Complaints about memory and thinking are common in women as they go through menopause and estrogen levels fall. The ovarian hormone estrogen is important for supporting normal cognitive function, and changes in brain activity and function occur when estrogen levels are decreased. Estrogen is also important for maintaining healthy blood vessels which also support normal cognitive function. In Alzheimer's disease and other types of dementia, there is significant damage to the blood vessels in the brain. This study will test whether changes in brain activity and function with the loss of estrogen are related to changes in vascular function. The investigators will measure vascular function using ultrasound, and brain activity using MRI scans in women who are enrolled in the Females, Aging, Metabolism and Exercise (FAME) study (NCT01712230). In the FAME study, healthy premenopausal women either take a medication to decrease their estrogen levels, or a placebo. This sub-study may provide new information about how estrogen affects vascular function and cognitive function, and lead to new ways to prevent or delay cognitive impairment or dementia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
17
Lupron 3.75 mg for depot suspension delivered by monthly intramuscular injection for 9 months. First 6 months under parent study (FAME) protocol (NCT01712230); months 6-9 under sub-study.
Climara transdermal patch 0.075mg/day applied weekly months 6-9
Provera 5mg tablets once daily by mouth for 12 days beginning at week 30.
placebo
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
University of Colorado Boulder Intermountain Neuroimaging Consortium
Boulder, Colorado, United States
Changes in Prefrontal Cortex Brain Activation at 6 Months
Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline, 6 months, and 9 months (GnRH agonist arm only). Beta weight is the percent signal change on the FMRI from one condition to another. The FMRI is measuring blood oxygen levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. A positive number/increase indicates more blood flow and brain activity in that area.
Time frame: Baseline, 6 months
Changes in Prefrontal Cortex Brain Activation at 9 Months
Changes in patterns of brain activation in the prefrontal cortex using functional magnetic resonance imaging (fMRI) during a task of working memory will be measured at baseline, 6 months, and 9 months (GnRH agonist arm only). Beta weight is the percent signal change on the FMRI from one condition to another. The FMRI is measuring blood oxygen levels and blood flow in different regions of the brain and using that to determine activity changes in the brain. A positive number/increase indicates more blood flow and brain activity in that area.
Time frame: Baseline, 9 months
Changes in Endothelial Function at 6 Months
Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 6 months
Time frame: Baseline, 6 months
Changes in Endothelial Function at 9 Months
Changes in endothelial function will be measured using brachial artery flow-mediated dilation at baseline, 9 months
Time frame: Baseline, 9 months
Changes in Artery Compliance at 6 Months
Changes in carotid artery compliance will be measured using ultrasound in at baseline, 6 months.
Time frame: Baseline, 6 months
Changes in Artery Compliance at 9 Months
Changes in carotid artery compliance will be measured using ultrasound in at baseline, 9 months.
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Trails A, 6 Months
Change in time (seconds) to complete Trails A test between baseline and 6 months. Negative value indicates faster time (better performance) at 6 months compared to baseline.
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Trails A, 9 Months
Change in time (seconds) to complete Trails A test between baseline and 9 months. Negative value indicates faster time (better performance) at 9 months compared to baseline.
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: RAVLT, 6 Months
Change in Rey Auditory Verbal Learning Test from baseline to 6 months. Score is the change in the number of items correct on delayed recall trial. Scores on the RAVLT range from 0-15 with higher scores indicating better performance. A positive change indicates improvement in recall.
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: RAVLT, 9 Months
Change in Rey Auditory Verbal Learning Test from baseline to 9 months. Score is the change in the number of items correct on delayed recall trial. Scores on the RAVLT range from 0-15 with higher scores indicating better performance. A positive change indicates improvement in recall.
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Trails B, 6 Months
Change in time (seconds) to complete Trails B test between baseline and 6 months. Negative value indicates faster time (better performance) at 6 months compared to baseline.
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Trails B, 9 Months
Change in time (seconds) to complete Trails B test between baseline and 9 months. Negative value indicates faster time (better performance) at 9 months compared to baseline.
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Stroop, 6 Months
Change in number of correct responses in one minute on Stroop Color Word Interference test between baseline and 6 months. A positive number indicates more items correct indicating better performance. There is no maximum score because the test measures how many correct responses a participant can return within one minute (minimum = 0), however 40 or fewer is considered low. The change in the number of correct responses is reported, and so a positive number indicates more correct responses and better/improved cognitive function.
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Stroop, 9 Months
Change in number of correct responses in one minute on Stroop Color Word Interference test between baseline and 9 months. Positive number indicates more items correct indicating better performance. There is no maximum score because the test measures how many correct responses a participant can return within one minute (minimum = 0), however 40 or fewer is considered low. The change in the number of correct responses is reported, and so a positive number indicates more correct responses and better/improved cognitive function.
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Digits Span Forward and Backward, 6 Months
Change in score on the Digit Span Test between baseline and 6 month. Raw scores on the Digit Span test range from 0-16 (Digits Forward) and 0-10 (Digits Backward) with higher scores indicating better performance. A positive change score indicates improved performance.
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Digits, 9 Months
Change in score on the Digit Span Test between baseline and 9 months. Raw scores on the Digit Span test range from 0-16 (Digits Forward) and 0-10 (Digits Backward) with higher scores indicating better performance. A positive change score indicates improved performance.
Time frame: Baseline, 9 months
Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 6 Months
Change in sum of scores on 3 COWAT trials (letters, F, A, and S) between baseline and 6 months. Participants are given one minute to think up as many words as they can associated with each letter (F, A, or S). Raw scores are the total number of words generated across all trials. Higher scores indicate more words generated and better performance. Positive change score indicates an increase in words generated, or improved performance.
Time frame: Baseline, 6 months
Changes in Executive Cognitive Function: Controlled Oral Word Association Test, 9 Months
Change in sum of scores on 3 COWAT trials (letters, F, A, and S) between baseline and 9 months. Participants are given one minute to think up as many words as they can associated with each letter (F, A, or S). Raw scores are the total number of words generated across all trials. Higher scores indicate more words generated and better performance. Positive change score indicates an increase in words generated, or improved performance.
Time frame: Baseline, 9 months
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