Age- and sex-related effects on the neuroanatomy of healthy elderly

Effects of age and sex, and their interaction on the structural brain anatomy of healthy elderly were assessed thanks to a cross-sectional study of a cohort of 662 subjects aged from 63 to 75 years. T1- and T2-weighted MRI scans were acquired in each subject and further processed using a voxel-based approach that was optimized for the identification of the cerebrospinal fluid (CSF) compartment. Analysis of covariance revealed a classical neuroanatomy sexual dimorphism, men exhibiting larger gray matter (GM), white matter (WM), and CSF compartment volumes, together with larger WM and CSF fractions, whereas women showed larger GM fraction. GM and WM were found to significantly decrease with age, while CSF volume significantly increased. Tissue probability map analysis showed that the highest rates of GM atrophy in this age range were localized in primary cortices, the angular and superior parietal gyri, the orbital part of the prefrontal cortex, and in the hippocampal region. There was no significant interaction between "Sex" and "Age" for any of the tissue volumes, as well as for any of the tissue probability maps. These findings indicate that brain atrophy during the seventh and eighth decades of life is ubiquitous and proceeds at a rate that is not modulated by "Sex".

[1]  Raquel E Gur,et al.  Brain region and sex differences in age association with brain volume: a quantitative MRI study of healthy young adults. , 2002, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[2]  M. Mesulam The cholinergic contribution to neuromodulation in the cerebral cortex , 1995 .

[3]  H. Braak,et al.  Neuropathology of Alzheimer’s disease: what is new since A. Alzheimer? , 1999, European Archives of Psychiatry and Clinical Neuroscience.

[4]  T. Erkinjuntti,et al.  White matter hyperintensities on MRI in the neurologically nondiseased elderly. Analysis of cohorts of consecutive subjects aged 55 to 85 years living at home. , 1995, Stroke.

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

[6]  N. Volkow,et al.  Association between age-related decline in brain dopamine activity and impairment in frontal and cingulate metabolism. , 2000, The American journal of psychiatry.

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

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

[9]  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.

[10]  K. Lim,et al.  Age‐related decline in brain white matter anisotropy measured with spatially corrected echo‐planar diffusion tensor imaging , 2000, Magnetic resonance in medicine.

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

[12]  Richard E Carson,et al.  In vivo muscarinic 2 receptor imaging in cognitively normal young and older volunteers , 2003, Synapse.

[13]  B. Turetsky,et al.  Sex Differences in Brain Gray and White Matter in Healthy Young Adults: Correlations with Cognitive Performance , 1999, The Journal of Neuroscience.

[14]  Nick C Fox,et al.  Imaging of onset and progression of Alzheimer's disease with voxel-compression mapping of serial magnetic resonance images , 2001, The Lancet.

[15]  D. Price,et al.  Age-related changes in multiple neurotransmitter systems in the monkey brain , 1989, Neurobiology of Aging.

[16]  A. Leventhal,et al.  Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys , 2000, Nature Neuroscience.

[17]  A. Dekaban,et al.  Changes in brain weights during the span of human life: Relation of brain weights to body heights and body weights , 1978, Annals of neurology.

[18]  A. Pfefferbaum,et al.  Differential rates of regional brain change in callosal and ventricular size: a 4-year longitudinal MRI study of elderly men. , 2002, Cerebral cortex.

[19]  J. Jolles,et al.  The relation between global and limbic brain volumes on MRI and cognitive performance in healthy individuals across the age range , 2000, Neurobiology of Aging.

[20]  J. Hohnsbein,et al.  Sensorimotor slowing with ageing is mediated by a functional dysregulation of motor-generation processes: evidence from high-resolution event-related potentials. , 2004, Brain : a journal of neurology.

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

[22]  M. Folstein,et al.  The Meaning of Cognitive Impairment in the Elderly , 1985, Journal of the American Geriatrics Society.

[23]  Erin D Bigler,et al.  Temporal lobe morphology in normal aging and traumatic brain injury. , 2002, AJNR. American journal of neuroradiology.

[24]  G. Alexander,et al.  Interactive effects of age and hypertension on volumes of brain structures. , 1997, Stroke.

[25]  Matthijs Oudkerk,et al.  Brain changes with aging: MR spectroscopy at supraventricular plane shows differences between women and men. , 2003, Radiology.

[26]  A Hofman,et al.  Human Brain Chemical Shift Imaging at Age 60 to 90: Analysis of the Causes of the Observed Sex Differences in Brain Metabolites , 2001, Investigative radiology.

[27]  G. Ratcliff,et al.  Sex differences in brain aging: a quantitative magnetic resonance imaging study. , 1998, Archives of neurology.

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

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

[30]  P. Goldman-Rakic,et al.  Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys , 1981, Neuroscience.

[31]  Naftali Raz,et al.  Hormone replacement therapy and age-related brain shrinkage: regional effects , 2004, Neuroreport.

[32]  D D Blatter,et al.  Quantitative volumetric analysis of brain MR: normative database spanning 5 decades of life. , 1995, AJNR. American journal of neuroradiology.

[33]  Faith M. Gunning-Dixon,et al.  Differential aging of the human striatum: a prospective MR imaging study. , 1998, AJNR. American journal of neuroradiology.

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

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

[36]  Haruyasu Yamada,et al.  Normal aging in the central nervous system: quantitative MR diffusion-tensor analysis , 2002, Neurobiology of Aging.

[37]  S. Resnick,et al.  Degenerative age changes in white matter connectivity visualized in vivo using magnetic resonance imaging. , 2002, Cerebral cortex.

[38]  W. Meier-Ruge,et al.  Age‐Related White Matter Atrophy in the Human Brain , 1992, Annals of the New York Academy of Sciences.

[39]  S. Lamberts,et al.  The endocrinology of aging and the brain. , 2002, Archives of neurology.

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

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

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

[43]  C. Jack,et al.  Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia , 2002, Neurology.

[44]  D. Salat,et al.  Selective preservation and degeneration within the prefrontal cortex in aging and Alzheimer disease. , 2001, Archives of neurology.

[45]  Naftali Raz,et al.  Neuroanatomical correlates of age-sensitive and age-invariant cognitive abilities: An in vivo MRI investigation , 1993 .

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

[47]  R. Woods,et al.  Mapping cortical thickness and gray matter concentration in first episode schizophrenia. , 2005, Cerebral cortex.

[48]  R N Bryan,et al.  Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study. , 1997, Radiology.

[49]  J. Mazziotta,et al.  Rapid Automated Algorithm for Aligning and Reslicing PET Images , 1992, Journal of computer assisted tomography.

[50]  E. Masson,et al.  Neuroendocrinology of ageing. , 2001, Age and ageing.

[51]  C. Jack,et al.  Memory and MRI-based hippocampal volumes in aging and AD , 2000, Neurology.

[52]  Suzanne E. Welcome,et al.  Mapping cortical change across the human life span , 2003, Nature Neuroscience.

[53]  C. Coffey,et al.  Quantitative cerebral anatomy of the aging human brain , 1992, Neurology.

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

[55]  G. Ratcliff,et al.  Relation of education to brain size in normal aging , 1999, Neurology.

[56]  P. Pietrini,et al.  Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging. , 1996, Archives of general psychiatry.

[57]  P. Roland,et al.  Comparison of spatial normalization procedures and their impact on functional maps , 2002, Human brain mapping.

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

[59]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

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

[61]  J. Townsend,et al.  Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. , 2000, Radiology.

[62]  J. Mendelson,et al.  Age-related temporal processing speed deterioration in auditory cortex , 2001, Hearing Research.

[63]  E Auffray,et al.  Longitudinal study of blood pressure and white matter hyperintensities , 2001, Neurology.

[64]  J C Gore,et al.  Automated measurement of latent morphological features in the human corpus callosum , 2001, Human brain mapping.

[65]  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.

[66]  J. Rinne,et al.  Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease , 2002, Neuroscience & Biobehavioral Reviews.

[67]  B. Pakkenberg,et al.  Neocortical neuron number in humans: Effect of sex and age , 1997, The Journal of comparative neurology.

[68]  D. Lindsley,et al.  The human brain in figures and tables : a quantitative handbook , 1968 .

[69]  A. Toga,et al.  Three-Dimensional Statistical Analysis of Sulcal Variability in the Human Brain , 1996, The Journal of Neuroscience.

[70]  J. Kaye,et al.  Neurologic evaluation of the optimally healthy oldest old. , 1994, Archives of neurology.