Alzheimer Disease, Dementia
Conditions
Keywords
anticholinergic, cognitive function, brain, aging
Brief summary
This study is an RCT to evaluate the effectiveness of Brain Safe on reducing anticholinergic exposure. Over 42 months, the trial will enroll 700 community-dwelling older adults who were prescribed one or more strong anticholinergics. Participants will be randomized to use the Brain Safe app or an attention control medication list app for 12 months, with monthly usage reminders.
Detailed description
This study is a randomized clinical trial (RCT) of the efficacy of a direct-to-consumer intervention called Brain Safe to primarily reduce older adults' exposure to prescription anticholinergics and secondarily improve cognitive function and health-related quality of life. Over 42 months, the trial will enroll 700 community-dwelling older adults who were prescribed one or more strong anticholinergics. Participants will be randomized to use the Brain Safe app or an attention control medication list app for 12 months, with monthly usage reminders. The primary objective is to test the effect of Brain Safe on anticholinergic exposure at 12 months. We hypothesize that anticholinergic exposure will be lower among those randomized to the Brain Safe intervention compared to those randomized to the attention control app at 12 months. Our primary, powered outcome is the total standard daily dose (TSDD) measure of anticholinergic exposure at 12 months, which is calculated over the preceding 6 months of prescription data. We will electronically capture prescription data monthly and compute TSDD at baseline, 6, and 12 months. The secondary objective is to test the effect of Brain Safe on: (a) cognitive function and (b) health-related quality of life at 12 months. We hypothesize older adults randomized to Brain Safe will have higher (a) cognitive function, measured by using an objective, performance-based composite, and (b) health-related quality of life (HRQOL), compared to those randomized to the attention control app, at 12 months. Exploratory objectives are to test the effect of Brain Safe on anticholinergic exposure, cognitive function, and HRQOL at 6 months. This aim will explore the presence of early effects of Brain Safe at 6 months.
Interventions
OTHERBrain Safe App
The Brain Safe app includes the medication list, a personalized risk calculator, multimedia educational content, and a conversation starter/doctor's report.
OTHERAttention Control App
The attention control app, called Med Safe, includes only the medication list feature.
Sponsors
Indiana University
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
The primary investigator and outcome assessor will be masked to the App assignment (Brain Safe vs Attention Control Medication list App)
Intervention model description
Enroll 700 community-dwelling older adults who were prescribed one or more strong anticholinergics. Participants will be randomized to use the Brain Safe app or an attention control medication list app for 12 months, with monthly usage reminders.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 1 primary care visit at Eskenazi Health or IU Health in past 12 months * Age ≥ 60 years * Written informed consent and HIPAA authorization for the release of personal health information. * English-speaking * At least one prescription for a strong anticholinergic medication with Anticholinergic Cognitive Burden (ACB) score 2 or 3 in prior 12 months, and currently using it * Community-dwelling in Central Indiana * Not cognitively impaired * Not terminally ill * Not sensory impaired (after correction)
Exclusion criteria
* Permanent resident of an extended care facility (nursing home); independent or assisted senior care living is allowed if managing own medications. * Diagnosis of Alzheimer's disease or related dementia (ADRD), determined by International Classification of Diseases (ICD)-9/ICD-10 codes or current use of a medication for ADRD * Diagnosis of schizophrenia, bipolar disorder, or schizoaffective disorder defined by ICD-9/ICD-10 codes * Involvement in another clinical trial that would prevent or interfere with study objectives * Sensory or other impairment prohibiting the use of a mobile touchscreen device or other study activity (after correction) * Not currently using anticholinergic medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Standardized Daily Dose (TSDD) - From Medical Records | Baseline, 6 months, 12 Months | To calculate the Total Standardized Daily Dose (TSDD), we first calculated the Standardized Daily Dose (SDD) for each anticholinergic medication with an ACB Score of 2 or 3. SDD was calculated by multiplying the strength by the units per dose and frequency per day and number of refills. The product was divided by the minimum effective daily dose (where available) or the minimum effective geriatric dose to standardize the quantity across multiple classes of medications. The SDD for all anticholinergics with an ACB score 2 or 3 was then summed for each participant for each 6-month period, and divided by the number of days in the relevant six month period to arrive at a TSDD. Range: The minimum possible value is 0 (optimal outcome; indicating zero exposure to ACB 2 or 3 medications). There is no fixed theoretical maximum score(higher value more exposure), as the upper limit is mathematically determined by the total volume and combination of medications a participant is prescribed. |
| Log Transformed Total Standardized Daily Dose (TSDD) - From Medical Records | Baseline, 6, and 12 Months | Construct: Measures natural log-transformed average daily exposure to medications with an Anticholinergic Cognitive Burden (ACB) score of 2 or 3 to normalize data distribution.How Computed: Medication Standardized Daily Dose (SDD) = (strength × units/dose × frequency/day × refills) / minimum effective daily or geriatric dose. The SDD for all eligible drugs is summed over 6 months, divided by the number of days in that period to find raw TSDD, and natural log-transformed ($\\ln(x+1)$ or similar) for the final score.Scale Range: Minimum value is 0 (representing 0 raw TSDD, or zero exposure). There is no fixed theoretical maximum, as it is mathematically determined by the volume of medications prescribed.Interpretation: A value of 0 is the optimal outcome (no exposure). Higher values represent greater exposure (worse outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Cognitive Score | Baseline, 6 months, and 12 months | An overall cognitive score evaluating three domains: memory/new learning, executive function, and processing speed. Calculated by taking the mean of standardized Z-scores from the following specific tests: Hopkins Verbal Learning Test-Revised (HVLT-R) total and delayed recall; Trail Making Test Parts A and B; Phonetic Fluency; Semantic Fluency (adjusted); and Symbol Digit Modalities Test (correct). A Z-score of 0 represents the baseline study population mean. Standardized scores theoretically range from -3.0 to +3.0. Higher positive Z-scores (standard deviations above the mean) represent better cognitive performance (better outcome). Lower negative Z-scores represent worse cognitive performance (worse outcome). No clinical threshold is defined. Z-scores were derived using baseline means, with timed tests (e.g., Trails) inverted prior to averaging so higher always means better performance. |
| Choice Reaction Time (CRT) | Baseline | Computer-based assessment of Choice Reaction Time (CRT). It is used to evaluate executive function, attention, and psychomotor speed by measuring the time elapsed between the presentation of one of multiple possible stimuli and the participant's correct response. The final score represents the average response time (in milliseconds/seconds) across all valid test trials. The minimum value is 0. There is no fixed theoretical maximum, as the upper limit is bounded only by the participant's maximum delay. Lower values represent faster reaction times, indicating better executive functioning and psychomotor speed (a better outcome). Higher values indicate slower reaction times (a worse outcome). |
| Health Utilities Index (HUI) Mark 3 | Baseline, 6 months, and 12 months | The Health Utilities Index Mark 3 (HUI3) is a self-reported, multi-attribute health status classification system used to measure overall health-related quality of life and functional capacity. The score is calculated using responses across eight dimensions of health (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain). These subscales are combined using a mathematically weighted scoring algorithm to compute a single total utility index score. The total utility score ranges from a minimum of -0.36 (representing a health state considered worse than death) to a maximum of 1.00 (representing perfect health). A score of 0.00 represents death. Higher values represent a better health-related quality of life (a better outcome). Lower values represent worse health status (a worse outcome). |
| Hopkins Verbal Learning Test (HVLT) Total Recall | Baseline, 6 months, and 12 months | Hopkins Verbal Learning Test (HVLT) Total Recall. It is a paper-based list learning and recall assessment used to evaluate verbal memory and new learning capacity. Participants are read a list of 12 words and asked to freely recall as many as possible across three consecutive learning trials. The total recall score is calculated by summing the number of correctly recalled words across all three trials. The total recall score ranges from a minimum of 0 to a maximum of 36. Higher values represent a greater number of words correctly recalled, indicating better memory and verbal learning function (a better outcome). Lower scores indicate worse memory function (a worse outcome). |
| Hopkins Verbal Learning Test (HVLT) Delayed Recall | Baseline, 6 months, 12 months | Hopkins Verbal Learning Test (HVLT) Delayed Recall. It is a paper-based assessment used to evaluate delayed verbal memory retention and recall capacity. After a standard delay interval (typically 20 to 25 minutes) following the initial learning trials, participants are asked to freely recall the original list of 12 words. The delayed recall score is the total number of words correctly recalled from memory. The score ranges from a minimum of 0 to a maximum of 12. Higher values represent a greater number of words retained and recalled after the delay, indicating better memory retention (a better outcome). Lower scores indicate worse memory retention (a worse outcome). |
| Trail Making Test (TMT) Parts A | Baseline, 6 months, and 12 months | Number Correct Line Segments. This is a performance-based metric derived from the Trail Making Test (TMT) used to assess visual search, scanning, processing speed, and executive function, particularly when a participant is unable to complete the full timed test. The score is calculated by counting the total number of correct line segments a participant successfully draws connecting the sequences of encircled numbers (or numbers and letters) within the allotted test parameters. The score ranges from a minimum of 0 to a maximum of 25. Higher values represent a greater number of correctly drawn segments, indicating better cognitive processing speed and executive functioning (a better outcome). Lower values indicate worse cognitive performance (a worse outcome). |
| Trail Making Test (TMT) Parts B | Baseline, 6 months, and 12 months | Number Correct Line Segments (TMT Part B). This is a performance-based metric derived from the Trail Making Test Part B used to assess executive function, cognitive flexibility, and visual-motor tracking. It is particularly useful for quantifying performance when a participant is unable to complete the full timed test. The score is calculated by counting the total number of correct line segments a participant successfully draws connecting the 25 encircled numbers and letters in an alternating sequence (1, A, 2, B, 3, C...) within the allotted test parameters. The score ranges from a minimum of 0 to a maximum of 25. Higher values represent a greater number of correctly drawn segments, indicating better cognitive flexibility and executive functioning (a better outcome). Lower values indicate worse cognitive performance (a worse outcome). |
| Digit-Symbol Substitution Test (DSST) Number of Correct Responses | Baseline, 6 months, and 12 months | Digit-Symbol Substitution Test (DSST), utilizing the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Coding subtest. It is a paper-based assessment used to evaluate processing speed, visual-motor coordination, and sustained attention. Participants are provided a key pairing numbers (1 through 9) with simple geometric symbols. They are given a strict time limit (120 seconds) to draw the correct corresponding symbols beneath a series of randomized numbers. The final score is the total number of correctly drawn symbols within the time limit. The score ranges from a minimum of 0 to a maximum of 135 (the maximum possible items on the WAIS-IV Coding form). Higher values represent a greater number of correctly matched symbols, indicating faster processing speed and better cognitive performance (a better outcome). Lower scores indicate slower processing speed (a worse outcome). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRichard J Holden, PhD
Indiana University
Participant flow
Pre-assignment details
21 participants consented but were not randomized.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 69.35 Years STANDARD_DEVIATION 6.47 |
| Charlson Comorbidity Index (CCI): | 1.09 Scores on a Scale STANDARD_DEVIATION 1.83 |
| Employment Missing | 2 Participants |
| Employment No | 242 Participants |
| Employment Yes, Full Time | 58 Participants |
| Employment Yes, Part Time | 40 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 666 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Highest Level of Education College Degree | 215 Participants |
| Highest Level of Education Grade/Middle/Some High School | 8 Participants |
| Highest Level of Education High School Graduate or GED | 115 Participants |
| Highest Level of Education Masters or other advanced degree | 154 Participants |
| Highest Level of Education Missing/Not reported | 2 Participants |
| Highest Level of Education Some College | 158 Participants |
| Highest Level of Education Trade School | 7 Participants |
| Medication Assistance Missing | 2 Participants |
| Medication Assistance No, I do it myself | 310 Participants |
| Medication Assistance Yes, from a friend or family member | 41 Participants |
| Medication Assistance Yes, from a healthcare professional | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants |
| Race (NIH/OMB) More than one race | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 578 Participants |
| Sex: Female, Male Female | 521 Participants |
| Sex: Female, Male Male | 159 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 342 | 7 / 343 |
| other Total, other adverse events | 13 / 342 | 16 / 343 |
| serious Total, serious adverse events | 96 / 342 | 103 / 343 |
Outcome results
None listed