A-76: When Biomarkers and Cognition Disagree: Clinical Implications of Amyloid Positivity Without Cognitive Impairment

Abstract

Objective: Advances in amyloid biomarkers, including positron emission tomography and cerebrospinal fluid or blood-based assays, have made it possible to detect Alzheimer’s disease pathology earlier. However, there are increasing cases in which biomarker positivity does not align with neuropsychological findings. Patients may demonstrate intact cognitive functioning or present without a typical amnestic pattern. This case series highlights these discrepancies and illustrates how multiple contributing factors can influence clinical presentation and complicate diagnostic decision-making. Method/Data Selection: Four older adults (ages 73–84) were completed outpatient neuropsychological evaluation forsubjective cognitive concerns. All demonstrated positive amyloid biomarkers. Clinical histories included cerebrovascular illness, mood symptoms, hearing loss, and family history of Alzheimer’s disease. One patient underwent repeat evaluation one year later. In one case, anti-amyloid treatment (lecanemab) was recommended. Available neuroimaging and medical data were reviewed. Results/Data Synthesis: Neuropsychological findings were largely normal, but with mild weaknesses in attention and executive functioning in some cases. None demonstrated an amnestic profile. One showed low visual memory likely secondary to poor visuoconstruction. One patient showed no memory decline over one year. Conclusions: These cases highlight that amyloid biomarker positivity does not necessarily correspond to current cognitive impairment or an amnestic memory profile. In some individuals, amyloid deposition may reflect a preclinical or risk state, with cognitive changes emerging later. Findings underscore the importance of integrating biomarker, cognitive, and clinical data and caution against assuming impairment based on biomarker positivity alone. Importantly, individuals may meet biological criteria for Alzheimer’s disease without clinical evidence of related cognitive decline, underscoring the need to avoid premature diagnostic labeling and guide treatment decisions.