Abstract
AbstractBackgroundMenopause is associated with changes in hormone balances, and also to cognition in some women. These changes have been proposed to lead to an increased risk of developing Alzheimer’s disease (AD). However, there is not a clear understanding of how these changes are linked to neurodegeneration. One theory of what may be driving cognitive changes may be linked to how estrogen depletion affects cholinergic system activity. Preclinical studies have shown that estrogen is necessary for normal cholinergic functioning and its withdrawal leads to cholinergic dysfunction and cognitive impairment. And previous studies in postmenopausal women have shown that anticholinergic blockade is effective at modulating activity when performing working memory tasks.MethodThe CHAMP study will determine whether menopause‐related cognitive changes correlate with both cholinergic functional integrity and established AD biomarkers in a sample of 120 healthy postmenopausal women aged 50‐70 years. Using an anticholinergic challenge model, this study will examine cognitive performance on memory tasks using fMRI. The present study will collect established AD biomarkers of amyloid and tau levels in both blood and CSF samples, as well as through amyloid PET imaging, and markers of neurodegeneration including medial temporal lobe volume through structure MRI. In addition, the study will also collect genomic markers of impairment, such as APOE and COMT genotypes.ResultWe predict that women with poor compensation following menopause will be more sensitive to anticholinergic blockade, and will show decreased working memory performance, reduced brain activation, and decreased basal forebrain cholinergic system volume.ConclusionIn addition, we predict that these cholinergic markers will also be related to menopausal factors associated with poor cognition and biomarkers that are related to AD.
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