Approved Research

Unraveling the Heterogeneity of White Matter Hyperintensity Pathophysiology through Spatial Patterns

Lay summary

White matter hyperintensities (WMH) are common abnormalities seen on brain MRIs of older adults. WMH are a major marker of cerebral small vessel disease (CSVD), a leading cause of strokes and dementia worldwide. However, WMH are not specific for CSVD. WMH are frequently seen in cognitively normal individuals but also occur due to Alzheimer's disease (AD), making it difficult to distinguish which disease process is predominant and predicting its impact on cognitive and general health of individuals who develops WMH during their lifetime. We previously used machine learning to analyze large amounts of brain MRIs and identified different locations (spatial patterns) of WMH that can distinguish between different causes of WMH. We propose a series of studies to examine the relationship between genetic, health factors, and blood-based biomarkers with the different WMH spatial patterns using data from the UK Biobank. This project will allow exploration of new disease mechanisms related to WMH development, and improve understanding of AD and CSVD pathobiology. The ability to better distinguish between vascular and non-vascular (AD-related) WMH at an individual level also has profound implications on both etiology-based diagnosis of dementia and developing personalized therapeutic strategies for AD and related dementias.