Mild Cognitive Impairment
Conditions
Keywords
Memory XL, Mild Cognitive Impairment, cognitive status
Brief summary
A vitamin nutriceutical, Memory XL, has been shown to provide maintenance of cognitive status in mild, moderate, and severe Alzheimer's disease patients (2 publications by T. Shea). Because this nutriceutical is now patented by the Univ. of Mass., other trials at that institution may be considered a conflict of interest. Therefore, a study of its effects on Mild Cognitive Impairment (MCI) patients will be conducted by PI who is not affiliated with Univ. of Mass. or with Dr. Shea. The study hypothesis is: Memory XL will maintain or improve the cognitive and behavioral status of patients diagnosed with MCI during the year of participation in the study; normally, 10-25% of MCI patients convert to mild Alzheimer's dementia each year.
Detailed description
This IRB-approved study is a randomized double blind study of patients diagnosed with Mild Cognitive Impairment (MCI) in the Center for Alzheimer's and Neurodegenerative Disorders (CANDO) at VAMC in Oklahoma City. Dr. Shea provided the pills (nutriceutical and placebos) from the same batches he used in former studies of Alzheimer's disease patients (produced by Nutricap Labs, Farmingdale, NY). Pills were dispensed by the OKC VAMC research pharmacist, using a random numbering system. The PI completed five cognitive testing sessions, lasting 1 to 1.5 hours, for each subject during the 12 months of participation in the study. Subject's spouse or family member completed 4 questionnaires about the subject's behavioral changes, and kept daily records of the times each day when the subject ingested the study pill assigned by the pharmacist. All subjects are patients in the VAMC memory loss clinic (CANDO) who are monitored by their neurologists (2 co-investigators in this study).
Interventions
DRUGMemory XL
An over-the-counter vitamin nutriceutical patented by Univ. of Mass. that contains folic acid 400 mg, Vit. B12 6 ug, alpha-tocopherol 30 IU, S-adenosyl methionine (SAM) 400 mg, N-acetyl cysteine (NAC) 600 mg, & acetyl-L-carnitine (ALCAR) 500 mg; 2 pills per day for 12 months
DRUGplacebo
placebo comparator
Sponsors
University of Oklahoma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* MCI patients diagnosed at the VAMC Center for Alzheimers and Neurodegenerative Disorder (CANDO). * Clinical Dementia Rating (CDR) score of 0.5. * fluent in English. * able to ambulate to the outpatient clinic and research laboratory * have sight and hearing levels sufficient to complete neuropsychological testing. * free from bipolar disorder and terminal illnesses such as cancer. * must live with a spouse or adult relative who will record nutriceutical ingestion daily. * subjects will be consecutively diagnosed patients from all ethnic groups.
Exclusion criteria
* patients from protected categories such as prisoners and pregnant women. * any MCI subject who develops a life-threatening disease such as terminal cancer, stroke, brain trauma, debilitating heart attack, etc. * indication of inability to make decisions regarding study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences in Instrumental Activities of Daily Living (IADL) Scores Over 12 Months, by Study Group | baseline to 12 months | IADL is a behavior rating scale using 9 domains of household and community activities, with a total score of 27 points indicating less competence than a normal function score of 9 points. Outcome measure is results of an ANOVA of the differences between baseline and end/last score, by study arm/group, to detect statistically significant differences (nutriceutical vs placebo). |
| Differences in Dementia Rating Scale (DRS) at 12 Months From Baseline, by Study Group | Baseline and 12 months | Dementia Rating Scale (DRS) is a cognitive test with 5 domains; raw scores can be converted to percentiles for age/education levels, so individuals can be compared. Higher scores mean more competence (0-36 points converted to percentiles so different ages can be compared). Total raw scores for the 5 domains were computed so that Mean and SD of differences between first and last assessments for all subjects, by study arms (nutriceutical = XL and placebo = PL) are reported here. |
| Differences in Clinical Dementia Rating Scale (CDR) Over 12 Months, by Study Group | baseline before intervention to 12 months of intervention | CDR is a rating scale for 8 aspects of behavior with 0-3 points allowed; higher scores indicate more pathology. Total minimum and maximum scores are 0 and 36 respectively.Clinician rates the patient's behavior and competence with input from family members who live with the patient. ANOVA of differences between baseline and end scores of the CDR scale are reported here, by the study arm/group. |
| Differences in Clock Drawing Test (CLOX) Scores Over 12 Months, by Study Group | baseline to 12 months | Clock Drawing Test is a cognitive screening instrument in which subjects are to draw a clock and set a specified time. Various scoring methods can be employed using 4 to 15 points, with more points showing more competence. This study used the 8-point scoring method, so that 0-8 points could be assigned during each of the baseline and 4 assessment periods during the 12-month study. ANOVA of the differences between baseline and end scores, by study arm/group was completed. |
| Differences in MiniMental State Exam (MMSE) Scores Over 12 Months, by Study Group | baseline to 12 months | MiniMental State Exam is a cognitive screening device with possible 30 points in several categories; higher points indicate greater competence. Clinician tests orientation, attention, language, & visuo-spatial construction. Outcome measure is results of an ANOVA of differences between baseline and end/last scores, by study arm/group was completed. |
| Differences in Neuropsychiatric Inventory (NPI) Scores Over 12 Months, by Study Group | baseline to 12 months | NPI is a behavior rating scale with 12 categories in which a maximum score of 36 points indicates more pathology than a minimum score of 0. Outcome measure reported here is results of an ANOVA of the differences between baseline and end scores, by study arm/group, to detect any statistically significant difference (nutriceutical vs placebo groups) was completed. |
| Differences in Activities of Daily Living (ADL) Scores Over 12 Months, by Study Group | baseline to 12 months | ADL is a behavior rating scale with 6 domains of self-care (feeding, toileting, etc.) in which a maximum score of 18 indicates less competence than a minimum score of 6 (normal skills). Outcome measure is results of ANOVA of the differences between baseline and last/end scores, by study arm/group, to detect any statistically significant differences. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Converted to Early Alzheimer's (Dementia). | 12 months | Neurological diagnosis is based on test scores that reach -1.6 SD of mean for age/education, and on radiological tests of brain structure (CT, MRI, PET). Usual cutoff for test score percentile is \<0.05 to diagnose dementia. |
Countries
United States
Participant flow
Recruitment details
Patients diagnosed with Mild Cognitive Impairment (MCI) in VA and OU campus clinics were given opportunity to participate in the trial, if they met inclusion/exclusion criteria.
Pre-assignment details
Over 1.5 yrs, only 19 of 533 memory clinic patients were diagnosed with Mild Cognitive Impairment and who met inclusion/exclusion criteria. Most of the MCI patients had serious medical problems that affected cognition. Ten subjects agreed to be in this study.
Participants by arm
| Arm | Count |
|---|---|
| Nutriceutical (MemoryXL) Effects on Cognition & Behavior Subjects diagnosed with Mild Cognitive Impairment (MCI) will take 2 Memory XL pills daily for 12 months (a vitamin nutriceutical developed by Thomas Shea, Ph.D., and patented by the Univ. of Mass.). They will be assessed cognitively each 3 months to determine if Memory XL prevents them from progressing to early dementia; 10-25% of MCI patients have been shown to convert to dementia each year. Therefore, at least 10% of patients in study would be expected to progress from MCI to early Alzheimer's dementia during the year of the study. | 8 |
| Placebo Effects on Cognition/Behavior Mild Cognitive Impairment subjects will take the placebo that has been formulated to look and taste the same as the nutriceutical being studied (Memory XL). Subjects will be cognitively & behaviorally assessed each 3 months of the study, with last testing done at the end of their 12 months of pill ingestion. Tests used in each arm of study are the same ones used in prior publications by the nutriceutical inventor, Dr. Shea, when he assessed mild, moderate, and severely demented Alzheimer's patients. The current study is double blind, whereas Dr. Shea's studies were open label. | 2 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | lung cancer | 1 | 0 |
| Overall Study | medical exclusion after 1st testing | 1 | 0 |
Baseline characteristics
| Characteristic | Nutriceutical (MemoryXL) Effects on Cognition & Behavior | Total | Placebo Effects on Cognition/Behavior |
|---|---|---|---|
| Activities of Daily Living (ADL) | 6.3 total initial raw scores by group STANDARD_DEVIATION 0.4 | 6.6 total initial raw scores by group STANDARD_DEVIATION 1.2 | 8.0 total initial raw scores by group STANDARD_DEVIATION 0.7 |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 9 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 0 Participants |
| Clock Drawing Test | 6.7 initial total raw score by group STANDARD_DEVIATION 0.3 | 6.8 initial total raw score by group STANDARD_DEVIATION 0.9 | 7.0 initial total raw score by group STANDARD_DEVIATION 0.7 |
| Dementia Rating Scale | 130 total raw score points for 5 domains STANDARD_DEVIATION 2.3 | 132 total raw score points for 5 domains STANDARD_DEVIATION 7.5 | 140 total raw score points for 5 domains STANDARD_DEVIATION 4.7 |
| Instrumental Activities of Daily Living (IADL) | 14.2 total initial scores by study group STANDARD_DEVIATION 1.8 | 14.0 total initial scores by study group STANDARD_DEVIATION 4.9 | 13.0 total initial scores by study group STANDARD_DEVIATION 3.7 |
| MiniMental State Exam (MMSE) | 27.5 total 1st MMSE score parameters STANDARD_DEVIATION 0.8 | 27.7 total 1st MMSE score parameters STANDARD_DEVIATION 2.1 | 28.5 total 1st MMSE score parameters STANDARD_DEVIATION 1.5 |
| Modified Clinical Dementia Rating scale (CDR) | 5.6 total raw scores by study group STANDARD_DEVIATION 1.4 | 5.8 total raw scores by study group STANDARD_DEVIATION 3.8 | 6.5 total raw scores by study group STANDARD_DEVIATION 2.8 |
| Neuropsychiatric Inventory NPI) | 3.6 total raw scores by group STANDARD_DEVIATION 1.3 | 3.5 total raw scores by group STANDARD_DEVIATION 3.4 | 3.0 total raw scores by group STANDARD_DEVIATION 2.6 |
| Region of Enrollment United States | 8 participants | 10 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 2 |
| serious Total, serious adverse events | 0 / 8 | 0 / 2 |
Outcome results
Primary
Differences in Activities of Daily Living (ADL) Scores Over 12 Months, by Study Group
ADL is a behavior rating scale with 6 domains of self-care (feeding, toileting, etc.) in which a maximum score of 18 indicates less competence than a minimum score of 6 (normal skills). Outcome measure is results of ANOVA of the differences between baseline and last/end scores, by study arm/group, to detect any statistically significant differences.
Time frame: baseline to 12 months
Population: All subjects who completed 12-month study were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutriceutical Arm | Differences in Activities of Daily Living (ADL) Scores Over 12 Months, by Study Group | 0.0 units on a scale | Standard Error 0.3 |
| Placebo Arm | Differences in Activities of Daily Living (ADL) Scores Over 12 Months, by Study Group | -1.0 units on a scale | Standard Error 0.6 |
Comparison: ANOVA used to detect significant difference in test scores between baseline and end assessments, by study arm (nutriceutical vs placebo).p-value: 0.18ANOVA
Primary
Differences in Clinical Dementia Rating Scale (CDR) Over 12 Months, by Study Group
CDR is a rating scale for 8 aspects of behavior with 0-3 points allowed; higher scores indicate more pathology. Total minimum and maximum scores are 0 and 36 respectively.Clinician rates the patient's behavior and competence with input from family members who live with the patient. ANOVA of differences between baseline and end scores of the CDR scale are reported here, by the study arm/group.
Time frame: baseline before intervention to 12 months of intervention
Population: All subjects who completed the 12-month study were included (placebo and nutriceutical arms/groups).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutriceutical Arm | Differences in Clinical Dementia Rating Scale (CDR) Over 12 Months, by Study Group | -1.7 units on a scale | Standard Error 1.6 |
| Placebo Arm | Differences in Clinical Dementia Rating Scale (CDR) Over 12 Months, by Study Group | 2.0 units on a scale | Standard Error 2.9 |
Comparison: ANOVA used to detect significant difference in test scores between baseline and end assessments, by study arm (nutriceutical vs placebo).p-value: 0.31ANOVA
Primary
Differences in Clock Drawing Test (CLOX) Scores Over 12 Months, by Study Group
Clock Drawing Test is a cognitive screening instrument in which subjects are to draw a clock and set a specified time. Various scoring methods can be employed using 4 to 15 points, with more points showing more competence. This study used the 8-point scoring method, so that 0-8 points could be assigned during each of the baseline and 4 assessment periods during the 12-month study. ANOVA of the differences between baseline and end scores, by study arm/group was completed.
Time frame: baseline to 12 months
Population: All subjects who completed the 12-month study were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutriceutical Arm | Differences in Clock Drawing Test (CLOX) Scores Over 12 Months, by Study Group | 0.5 units on a scale | Standard Error 0.6 |
| Placebo Arm | Differences in Clock Drawing Test (CLOX) Scores Over 12 Months, by Study Group | -1.0 units on a scale | Standard Error 1.1 |
Comparison: ANOVA used to detect significant difference in test scores between baseline and end assessments, by study arm (nutriceutical vs placebo).p-value: 0.27ANOVA
Primary
Differences in Dementia Rating Scale (DRS) at 12 Months From Baseline, by Study Group
Dementia Rating Scale (DRS) is a cognitive test with 5 domains; raw scores can be converted to percentiles for age/education levels, so individuals can be compared. Higher scores mean more competence (0-36 points converted to percentiles so different ages can be compared). Total raw scores for the 5 domains were computed so that Mean and SD of differences between first and last assessments for all subjects, by study arms (nutriceutical = XL and placebo = PL) are reported here.
Time frame: Baseline and 12 months
Population: All participants who completed 12-month study were included in the ANOVA analysis of the differences in scores of tests between baseline and end assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutriceutical Arm | Differences in Dementia Rating Scale (DRS) at 12 Months From Baseline, by Study Group | -1.0 units on a scale | Standard Deviation 3 |
| Placebo Arm | Differences in Dementia Rating Scale (DRS) at 12 Months From Baseline, by Study Group | -2.5 units on a scale | Standard Deviation 5.3 |
Comparison: ANOVA used to detect significant difference in test scores between baseline and end assessments, by study arm (nutriceutical vs placebo).p-value: 0.8133ANOVA
Primary
Differences in Instrumental Activities of Daily Living (IADL) Scores Over 12 Months, by Study Group
IADL is a behavior rating scale using 9 domains of household and community activities, with a total score of 27 points indicating less competence than a normal function score of 9 points. Outcome measure is results of an ANOVA of the differences between baseline and end/last score, by study arm/group, to detect statistically significant differences (nutriceutical vs placebo).
Time frame: baseline to 12 months
Population: All subjects who completed 12-month study were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutriceutical Arm | Differences in Instrumental Activities of Daily Living (IADL) Scores Over 12 Months, by Study Group | 0.0 units on a scale | Standard Error 1 |
| Placebo Arm | Differences in Instrumental Activities of Daily Living (IADL) Scores Over 12 Months, by Study Group | -2.0 units on a scale | Standard Error 1.7 |
Comparison: ANOVA used to detect significant difference in test scores between baseline and end assessments, by study arm (nutriceutical vs placebo).p-value: 0.34ANOVA
Primary
Differences in MiniMental State Exam (MMSE) Scores Over 12 Months, by Study Group
MiniMental State Exam is a cognitive screening device with possible 30 points in several categories; higher points indicate greater competence. Clinician tests orientation, attention, language, & visuo-spatial construction. Outcome measure is results of an ANOVA of differences between baseline and end/last scores, by study arm/group was completed.
Time frame: baseline to 12 months
Population: All subjects who completed the 12-month study were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutriceutical Arm | Differences in MiniMental State Exam (MMSE) Scores Over 12 Months, by Study Group | -0.33 units on a scale | Standard Error 0.5 |
| Placebo Arm | Differences in MiniMental State Exam (MMSE) Scores Over 12 Months, by Study Group | 1.0 units on a scale | Standard Error 0.9 |
Comparison: ANOVA used to detect significant difference in test scores between baseline and end assessments, by study arm (nutriceutical vs placebo).p-value: 0.24ANOVA
Primary
Differences in Neuropsychiatric Inventory (NPI) Scores Over 12 Months, by Study Group
NPI is a behavior rating scale with 12 categories in which a maximum score of 36 points indicates more pathology than a minimum score of 0. Outcome measure reported here is results of an ANOVA of the differences between baseline and end scores, by study arm/group, to detect any statistically significant difference (nutriceutical vs placebo groups) was completed.
Time frame: baseline to 12 months
Population: All subjects who completed 12-month study were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutriceutical Arm | Differences in Neuropsychiatric Inventory (NPI) Scores Over 12 Months, by Study Group | -4.0 units on a scale | Standard Error 1.9 |
| Placebo Arm | Differences in Neuropsychiatric Inventory (NPI) Scores Over 12 Months, by Study Group | -2.5 units on a scale | Standard Error 3.3 |
Comparison: ANOVA used to detect significant difference in test scores between baseline and end assessments, by study arm (nutriceutical vs placebo).p-value: 0.71ANOVA
Secondary
Number of Subjects Who Converted to Early Alzheimer's (Dementia).
Neurological diagnosis is based on test scores that reach -1.6 SD of mean for age/education, and on radiological tests of brain structure (CT, MRI, PET). Usual cutoff for test score percentile is \<0.05 to diagnose dementia.
Time frame: 12 months
Population: Subjects diagnosed as Mild Cognitive Impairment (MCI) in VA clinic were given opportunity to participate in the study if they met inclusion/exclusion criteria (no illnesses that cause brain damage or are uncontrolled such as brittle diabetes).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nutriceutical Arm | Number of Subjects Who Converted to Early Alzheimer's (Dementia). | 0 participants |
| Placebo Arm | Number of Subjects Who Converted to Early Alzheimer's (Dementia). | 1 participants |