Association of White-Matter Lesions with Brain Atrophy Markers: The Three-City Dijon MRI Study

Background: Brain atrophy and white-matter lesions (WML) are common features at cerebral MRI of both normal and demented elderly people. In a population-based study of 1,792 elderly subjects aged 65–80 years, free of dementia, who had a cerebral MRI at entry, we investigated the relationship between WML volume and brain atrophy markers estimated by hippocampal, gray matter (GM) and cerebrospinal fluid (CSF) volumes. Methods: An automated algorithm of detection and quantification of WML was developed, and voxel-based morphometry methods were used to estimate GM, CSF and hippocampal volumes. To evaluate the relation between those volumes and WML load, we used analysis of covariance and multiple linear regression models adjusting for potential confounders and total intracranial volumes. Results: Age was highly correlated with WML load and all brain atrophy markers. Total WML volume was negatively associated with both GM (β = –0.03, p < 0.0001) and hippocampal volumes (β = –0.75, p = 0.0009) and positively with CSF volumes (β = 0.008, p = 0.02) after controlling for sex, age, education level, hypertension and apolipoprotein E genotype. Evidence for a relationship between brain atrophy markers and WML was stronger for periventricular WML. We found that the relationship between WML and hippocampal volumes was independent of other brain tissue volumes. Conclusion: These results suggest that, in the brain of nondemented elderly subjects, degenerative processes and vascular changes co-occur and are related independently of vascular risk factors.

[1]  W. M. van der Flier,et al.  Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD , 2004, Neurology.

[2]  R. Baldwin,et al.  Severe deep white matter lesions and outcome in major depressive disorder. Further investigation of deep white matter lesions is necessary. , 1999, BMJ.

[3]  M W Weiner,et al.  Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease , 2000, Neurology.

[4]  M. O’Sullivan,et al.  Brain Atrophy Is Related to Lacunar Lesions and Tissue Microstructural Changes in CADASIL , 2007, Stroke.

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

[6]  J T O'Brien,et al.  Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects , 2004, Neurology.

[7]  Norbert Schuff,et al.  White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy , 2004, Neurobiology of Aging.

[8]  Frederik Barkhof,et al.  White matter lesions and hippocampal atrophy in Alzheimer’s disease , 2004, Neurology.

[9]  P. J. Koudstaal,et al.  Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe , 2005, Neurology.

[10]  James M Provenzale,et al.  Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression , 2003, Biological Psychiatry.

[11]  Carole Dufouil,et al.  No ɛ4 gene dose effect on hippocampal atrophy in a large MRI database of healthy elderly subjects , 2005, NeuroImage.

[12]  M H Buonocore,et al.  Brain structure and cognition in a community sample of elderly Latinos , 2002, Neurology.

[13]  J. Meyer,et al.  Human aging: risk factors for cerebral atrophy. , 1997, Annals of the New York Academy of Sciences.

[14]  R. Holman,et al.  Vascular Factors and Risk of Dementia: Design of the Three-City Study and Baseline Characteristics of the Study Population , 2003, Neuroepidemiology.

[15]  Yasuo Terayama,et al.  Normal human aging: factors contributing to cerebral atrophy , 1997, Journal of the Neurological Sciences.

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

[17]  Eric Vermetten,et al.  Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment , 2004, Biological Psychiatry.

[18]  Leonardo Pantoni,et al.  Pathophysiology of Age-Related Cerebral White Matter Changes , 2002, Cerebrovascular Diseases.

[19]  J. Haxby,et al.  Brain atrophy in hypertension. A volumetric magnetic resonance imaging study. , 1992, Hypertension.

[20]  A. Algra,et al.  Automated and Visual Scoring Methods of Cerebral White Matter Hyperintensities: Relation with Age and Cognitive Function , 2007, Cerebrovascular Diseases.

[21]  Ian G. McKeith,et al.  Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales , 2001, The Lancet.

[22]  R. Kahn,et al.  Hippocampal changes and white matter lesions in early-onset depression , 2004, Biological Psychiatry.

[23]  Wiro J. Niessen,et al.  Brain tissue volumes in the general elderly population The Rotterdam Scan Study , 2008, Neurobiology of Aging.

[24]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

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

[26]  Michael Weiner,et al.  Effects of white matter lesions and lacunes on cortical function. , 2004, Archives of neurology.

[27]  J. Haxby,et al.  The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults , 1995, Neurology.

[28]  D. Louis Collins,et al.  Design and construction of a realistic digital brain phantom , 1998, IEEE Transactions on Medical Imaging.

[29]  Dinggang Shen,et al.  Very High-Resolution Morphometry Using Mass-Preserving Deformations and HAMMER Elastic Registration , 2003, NeuroImage.

[30]  P. Matthews,et al.  White matter lesion progression, brain atrophy, and cognitive decline: The Austrian stroke prevention study , 2005, Annals of neurology.

[31]  T. Bekinschtein,et al.  White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[32]  J. V. van Swieten,et al.  Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces. , 1991, Brain : a journal of neurology.

[33]  K. Unsicker,et al.  Morphological alterations in the amygdala and hippocampus of mice during ageing , 2002, The European journal of neuroscience.

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

[35]  Jeffrey L. Saver,et al.  Cerebral White Matter Hyperintensities on MRI: Current Concepts and Therapeutic Implications , 2006, Cerebrovascular Diseases.

[36]  Marko Wilke,et al.  Bright spots: correlations of gray matter volume with IQ in a normal pediatric population , 2003, NeuroImage.

[37]  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.