Eligibility for Anti-Amyloid Treatment in a Population-Based Cohort Study of Aging
Rioghna Pittock1, Jeremiah Aakre2, Anna Castillo2, Vijay Ramanan1, Clifford Jack3, Prashanthi Vemuri3, David Knopman1, Ronald Petersen1, Jonathan Graff-Radford1, Maria Vassilaki2
1Department of Neurology, 2Department of Quantitative Health Sciences, 3Department of Radiology, Mayo Clinic
Objective:
To apply the aducanumab clinical trials’ eligibility criteria to the Mayo Clinic Study of Aging (MCSA) participants to understand the application of the eligibility criteria and generalizability of this anti-amyloid treatment in Alzheimer’s Disease (AD).
Background:
Aducanumab is a monoclonal antibody targeting amyloid beta. While Alzheimer’s is the most common form of dementia, inclusion and exclusion criteria in clinical trials may limit the number finally eligible for treatment. Understanding treatment generalizability is crucial. The MCSA is a relevant study population because of the clinical phenotyping, detailed medical history, and availability of neuroimaging including amyloid PET.
Design/Methods:
MCSA is a population-based cohort study of cognitive aging in Olmsted County (MN); 2152 MCSA participants (aged 50-90) had MRI and amyloid PET. We applied available inclusion and exclusion criteria from EMERGE and ENGAGE to assess how many participants would be eligible for aducanumab.
Results:
Participants with cognitive impairment (MCI; n=366) or mild dementia (n=30) were evaluated for inclusion, a subset of 240 (60%) participants with cognitive impairment had a positive amyloid PET scan (SUVR ≥ 1.48). 96 of the 240 (40%) participants fulfilled the trial inclusion criteria (i.e., age 50 to 85 years, ≥ 6 years of education, CDR global = 0.5, and MMSE ≥ 24). The mean age (standard deviation) was 78.4 (5.1) years, 56 (58.3%) were male, and 52 (55.3%) were apolipoprotein E ε4 positive. Exclusion criteria such as history of cancer (25 (26.0%)), neuroimaging abnormalities (33 (34.4%)), and uncontrolled hypertension (17 (17.7%)) further narrowed the eligible patients from 96 to 28 (29.2%).
Conclusions:
Eligibility criteria eliminated 88.3% of the MCI/mild dementia participants with positive PiB PET, mainly due to other chronic conditions and neuroimaging findings. Findings highlight major concerns on the eligibility for treatments excluding those with common conditions to the typical older patient populations.