Table 5.

Research questions.

Efficacy and clinical impact

1. Are there subgroups with a larger treatment response, and can they be predicted?

2. What is the perspective of patients, care partners and caregivers on treatment outcomes and treatment desirability?

3. What is the effect of treatment on a broader range of patient-reported outcomes, including quality of life and neuropsychiatric symptoms?

4. What are the long-term effects of treatment after 18 months?

ARIA

1. Does the risk of treating APOE ε4 homozygotes outweigh any clinical benefits?

2. Can the risk of ARIA be predicted before treatment?

3. Are there diagnostic biomarkers of ARIA that could be used in place of MRI scans?

4. Are there pharmacological approaches to prevent or treat ARIA?

Subgroup responses

1. Do females benefit from treatment with lecanemab?

2. Is treatment effective in young onset AD (<65 years old)?

3. Is amyloid-beta removal effective in preclinical AD (amyloid-beta positive without symptoms)?

4. Is treatment effective in patients who are frail or have comorbidities?

MRI imaging

1. What is the accuracy and reliability of diagnosing ARIA in routine practice?

2. Can higher resolution, more sensitive SWI be substituted for GRE for determining treatment eligibility and detecting ARIA-H?

3. What is the projected impact of anti-Aβ mAbs use on MRI and PET utilization in Canada?

Organizing clinical care

1. What should be the thresholds for stopping treatment, whether based on time, disease progression, or amyloid status?

2. For patients that stop treatment due to effect removal of amyloid-beta, how quickly does it reaccumulate and should patients be treated again if it does?

3. What is the clinical and safety profile of anti-Aβ mAbs in routine clinical practice?

4. To obviati the need for intravenous infusion, can subcutaneous formulations with equivalent efficacy be developed?

Patient selection

1. Would individuals with mixed disease (e.g., AD plus vascular disease) benefit from treatment?

2. Would persons with atypical clinical syndromes (posterior cortical atrophy, frontal variant, logopenic aphasia) benefit from treatment?

3. Would selecting based on tau markers identify a population with greater treatment benefits?

AD diagnostic markers

1. Can capacity for CSF and PET testing in Canada be expanded to test all the patients that desire anti-Aβ mAbs?

2. Are blood markers of AD accurate enough to be used for prescreening or diagnosis for eligibility for anti-Aβ mAbs?

Role of primary care and access to treatment

1. How can MCI and dementia be diagnosed more accurately and efficiently in primary care?

2. How can patients in remote and rural areas get access to diagnosis and treatment?

3. Can anti-Aβ mAbs be provided to the population without causing disparities?

Potential eligible population

1. What are patient and caregiver preferences for treatment?

2. What is the prevalence of MCI due to AD in Canada?

3. How many patients would be eligible for and select treatment?