# Should all MCI with Alzheimer’s biological diagnosis receive anti-amyloid therapy?

## TL;DR

The paper discusses whether everyone with mild cognitive impairment and Alzheimer’s biomarkers should receive anti-amyloid therapy, highlighting risks, costs, and the need for better risk assessment.

## Contribution

The paper introduces a framework for risk-stratified treatment using multiple biomarkers and calls for interdisciplinary collaboration to ensure ethical and equitable implementation.

## Key findings

- More than half of MCI patients with amyloid biomarkers do not progress to dementia over long-term follow-up.
- Anti-amyloid therapies have high costs, risks like amyloid-related imaging abnormalities, and uncertain long-term benefits.
- Indiscriminate use of these therapies could harm patients and strain healthcare systems.

## Abstract

Our perspective addresses one of the most pressing and timely debates in contemporary neurology and health policy: whether the recent approval of anti-amyloid monoclonal antibodies for Alzheimer’s disease should extend to all individuals with mild cognitive impairment (MCI; a large population of tens of millions of individuals worldwide mainly represented in Countries with aged population) who test positive for amyloid biomarkers, despite wide variability in prognosis and therapeutic response and the epidemiological demonstration that only about half of them manifest symptoms of dementia. The manuscript highlights three central themes. First, while epidemiological and meta-analytic data confirm that MCI significantly increases the risk of dementia, more than half of affected individuals—many of whom are biomarker-positive for amyloid/tau—do not progress to dementia even over long- term follow-up. Second, recently approved anti-amyloid therapies, although representing a landmark in disease-modifying treatments, carry high costs, non-negligible risks (particularly amyloid-related imaging abnormalities), and uncertain long-term real-world benefits. Third, indiscriminate prescription of these agents risks exposing large numbers of subjects to unnecessary harm while placing unsustainable burdens on healthcare systems. We argue that the field should urgently move to identify and validate accurate and sustainable instruments for risk-stratified treatment pathways, integrating genetic, clinical, neuropsychological, neuroimaging, and fluid biomarker data including risk and resilience factors to refine prognostication. In addition, we call on the scientific community, journals, and policymakers to foster dialog that bridges neurology, geriatrics, bioethics, health economics, and patient advocacy, so that clinical innovation is matched by ethical responsibility and equitable implementation.