Alzheimer's & dementia : the journal of the Alzheimer's Association
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Randomized Controlled Trial Multicenter Study
Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data.
Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. ⋯ This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.
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Apolipoprotein E (APOE) ε2 carriers may be protected from dementia because of reduced levels of cortical β-amyloid. In the oldest-old, however, APOE ε2 carriers have high β-amyloid plaque scores and preserved cognition. We compared different measures of β-amyloid pathology across APOE genotypes in the oldest-old, and their relationship with dementia. ⋯ Lower levels of percent area in APOE ε2 carriers may reflect lower total β-amyloid and may contribute to APOE ε2 carriers' decreased risk of dementia, despite high β-amyloid plaque scores. The relationship between β-amyloid plaques and dementia in the oldest-old may vary by APOE genotype.
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Current hypothetical models of Alzheimer's disease (AD) pathogenesis emphasize the role of β-amyloid (Aβ), tau deposition, and neurodegenerative changes in the mesial temporal lobe, particularly the entorhinal cortex and hippocampus. However, many individuals with clinical AD who come to autopsy also exhibit cerebrovascular disease. The relationship between AD and vascular pathology is unclear, especially whether they represent additive and independent effects on neuronal injury. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to (1) confirm whether entorhinal cortex and hippocampal volume are associated with memory among individuals with amnestic mild cognitive impairment (MCI) who are at risk for AD; and (2) determine whether regional white matter hyperintensity (WMH) volume, a radiological marker of small-vessel cerebrovascular disease, is associated with entorhinal cortex and hippocampal volume independent of putative AD biomarkers in this group. ⋯ The findings confirm the role of entorhinal cortex and hippocampus volume in influencing memory decline in amnestic MCI, and emphasize that even in this nominally AD prodromal condition, WMH may be influencing regional neurodegeneration.
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Clinical studies of β-amyloid (Aβ) immunotherapy in Alzheimer's disease (AD) patients have demonstrated reduction of central Aβ plaque by positron emission tomography (PET) imaging and the appearance of amyloid-related imaging abnormalities (ARIA). To better understand the relationship between ARIA and the pathophysiology of AD, we undertook a series of studies in PDAPP mice evaluating vascular alterations in the context of central Aβ pathology and after anti-Aβ immunotherapy. ⋯ These data suggest that vascular leakage events, such as microhemorrhage, may be related to the removal of vascular Aβ. With continued treatment, this initial susceptibility period is followed by restoration of vascular morphology and reduced vulnerability to further vascular leakage events. The data collectively suggested a vascular amyloid clearance model of ARIA, which accounts for the currently known risk factors for the incidence of ARIA in clinical studies.
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Pharmacological treatment of older adults with cognitive impairment represents a challenge for prescribing physicians, and polypharmacy is common in these complex patients. The aim of the current study is to assess prevalence and factors related to polypharmacy in a sample of nursing home (nursing home) residents with advanced cognitive impairment. ⋯ Polypharmacy and excessive polypharmacy are common among nursing home residents with advanced cognitive impairment. Determinants of polypharmacy status includes not only comorbidities, but also specific symptoms, age, and functional status. A geriatrician in the facility is associated with lower prevalence of excessive polypharmacy.