Alzheimer Disease and Related Dementias (ADRD)NCT05231954
Digital Detection of Dementia (D Cubed) Studies: D2
A study testing Passive Digital Marker for screening for ADRD in people with Alzheimer Disease and Related Dementias (ADRD), run by Indiana University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Alzheimer Disease and Related Dementias (ADRD)
- What is being tested?
- Passive Digital Marker for screening for ADRD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,325 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jul 2022to 5 Jul 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 65 years or older
- At least one visit to primary care practice within the past year
- Ability to provide informed consent
- Ability to communicate in English or Spanish
- Available EHR data from at least the past three years
Who cannot join
- Prior ADRD or mild cognitive impairment diagnosis as determined by ICD-10 code
- Evidence of any history of prescription for a cholinesterase inhibitors or memantine.
- Has serious mental illness such as bipolar or schizophrenia as determined by ICD-10 code
- Permanent resident of a nursing facility
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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.
- Being tested
- Passive Digital Marker for screening for ADRD
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Passive Digital Marker for screening for ADRDOther
Also called Patient reported outcome (QDRS) 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.
| Study group | Role | What they receive |
|---|---|---|
| Annual Well Visit or any other visit to Primary Care Doctor | No intervention | 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) | Experimental | 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. Receives: Other: Passive Digital Marker for screening for ADRD |
| Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) | Active comparator | 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. Receives: Other: Passive Digital Marker for screening for ADRD |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 months after index visit
Secondary outcomes (1)
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
Measured: 12 months after index visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2022
- Study start5 Jul 2022
- Primary completion5 Jul 2024
- Study completion5 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease and Related Dementias (ADRD)Studies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a pragmatic cluster randomized control trial with randomizing clinic and with wavier of consent for human subjects. The data collection is from the EHR. There is no research data collection outside the EHR.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 5,325 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, MALAZ BOUSTANI, Indiana University
- Investigators
- Malaz Boustani, MD, MPH, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05231954
- Sponsor's protocol ID
- 2008372812a
- Other IDs
- R01AG069765-01
- Status last verified
- Aug 2025
- First submitted
- 28 Jan 2022
- Last updated
- 20 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We are collecting clinic based aggregated data.
Publications
Boustani MA, Ben Miled Z, Owora AH, Fowler NR, Dexter P, Puster E, Grout RW, Summanwar D, Erazo SF, Disla S, Coppedge K, Galvin JE. Digital Detection of Dementia in Primary Care: A Randomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2542222. doi: 10.1001/jamanetworkopen.2025.42222.
PubMed 41212562Kleiman MJ, Plewes AD, Owora A, Grout RW, Dexter PR, Fowler NR, Galvin JE, Miled ZB, Boustani M. Digital detection of dementia (D3): a study protocol for a pragmatic cluster-randomized trial examining the application of patient-reported outcomes and passive clinical decision support systems. Trials. 2022 Oct 11;23(1):868. doi: 10.1186/s13063-022-06809-5.
PubMed 36221141
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Digital Detection of Dementia (D Cubed) Studies: D2
- ClinicalTrials.gov ID
- NCT05231954
- Acronym / sponsor ID
- 2008372812a
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,325 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 5 Jul 2022 (actual)
- Primary completion
- 5 Jul 2024 (actual)
- Study completion
- 5 Jul 2024 (actual)
- First posted
- 9 Feb 2022 (actual)
- Results
- Posted 20 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- This is a pragmatic cluster randomized control trial with randomizing clinic and with wavier of consent for human subjects. The data collection is from the EHR. There is no research data collection outside the EHR.
| Arm | Type | Receives |
|---|---|---|
| Annual Well Visit or any other visit to Primary Care Doctor | No intervention | –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) | Experimental | Other: Passive Digital Marker for screening for ADRDPassive 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. |
| Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) | Active comparator | Other: Passive Digital Marker for screening for ADRDPatients 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- 65 years or older
- At least one visit to primary care practice within the past year
- Ability to provide informed consent
- Ability to communicate in English or Spanish
- Available EHR data from at least the past three years
Key exclusion criteria (4 listed)
- Prior ADRD or mild cognitive impairment diagnosis as determined by ICD-10 code
- Evidence of any history of prescription for a cholinesterase inhibitors or memantine.
- Has serious mental illness such as bipolar or schizophrenia as determined by ICD-10 code
- Permanent resident of a nursing facility
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Passive Digital Marker for screening for ADRDAlso: Patient reported outcome (QDRS) for screening for ADRDPatients 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 (PDM), Passive Digital Marker (PDM) + Quick Dementia Rating Scale (QDRS) |
Primary outcome
12-Month Cumulative Incidence of ADRD Diagnoses
Time frame: 12 months after index visit
Any new ADRD case identified (documented in the EHR) within 12 months of the Annual Wellness Visit (index visit).
1 secondary outcome
12-Month Cumulative Incidence of ADRD Services
Time frame: 12 months after index visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41212562Boustani MA, Ben Miled Z, Owora AH, Fowler NR, Dexter P, Puster E, Grout RW, Summanwar D, Erazo SF, Disla S, Coppedge K, Galvin JE. Digital Detection of Dementia in Primary Care: A Randomized Clinical Trial. JAMA Netw Open. 2025 Nov 3;8(11):e2542222. doi: 10.1001/jamanetworkopen.2025.42222.
- Derived from this study: PubMed 36221141Kleiman MJ, Plewes AD, Owora A, Grout RW, Dexter PR, Fowler NR, Galvin JE, Miled ZB, Boustani M. Digital detection of dementia (D3): a study protocol for a pragmatic cluster-randomized trial examining the application of patient-reported outcomes and passive clinical decision support systems. Trials. 2022 Oct 11;23(1):868. doi: 10.1186/s13063-022-06809-5.
- Individual participant dataSharing planned: No. We are collecting clinic based aggregated data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Malaz Boustani, MD, MPH principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Passive Digital Marker for screening for ADRD in people with Alzheimer Disease and Related Dementias (ADRD), run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
12-Month Cumulative Incidence of ADRD Diagnoses (time frame: 12 months after index visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05231954, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2025.