Cognitive Function
Conditions
Brief summary
Between 2000 and 2015, mortality due to Alzheimer's disease (AD) increased by 123%. No drugs have yet been approved to stop or slow the progression of AD. A delay of five years in the expression of AD would reduce the incidence rate by half. Thus, it is critical to develop novel prevention strategies to delay the onset of this common disease. As an ancillary study conducted within a precision-based randomized trial (R01CA149633; PI, Dai & Yu\]), the investigators reduced Ca:Mg ratios to 2.3 through 3-month personalized Mg supplementation among those who consumed high Ca:Mg ratio diet, but otherwise in good general health. The investigators test the hypothesis that actively reducing the Ca:Mg ratio among those aged \>65 years who consume high Ca:Mg ratio diets improves cognitive function compared to the placebo arm. The investigators further conduct molecular epidemiologic studies to understand the molecular mechanisms.
Interventions
DIETARY_SUPPLEMENTMagnesium glycinate
Oral administration of magnesium glycinate daily for 12 weeks
DIETARY_SUPPLEMENTPlacebo
Oral administration of identical-appearing placebo daily for 12 weeks
Sponsors
National Cancer Institute (NCI)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants from our parent study (Personalized Prevention of Colorectal Cancer Trial, NCT#01105169, IRB#100106); 2. Participants who completed the MoCA
Exclusion criteria
1\. Participants did not provide their blood samples in the parent study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo | 12 weeks | Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline. |
| Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged ≤65 Years Old) | 12 weeks | Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline. |
| Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged >65 Years Old) | 12 weeks | Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline. |
| Changes From Baseline of 5-mC Methylation (CpG Sites) in Apolipoprotein E (APOE) by Magnesium Treatment vs. Placebo | 12 weeks | 5-mC methylation (CpG sites) in Apolipoprotein E (APOE) were measure by TET-assisted bisulfite (TAB)-Array. 5-mC methylation changes=value at 12 weeks minus value at baseline. |
Participant flow
Recruitment details
Participants, aged 40-85 y, with colorectal polyp or polyp-free individuals with high risk of colorectal cancer and had a calcium intake of ≥700 and \<2000 mg/d, and their calcium-to-magnesium intake ratio was \>2.6 (based on baseline two 24-hour dietary recalls) and completed MoCA assessment were recruited from Vanderbilt patient sources from Dec. 12, 2012 to Jan 30, 2016.
Participants by arm
| Arm | Count |
|---|---|
| Participants Will be Assigned to Magnesium Glycinate Magnesium glycinate: Oral administration of magnesium glycinate daily for 12 weeks | 62 |
| Participants Will be Assigned to Placebo Placebo: Oral administration of identical-appearing placebo daily for 12 weeks | 67 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Participants Will be Assigned to Magnesium Glycinate | Participants Will be Assigned to Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 19 Participants | 38 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 48 Participants | 91 Participants |
| Age, Continuous | 60.1 years STANDARD_DEVIATION 7.7 | 61.2 years STANDARD_DEVIATION 8 | 60.7 years STANDARD_DEVIATION 7.9 |
| Overall MoCA Score at Baseline | 27.0 units on a scale STANDARD_DEVIATION 2.7 | 27.2 units on a scale STANDARD_DEVIATION 2.2 | 27.1 units on a scale STANDARD_DEVIATION 2.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 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 | 60 Participants | 66 Participants | 126 Participants |
| Region of Enrollment United States | 62 participants | 67 participants | 129 participants |
| Sex: Female, Male Female | 34 Participants | 38 Participants | 72 Participants |
| Sex: Female, Male Male | 28 Participants | 29 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 67 |
| other Total, other adverse events | 4 / 62 | 2 / 67 |
| serious Total, serious adverse events | 0 / 62 | 0 / 67 |
Outcome results
Primary
Changes From Baseline of 5-mC Methylation (CpG Sites) in Apolipoprotein E (APOE) by Magnesium Treatment vs. Placebo
5-mC methylation (CpG sites) in Apolipoprotein E (APOE) were measure by TET-assisted bisulfite (TAB)-Array. 5-mC methylation changes=value at 12 weeks minus value at baseline.
Time frame: 12 weeks
Population: 123 participants who completed both pre- and post-treatment MoCA tests were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Were Assigned to Magnesium Glycinate | Changes From Baseline of 5-mC Methylation (CpG Sites) in Apolipoprotein E (APOE) by Magnesium Treatment vs. Placebo | cg18768621 | 0.006 CpG sites | Standard Deviation 0.025 |
| Participants Were Assigned to Magnesium Glycinate | Changes From Baseline of 5-mC Methylation (CpG Sites) in Apolipoprotein E (APOE) by Magnesium Treatment vs. Placebo | cg13496662 | -0.018 CpG sites | Standard Deviation 0.06 |
| Participants Were Assigned to Placebo | Changes From Baseline of 5-mC Methylation (CpG Sites) in Apolipoprotein E (APOE) by Magnesium Treatment vs. Placebo | cg18768621 | -0.003 CpG sites | Standard Deviation 0.025 |
| Participants Were Assigned to Placebo | Changes From Baseline of 5-mC Methylation (CpG Sites) in Apolipoprotein E (APOE) by Magnesium Treatment vs. Placebo | cg13496662 | 0.006 CpG sites | Standard Deviation 0.067 |
p-value: 0.05general linear model
Primary
Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo
Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline.
Time frame: 12 weeks
Population: IRB approval was obtained to add the MoCA component on Dec.11 2012. From Dec. 12, 2012 to Jan 30, 2016, 129 participants enrolled the study. Among them, 123 (95.3%) completed pre-and post- treatment MoCA were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Were Assigned to Magnesium Glycinate | Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo | 1.1 score on a scale | Standard Deviation 2.3 |
| Participants Were Assigned to Placebo | Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo | 0.6 score on a scale | Standard Deviation 2.6 |
p-value: 0.2general linear model
Primary
Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged ≤65 Years Old)
Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline.
Time frame: 12 weeks
Population: 123 participants who completed both pre- and post-treatment MoCA tests are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Were Assigned to Magnesium Glycinate | Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged ≤65 Years Old) | 0.7 score on a scale | Standard Deviation 2 |
| Participants Were Assigned to Placebo | Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged ≤65 Years Old) | 0.6 score on a scale | Standard Deviation 2.8 |
p-value: 0.9general linear model
Primary
Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged >65 Years Old)
Montreal Cognitive Assessment (MoCA) Scoring: The test consists of 30 items, and each item is worth one point, resulting in a maximum score of 30. A higher score indicates better cognitive functioning. The changes of MoCA score=Score at 12 weeks minus Score at baseline.
Time frame: 12 weeks
Population: 123 participants who completed pre-and post- treatment MoCA were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants Were Assigned to Magnesium Glycinate | Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged >65 Years Old) | 2.3 score on a scale | Standard Deviation 2.7 |
| Participants Were Assigned to Placebo | Overall Score Changes From Baseline by Magnesium Treatment vs. Placebo (Aged >65 Years Old) | 0.5 score on a scale | Standard Deviation 1.9 |
p-value: 0.01general linear model