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This study evaluated the utility of baseline and longitudinal magnetic resonance imaging (MRI) measures of medial temporal lobe brain regions collected when participants were cognitively normal and largely in middle age (mean age 57 years) to predict the time to onset of clinical symptoms associated with mild cognitive impairment (MCI). Furthermore, we(More)
Recurrent event data are frequently encountered in longitudinal follow-up studies. In statistical literature, noninformative censoring is typically assumed when statistical methods and theory are developed for analyzing recurrent event data. In many applications, however, the observation of recurrent events could be terminated by informative dropouts or(More)
In this paper, we study panel count data with informative observation times. We assume nonparametric and semiparametric proportional rate models for the underlying event process, where the form of the baseline rate function is left unspecified and a subject-specific frailty variable inflates or deflates the rate function multiplicatively. The proposed(More)
This paper examines MRI analysis of neurodegeneration in Alzheimer's Disease (AD) in a network of structures within the medial temporal lobe using diffeomorphometry methods coupled with high-field atlasing in which the entorhinal cortex is partitioned into eight subareas. The morphometry markers for three groups of subjects (controls, preclinical AD, and(More)
OBJECTIVE This study evaluated longitudinal CSF biomarker measures collected when participants were cognitively normal to determine the magnitude and time course of biomarker changes before the onset of clinical symptoms in subjects with mild cognitive impairment (MCI). METHODS Longitudinal CSF collection and cognitive assessments were performed on a(More)
This paper examines morphometry of MRI biomarkers derived from the network of temporal lobe structures including the amygdala, entorhinal cortex and hippocampus in subjects with preclinical Alzheimer's disease (AD). Based on template-centered population analysis, it is demonstrated that the structural markers of the amygdala, hippocampus and entorhinal(More)
The levels of β-amyloid (Aβ) and phosphorylated tau (p-tau), as measured in cerebrospinal fluid, have been associated with the risk of progressing from normal cognition to onset of clinical symptoms during preclinical Alzheimer's disease. We examined whether cognitive reserve (CR) modifies this association. Cerebrospinal fluid was obtained at baseline from(More)
IMPORTANCE Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial. OBJECTIVE To(More)
The APOE ε4 allele increases the risk of developing Alzheimer's disease, whereas the APOE ε2 allele reduces risk. We examined whether cognitive reserve (CR), as measured by an index consisting of education, reading, and vocabulary, modifies these associations. CR was measured at baseline in 257 cognitively normal individuals (mean age 57.2 years) who have(More)
Mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia are preceded by a phase of disease, referred to as 'preclinical AD', during which cognitively normal individuals have evidence of AD pathology in the absence of clinical impairment. This study examined whether a magnetic resonance imaging (MRI) measure of cortical thickness in brain(More)