Clinical trial NCT05002699: Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia
Official title: Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Alzheimer Disease
Dementia
Cognitive Impairment
Mild Cognitive Impairment
Keywords: Biomarkers
Cerebrospinal fluid
Amyloid beta-Peptides
tau Proteins
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Brain Canada
name: Health Canada
name: Michael Smith Foundation for Health Research
name: Women's Brain Health Initiative
name: St. Paul's Foundation
First posted: 2021-08-12
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient participants presenting with suspected preclinical, prodromal and Alzheimer's dementia, and meeting the appropriate use criteria for lumbar puncture and CSF biomarker testing (Shaw et al., 2018), will be enrolled along with their study partner and referring dementia specialist. A dementia specialist is defined as a self-identified physician trained and board-certified in neurology, psychiatry, or geriatric medicine who devotes a substantial proportion (≥ 25%) of patient contact time to the evaluation and care of adults with acquired cognitive impairment or dementia (Johnson et al., 2013).

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 12 months
measure: To describe the participant's experience with Alzheimer's disease CSF biomarker testing.
timeFrame: 6 months
measure: To describe the study partner's experience with Alzheimer's disease CSF biomarker testing.
timeFrame: 6 months
Secondary outcomes:
measure: To assess changes in participant management among various clinical presentations.
timeFrame: 12 months
measure: To assess changes in participant management by clinical disease stage.
timeFrame: 12 months
measure: To assess the impact of Alzheimer's disease core CSF biomarker testing on the change in diagnosis and diagnostic confidence.
timeFrame: 12 months
Other outcomes:
Locations:
city: Prince George
country: Canada
facility: Northern Health
state: British Columbia
city: Vancouver
country: Canada
facility: Providence Health Care
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver Coastal Health
state: British Columbia
city: Victoria
country: Canada
facility: Island Health
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Mari L. DeMarco, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
citation: DeMarco ML, Nguyen Q, Fok A, Hsiung GR, van der Gugten JG. An automated clinical mass spectrometric method for identification and quantification of variant and wild-type amyloid-beta 1-40 and 1-42 peptides in CSF. Alzheimers Dement (Amst). 2020 Jun 30;12(1):e12036. doi: 10.1002/dad2.12036. eCollection 2020.
citation: American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV [Internet]. 4th ed. Washington (DC): American Psychiatric Association; 1994 [cited 2010 Mar 8]. 866 p.
citation: Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, Karlawish JH, Rowe CC, Hedrick S, Pappas V, Carrillo MC, Hartley DM. Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. J Nucl Med. 2013 Jul;54(7):1011-3. doi: 10.2967/jnumed.113.127068. Epub 2013 Jun 10.
citation: McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.
citation: Shaw LM, Arias J, Blennow K, Galasko D, Molinuevo JL, Salloway S, Schindler S, Carrillo MC, Hendrix JA, Ross A, Illes J, Ramus C, Fifer S. Appropriate use criteria for lumbar puncture and cerebrospinal fluid testing in the diagnosis of Alzheimer's disease. Alzheimers Dement. 2018 Nov;14(11):1505-1521. doi: 10.1016/j.jalz.2018.07.220. Epub 2018 Oct 10.