Screening for Anti-amyloid Treatment Eligibility Using Digital Cognition and Blood-based Biomarkers

Официальное название

A Cohort Study on Screening for Anti-amyloid Treatment Eligibility Using Digital Cognition and Blood-based Biomarkers

Обзор

This study evaluates a diagnostic screening solution for Alzheimer's disease (AD) using digital cognitive assessments and blood-based biomarkers. The aim is to reduce time-to-treatment for patients who may benefit from disease-modifying therapy (DMT). The study involves 500 patients referred to the MoCA Clinic in Montreal. Clinical stages will be assessed using digital tools from MoCA Test Inc. (MoCA Cognition), and biological stages via blood biomarkers. Data collected includes demographics, cognitive scores, health questionnaires, biomarker levels, and neurologist-determined eligibility for DMT. The study will result in an algorithm to support diagnostic triage and estimate the efficiency and equity of a fast-track diagnostic pathway. Exploratory endpoints include validation of self-administered digital tools, health-economic estimates, and predictors of cognitive decline.

Подробное описание

This study will evaluate a diagnostic screening solution based on clinical and biological stages of Alzheimer's disease (AD) ("Study"). The clinical stages will be screened using the digital tools from MoCA Test Inc. ("MoCA Cognition"). The biological stages will be screened using blood-based biomarkers ("BBM"). Based on the results of this Study, we will establish efficient and equitable criteria for diagnostic triage. The Study will result in an algorithm that can assist in assigning patients into a fast-track diagnostic pathway to determine if they are eligible or not for AD treatment with a disease modifying therapy ("DMT").

Primary objective: To develop and evaluate a diagnostic screening solution based on blood-based biomarkers and digital measures of cognition that could reduce the time-to-treatment for patients who are candidates for AD treatment with a disease modifying therapy.

Primary endpoint: Detailed cohort description of patients referred to the memory clinic MoCA Clinic Inc. ("MoCA Clinic"). This includes: (1) demographic characteristics; (2) cognitive screening scores measured by a digital MoCA via the MoCA score and XpressO application; (3) biomarker levels including PrecivityAD2 and MTBR; (4) the proportion of DMT candidates determined by a neurologist, (5) the causes and frequencies of why patients are not eligible for AD treatment (6) the number of diagnostic follow-up tests required after screening (MRI, PET/CSF), (7) the baseline referral times for future comparison against the fast-track pathway and (8) the time-until-diagnosis.

Secondary endpoints: Based on the primary endpoints, we will estimate the potential benefits of a diagnostic screening solution. This includes an estimation of the number of patients that would potentially miss out on the treatment window in the current diagnostic workflow.

Exploratory endpoints: (1) Validation of a self-administered digital version of the MoCA test ("MoCA Solo") compared to the paper MoCA test, (2) Evaluation of MoCA Solo as digital biomarker within the screening algorithm, (3) Health-economic estimation of the number and costs of follow-up tests at different levels of specificity, (4) The role of age, sex and education on the performance of the screening solution, (5) Prediction of time until patient would progress to moderate dementia based on baseline MoCA score and age, (6) Description of participant's history of symptoms and healthcare usage, (7) Correlation between the patient-centered version and the clinician versions of the Amyloid Treatment Screening Tool (ATST), (8) Evaluate the correlation between the MoCA Brain Health Questionnaire (MBHQ) score and participant diagnosis, (9) Evaluate the effect of the addition of MTBR results into screening algorithm.

Participants: Study population will include 500 patients who have been referred to the MoCA Clinic, including both new patients and existing patients. Based on prior referrals, we anticipate 60% female, 55-90 years, 80% French / 20% English, approximately 20% subjective cognitive decline (SCD), 60% mild cognitive impairment (MCI) and 20% mild dementia.

Study Location: The study is conducted as a single-center study with patients from the Montreal area. Patients will be enrolled at the MoCA Clinic where full informed consent will be obtained.

Study Visits: In the active study period, two MoCA Clinic visits will be planned within 1-3 months: Visit 1 includes data collection feasible at a primary care physician: digital cognitive assessments, blood sample collection and amyloid-treatment screening test. Visit 2 includes cognitive assessment, data collection and diagnosis typical for a neurological visit. After the blood sample is analyzed, the prediction of diagnosis and eligibility for DMT will be made using our algorithm. After the active study period, at 6 months, information from the medical records will be reviewed to evaluate clinical follow-up.

This study is supported by an independent research grant from Eli Lilly Canada Inc.

Вмешательства

• Диагностический тест Digital MoCA
  A digital version of the Montreal Cognitive Assessment used to evaluate cognitive function. Administered on a tablet at Visit 1 or Visit 2 (randomized).
• Диагностический тест XpressO
  A digital cognitive pre-screening tool used to screen for cognitive function. Administered on a tablet at Visit 1.
• Диагностический тест MoCA
  The standard paper-baed Montreal Cognitive Assessment used to evaluate cognitive function. Administered at Visit 1 or Visit 2 (randomized), opposite the digital MoCA.
• Диагностический тест Blood-based Biomarkers (BBM)
  Participants provide a blood sample that is analyzed for Alzheimer's disease-related biomarkers, including PrecivityAD2 and MTBR. These biomarkers are used to assess the biological stage of disease and support diagnostic triage and eligibility assessment for disease-modifying therapy (DMT)
• Другое Amyloid Treatment Screening Tool (ATST)
  A questionnaire administered to assess eligibility for amyloid-targeted therapies. Both clinician and patient-centered versions are used.
• Другое MoCA Brain Health Questionnaire (MBHQ)
  A questionnaire designed to capture participants' physical health, emotional well-being, diet, exercise, and social engagement as it relates to cognitive health. Responses are used as part of exploratory analyses to evaluate associations with cognitive status and Alzheimer's disease diagnosis.
• Другое MoCA Medical Questionnaire
  A structured questionnaire administered to participants to gather information on their medical history, including prior diagnoses, medications, and other health conditions. This data helps to contextualize cognitive symptoms and support diagnostic decision-making in the study.
• Другое Functional Activities Questionnaire+ (FAQ+)
  A questionnaire designed to assess the participant's ability to perform daily activities, providing insights into their functional status and cognitive impairment. It is a longer version of the original FAQ questionnaire. It is used as part of the screening and exploratory analysis to better understand the relationship between functional abilities and Alzheimer's disease progression.

Первичные конечные точки

• Time to diagnosis [Срок оценки: From enrollment to 6-month follow-up]

Вторичные конечные точки (1)

• Benefit of Diagnostic Screening [Срок оценки: Baseline to 6-month follow-up]

Критерии участия

Критерии включения

• Must be referred to the MoCA Clinic; including both new patients and existing patients who have been seen >1 year ago
• Present with cognitive impairment or cognitive complaints.
• Must have the ability to understand the purpose and risk of the Study and provide informed consent.
• Must have an identified study partner (informant/care partner), who has frequent and sufficient contact with the participant to be able to provide accurate information about the participant's cognitive and functional abilities. The study partner must be available by phone to provide information to the study staff about the participant and agrees to attend one in-person visit at the MoCA Clinic which requires partner input. The study partner should be available for the duration of the study.

Критерии исключения

• An established diagnosis (other than AD), that is a cause for a candidate's cognitive impairment (e.g. substance abuse, cerebrovascular conditions, Lewy body dementia, fronto-temporal dementia, recent head trauma).
• Blood donation (1 unit) within 1 month prior to Study screening.
• Inability to comply with requirements to complete essential components of the Study (e.g. visual impairment, severe kidney disease or ongoing kidney treatment)
• Patients already enrolled in any clinical trial for AD at time of Study screening
• Other unspecified reasons that, in the opinion of the Principal Investigator, or MoCA Clinic and Institute, make the candidate unsuitable for enrolment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Канада · 1 центр

• MoCA Clinic and Institute — Greenfield Park

Публикации

• Klil-Drori S, Bodenstein KC, Sun S, Kojok L, Gruber J, Ghantous Y, Cummings J, Nasreddine Z. Montreal Cognitive Assessment (MoCA) XpressO: Validation of a digital self-administered cognitive prescreening tool. J Am Geriatr Soc. 2024 Aug;72(8):2516-2522. doi: 10.1111/jgs.18902. Epub 2024 Apr 1. PMID 38558263

Идентификаторы

NCT: NCT07041450 · : BBM-01-2025

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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