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BACKGROUND Mild cognitive impairment (MCI) is considered to be a transitional stage between aging and Alzheimer disease (AD). OBJECTIVE To determine whether MCI represents early-stage AD by examining its natural history and neuropathologic basis. DESIGN A prospective clinical and psychometric study of community-living elderly volunteers, both(More)
The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects. The protocol provides neuropathologic definitions of such terms as "definite Alzheimer's disease" (AD), "probable AD,"(More)
OBJECTIVE To study differences between subjects with Alzheimer disease (AD) and cognitively intact control subjects, with respect to brain histologic markers of AD, and the relationship of those markers in the AD group to severity of dementia, age at death, sex, and apolipoprotein E genotype. SETTING Washington University Alzheimer's Disease Research(More)
Structural deformity of the hippocampus is characteristic of individuals with very mild and mild forms of dementia of the Alzheimer type (DAT). The purpose of this study was to determine whether a similar deformity of the hippocampus can predict the onset of dementia in nondemented elders. Using high dimensional diffeomorphic transformations of a(More)
The entorhinal cortex (EC) plays a crucial role as a gateway connecting the neocortex and the hippocampal formation. Layer II of the EC gives rise to the perforant pathway, the major source of the excitatory input to the hippocampus, and layer IV receives a major hippocampal efferent projection. The EC is affected severely in Alzheimer disease (AD), likely(More)
Clinical investigations of Alzheimer's disease (AD) have been limited by diagnostic inaccuracy. We employed explicit clinical inclusion and exclusion criteria to identify subjects with senile dementia of the Alzheimer type (SDAT). In a consecutive series of 26 postmortem examinations from this sample, AD was histologically verified in all subjects and was(More)
To better define the pattern of hippocampal deformity early in the course of Alzheimer's disease, we compared the pattern of hippocampal surface variation in subjects with very mild dementia of the Alzheimer type (DAT) and nondemented subjects. The surface of the hippocampus was divided a priori on a neuroanatomical template into three zones approximating(More)
We compare clinicopathologic data from 10 subjects identified in the very mild stage of senile dementia of the Alzheimer type with findings from similar studies in four cognitively normal subjects. We based the diagnosis of very mild dementia in the 10 subjects on informant reports and the judgment of experienced clinicians. Deficits of some psychometric(More)
To explore the hypothesis that alterations in ethanolamine plasmalogen may be directly related to the severity of dementia in Alzheimer's disease (AD), we performed a systematic examination of plasmalogen content in cellular membranes of gray and white matter from different regions of human subjects with a spectrum of AD clinical dementia ratings (CDR)(More)
Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon4 > epsilon3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-beta (Abeta) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Abeta deposition and AD pathology, we compared APP(V717F)(More)