Alzheimer's Disease, Dementia
Conditions
Keywords
deprescribing, medication therapy management
Brief summary
The study will examine the impact on cognitive reserve of a pharmacist-physician patient-centered medication therapy management intervention to address inappropriate medication use as identified by the Beers 2015 list. By bolstering cognitive reserve, this project will directly address the National Alzheimer's Project Act 2015 priorities serving to delay onset of symptoms in preclinical dementia. The results of this study will provide valuable insights on how to expand this intervention to reduce the prevalence and associated healthcare costs of symptomatic Alzheimer's disease.
Detailed description
This is a 12-month, parallel arm, study to be conducted at the University of Kentucky. The study will involve assessing medication use and identifying any medicines that may be inappropriate for elderly adults. At the beginning of the study, participants will be asked to undergo one amyloid-PET scan to detect early amyloid plaques in their brain which could increase the risk of Alzheimer's disease in the near future. In addition, at the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities. Part of the study includes collecting information regarding participants memory and thinking abilities. Participants will be asked to complete questionnaires as well as memory and thinking tests. A study doctor will review participants medical history and then perform routine medical (physical and neurological) examinations. Two of the study visits will be conducted by phone to check up on the participants. At the beginning, middle, and end of the study, participants will meet with a doctor and pharmacist to review and make any changes deemed appropriate to their current medicines. This will be done in order to try and eliminate medicines that are not recommended for the elderly. These visits are referred to as the Medication Therapy Management (MTM).
Interventions
OTHERPlacebo
Participants will receive educational materials, but will not receive MTM.
OTHERMedication Therapy Management (MTM)
Participants will receive MTM in addition to the educational materials.
At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve.
Sponsors
National Institute on Aging (NIA)
Daniela Moga
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
* Non-demented * No previous reaction or contraindication to scopolamine patch, or medical condition warranting dose adjustment in scopolamine including but not limited to: open angle glaucoma, gastrointestinal or urinary outlet obstructions, seizures, or psychosis. * No contraindications to Aβ-PET scan including hypersensitivity to PET ligand or radiation exposures in the past year that would exceed the acceptable safe annual exposure in combination with the Aβ PET * Medically stable and able to complete all study activities, as determined by the investigator * Reporting at least one potentially inappropriate medication as listed in the Beers 2015 criteria * Living in the community * Willing to participate in this intervention study
Exclusion criteria
* Allergy or other know intolerance to scopolamine patches * Narrow-angle glaucoma * Difficulty swallowing * Stomach or bowel problems (e.g., blockage, muscle weakness, ulcerative colitis) * Bleeding * Acid reflux disease * Myasthenia gravis * Blockage of the urinary tract. * Seizures * Psychosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medication Appropriateness Index | change from baseline to end of study, an average of 1 year | Change from baseline to end of study. The Medication Appropriateness Index (MAI) rates medications as appropriate, marginally appropriate, or inappropriate based on ten criteria. All medications reported by study participants were evaluated by the study team and assigned a medication-specific MAI. As an outcome measure, the total MAI was obtained by adding the medication specific MAIs for all medications reported by the participant. Minimum score for one medication is 0 (appropriate) and the maximum is 18 (inappropriate for all criteria). Total MAI depends on the number of medications taken by participant. A decrease in MAI from baseline to end of study indicates improvement in medication appropriateness. |
| Trail Making Test B With the Scopolamine Patch | baseline to end of study, an average of 1 year | End of study for Trail Making Test B with the scopolamine patch. The mean and standard used to compute the TMTB z-scores were taken from a sample of cognitively intact older adult research volunteers (Weintraub et al. 2009; mean = 90.3, SD = 50) (22). Z-scores were then multiplied by -1 to facilitate interpretation, since higher TMTB scores are worse. For the z-score, we converted time in seconds to units of standard deviations from a mean of 0, where 0 represents the mean performance of cognitively intact (normal) older adult research volunteers enrolled in longitudinal studies at Alzheimer's Disease Research Centers in the United States. Scores that are at least 1.5 standard deviations below the mean are indicative of potential cognitive impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Reserve: Montreal Cognitive Assessment | change from baseline to end of study, an average of 1 year | Change from baseline to end of study for Montreal Cognitive Assessment. Z score is based on the NACC cognitively normal population (https://files.alz.washington.edu/documentation/weintraub-2018-v3.pdf), Z score = 0 corresponds mean MoCA score for cognitively normal older adults; higher Z scores are better; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test. |
| Cognitive Reserve: California Verbal Learning Test | change from baseline to end of study, an average of 1 year | Change from baseline to end of study for California Verbal Learning test. Z scores (higher scores are better; Z score = 0 corresponds mean CVLT score for cognitively normal older adults; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test) are adjusted for age and sex and are based on the normative population used to develop norms for CVLT-II; individuals sampled to create the normative data were tested cross-sectionally, demographically matched to the most recent U.S. Censuses, and screened for self-reported neurological, psychiatric, or debilitating medical illnesses. Delis, D. C., Kramer, J. H., Kaplan, E., & Ober, B. A. (1987-2000). California Verbal Learning Test--Second Edition (CVLT -II) \[Database record\]. APA PsycTests. https://doi.org/10.1037/t15072-000 |
| Perceived Health Status | change from baseline to end of study, an average of 1 year | Change from baseline to end of study for Short Form Health Survey (SF-36). T scores have a mean of 50 and SD of 10; higher scores are better; mean = 50 represents expected mean in general US adult population, with no available clinically relevant thresholds . |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants enrolled into this arm will only receive educational materials, but will not receive specific recommendations to make changes to the medications they are taking.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Placebo: Participants will receive educational materials, but will not receive MTM.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve. | 44 |
| Medication Therapy Management (MTM) Participants enrolled into this arm will receive educational materials and will have their medications assessed; recommendations for changes in the medications taken will be made when appropriate.
Cognitive testing at the beginning and the end of the study will be done with and without a scopolamine patch to reveal cognitive reserve.
Medication Therapy Management (MTM): Participants will receive MTM in addition to the educational materials.
Scopolamine patch: At the beginning and end of the study, participants will be asked to use a scopolamine patch. This patch is not being used to prevent motion sickness (as approved by the FDA), but instead is being used to challenge the participant's memory and thinking abilities and determine cognitive reserve. | 46 |
| Total | 90 |
Baseline characteristics
| Characteristic | Placebo | Medication Therapy Management (MTM) | Total |
|---|---|---|---|
| Age, Continuous | 74.1 years STANDARD_DEVIATION 6.6 | 73.4 years STANDARD_DEVIATION 5.6 | 73.9 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 46 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Medication appropriateness index | 10.6 units on a scale STANDARD_DEVIATION 7.4 | 13.5 units on a scale STANDARD_DEVIATION 9.4 | 12.1 units on a scale STANDARD_DEVIATION 8.5 |
| Number of medications on 2015 Beers list | 2.2 medications STANDARD_DEVIATION 1.2 | 2.5 medications STANDARD_DEVIATION 1.2 | 2.4 medications STANDARD_DEVIATION 1.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 8 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 | 40 Participants | 40 Participants | 80 Participants |
| Sex: Female, Male Female | 23 Participants | 34 Participants | 57 Participants |
| Sex: Female, Male Male | 21 Participants | 12 Participants | 33 Participants |
| Standardized Uptake Value ratio 1.2<=SUVr<1.4 | 17 Participants | 17 Participants | 34 Participants |
| Standardized Uptake Value ratio SUVr<1.2 | 13 Participants | 14 Participants | 27 Participants |
| Standardized Uptake Value ratio SUVr>=1.4 | 14 Participants | 15 Participants | 29 Participants |
| Total number of medications | 12.9 medications STANDARD_DEVIATION 4.8 | 12.7 medications STANDARD_DEVIATION 5 | 12.8 medications STANDARD_DEVIATION 4.8 |
| Years of education | 16.4 years STANDARD_DEVIATION 2.6 | 16.5 years STANDARD_DEVIATION 3 | 16.5 years STANDARD_DEVIATION 2.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 44 | 0 / 46 |
| other Total, other adverse events | 42 / 44 | 41 / 46 |
| serious Total, serious adverse events | 9 / 44 | 7 / 46 |
Outcome results
Primary
Medication Appropriateness Index
Change from baseline to end of study. The Medication Appropriateness Index (MAI) rates medications as appropriate, marginally appropriate, or inappropriate based on ten criteria. All medications reported by study participants were evaluated by the study team and assigned a medication-specific MAI. As an outcome measure, the total MAI was obtained by adding the medication specific MAIs for all medications reported by the participant. Minimum score for one medication is 0 (appropriate) and the maximum is 18 (inappropriate for all criteria). Total MAI depends on the number of medications taken by participant. A decrease in MAI from baseline to end of study indicates improvement in medication appropriateness.
Time frame: change from baseline to end of study, an average of 1 year
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Medication Appropriateness Index | 11.2 units on a scale | Standard Error 0.6 |
| Medication Therapy Management (MTM) | Medication Appropriateness Index | 9.4 units on a scale | Standard Error 0.6 |
Primary
Trail Making Test B With the Scopolamine Patch
End of study for Trail Making Test B with the scopolamine patch. The mean and standard used to compute the TMTB z-scores were taken from a sample of cognitively intact older adult research volunteers (Weintraub et al. 2009; mean = 90.3, SD = 50) (22). Z-scores were then multiplied by -1 to facilitate interpretation, since higher TMTB scores are worse. For the z-score, we converted time in seconds to units of standard deviations from a mean of 0, where 0 represents the mean performance of cognitively intact (normal) older adult research volunteers enrolled in longitudinal studies at Alzheimer's Disease Research Centers in the United States. Scores that are at least 1.5 standard deviations below the mean are indicative of potential cognitive impairment.
Time frame: baseline to end of study, an average of 1 year
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trail Making Test B With the Scopolamine Patch | -0.1 z-scores | Standard Error 0.14 |
| Medication Therapy Management (MTM) | Trail Making Test B With the Scopolamine Patch | 0.03 z-scores | Standard Error 0.14 |
Secondary
Cognitive Reserve: California Verbal Learning Test
Change from baseline to end of study for California Verbal Learning test. Z scores (higher scores are better; Z score = 0 corresponds mean CVLT score for cognitively normal older adults; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test) are adjusted for age and sex and are based on the normative population used to develop norms for CVLT-II; individuals sampled to create the normative data were tested cross-sectionally, demographically matched to the most recent U.S. Censuses, and screened for self-reported neurological, psychiatric, or debilitating medical illnesses. Delis, D. C., Kramer, J. H., Kaplan, E., & Ober, B. A. (1987-2000). California Verbal Learning Test--Second Edition (CVLT -II) \[Database record\]. APA PsycTests. https://doi.org/10.1037/t15072-000
Time frame: change from baseline to end of study, an average of 1 year
Population: CVLT Long Delay (Z score), challenged condition
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cognitive Reserve: California Verbal Learning Test | -0.10 z-score | Standard Error 0.15 |
| Medication Therapy Management (MTM) | Cognitive Reserve: California Verbal Learning Test | -0.083 z-score | Standard Error 0.14 |
Secondary
Cognitive Reserve: Montreal Cognitive Assessment
Change from baseline to end of study for Montreal Cognitive Assessment. Z score is based on the NACC cognitively normal population (https://files.alz.washington.edu/documentation/weintraub-2018-v3.pdf), Z score = 0 corresponds mean MoCA score for cognitively normal older adults; higher Z scores are better; typical neuropsych interpretation of z scores is that -1.5 indicates impaired performance on that test.
Time frame: change from baseline to end of study, an average of 1 year
Population: MoCA (Z score, NACC UDS norms), challenged condition
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cognitive Reserve: Montreal Cognitive Assessment | -0.15 z-score | Standard Error 0.12 |
| Medication Therapy Management (MTM) | Cognitive Reserve: Montreal Cognitive Assessment | -0.31 z-score | Standard Error 0.13 |
Secondary
Perceived Health Status
Change from baseline to end of study for Short Form Health Survey (SF-36). T scores have a mean of 50 and SD of 10; higher scores are better; mean = 50 represents expected mean in general US adult population, with no available clinically relevant thresholds .
Time frame: change from baseline to end of study, an average of 1 year
Population: SF-36 Mental Component Score (T score), challenged condition
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Perceived Health Status | 41.4 t-score | Standard Error 1.2 |
| Medication Therapy Management (MTM) | Perceived Health Status | 41.2 t-score | Standard Error 1.3 |