White Matter Disease is Associated with Widespread Grey Matter Atrophy in APOE4 non‐carriers with Early‐Stage Dementia

The APOE‐ε4 (APOE4) allele and cerebrovascular disease (CVD), represented by surrogate MRI measures involving white matter hyperintensities (WMH) are key dementia risk factors [Tosto et al.,2015; Mahley et al.,2006]. They relate to grey matter volume (GMV) and cognitive decline, and demonstrate increased occurrence with lowered age of dementia onset [Boyle et al.,2016; Brickman et al.,2014]. Whether APOE4 is a key effect modifier in the relationship between WMH and GMV needs further exploration. Therefore, we examined independent and interactive effects of WMH and APOE4 on GMV and cognition in cognitively unimpaired (CU) and early‐stage dementia (ESD) participants. We hypothesized that participants with higher WMH load would demonstrate worse GMV atrophy and greater cognitive impairment, especially among APOE4 carriers.