Diabetes Type 2, Dementia
Conditions
Keywords
women's health, estradiol, postmenopausal
Brief summary
The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
Detailed description
Epidemiological studies suggest there may be an interaction between type 2 diabetes and estrogen in postmenopausal women, such that diabetes may interact with estrogen levels over time to increase risk for dementia. The mechanism for this effect is now known. However, animal research suggests that it may occur through estrogen's effects on cellular metabolism of glucose and ketone bodies. The primary aim of this study is to test whether type 2 diabetes interacts with estradiol on brain metabolism in vivo in humans. This will be accomplished by imaging brain metabolism using positron emission tomography before and after short-term administration of transdermal 17β-estradiol in 10 postmenopausal women with diabetes and 10 non-diabetic postmenopausal women.
Interventions
DRUGEstradiol patch
transdermal 17β-estradiol patch
Sponsors
National Institute on Aging (NIA)
Wake Forest University Health Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Primary Objective: The primary objective is to determine whether the effects of glucose and ketone body uptake to the brain in response to 8-week administration of transdermal 17β-estradiol differ in postmenopausal women with and without type 2 diabetes.
Eligibility
Sex/Gender
FEMALE
Age
60 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Willing to provide written informed consent 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Female, postmenopausal, aged 60-80 4. Normal results on recommended healthcare screenings (e.g., mammogram, pap smear, colonoscopy) 5. BMI 20-35 kg/m2 6. No evidence of dementia or mild cognitive impairment (MoCA score \>25) 7. Able to access reliable transportation to study and intervention visits
Exclusion criteria
1. Use of hormone replacement therapy within the past 3 months 2. History of renal, heart, liver, or neurological disease; head injury with loss of consciousness in the past 5 years; chronic pain, anxiety or depression 3. Presence of medical conditions that might contraindicate estrogen use (e.g., unexplained vaginal bleeding, history of reproductive tissue cancer, thrombosis) 4. Currently taking insulin, metformin, or any other drug or medication judged by the study physician to affect safety or research outcomes of interest 5. Involved in another research study 6. Contraindications for MRI or PET scanning 7. Current smoker
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acetoacetate Uptake (AcAc) PET--Whole Brain | Baseline | Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified. |
| Change in Uptake of Glucose and Ketone Bodies in Whole Brain and Alzheimer's Disease-related Regions of Interest. | Baseline and 8 weeks | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET) and ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG and AcAc tracers will be quantified, as well as uptake of AcAc relative to FDG to find potential regions of compensatory ketone use |
| AcAc PET--Whole Brain | Week 8 | Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified. |
| Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain | Baseline | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified. |
| FDG PET--Whole Brain | Week 8 | Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Benton Visual Retention Task (BVRT) Total Score | Baseline and Week 8 | The BVRT tests figural memory by testing memory for a line drawing. The minimum score is 0. The scoring used is total correct, the maximum score is 10, and a higher score represents better performance. The total score is reported. |
| Prospective Memory | Baseline and Week 8 | The Prospective Memory test is a test of everyday memory where participants are given instructions for 3 tasks that will occur later on during the testing session. The minimum score is 0. The maximum score is 12 points, a higher score represents better performance, and the total score is reported |
| Verbal Fluency (Letters) | Baseline and Week 8 | Participants were given a letter and asked to say aloud as many words as they could think of beginning with that letter. The three letters were F, A, and S, and the participant had one minute per letter to list words. The total score reported is the sum of the correct words generated for all three letters. Although there is no set maximum score, based on published data, it was anticipated that scores could range from 1 to no more than 120. A higher value reflects better performance. |
| Verbal Fluency Score (Fruits and Vegetables) | Baseline and Week 8 | Participants were given one minute to say aloud as many fruits as possible and one minute to list as many vegetables as possible. The total score reported is the sum of all correct fruits and vegetables listed. Although there is no set maximum score, it was anticipated that scores could range from 0 to no more than 60. A higher value reflects better performance. |
| Digit Span Backward Total Correct | Baseline and Week 8 | Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in reverse order. The outcome measure reported here is the longest span of numbers recalled (range of scores 0-9). Higher scores reflect better performance. |
| Finger Tapping Score--Dominant Hand | Baseline and Week 8 | The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance. |
| Finger Tapping Score--Non-Dominant Hand | Baseline and Week 8 | The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the non-dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance. |
| Card Rotations Test Score | Baseline and Week 8 | The Card Rotations Test is used to assess the ability to mentally rotate figures in space. The test has two parts, each of which last 3 minutes. During each part, the participant is given a sheet of paper with 10 simple geometric figures. Next to each figure is a row of 8 similar figures. Participants are asked to mark whether each of the figures in the row is the same or different than the first figure in the row. The score reported is the number of correct responses. The minimum score is 0. The maximum possible score is 160 and a higher score reflects better performance. |
| Change in Short-term Memory and Executive Function Composite Scores. | Baseline and 8 weeks | A battery of cognitive tasks will be administered before and after estrogen administration. Composite z-scores will be calculated by calculating a z-score for each cognitive task and summing z-scores from -5 (low) to 5 (high) for the tasks designated as short-term memory and executive function.Higher scores denotes better outcomes. |
| Digit Span Forward Total Correct | Baseline and Week 8 | Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in the same order the numbers were presented. The outcome measure reported here is the total number of correct responses (range of scores 0-9). Higher scores reflect better performance. |
| Short-Term Memory Composite Score | Baseline and Week 8 | A composite memory score was created by averaging z-scores for CVLT delayed recall, BVRT delayed recall, and prospective memory. A composite executive function score was created by averaging digit span forwards total correct, digit span backwards total correct, and both verbal fluency scores. Summed z-score ranging from -2 to 2 where higher score indicates better performance. |
| Executive Function Composite Score | Baseline and Week 8 | The California Verbal Learning Test (CVLT) is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after the short delay (immediately after learning lists) and long delay (25 minutes) are reported. Summed z-score ranging from -2 to 2 where higher score indicates better performance. |
| California Verbal Learning Task (CVLT) Long Delay Free Recall | Baseline and Week 8 | The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after long delay (25 minutes). The minimum score is 0. The maximum score is 16 and a higher score represents better performance. |
| CVLT Short Delay Free Recall | Baseline and Week 8 | The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Short delay free recall is immediately after learning lists. The minimum score is 0. The maximum score is 16 and a higher score represents better performance. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Regional Ratio of Ketone/Glucose Uptake | Baseline and Week 8 | — |
| Number of Microbleeds | Baseline and Week 8 | Attained from a susceptibility-weighted image |
| Number of White Matter Hypertensities | Baseline and Week 8 | Attained from a T2-weighted FLAIR image, an indicator of small-vessel disease correlated with diabetes status and hypertension |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Post Menopausal Women With Diabetes 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women with type 2 diabetes
Estradiol patch: transdermal 17β-estradiol patch | 8 |
| Post Menopausal Women Without Diabetes 8-week administration of transdermal 17β-estradiol (Climara) patch in postmenopausal women without type 2 diabetes.
Estradiol patch: transdermal 17β-estradiol patch | 4 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | COVID | 1 | 0 |
| Overall Study | prolonged bleeding | 1 | 0 |
| Overall Study | veins would not stay open during the PET scan. | 0 | 1 |
Baseline characteristics
| Characteristic | Post Menopausal Women With Diabetes | Total | Post Menopausal Women Without Diabetes |
|---|---|---|---|
| Age, Continuous | 69.9 years STANDARD_DEVIATION 6.1 | 70.0 years STANDARD_DEVIATION 5.2 | 70.3 years STANDARD_DEVIATION 3.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 11 Participants | 3 Participants |
| Region of Enrollment United States | 8 participants | 12 participants | 4 participants |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 8 |
| other Total, other adverse events | 2 / 4 | 7 / 8 |
| serious Total, serious adverse events | 0 / 4 | 0 / 8 |
Outcome results
Primary
AcAc PET--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified.
Time frame: Week 8
Population: Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Post Menopausal Women Without Diabetes | AcAc PET--Whole Brain | 0.027 micromoles/min/100g tissue | Standard Deviation 0.003 |
| Post Menopausal Women With Diabetes | AcAc PET--Whole Brain | 0.028 micromoles/min/100g tissue | Standard Deviation 0.015 |
Primary
Acetoacetate Uptake (AcAc) PET--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of AcAc tracers will be quantified.
Time frame: Baseline
Population: Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Post Menopausal Women Without Diabetes | Acetoacetate Uptake (AcAc) PET--Whole Brain | 0.031 micromoles/min/100g tissue | Standard Deviation 0.009 |
| Post Menopausal Women With Diabetes | Acetoacetate Uptake (AcAc) PET--Whole Brain | 0.024 micromoles/min/100g tissue | Standard Deviation 0.005 |
Primary
Change in Uptake of Glucose and Ketone Bodies in Whole Brain and Alzheimer's Disease-related Regions of Interest.
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET) and ketone body (acetoacetate) uptake (AcAc). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG and AcAc tracers will be quantified, as well as uptake of AcAc relative to FDG to find potential regions of compensatory ketone use
Time frame: Baseline and 8 weeks
Population: This outcome measure is actually many outcome measures. It was broken down into the other four primary outcome measures listed, so no no results will be listed here. Also, rather than change in, results will be reported as mean/standard deviation in the other outcomes.
Primary
FDG PET--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified.
Time frame: Week 8
Population: Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Post Menopausal Women Without Diabetes | FDG PET--Whole Brain | 8.74 micromoles/min/100g tissue | Standard Deviation 2.59 |
| Post Menopausal Women With Diabetes | FDG PET--Whole Brain | 6.87 micromoles/min/100g tissue | Standard Deviation 0.88 |
Primary
Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain
Brain metabolism will be measured using PET tracers to examine brain glucose uptake (FDG PET). PET imaging data are co-registered to T1 structural MRI data to conduct region-of-interest based analyses. Absolute global and regional uptake of FDG will be quantified.
Time frame: Baseline
Population: Non-Diabetes: n=2, technical error resulted in issues reconstructing PET images for one participant. Results only reported for subjects who completed study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Post Menopausal Women Without Diabetes | Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain | 12.28 micromoles/min/100g tissue | Standard Deviation 11.39 |
| Post Menopausal Women With Diabetes | Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)--Whole Brain | 11.75 micromoles/min/100g tissue | Standard Deviation 12.42 |
Secondary
Benton Visual Retention Task (BVRT) Total Score
The BVRT tests figural memory by testing memory for a line drawing. The minimum score is 0. The scoring used is total correct, the maximum score is 10, and a higher score represents better performance. The total score is reported.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Benton Visual Retention Task (BVRT) Total Score | Baseline | 8.67 score on a scale | Standard Deviation 0.58 |
| Post Menopausal Women Without Diabetes | Benton Visual Retention Task (BVRT) Total Score | Week 8 | 9.33 score on a scale | Standard Deviation 0.58 |
| Post Menopausal Women With Diabetes | Benton Visual Retention Task (BVRT) Total Score | Baseline | 6.5 score on a scale | Standard Deviation 2.07 |
| Post Menopausal Women With Diabetes | Benton Visual Retention Task (BVRT) Total Score | Week 8 | 5.5 score on a scale | Standard Deviation 2.51 |
Secondary
California Verbal Learning Task (CVLT) Long Delay Free Recall
The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after long delay (25 minutes). The minimum score is 0. The maximum score is 16 and a higher score represents better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | California Verbal Learning Task (CVLT) Long Delay Free Recall | Baseline | 12.0 score on a scale | Standard Deviation 4.36 |
| Post Menopausal Women Without Diabetes | California Verbal Learning Task (CVLT) Long Delay Free Recall | Week 8 | 12.67 score on a scale | Standard Deviation 2.08 |
| Post Menopausal Women With Diabetes | California Verbal Learning Task (CVLT) Long Delay Free Recall | Baseline | 10.83 score on a scale | Standard Deviation 3.25 |
| Post Menopausal Women With Diabetes | California Verbal Learning Task (CVLT) Long Delay Free Recall | Week 8 | 13.17 score on a scale | Standard Deviation 2.14 |
Secondary
Card Rotations Test Score
The Card Rotations Test is used to assess the ability to mentally rotate figures in space. The test has two parts, each of which last 3 minutes. During each part, the participant is given a sheet of paper with 10 simple geometric figures. Next to each figure is a row of 8 similar figures. Participants are asked to mark whether each of the figures in the row is the same or different than the first figure in the row. The score reported is the number of correct responses. The minimum score is 0. The maximum possible score is 160 and a higher score reflects better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Card Rotations Test Score | Baseline | 76.0 score on a scale | Standard Deviation 35.59 |
| Post Menopausal Women Without Diabetes | Card Rotations Test Score | Week 8 | 89.33 score on a scale | Standard Deviation 5.86 |
| Post Menopausal Women With Diabetes | Card Rotations Test Score | Baseline | 90.67 score on a scale | Standard Deviation 34.6 |
| Post Menopausal Women With Diabetes | Card Rotations Test Score | Week 8 | 97.0 score on a scale | Standard Deviation 28.71 |
Secondary
Change in Short-term Memory and Executive Function Composite Scores.
A battery of cognitive tasks will be administered before and after estrogen administration. Composite z-scores will be calculated by calculating a z-score for each cognitive task and summing z-scores from -5 (low) to 5 (high) for the tasks designated as short-term memory and executive function.Higher scores denotes better outcomes.
Time frame: Baseline and 8 weeks
Population: This outcome should have been separated into many other outcomes. So we have separated out all the scores and results will be reported in the other separated memory and executive function score outcomes. No results will be reported in this outcome. Also, rather than change in, results will be reported as mean/standard deviation in the other outcomes.
Secondary
CVLT Short Delay Free Recall
The CVLT is a word list recall task that can be used to test immediate and delayed verbal memory. Short delay free recall is immediately after learning lists. The minimum score is 0. The maximum score is 16 and a higher score represents better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | CVLT Short Delay Free Recall | Baseline | 11.67 score on a scale | Standard Deviation 2.08 |
| Post Menopausal Women Without Diabetes | CVLT Short Delay Free Recall | Week 8 | 12.33 score on a scale | Standard Deviation 1.15 |
| Post Menopausal Women With Diabetes | CVLT Short Delay Free Recall | Baseline | 10.00 score on a scale | Standard Deviation 3.91 |
| Post Menopausal Women With Diabetes | CVLT Short Delay Free Recall | Week 8 | 11.67 score on a scale | Standard Deviation 3.93 |
Secondary
Digit Span Backward Total Correct
Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in reverse order. The outcome measure reported here is the longest span of numbers recalled (range of scores 0-9). Higher scores reflect better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Digit Span Backward Total Correct | Baseline | 4.0 span of numbers recalled | Standard Deviation 1.73 |
| Post Menopausal Women Without Diabetes | Digit Span Backward Total Correct | Week 8 | 6.0 span of numbers recalled | Standard Deviation 1 |
| Post Menopausal Women With Diabetes | Digit Span Backward Total Correct | Week 8 | 5.33 span of numbers recalled | Standard Deviation 2.07 |
| Post Menopausal Women With Diabetes | Digit Span Backward Total Correct | Baseline | 4.67 span of numbers recalled | Standard Deviation 0.82 |
Secondary
Digit Span Forward Total Correct
Participants listened to a sequence of two to nine numbers and were asked to repeat each sequence back to the tester in the same order the numbers were presented. The outcome measure reported here is the total number of correct responses (range of scores 0-9). Higher scores reflect better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Digit Span Forward Total Correct | Baseline | 8.0 number of correct responses | Standard Deviation 0 |
| Post Menopausal Women Without Diabetes | Digit Span Forward Total Correct | Week 8 | 7.67 number of correct responses | Standard Deviation 2.08 |
| Post Menopausal Women With Diabetes | Digit Span Forward Total Correct | Baseline | 7.5 number of correct responses | Standard Deviation 0.55 |
| Post Menopausal Women With Diabetes | Digit Span Forward Total Correct | Week 8 | 7.67 number of correct responses | Standard Deviation 2.07 |
Secondary
Executive Function Composite Score
The California Verbal Learning Test (CVLT) is a word list recall task that can be used to test immediate and delayed verbal memory. Free recall after the short delay (immediately after learning lists) and long delay (25 minutes) are reported. Summed z-score ranging from -2 to 2 where higher score indicates better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Executive Function Composite Score | Baseline | 0.20 z-score | Standard Deviation 1.36 |
| Post Menopausal Women Without Diabetes | Executive Function Composite Score | Week 8 | 1.66 z-score | Standard Deviation 4.83 |
| Post Menopausal Women With Diabetes | Executive Function Composite Score | Baseline | -0.10 z-score | Standard Deviation 1.78 |
| Post Menopausal Women With Diabetes | Executive Function Composite Score | Week 8 | 0.30 z-score | Standard Deviation 5.78 |
Secondary
Finger Tapping Score--Dominant Hand
The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Finger Tapping Score--Dominant Hand | Baseline | 40.47 number of taps | Standard Deviation 4.65 |
| Post Menopausal Women Without Diabetes | Finger Tapping Score--Dominant Hand | Week 8 | 40.27 number of taps | Standard Deviation 2.25 |
| Post Menopausal Women With Diabetes | Finger Tapping Score--Dominant Hand | Baseline | 43.53 number of taps | Standard Deviation 6.45 |
| Post Menopausal Women With Diabetes | Finger Tapping Score--Dominant Hand | Week 8 | 44.07 number of taps | Standard Deviation 5.2 |
Secondary
Finger Tapping Score--Non-Dominant Hand
The Finger Tapping test assesses fine motor speed by asking participants to tap a button as many times as possible. Seven trials were administered. The highest and lowest scores were dropped, and the reported score is the average of the remaining 5 trials. Results for the non-dominant hand are reported here. There is no set maximum score. However, published averages for women in this age range suggest that a value over 57 would be highly unusual. A higher value (more taps) is better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Finger Tapping Score--Non-Dominant Hand | Baseline | 39.4 number of taps | Standard Deviation 4.1 |
| Post Menopausal Women Without Diabetes | Finger Tapping Score--Non-Dominant Hand | Week 8 | 42.7 number of taps | Standard Deviation 3.5 |
| Post Menopausal Women With Diabetes | Finger Tapping Score--Non-Dominant Hand | Baseline | 38.2 number of taps | Standard Deviation 5.6 |
| Post Menopausal Women With Diabetes | Finger Tapping Score--Non-Dominant Hand | Week 8 | 41.7 number of taps | Standard Deviation 6.7 |
Secondary
Prospective Memory
The Prospective Memory test is a test of everyday memory where participants are given instructions for 3 tasks that will occur later on during the testing session. The minimum score is 0. The maximum score is 12 points, a higher score represents better performance, and the total score is reported
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Prospective Memory | Baseline | 10.67 score on a scale | Standard Deviation 1.53 |
| Post Menopausal Women Without Diabetes | Prospective Memory | Week 8 | 10.0 score on a scale | Standard Deviation 2 |
| Post Menopausal Women With Diabetes | Prospective Memory | Baseline | 5.83 score on a scale | Standard Deviation 3.97 |
| Post Menopausal Women With Diabetes | Prospective Memory | Week 8 | 8.17 score on a scale | Standard Deviation 1.72 |
Secondary
Short-Term Memory Composite Score
A composite memory score was created by averaging z-scores for CVLT delayed recall, BVRT delayed recall, and prospective memory. A composite executive function score was created by averaging digit span forwards total correct, digit span backwards total correct, and both verbal fluency scores. Summed z-score ranging from -2 to 2 where higher score indicates better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Short-Term Memory Composite Score | Baseline | 1.04 z-score | Standard Deviation 0.31 |
| Post Menopausal Women Without Diabetes | Short-Term Memory Composite Score | Week 8 | 1.56 z-score | Standard Deviation 0.53 |
| Post Menopausal Women With Diabetes | Short-Term Memory Composite Score | Baseline | -0.52 z-score | Standard Deviation 2.01 |
| Post Menopausal Women With Diabetes | Short-Term Memory Composite Score | Week 8 | -0.56 z-score | Standard Deviation 2.04 |
Secondary
Verbal Fluency (Letters)
Participants were given a letter and asked to say aloud as many words as they could think of beginning with that letter. The three letters were F, A, and S, and the participant had one minute per letter to list words. The total score reported is the sum of the correct words generated for all three letters. Although there is no set maximum score, based on published data, it was anticipated that scores could range from 1 to no more than 120. A higher value reflects better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Verbal Fluency (Letters) | Baseline | 48.67 number of correct words generated | Standard Deviation 16.5 |
| Post Menopausal Women Without Diabetes | Verbal Fluency (Letters) | Week 8 | 46.33 number of correct words generated | Standard Deviation 12.58 |
| Post Menopausal Women With Diabetes | Verbal Fluency (Letters) | Baseline | 42.67 number of correct words generated | Standard Deviation 9.56 |
| Post Menopausal Women With Diabetes | Verbal Fluency (Letters) | Week 8 | 41.33 number of correct words generated | Standard Deviation 7.66 |
Secondary
Verbal Fluency Score (Fruits and Vegetables)
Participants were given one minute to say aloud as many fruits as possible and one minute to list as many vegetables as possible. The total score reported is the sum of all correct fruits and vegetables listed. Although there is no set maximum score, it was anticipated that scores could range from 0 to no more than 60. A higher value reflects better performance.
Time frame: Baseline and Week 8
Population: Results only reported for subjects who completed study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Post Menopausal Women Without Diabetes | Verbal Fluency Score (Fruits and Vegetables) | Baseline | 31.0 number of correct fruits and vegetables | Standard Deviation 4.36 |
| Post Menopausal Women Without Diabetes | Verbal Fluency Score (Fruits and Vegetables) | Week 8 | 32.67 number of correct fruits and vegetables | Standard Deviation 7.23 |
| Post Menopausal Women With Diabetes | Verbal Fluency Score (Fruits and Vegetables) | Baseline | 28.67 number of correct fruits and vegetables | Standard Deviation 8.62 |
| Post Menopausal Women With Diabetes | Verbal Fluency Score (Fruits and Vegetables) | Week 8 | 29.17 number of correct fruits and vegetables | Standard Deviation 8.28 |
Other Pre-specified
Number of Microbleeds
Attained from a susceptibility-weighted image
Time frame: Baseline and Week 8
Other Pre-specified
Number of White Matter Hypertensities
Attained from a T2-weighted FLAIR image, an indicator of small-vessel disease correlated with diabetes status and hypertension
Time frame: Baseline and Week 8
Other Pre-specified
Regional Ratio of Ketone/Glucose Uptake
Time frame: Baseline and Week 8