The role of cortical microstructural changes on longitudinal accumulation of tau and cognitive decline in at risk older adults

Non‐invasive diffusion‐weighted imaging (DWI) to assess brain microstructural changes via cortical mean diffusivity (cMD) was recently shown to be cross‐sectionally associated with tau in cognitively‐normal older adults (Rodriguez‐Vieitez et al., Mol. Psych. 2021), suggesting that it might be an early marker of neuronal injury. However, the impact of cMD on longitudinal accumulation of tau pathology is currently unknown. Moreover, APOE‐e4 — the strongest genetic risk factor for sporadic AD — has been shown to be related to tau aggregation (Therriault et al.,JAMA Network 2019) and cognitive impairment in older adults. Here, we investigated whether cMD at baseline can predict longitudinal accumulation of tau as well as cognitive decline in cognitively‐normal adults with and without an APOE‐e4.