One-Year Brain Atrophy Evident in Healthy Aging

An accurate description of changes in the brain in healthy aging is needed to understand the basis of age-related changes in cognitive function. Cross-sectional magnetic resonance imaging (MRI) studies suggest thinning of the cerebral cortex, volumetric reductions of most subcortical structures, and ventricular expansion. However, there is a paucity of detailed longitudinal studies to support the cross-sectional findings. In the present study, 142 healthy elderly participants (60–91 years of age) were followed with repeated MRI, and were compared with 122 patients with mild to moderate Alzheimer's disease (AD). Volume changes were measured across the entire cortex and in 48 regions of interest. Cortical reductions in the healthy elderly were extensive after only 1 year, especially evident in temporal and prefrontal cortices, where annual decline was ∼0.5%. All subcortical and ventricular regions except caudate nucleus and the fourth ventricle changed significantly over 1 year. Some of the atrophy occurred in areas vulnerable to AD, while other changes were observed in areas less characteristic of the disease in early stages. This suggests that the changes are not primarily driven by degenerative processes associated with AD, although it is likely that preclinical changes associated with AD are superposed on changes due to normal aging in some subjects, especially in the temporal lobes. Finally, atrophy was found to accelerate with increasing age, and this was especially prominent in areas vulnerable to AD. Thus, it is possible that the accelerating atrophy with increasing age is due to preclinical AD.

[1]  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.

[2]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[3]  M Haupt,et al.  [Clinical diagnosis of Alzheimer's disease]. , 1988, Deutsche medizinische Wochenschrift.

[4]  Gwenn S. Smith,et al.  EARLY MARKER FOR ALZHEIMER'S DISEASE: THE ATROPHIC HIPPOCAMPUS , 1989, The Lancet.

[5]  Terry L. Jernigan,et al.  Cerebral structure on MRI, Part I: Localization of age-related changes , 1991, Biological Psychiatry.

[6]  M I Miller,et al.  Mathematical textbook of deformable neuroanatomies. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Dale,et al.  Improved Localizadon of Cortical Activity by Combining EEG and MEG with MRI Cortical Surface Reconstruction: A Linear Approach , 1993, Journal of Cognitive Neuroscience.

[8]  Michael I. Miller,et al.  Deformable templates using large deformation kinematics , 1996, IEEE Trans. Image Process..

[9]  J. Grandy Efficient computation of volume of hexahedral cells , 1997 .

[10]  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.

[11]  Nick C Fox,et al.  Modeling brain deformations in Alzheimer disease by fluid registration of serial 3D MR images. , 1998, Journal of computer assisted tomography.

[12]  C. Jack,et al.  Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease , 1998, Neurology.

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

[14]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[15]  A. Dale,et al.  High‐resolution intersubject averaging and a coordinate system for the cortical surface , 1999, Human brain mapping.

[16]  Anders M. Dale,et al.  Cortical Surface-Based Analysis I. Segmentation and Surface Reconstruction , 1999, NeuroImage.

[17]  C. Jack,et al.  Prediction of AD with MRI-based hippocampal volume in mild cognitive impairment , 1999, Neurology.

[18]  E. Yeterian,et al.  MRI-Based Topographic Parcellation of Human Cerebral White Matter and Nuclei II. Rationale and Applications with Systematics of Cerebral Connectivity , 1999, NeuroImage.

[19]  Karl J. Friston,et al.  High-Dimensional Image Registration Using Symmetric Priors , 1999, NeuroImage.

[20]  M Skalej,et al.  Patterns of age-related shrinkage in cerebellum and brainstem observed in vivo using three-dimensional MRI volumetry. , 1999, Cerebral cortex.

[21]  A. Dale,et al.  Cortical Surface-Based Analysis II: Inflation, Flattening, and a Surface-Based Coordinate System , 1999, NeuroImage.

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

[23]  A M Dale,et al.  Measuring the thickness of the human cerebral cortex from magnetic resonance images. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

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

[25]  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.

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

[27]  Nick C Fox,et al.  Mapping the evolution of regional atrophy in Alzheimer's disease: Unbiased analysis of fluid-registered serial MRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[28]  A. Dale,et al.  Whole Brain Segmentation Automated Labeling of Neuroanatomical Structures in the Human Brain , 2002, Neuron.

[29]  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.

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

[31]  Karen M Rodrigue,et al.  Differential age-related changes in the regional metencephalic volumes in humans: a 5-year follow-up , 2003, Neuroscience Letters.

[32]  B. L. Miller,et al.  Atrophy rates of entorhinal cortex in AD and normal aging , 2003, Neurology.

[33]  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.

[34]  Nikos Makris,et al.  Automatically parcellating the human cerebral cortex. , 2004, Cerebral cortex.

[35]  Norbert Schuff,et al.  Comparisons between Global and Focal Brain Atrophy Rates in Normal Aging and Alzheimer Disease: Boundary Shift Integral versus Tracing of the Entorhinal Cortex and Hippocampus , 2004, Alzheimer disease and associated disorders.

[36]  Adolf Pfefferbaum,et al.  Effects of age and sex on volumes of the thalamus, pons, and cortex , 2004, Neurobiology of Aging.

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

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

[39]  Benjamin J. Shannon,et al.  Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory , 2005, The Journal of Neuroscience.

[40]  F. Woermann,et al.  Transient lesion in the splenium of the corpus callosum and antiepileptic drug withdrawal , 2005, Neurology.

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

[42]  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.

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

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

[45]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[46]  N. Raz,et al.  Differential Aging of the Brain: Patterns, Cognitive Correlates and Modifiers , 2022 .

[47]  N. Schuff,et al.  Age effects on atrophy rates of entorhinal cortex and hippocampus , 2006, Neurobiology of Aging.

[48]  Anders M. Dale,et al.  Reliability in multi-site structural MRI studies: Effects of gradient non-linearity correction on phantom and human data , 2006, NeuroImage.

[49]  Alan C. Evans,et al.  Spatial patterns of cortical thinning in mild cognitive impairment and Alzheimer's disease. , 2006, Brain : a journal of neurology.

[50]  N. Schuff,et al.  Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia. , 2006, Brain : a journal of neurology.

[51]  K. Walhovd,et al.  Morphometric Changes in the Episodic Memory Network and Tau Pathologic Features Correlate with Memory Performance in Patients with Mild Cognitive Impairment , 2008, American Journal of Neuroradiology.

[52]  James R. MacFall,et al.  Aging, gender, and the elderly adult brain: An examination of analytical strategies , 2008, Neurobiology of Aging.

[53]  P1-249: Longitudinal nonlinear registration and quantitative analysis of change in whole brain and regions of interest , 2008, Alzheimer's & Dementia.

[54]  C. Jack,et al.  MRI of hippocampal volume loss in early Alzheimer's disease in relation to ApoE genotype and biomarkers , 2008, Brain : a journal of neurology.

[55]  H. Uylings,et al.  Prefrontal cortex atrophy predicts dementia over a six-year period , 2009, Neurobiology of Aging.

[56]  A. Dale,et al.  High consistency of regional cortical thinning in aging across multiple samples. , 2009, Cerebral cortex.

[57]  Jelle Jolles,et al.  The prevalence of cortical gray matter atrophy may be overestimated in the healthy aging brain. , 2009, Neuropsychology.

[58]  J. Morris,et al.  The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals , 2008, Cerebral cortex.

[59]  Bruce Fischl,et al.  Minute Effects of Sex on the Aging Brain: A Multisample Magnetic Resonance Imaging Study of Healthy Aging and Alzheimer's Disease , 2009, The Journal of Neuroscience.

[60]  Nick C. Fox,et al.  A meta-analysis of hippocampal atrophy rates in Alzheimer's disease , 2009, Neurobiology of Aging.

[61]  André J. W. van der Kouwe,et al.  Age-associated alterations in cortical gray and white matter signal intensity and gray to white matter contrast , 2009, NeuroImage.

[62]  A. Dale,et al.  Alzheimer disease: quantitative structural neuroimaging for detection and prediction of clinical and structural changes in mild cognitive impairment. , 2009, Radiology.

[63]  A. Dale,et al.  Regional rates of neocortical atrophy from normal aging to early Alzheimer disease , 2009, Neurology.

[64]  A. Dale,et al.  Structural MRI biomarkers for preclinical and mild Alzheimer's disease , 2009, Human brain mapping.

[65]  Anders M. Dale,et al.  Increased sensitivity to effects of normal aging and Alzheimer's disease on cortical thickness by adjustment for local variability in gray/white contrast: A multi-sample MRI study , 2009, NeuroImage.

[66]  S. Resnick,et al.  Longitudinal pattern of regional brain volume change differentiates normal aging from MCI , 2009, Neurology.

[67]  S. Resnick,et al.  Longitudinal progression of Alzheimer's-like patterns of atrophy in normal older adults: the SPARE-AD index. , 2009, Brain : a journal of neurology.

[68]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[69]  Anders M. Dale,et al.  Consistent neuroanatomical age-related volume differences across multiple samples , 2011, Neurobiology of Aging.

[70]  S. Ropele,et al.  Risk factors for progression of brain atrophy in aging Six-year follow-up of normal subjects , 2022 .