Introduction: Vascular factors increase the risk of Alzheimer's disease (AD). We investigated the associations between such factors, longitudinal AD cerebrospinal fluid biomarkers, and cognition. Methods: 433 cognitively normal participants were classified into four biomarker groups using their baseline amyloid (A+/−) and tau status (T+/−). 184 participants had undergone serial cerebrospinal fluid collection. Frequencies of risk factors and the Framingham Risk Score (FRS) were compared, and we tested the influence of risk factors on change in biomarker concentrations and cognition. Results: The absence of obesity, presence of hypertension, and a high FRS were associated with an increase in tau levels, particularly in A+T+ individuals. Risk factors were not associated with amyloid. Depression was associated with higher cognitive scores, whereas high FRS was associated with lower scores and a faster decline. Discussion: Our results demonstrate that vascular risk factors may enhance neurodegeneration but not amyloid accumulation in preclinical AD.