AbstractAimsThe aim of this study was to investigate the associations of enlarged perivascular spaces (EPVS) in the basal ganglia (BG) and centrum semiovale (CSO) with beta‐amyloid (Aβ) and tau deposition in older adults with a diverse cognitive spectrum.MethodsA total of 163 (68 cognitively normal and 95 cognitively impaired) older participants underwent [11C] Pittsburgh compound B and [18F] AV‐1451 PET, and MRI. EPVS in the BG and CSO and other small vessel disease markers, such as white matter hyperintensities, lacunes, and deep and lobar microbleeds, were assessed.ResultsIncreased EPVS in the BG showed a significant association with lower cerebral tau deposition, even after controlling for other small vessel disease markers. Further exploratory analyses showed that this association was significant in cognitively impaired, Aβ‐positive, or APOE4‐positive individuals, but not significant in the cognitively normal, Aβ‐negative, or APOE4‐negative participants. In contrast to EPVS in the BG, EPVS in the CSO did not have any relationship with cerebral tau deposition. In addition, none of the two types of EPVS were associated with cerebral Aβ deposition.ConclusionBrain tau deposition appears to be reduced with increased EPVS in the BG, especially in individuals with cognitive impairment, pathological amyloid burden, or genetic Alzheimer's disease risk.