Journal of Alzheimer's disease : JAD
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Alzheimer's disease (AD) is characterized by progressive cognitive deficits, accumulation of amyloid-β (Aβ) and intracellular neurofibrillary tangles, and neuronal death. Additionally, mitochondrial dysfunction and free radical damage are hallmarks of AD brain. Here we set out to define the role of oxidative stress in AD pathogenesis and progression by chronically treating 3xTg-AD mice with the superoxide dismutase (SOD)/catalase mimetic, EUK-207. ⋯ The effects of a 3-month treatment after pathology onset at 9 months on cognitive performance, brain oxidative stress, Aβ, and tau pathology were also evaluated. EUK-207-treated 3xTg-AD mice did not display any deficit in fear conditioning and were protected against increases in brain levels of oxidized nucleic acids and lipid peroxidation; they also had reduced Aβ, tau, and hyperphosphorylated tau accumulation in amygdala and hippocampus. Our results confirm a critical role for oxidative stress in AD pathogenesis and progression and suggest the potential usefulness of EUK-207 in AD treatment.
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Cumulative evidence of gray matter abnormalities in semantic dementia (SD) has been reported using voxel-based morphometry (VBM). However, these studies have not been reviewed quantitatively. To estimate gray matter changes in SD quantitatively, we systematically searched whole-brain VBM studies comparing SD patients with healthy controls in the PubMed, ISI Web of Science, and EMABSE databases from January 1990 to August 2011. ⋯ Gray matter volume reductions were found in bilateral fusiform and inferior temporal gyri, extending to the medial portion of the temporal lobes (including amygdala and parahippocampal gyri), left temporal pole, middle temporal gyrus, and caudate. No significant increase in gray matter volume was found. Our findings provide strong evidence of atrophy in bilateral temporal lobes with predominate impairment on the left side, parahippocampal gyrus/amygdala, and left caudate, representing the pathophysiology of SD.
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Biomarkers, both biological and imaging, are indicators of specific changes that characterize Alzheimer's disease (AD) progression in vivo. Knowing the precise relationship between biomarkers and disease severity would allow for accurate disease staging and possible forecasting of decline. Jack et al. suggested as an initial hypothesis that this relationship be sigmoidal; the objective of this article is to determine, using large-scale population data from ADNI, the precise shape of this association. ⋯ Analysis of this cross-sectional dataset showed that a local quadratic regression model was 42% more likely than a sigmoid to be the best model for Aβ42. This ratio augments to 22% and 73% for Penalized B-Spline in the case of p-tau and t-tau, respectively; to 3500% for the linear model for FDG-PET; and to 6700% for the Penalized B-Spline for hippocampal volumes. Preliminary, cross-sectional evidence therefore indicates that the shape of the association with disease severity is non-linear and differs between biomarkers.
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Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). ⋯ Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.
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The Inferior parietal cortex (IPC), including the intraparietal sulcus (IPS), angular gyrus (AG), and supramarginal gyrus (SG), plays an important role in episodic memory, and is considered to be one of the specific neuroimaging markers in predicting the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, it is still unclear whether the connectivity of the IPC is impaired in MCI patients. In the present study, we used resting state fMRI to examine the functional connectivity of the three subdivisions of the IPC in MCI patients after controlling the impact of regional grey matter atrophy. ⋯ In contrast to the healthy controls, it was found that in MCI patients: 1) AG connectivity was significantly reduced within the DMN; 2) IPS showed decreased connectivity with the right inferior frontal gyrus while showing increased connectivity with the left frontal regions within the ECN; and 3) SG displayed decreased connectivity with a distribution of regions including the frontal and parietal regions, and increased connectivity with some sub-cortical areas within the SN. Moreover, the connectivity within the three networks was correlated with episodic memory and general cognitive impairment in MCI patients. These results extend well beyond the DMN, and further suggest that MCI is associated with alteration of large-scale functional brain networks.