Anti-amyloid drugs: Integrated clinical pathways for treating older patients with frailty and dementia

The introduction of anti-amyloid therapies for Alzheimer's disease challenged current care models, particularly for older adults with frailty. The potential low efficacy of anti-amyloid drugs in these patients may be attributed to chronic inflammation, impaired repair mechanisms, and multisystem dysregulation. Neuropathological studies suggested that the accumulation of common brain pathologies may contribute to progressive physical frailty in older age. At present, there is no certified diagnostic-therapeutic pathway governing the management of patients eligible for anti-amyloid treatment, regardless of the presence of frailty. In the present view point, we argued that frailty should not be treated as an exclusion criterion for anti-amyloid therapies, but as a stratification dimension requiring integrated, multidimensional clinical pathways. Without embedding frailty assessment into eligibility, monitoring, and outcome evaluation, the real-world implementation of disease-modifying therapies risks being ineffective, inequitable, and ethically problematic. Here, we proposed to integrate frailty assessment with biological and neuroimaging criteria to promote ethical, equitable, and clinically-feasible access to disease-modifying treatments in real-world settings.