  Clifford R Jack,et al.  Neuroimaging in Alzheimer disease: an evidence-based review. , 2003, Neuroimaging clinics of North America.

[61]  J. Baron,et al.  In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease , 2001, NeuroImage.

[62]  A. Toga,et al.  Mapping brain maturation , 2006, Trends in Neurosciences.

[63]  D Comar,et al.  Regional Cerebral Blood Flow and Oxygen Consumption in Human Aging , 1984, Stroke.

[64]  C. Svarer,et al.  Integrated software for the analysis of brain PET/SPECT studies with partial-volume-effect correction. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[65]  Takashi Asada,et al.  Longitudinal evaluation of both morphologic and functional changes in the same individuals with Alzheimer's disease. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[66]  Karl J. Friston,et al.  Voxel based morphometry of 465 normal adult human brains , 2000, NeuroImage.

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

[68]  Francis Eustache,et al.  The Functional Neuroanatomy of Episodic Memory: The Role of the Frontal Lobes, the Hippocampal Formation, and Other Areas , 1998, NeuroImage.

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

[70]  F. Craik,et al.  The handbook of aging and cognition , 1992 .

[71]  M. Albert,et al.  fMRI studies of associative encoding in young and elderly controls and mild Alzheimer’s disease , 2003, Journal of neurology, neurosurgery, and psychiatry.

[72]  S. M. Resnick,et al.  I. Longitudinal changes in aging brain function , 2008, Neurobiology of Aging.

[73]  Francis Eustache,et al.  The Neural Basis of Intrusions in Free Recall and Cued Recall: A PET Study in Alzheimer's Disease , 2002, NeuroImage.

[74]  A. Evans,et al.  Correction for partial volume effects in PET: principle and validation. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[75]  Stefanie Brassen,et al.  Combining voxel-based morphometry and diffusion tensor imaging to detect age-related brain changes , 2006, Neuroreport.

[76]  Richard S. J. Frackowiak,et al.  Age effects on the neural correlates of successful memory encoding. , 2003, Brain : a journal of neurology.

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

[78]  M. Daube-Witherspoon,et al.  Quantitative functional brain imaging with positron emission tomography , 1998 .

[79]  Fabrice Crivello,et al.  Age- and sex-related effects on the neuroanatomy of healthy elderly , 2005, NeuroImage.

[80]  D. Schacter,et al.  Medial temporal lobe activations in fMRI and PET studies of episodic encoding and retrieval , 1999, Hippocampus.

[81]  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.

[82]  J. Becker,et al.  Positron emission tomography imaging of the aging brain. , 2003, Neuroimaging clinics of North America.

[83]  D. Head,et al.  Differential aging of the medial temporal lobe , 2004, Neurology.

[84]  A. Convit,et al.  Reduced hippocampal metabolism in MCI and AD , 2005, Neurology.

[85]  B. Landeau,et al.  Effects of Healthy Aging on the Regional Cerebral Metabolic Rate of Glucose Assessed with Statistical Parametric Mapping , 1996, NeuroImage.

[86]  S. M. Resnick,et al.  II. Temporal patterns of longitudinal change in aging brain function , 2008, Neurobiology of Aging.

[87]  Leanne M Williams,et al.  Preservation of limbic and paralimbic structures in aging , 2005, Human brain mapping.

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

[89]  Y. Joanette,et al.  [Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level]. , 1990, Acta neurologica Belgica.

[90]  E. Bigler,et al.  Hippocampal volume in normal aging and traumatic brain injury. , 1997, AJNR. American journal of neuroradiology.

[91]  N. Raz Aging of the brain and its impact on cognitive performance: Integration of structural and functional findings. , 2000 .

[92]  L. Nyberg,et al.  Altered brain activity in healthy seniors: what does it mean? , 2006, Progress in brain research.

[93]  R. Sutherland,et al.  The aging hippocampus: cognitive, biochemical and structural findings. , 2003, Cerebral cortex.

[94]  H. Zaidi,et al.  Quantitative Analysis in Nuclear Medicine Imaging , 2007, Journal of Nuclear Medicine.

[95]  J. Baron,et al.  Efficient principal component analysis for multivariate 3D voxel‐based mapping of brain functional imaging data sets as applied to FDG‐PET and normal aging , 2003, Human brain mapping.