The Cost of Precision: Eligibility Barriers Across Alzheimer's Disease Intervention Classes

The recent arrival of disease-modifying Alzheimer's therapies, lecanemab and donanemab foremost among them, is routinely described as the field's most significant advance in a generation. Less routinely asked is whether the trials that produced this advance were ever built to reach anyone beyond a narrow slice of the Alzheimer's population to begin with. This paper reclassifies an original 200-trial Alzheimer's disease sample, first assembled for a broader monograph comparing global equity in Alzheimer's disease and cancer research, by intervention class rather than by disease stage, and finds that the eligibility barrier problem already documented for Alzheimer's trials generally is not evenly distributed across treatment types. Among the 82 trials, 41% of the sample that could be classified by intervention class, disease-modifying trials targeting amyloid or tau pathology showed a 42.9% biomarker or imaging confirmation requirement, nearly three times the whole-sample rate of 15%, alongside a 78.6% comorbidity exclusion rate and a 71.4% prior-treatment exclusion rate, both well above the 54.0% and 29.0% rates reported across the full Alzheimer's sample. Symptomatic and non-pharmacological trials showed no such elevation on the biomarker dimension, though non-pharmacological trials carried the highest comorbidity exclusion of any intervention class at 82.4%. A parallel classification by disease stage found real but weaker variation, with moderate-to-severe trials showing no biomarker requirement at all, consistent with biomarker confirmation mattering most where a diagnosis is still uncertain. These findings are then read against existing population-based research quantifying just how narrow the disease-modifying eligibility window already is in practice, independent of geography: one prospective analysis found fewer than 15% of real-world individuals with mild cognitive impairment or early Alzheimer's disease would qualify for the pivotal amyloid-lowering antibody trials at all, driven overwhelmingly by cardiovascular disease and anticoagulant use, the same categories this paper's own comorbidity-exclusion finding independently reproduces. Read together, the two results suggest that the newest, most consequential class of Alzheimer's treatment carries an eligibility barrier that is not simply steep everywhere, but steepest exactly where diagnostic and monitoring infrastructure, PET scanners, CSF sampling capacity, specialist neurology access, is already scarcest, with direct implications for how blood-based biomarker rollout and eligibility-criteria reform should be prioritized.