AbstractBackgroundThe Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score, a validated tool estimating dementia risk, has been suggested to be associated with accelerated brain atrophy but the imaging biomarkers and AD pathologies remains to be elucidated. We aimed to explore the relationships of CAIDE score with cognition and AD‐related brain changes, including beta‐amyloid (Aβ) deposition and glucose metabolism and the mediation effect of the WMH on these associations.MethodA sample of 1,285 participants underwent CAIDE dementia risk assessment, of these, 958 individuals had a CAIDE score of less than or equal to 8. Memory and executive function were used to measure cognitive performance. We analyzed data using linear mixed‐effects and mediation.ResultCAIDE score was significantly associated with WMH volume, and also had significant association with Aβ deposition, AD‐metabolism, and memory and executive function. WMH volume mediated 6.04%, 12.87%, 6.93% and 7.92% of the total association of CAIDE score with memory, executive function, FDG‐PET and AV45‐PET, respectively.ConclusionMemory, executive function, AD‐metabolism and Aβ deposition are strongly associated with dementia risk. Besides, the associations could be mediated by WMH volume and whether this represents a causal relationship remains to be determined.