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Principal Investigator  
Principal Investigator's Name: April Au
Institution: University of Toronto
Department: Psychology
Proposed Analysis: Estrogen deprivation induced by oophorectomy has been linked to a significantly higher risk of developing Alzheimer’s disease (AD; Rocca et al., 2008), and cognitive deficits within six months of surgery (Sherwin, 1988). Nevertheless, little is known about whether having an oophorectomy affects the severity and progression of AD. The purpose of this preliminary study is to understand how the pathological and cognitive manifestations of AD in women are affected by a history of an oophorectomy. It is hypothesized that in patients with AD, women who had undergone an oophorectomy in earlier life will exhibit 1) greater cognitive impairment, and 2) reduced volume in the hippocampus and entorhinal cortex. A retrospective data analysis will be conducted using the ADNI database. Subjects with oophorectomy and subjects with intact ovaries will be compared at two time points, one year apart. Subjects with oophorectomy will be matched with subjects with intact ovaries based on CDR scores to account for dementia severity. If permissible in the data, subjects will also be matched on age and years of education at the first point of comparison, To examine changes in overall cognitive functioning over time, MMSE scores will be compared between subjects with and without oophorectomy. Verbal memory and fluency will be examined using the Boston Naming and Category Fluency tasks. These cognitive tasks do not have discernible floor effects and exhibit a linear decline with AD severity, hence appropriate for the study population (Lorcasio, Growdon & Corkin, 1995). All cognitive measures will be compared at one, and two years after the initial match. At each time point, volumes of the hippocampus and entorhinal cortex will be compared across subjects with and without oophorectomy. These regions of interest were selected as they are amongst the first areas in the brain affected in AD (Gomez-Isla et al., 1995; Schuff et al., 2001), and will conceivably show the greatest between-group difference. Data analysis for both cognitive and volumetric measures will be performed by comparing across the means of two groups: subjects with oophorectomy, and subjects with intact ovaries. Results of this preliminary study will determine whether women with an altered estrogen milieu exhibit greater cognitive and neuropathological symptoms of AD. Further, results will help determine whether the time course of disease progression will be altered by a history of an oophorectomy. The characterization of individual risk factors is becoming increasingly important as it is now estimated that two thirds of AD patients are female (Alzheimer’s Association, 2011). Thus, identifying women at risk of more severe or rapidly progressing AD will be crucial to improved prognosis.
Additional Investigators  
Investigator's Name: Gillian Einstein
Proposed Analysis: Same as previously indicated.
Investigator's Name: Nicole Gervais
Proposed Analysis: Nicole will be using structural MRI data to assess the relationship between the volumes of the hippocampus, entorhinal, perirhinal, and parahippocampal cortices and performance on memory tests in women who have undergone an oophorectomy.