Alzheimer disease–related biomarkers and cancer-related cognitive decline: the Thinking and Living with Cancer study

Abstract Purpose We evaluated whether plasma Alzheimer disease (AD)–related biomarkers were associated with cancer-related cognitive decline among older breast cancer survivors. Methods We included survivors aged 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched noncancer control paricipant (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (presystemic therapy) and annually for up to 60 months. Cognition was measured using tests of attention, processing speed, and executive function and learning and memory; perceived cognition was measured by the Functional Assessment of Cancer Therapy-Cognitive Function v3 Perceived Cognitive Impairments. Baseline plasma neurofilament light, glial fibrillary acidic protein, β-amyloid 42 and 40 and phosphorylated tau 181 were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD biomarkers, time, group (survivor vs control participant), and their 2- and 3-way interactions, controlling for age, race, Wide Range 4 Achievement Test Word Reading score, comorbidity, and body mass index; 2-sided P values of .05 were considered statistically significant. Results There were no group differences in baseline AD-related biomarkers except survivors had higher baseline neurofilament light levels than control participants (P = .013). Survivors had lower adjusted longitudinal attention, processing speed, and executive function than control participants starting from baseline and continuing over time (P ≤ .002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except control participants had lower attention, processing speed, and executive function scores with higher glial fibrillary acidic protein levels (P = .008). Conclusion The results do not support a relationship between baseline AD-related biomarkers and cancer-related cognitive decline. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers, and examine other mechanisms and factors affecting cognition presystemic therapy.