<p>White matter hyperintensities (WMH) are common in older adults and are associated with cognitive disorders. They typically arise from small vessel disease, leading to demyelination and axonal loss. WMH are thus considered markers of cerebrovascular changes. However, other pathophysiological processes can lead to WMH, particularly in Alzheimer’s disease (AD). Understanding the diverse origins of WMH could enhance the diagnosis and treatment of AD patients. We hypothesize that multimodal neuroimaging could help understand the heterogeneity of WMH and pinpoint their specific origin. We included 142 older adults from the community and memory clinic (with an emphasis on patients within the Alzheimer’s continuum), and tested if multimodal neuroimaging signal within regional WMH (including T1w, T2w, ¹⁸F-florbetapir [AV45] and ¹⁸F-fluorodeoxyglucose [FDG] PET), is associated with amyloid load and cognition. We showed that intra-WMH T1w and T2w signal in the parietal and frontal lobes were linked to amyloid status; intra-WMH T2w signal in all regions negatively correlated with amyloid load, while intra-WMH T1w signals in the parietal lobe positively correlated with amyloid load; finally, intra-WMH T1w signal negatively correlated with cognition while T2w and marginally AV45 signals positively correlated with cognition. This study demonstrates the potential of multimodal neuroimaging to unravel the heterogeneity of WMH, which could enhance their interpretation and improve clinical decision-making.</p>