Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia

Study Overview
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Brief Summary
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The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT-AD BC) study is an observational, longitudinal cohort study that will examine the impact of cerebrospinal fluid (CSF) testing for core Alzheimer's disease biomarkers on clinical decision making, diagnosis and health system utilization. In addition to data collection from physicians, the study will engage patients and their care partners in assessing the value of biomarker testing. IMPACT-AD BC investigators hypothesize that testing for CSF biomarkers of Alzheimer's disease in individuals with cognitive impairment, as part of routine clinical care, improves clinical management, diagnostic certainty, diagnostic accuracy, and healthcare resource utilization, and that patients and their care partners find the information valuable in planning for the future.

Detailed Description
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The IMPACT-AD BC study is an observational, longitudinal cohort study designed to understand the impact of cerebrospinal fluid (CSF) testing for core Alzheimer's disease biomarkers on clinical decision making, diagnosis, health system utilization, and patients and their care partners. Dementia specialists from multiple sites in the Canadian province of British Columbia will be approached to provide informed consent to participate. When these physicians order Alzheimer's disease CSF biomarker testing as part of routine care (DeMarco et al 2020), their patients will be eligible to participate in the study. Eligible patients (the patient participants) and their study partners (e.g., a family member or care partner) will be approached to provide informed consent to participate. The dementia specialists will provide diagnosis and management plans for their consenting patient participants before and after Alzheimer's disease CSF biomarker results. One year after release of the Alzheimer's disease CSF biomarker results, dementia specialists complete another questionnaire to assess the stability of their responses. In addition to these data, the study will collect patient participant/care partner perspectives on CSF biomarker testing post-results disclosure. Via the IMPACT-AD BC study, the investigators will collect the first data of its kind on the utility of CSF biomarkers in routine care in Canada, with the overall goal of improving care and support systems for individuals living with neurodegenerative disorders.

Official Title
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Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC)

Conditions
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Alzheimer Disease, Dementia, Cognitive Impairment, Mild Cognitive Impairment

Intervention / Treatment
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* Diagnostic Test: Alzheimer's disease CSF biomarkers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is either a dementia specialist, or a patient of a consenting dementia specialist; Patient participant is age 40 and older; Patient participant has a diagnosis verified by a dementia specialist within 24 months of: subjective cognitive decline (Shaw et al., 2018), or mild cognitive impairment or dementia, according to DSM-IV (DSM-IV-TR, 2000) and/or National Institutes of Aging-Alzheimer's Association (Albert et al., 2011; McKhann et al., 2011) criteria; The etiologic cause of cognitive impairment is uncertain after a comprehensive evaluation by a dementia specialist, including general medical and neurological examination, mental status testing including standard measures of cognitive impairment, laboratory testing, and structural neuroimaging; Cognitive disorder is considered to be on the Alzheimer's continuum, including, but not limited to, mild cognitive impairment with suspected Alzheimer's pathology that does not reach the criteria for dementia; Dementia specialist deems that CSF Alzheimer's disease biomarkers are appropriate as per routine clinical care; Patient participant consents to a lumbar puncture for CSF analysis as part of clinical care. Exclusion Criteria: Patient participant has normal cognition; Patient participant lumbar puncture requires imaging guidance; Knowledge of amyloid status, in the opinion of the treating dementia specialist, may cause significant psychological harm or otherwise negatively impact the patient or family; Amyloid status already known to patient or dementia specialist based on prior Aβ positron emission tomography (PET) imaging or previous CSF analysis; Aβ and tau CSF biomarkers ordered solely based on a family history of dementia, presence of apolipoprotein E4 genotype, or as a screening test for asymptomatic individuals; Aβ and tau CSF biomarkers ordered for non-medical purposes (e.g., legal, employment screening, insurance coverage, patient or family member curiosity); Current (i.e., active) patient participation in an anti-amyloid or anti-tau therapeutic trial; Presence of other significant chronic brain disease in patient (e.g., malignant tumor); Patient had symptomatic stroke or transient ischemic attack within the previous 12 months; Life expectancy of patient is less than 24 months based on medical co-morbidities; Lack of caregiver who can provide corroborative information if the patient participant lacks capacity to do so themselves.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Alzheimer's disease CSF biomarkers|Measurement of amyloid beta peptide 1-42, amyloid beta peptide 1-40, and total tau in cerebrospinal fluid.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the impact of Alzheimer's disease core CSF biomarker testing on the management of patients meeting the appropriate use criteria for lumbar puncture and testing. | Determine the percent change between intended management (without biomarkers) and actual patient management (with biomarkers) in a composite measure of at least one of the following: Alzheimer's disease drug therapy; Other relevant drug therapy; Diagnostic procedure, imaging, other biofluid testing; Referral or counselling. | 12 months | 
| To describe the participant's experience with Alzheimer's disease CSF biomarker testing. | Describe the participant's experience with Alzheimer's disease CSF biomarker testing and evaluate the impact of testing on their planning and decision-making via interviews one-month and six-months post-disclosure of CSF biomarker results. | 6 months | 
| To describe the study partner's experience with Alzheimer's disease CSF biomarker testing. | Describe the study partner's experience with Alzheimer's disease CSF biomarker testing and evaluate the impact of testing on their planning and decision-making via interviews one-month and six-months post-disclosure of CSF biomarker results. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess changes in participant management among various clinical presentations. | Describe the association of Alzheimer's disease CSF biomarker testing results with changes in management in individuals, from prodromal to dementia stage, presenting with typical clinical presentations of Alzheimer's disease versus atypical clinical presentations of Alzheimer's disease versus non-Alzheimer's neurodegenerative disorders. | 12 months | 
| To assess changes in participant management by clinical disease stage. | Describe the association of Alzheimer's disease CSF biomarker testing results with changes in management in individuals presenting with mild cognitive symptoms versus dementia. | 12 months | 
| To assess the impact of Alzheimer's disease core CSF biomarker testing on the change in diagnosis and diagnostic confidence. | Determine the percentage change in diagnosis and physician-rated diagnostic confidence from the pre-biomarker time-point to the post-biomarker time-point. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarkers, Cerebrospinal fluid, Amyloid beta-Peptides, tau Proteins