White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy

Magnetic Resonance Unit (114M), Department of Veterans Affairs Medical Center, 4150, Clement Street, San Francisco, CA 94121, USA.
Neurobiology of Aging (Impact Factor: 4.85). 05/2005; 26(4):553-9. DOI: 10.1016/j.neurobiolaging.2004.05.002
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ABSTRACT The goal of this study was to examine the relationship between subcortical vascular disease and brain atrophy in patients with Alzheimer's disease (AD) and mixed dementia (i.e., AD and subcortical vascular disease together). MRI was performed on 77 cognitively normal (CN) subjects, 50 AD and 13 mixed dementia patients. Subcortical vascular disease was determined by white matter hyperintensities (WMH) volume and presence of subcortical lacunes. Brain atrophy was measured using total brain cortical gray matter (CGM), entorhinal cortex (ERC) and hippocampal volumes. CGM volume, but not ERC or hippocampal volume was inversely related to WMH volume in patients and controls. In contrast, no relationship was detected between CGM, ERC, or hippocampal volumes and subcortical lacunes. Furthermore, no interaction was found between WMH and diagnosis on cortical atrophy, implying that WMH affect cortical atrophy indifferently of group. These results suggest that subcortical vascular disease, manifested as WMH, may affect cortical atrophy more than ERC and hippocampal atrophy. Further, AD pathology and subcortical vascular disease may independently affect cortical atrophy.

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Available from: Linda L Chao, Mar 25, 2015
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    • "This is consistent to a previous study that showed that neither the number or volume of lacunes was associated with cGM volume [35]. Another study also found no such relationship in patients with Alzheimer's disease and mixed dementia, which may reflect a more prominent degenerative cause for cGM in these patients [8]. "
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    ABSTRACT: Our previous study found that cortical gray matter (cGM) volume predicted vascular cognitive impairment independent of age-related white matter changes (WMC). We aimed to investigate predictors for cGM volume in ischemic stroke patients with confluent WMC. One-hundred post-stroke patients with confluent WMC were recruited into the study. All volumetric measures were standardized by intracranial volume as volume ratio. Univariate analyses and multivariate linear regression models were used to test relationship of cGM volume with basic demography, vascular risk factors, APOE status, WMC volume (periventricular and deep WMC), infarct measures (volume, number and location) and microbleed (number, presence and location). After controlling for significant variables in the univariate analyses, multivariate linear regression models found that old age (β=-0.288, p=0.001), low triglyceride (β=0.194, p=0.027), periventricular WMC (PVWMC) (β=-0.392, p<0.001) and presence of thalamic microbleed (β=-0.197, p=0.041) were independently predictive of less cGM volume ratio. Age, PVWMC and left thalamic microbleed predict less cGM volume.
    Journal of the neurological sciences 01/2014; 338(1-2). DOI:10.1016/j.jns.2013.12.044 · 2.26 Impact Factor
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    • "Additional analyses that are beyond the scope of this report are warranted to further explore the cognitive correlates of hippocampal volume changes. We also found significant hippocampal loss in the normal group over 1 year, in agreement with several prior MRI studies (Fox and Schott, 2004; Du et al., 2005; Jack et al., 2005) as well as with autopsy findings of neuronal loss in the ageing hippocampus (West, 1993; Simic et al., 1997). However, to determine if hippocampal loss in normal subjects is already an indication of incipient Alzheimer's disease or other pathologies affecting the hippocampus requires clinical follow-up of the subjects to determine their cognitive decline and ultimate development of Alzheimer's disease. "
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    ABSTRACT: Hippocampal volume change over time, measured with MRI, has huge potential as a marker for Alzheimer's disease. The objectives of this study were: (i) to test if constant and accelerated hippocampal loss can be detected in Alzheimer's disease, mild cognitive impairment and normal ageing over short periods, e.g. 6-12 months, with MRI in the large multicentre setting of the Alzheimer's Disease Neuroimaging Initiative (ADNI); (ii) to determine the extent to which the polymorphism of the apolipoprotein E (ApoE) gene modulates hippocampal change; and (iii) to determine if rates of hippocampal loss correlate with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease, such as the beta-amyloid (Abeta(1-42)) and tau proteins (tau). The MRI multicentre study included 112 cognitive normal elderly individuals, 226 mild cognitive impairment and 96 Alzheimer's disease patients who all had at least three successive MRI scans, involving 47 different imaging centres. The mild cognitive impairment and Alzheimer's disease groups showed hippocampal volume loss over 6 months and accelerated loss over 1 year. Moreover, increased rates of hippocampal loss were associated with presence of the ApoE allele epsilon4 gene in Alzheimer's disease and lower CSF Abeta(1-42) in mild cognitive impairment, irrespective of ApoE genotype, whereas relations with tau were only trends. The power to measure hippocampal change was improved by exploiting correlations statistically between successive MRI observations. The demonstration of considerable hippocampal loss in mild cognitive impairment and Alzheimer's disease patients over only 6 months and accelerated loss over 12 months illustrates the power of MRI to track morphological brain changes over time in a large multisite setting. Furthermore, the relations between faster hippocampal loss in the presence of ApoE allele epsilon4 and decreased CSF Abeta(1-42) supports the concept that increased hippocampal loss is an indicator of Alzheimer's disease pathology and a potential marker for the efficacy of therapeutic interventions in Alzheimer's disease.
    Brain 03/2009; 132(Pt 4):1067-77. DOI:10.1093/brain/awp007 · 10.23 Impact Factor
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    • "The prevalence of HWM lesions has been reported to be as high as 60–100% in normal subjects 60 years old and older (de Leeuw et al., 2001, 2005). These lesions appear more often in frontal regions (Fazekas et al., 2005; Raz et al., 2003) and their volume is correlated with global decreases in cerebral blood flow (Kraut et al., 2008; ten Dam et al., 2007), reduction in cerebral WM and GM volumes (Du et al., 2005; Wen et al., 2006) and reduction in global and regional FA values (Kochunov et al., 2007). "
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    ABSTRACT: Relationships between structural MRI-based markers of declining cerebral integrity, and regional PET measurements of (18)FDG uptake have not been studied well in normal aging. In this manuscript we relate changes in cerebral morphology to regional cerebral glucose uptake for 14 major cortical areas in 19 healthy older individuals (age 59-92 years). Measurements of cerebral integrity included gray matter (GM) thickness, sulcal and intergyral spans, fractional anisotropy (FA) of water diffusion and volume of hyperintense WM (HWM) lesions. (18)FDG-PET measurements were converted to standard uptake values and corrected for partial volume artifact. Following this, cortical FDG uptake was significantly correlated with several indices of WM integrity that we previously observed to be sensitive to cognitive decline in executive function, including intergyral span and HWM volumes. Our findings suggest that the age-related decline in white matter integrity, observed as increases in HWM lesions, intergyral spans and reduction in FA, correlated with a decline in the global and regional cerebral glucose uptake. Our findings support the emerging consensus that WM integrity indices are sensitive predictors of declining cerebral health in normal aging. Specifically, age-related WM degradation in the thinly myelinated association tracts appears to track the decreases in global and regional rates of glucose uptake.
    NeuroImage 12/2008; 45(1):17-28. DOI:10.1016/j.neuroimage.2008.11.010 · 6.36 Impact Factor
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