Beyond memory: leveraging CSF biomarkers in all MCI patients ahead of anti-amyloid therapies

In the era of anti-amyloid (Aβ) monoclonal antibodies (AMABs), with the recent marketing authorization granted for lecanemab by European Medicines Agency (EMA), randomized clinical trial selection criteria typically include memory impairment detection. In a cohort of patients with Mild Cognitive Impairment (MCI), we observed a non-biunivocal relationship between Aβ pathology and memory deficits, with Aβ pathology present even in patients with atypical clinical presentations. This suggests that using MCI, regardless of the presence of memory impairment, as the sole general criteria along with amyloid pathology biomarkers, could expand the pool of eligible patients. The presence of patients with non-amnestic MCI and underlying Alzheimer’s Disease (AD) pathology makes a timely biomarker-based diagnosis necessary, as they may be considered eligible for treatment with AMABs according to current prescribing guidelines, even in the absence of memory impairment. However, it remains unclear whether, for such patients, the potential efficacy of AMABs actually outweighs the risks associated with treatment.