An interventional study of Passive Digital Marker for screening for ADRD in Alzheimer Disease and Related Dementias (ADRD), sponsored by Indiana University. Completed at 1 site in United States. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2025-08-20.
Sponsored by Indiana University · Not applicable, Interventional, and Screening
The specific aim of the pragmatic trial is to evaluate the practical utility and effect of the PDM, the QDRS, and the combined approach (PDM + QDRS) in improving the annual rate of new documented ADRD diagnosis in primary care practices.
Alzheimer's disease and related dementias (ADRD) negatively impact millions of Americans with an annual societal cost of more than $200 million.1 Currently, half of Americans living with ADRD never receive a diagnosis.2-7 For those who do, the diagnosis often occurs two to five years after the onset of symptoms.6-9 As stated by the National Institute on Aging (NIA) (RFA-AG-20-051) "The inability to diagnose and treat cognitive impairment results in prolonged and expensive medical care" and "early detection could help persons with dementia and their care partners plan for the future". Furthermore, if the development of disease modifying therapeutics for ADRD is successful, this may require the use of such therapeutics at a very early stage of ADRD.1 However, the current approaches of using cognitive tests or biomarkers for early detection of ADRD are not scalable due to their low acceptance, their invasive nature, their cost, or their lack of accessibility in rural or underserved areas. Thus, the NIA called out for the development of low cost, effective, and scalable approaches for early detection of ADRD (RFA-AG-20-051).
In response to the RFA-AG-20-051 call for the "validation, and translation of screening and assessment tools for measuring cognitive decline a pragmatic cluster-randomized controlled comparative effectiveness (NIH Stage IV) trial will be executed in Eskenazi Health in central Indiana and one additional replicated pragmatic trial among patients from diverse rural, suburban and urban primary care practices in south Florida. The pragmatic trial will incorporate the Passive Digital Marker (PDM) and the Quick Dementia Rating Scale (QDRS) within the Medicare paid Annual Wellness Visit (AWV) for a cohort of patients from practices across the two independent sites, with practices randomized in each pragmatic trial to one of the 3 arms (AWV alone, the AWV with PDM and the PDM and the QDRS).
Quick Dementia Rating Scale (QDRS)- is a validated patient reported outcome (PRO) tool.
Passive Digital Marker (PDM) - is a Machine Learning (ML) algorithm which can predict ADRD one year and three years prior to its onset by using routine care electronic health record (EHR) data. The algorithm was trained using structured and unstructured data from three EHR datasets: diagnosis (Dx), prescriptions (Rx), and medical notes (Nx). Individual algorithms derived from each of the three datasets were developed and compared to a combined one that included all three datasets.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 5,325 is above the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Indiana University is the lead sponsor of 958 studies on the registry; 200 are open to participants now.
Of its 142 completed or terminated interventional studies of FDA-regulated products, 112 (79%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Annual Well Visit or any other visit to Primary Care Doctor: This is the usual care arm. Electronic Health Record Data for patients from the clinics randomized to usual care will be collected for comparison with the other 2 arms. Patients from these primary care clinics must have had a visit to their doctor either as an annual well visit (AWV) or any other type of visit. These clinics will not have to do anything for the study but run their business as usual without altering anything.
Passive Digital Marker (PDM): Electronic Health Record Data from those clinics randomized to PDM will be run through the PDM, a machine learning algorithm which can predict ADRD one year and three years prior to its onset.
Other: Passive Digital Marker for screening for ADRD
Patients in the primary care clinics randomized to PDM+QDRS will have Electronic Health Record Data of their patients run through the PDM, a machine learning algorithm which can predict ADRD one year and three years prior to its onset. In addition, patients from these clinics will have their patients complete the QDRS, a validated patient reported outcome (PRO) tool. This combined approach will assess the value of early detection of ADRD and if the annual well visit can overcome the barriers related to early detection of ADRD.
Other: Passive Digital Marker for screening for ADRD
Patients in the primary care clinics randomized to PDM+QDRS will have Electronic Health Record Data of their patients run through the PDM, a machine learning algorithm which can predict ADRD one year and three years prior to its onset. In addition, patients from these clinics will have their patients complete the QDRS, a validated patient reported outcome (PRO) tool. This combined approach will assess the value of early detection of ADRD and if the annual well visit can overcome the barriers related to early detection of ADRD.
Also known as: Patient reported outcome (QDRS) for screening for ADRD
12-Month Cumulative Incidence of ADRD Diagnoses
Any new ADRD case identified (documented in the EHR) within 12 months of the Annual Wellness Visit (index visit).
Time frame: 12 months after index visit
12-Month Cumulative Incidence of ADRD Services
The secondary outcome measures is receipt of any services related to cognitive diagnostic assessment in the post Annual Wellness Visit (index) period that providers may order to diagnose or exclude ADRD. Specifically, the metrics of diagnostic assessment are evaluated as proportions of patients with a record of 1 or more of: * Laboratory tests for TSH, serum B12, folate, or syphilis; individually or combined at any point during the 90 days after index * Neuropsychological testing, including testing by psychologist or physician, technician administrator, computer, or other providers during the 12 months after index date * Brain imaging testing (computed tomography, magnetic resonance imaging, positron emission tomography, magnetic resonance angiogram) of the head and neck, brain, or skull during the 12 months after index date * Medications approved for management of ADRD (cholinesterase inhibitors, memantine) during the 12 months after index date
Time frame: 12 months after index visit
D2 trial was launched at 9 clinics on July 5, 2022 (3 clinics in each study arm). D2 trial was completed in July 2024. The D2 trial deployed the Passive Digital Marker (PDM) on 5,325 older patients who were eligible and enrolled to receive primary care services within one of the 9 randomized clinics.
| Milestone | Annual Well Visit or Any Other Visit to Primary Care Doctor | Passive Digital Marker (PDM) | Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) |
|---|---|---|---|
| Started | 1724 | 1300 | 2301 |
| Completed | 1724 | 1300 | 2301 |
| Not completed | 0 | 0 | 0 |
Any new ADRD case identified (documented in the EHR) within 12 months of the Annual Wellness Visit (index visit).
| Number of new ADRD cases | Annual Well Visit or Any Other Visit to Primary Care Doctor | Passive Digital Marker (PDM) | Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) |
|---|---|---|---|
| 12-Month Cumulative Incidence of ADRD Diagnoses | 213 | 134 | 355 |
The secondary outcome measures is receipt of any services related to cognitive diagnostic assessment in the post Annual Wellness Visit (index) period that providers may order to diagnose or exclude ADRD. Specifically, the metrics of diagnostic assessment are evaluated as proportions of patients with a record of 1 or more of: * Laboratory tests for TSH, serum B12, folate, or syphilis; individually or combined at any point during the 90 days after index * Neuropsychological testing, including testing by psychologist or physician, technician administrator, computer, or other providers during the 12 months after index date * Brain imaging testing (computed tomography, magnetic resonance imaging, positron emission tomography, magnetic resonance angiogram) of the head and neck, brain, or skull during the 12 months after index date * Medications approved for management of ADRD (cholinesterase inhibitors, memantine) during the 12 months after index date
| Participants with ADRD related servicess | Annual Well Visit or Any Other Visit to Primary Care Doctor | Passive Digital Marker (PDM) | Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) |
|---|---|---|---|
| 12-Month Cumulative Incidence of ADRD Services | 879 | 636 | 1366 |
Collected over 12-Months of follow-up after index visit (enrollment date). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Annual Well Visit or Any Other Visit to Primary Care Doctor | 26/1,724 (1.5%) | 561/1,724 (32.5%) | 0/1,724 (0%) |
| Passive Digital Marker (PDM) | 7/1,300 (0.5%) | 398/1,300 (30.6%) | 0/1,300 (0%) |
| Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) | 25/2,301 (1.1%) | 816/2,301 (35.5%) | 0/2,301 (0%) |
| Event | Annual Well Visit or Any Other Visit to Primary Care Doctor | Passive Digital Marker (PDM) | Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) |
|---|---|---|---|
| Positive for PDM and had PCC visitGeneral disorders | 561/561 | 398/398 | 816/816 |
| Positive for PDM and had ER visitGeneral disorders | 243/561 | 175/398 | 392/816 |
| Positive for PDM and had NEW Dementia DiagnosisGeneral disorders | 87/561 | 70/398 | 186/816 |
| Positive for PDM and had HospitalizationGeneral disorders | 88/561 | 65/398 | 148/816 |
| Positive for PDM and had Memory clinic visitGeneral disorders | 33/561 | 33/398 | 62/816 |
| Positive for PDM and had NEW significant incapacity DiagnosisGeneral disorders | 35/561 | 29/398 | 41/816 |
| Positive for PDM and had NEW Depression DiagnosisGeneral disorders | 31/561 | 18/398 | 32/816 |
| Positive for PDM and had NEW Suicidal Ideation DiagnosisGeneral disorders | 2/561 | 1/398 | 3/816 |
* At least 65 years old as of date of data pull. * At least 3 years of EHR data available as of date of data pull. * Alive as of date of data pull. * No prior ADRD, MCI, bipolar, or schizophrenia diagnosis as determined by ICD-10 code. * No evidence for any history of cholinesterase inhibitors or memantine prescription." Enrolled patients include only those who: * Meet the above eligibility criteria * Have at least one visit to a randomized clinic during the study period.
| Age, Continuous(years) | Annual Well Visit or Any Other Visit to Primary Care Doctor | Passive Digital Marker (PDM) | Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) | Total |
|---|---|---|---|---|
| Mean | 71 ± 6 | 71 ± 6 | 71 ± 6 | 71 ± 6 |
| Sex/Gender, Customized(Participants) | Annual Well Visit or Any Other Visit to Primary Care Doctor | Passive Digital Marker (PDM) | Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) | Total |
|---|---|---|---|---|
| Sex/Gender — Female | 1036 | 827 | 1449 | 3312 |
| Sex/Gender — Male | 688 | 473 | 852 | 2013 |
| Race (NIH/OMB)(Participants) | Annual Well Visit or Any Other Visit to Primary Care Doctor | Passive Digital Marker (PDM) | Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 9 | 12 | 9 | 30 |
| Asian | 10 | 13 | 14 | 37 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 986 | 605 | 1336 | 2927 |
| White | 575 | 471 | 743 | 1789 |
| More than one race | 104 | 157 | 157 | 418 |
| Unknown or Not Reported | 40 | 42 | 42 | 124 |
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Plan to share: No — We are collecting clinic based aggregated data.
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