This study aimed to determine associations between modifiable dementia risk factors (MDRF), across domains mood symptomatology, lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology, with cognition, beta-amyloid (Aβ) and tau, and brain volume. Middle-aged/older adults (n=82) enrolled in a sub-study of the Healthy Brain Project completed self-report questionnaires and a neuropsychological battery. Cerebrospinal fluid levels of Aβ 1–42, total tau (t-tau), and phosphorylated tau (p-tau181) (Roche Elecsys), and MRI markers of hippocampal volume and total brain volume were obtained. Participants were classified as no/single domain risk (≤1 domains) or multidomain risk (≥2 domains). Compared to the no/single domain risk group, the multidomain risk group performed worse on the Preclinical Alzheimer’s Cognitive Composite (d=0.63, p=.005), and Executive Function (d=0.50, p=.016), and had increased p-tau181 (d=0.47, p=.042) and t-tau (d=0.54, p=.021). In middle-aged/older adults, multidomain MDRFs were related to increases in tau and worse cognition, but not Aβ or brain volume. Findings suggest that increases in AD biomarkers are apparent in midlife, particularly for individuals with greater burden, or variety of MDRFs.