INTRODUCTION: This retrospective study investigates whether exposure to levodopa/carbidopa (LA/CA) medication is associated with modified Alzheimer's disease (AD) trajectories. METHODS: Multivariate analysis used cerebrospinal fluid (CSF) biomarker information included in the National Alzheimer's Coordinating Center Uniform Data Set for subjects with normal cognition (NC), mild cognitive impairment (MCI), and dementia (DE). Survival analyses examined the progression to MCI/DE and death events. RESULTS: LA/CA use is associated with lower levels of CSF amyloid beta, phosphorylated-tau (p-tau) and total-tau. After adjusting for age, sex, and apolipoprotein E (APOE) ε4 allele presence, that effect was quantified by negative coefficients of the fitted linear mixed models: p-values < 0.01 in all cases except for p-tau in the MCI subgroup (p = 0.02). No similar effects were identified for other antiparkinsonians. Exposure to LA/CA decreased the progression from MCI to DE (p = 0.03). DISCUSSION: The identified association between LA/CA exposure, AD biomarkers, and progression deserves further investigation in controlled clinical trials. HIGHLIGHTS: LA/CA is associated with lower levels of CSF biomarkers for AD. This effect is not observed when other antiparkinsonian drugs are used. LA/CA is also associated with delayed progression to dementia by AD patients with MCI.