Neurobiology of aging
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Neurobiology of aging · Jan 2014
Selective benefits of simvastatin in bitransgenic APPSwe,Ind/TGF-β1 mice.
Cognitive and cerebrovascular deficits are 2 landmarks of Alzheimer's disease (AD) to target for effective therapy. Here, we evaluated the efficacy of simvastatin in bitransgenic A/T mice overexpressing a mutated form of the human amyloid precursor protein (APP(Swe,Ind)) and a constitutively active form of transforming growth factor-β1. These mice feature the AD amyloid beta (Aβ) and cerebrovascular pathology. ⋯ However, simvastatin failed to improve spatial learning and memory deficits and the decreased baseline levels of the memory-related protein early growth response-1 (Egr-1) in the hippocampus CA1 area. The impaired hyperemic response to whisker stimulation in A/T mice was not improved with treatment, but simvastatin fully restored constitutive nitric oxide synthesis in vessel walls and exacerbated agonist-mediated dilatory deficits. These findings point to the efficacy of simvastatin on selective AD features in a complex model of the disease, likely reflecting the challenges faced by recent clinical trials in assessing statin efficacy.
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Neurobiology of aging · Jan 2014
Comparative StudyComparison of neuroimaging modalities for the prediction of conversion from mild cognitive impairment to Alzheimer's dementia.
In this study we compared Pittsburgh compound-B (PIB) positron emission tomography (PET) amyloid imaging, fluorodeoxyglucose PET for metabolism, and magnetic resonance imaging (MRI) for structure to predict conversion from amnestic mild cognitive impairment (MCI) to Alzheimer's dementia using data from the Alzheimer's Disease Neuroimaging Initiative cohort. Numeric neuroimaging variables generated by the Alzheimer's Disease Neuroimaging Initiative-funded laboratories for each neuroimaging modality along with apolipoprotein-E genotype (n = 29) were analyzed. ⋯ Individually, PIB-PET generated the best sensitivity, and fluorodeoxyglucose PET had the lowest. Among individual brain regions, the temporal cortex was found to be most predictive for MRI and PIB-PET.
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Neurobiology of aging · Jan 2014
Cortical thinning and its relation to cognition in amyotrophic lateral sclerosis.
Clinical, genetic, and pathological findings suggest a close relationship between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We studied the patterns of cortical atrophy across the spectrum between ALS and ALS-FTD. A surface-based morphometry analysis based on an age- and sex-matched sample of 81 ALS patients and 62 healthy control subjects (HC) was conducted. ⋯ ALS-FTD patients showed cortical thinning in regions including the frontal and temporal gyri and the posterior cingulate cortex. Cognitively impaired ALS patients showed cortical thinning in regions largely overlapping with those found in ALS-FTD, but changes were less widespread. In conclusion, the cognitive status of ALS subjects is associated with different patterns of cortical atrophy.