O1-02-02 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: 5.01). 05/2005; 26(4):553-9. DOI: 10.1016/j.neurobiolaging.2004.05.002
Source: PubMed


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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    • "Individuals with AD show significant cortical and hippocampal atrophy relative to non-demented age matched controls (Alavi et al., 1993; Raz et al., 1998) and losses in brain volume correlate with cognitive decline (Ezekiel et al., 2004; Du et al., 2005). Similar events are seen in aged canines. "
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    ABSTRACT: Aged dogs spontaneously develop many features of human aging and Alzheimer's disease (AD) including cognitive decline and neuropathology. In this review, we discuss age-dependent learning tasks, memory tasks, and functional measures that can be used in aged dogs for sensitive treatment outcome measures. Neuropathology that is linked to cognitive decline is described along with examples of treatment studies that show reduced neuropathology in aging dogs (dietary manipulations, behavioral enrichment, immunotherapy, and statins). Studies in canine show that multi-targeted approaches may be more beneficial than single pathway manipulations (e.g., antioxidants combined with behavioral enrichment). Aging canine studies show good predictive validity for human clinical trials outcomes (e.g., immunotherapy) and several interventions tested in dogs strongly support a prevention approach (e.g., immunotherapy and statins). Further, dogs are ideally suited for prevention studies as they the age because onset of cognitive decline and neuropathology strongly support longitudinal interventions that can be completed within a 3-5 year period. Disadvantages to using the canine model are that they lengthy, use labor-intensive comprehensive cognitive testing, and involve costly housing (almost as high as that of non-human primates). However, overall, using the dog as a preclinical model for testing preventive approaches for AD may complement work in rodents and non-human primates.
    Frontiers in Pharmacology 03/2014; 5:47. DOI:10.3389/fphar.2014.00047 · 3.80 Impact Factor
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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 · 2.47 Impact Factor
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    • "It was thus proposed that cognitive decline in patients with WMC was mediated by brain atrophy [96]. The hypothesized mechanisms of how WMC induce cortical atrophy include demyelination of axons leading to cortical-subcortical deafferentation and subsequent secondary cortical neuronal loss, [99, 100] hypoperfusion, and hypometabolism [101, 102], as well as concomitant cortical microinfarct, which its detection is beyond the ability of current neuroimaging techniques [102].A recent study also showed that severe WMC were associated with hippocampus atrophy [103]. Moreover, Smith et al. study in community residents revealed that WMC progression might predict normal to mild cognitive impairment, whereas global atrophy predicted mild cognitive impairment to dementia [104]. "
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    ABSTRACT: Age-related white matter changes (WMC) are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC.
    Journal of aging research 08/2011; 2011(8):617927. DOI:10.4061/2011/617927
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