<scp>MRI</scp> ‐based surrogates of brain clearance in narcolepsy type 1

Brain clearance involves the drainage of waste molecules from the brain, a process that is suggested to be amplified during sleep. Recently proposed MRI-based methods attempt to approximate human brain clearance with surrogate measures. The current study aimed to explore whether two brain clearance surrogates are altered in narcolepsy. We processed diffusion-weighted and functional resting-state images to extract two surrogates: Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS index), and dBOLD-CSF coupling. Both measures were analysed in 12 drug-free, awake people with narcolepsy type 1 and 11 age- and sex-matched controls, as well as in relation to clinical features. We also assessed the correlation between the DTI-ALPS index and dBOLD-CSF coupling. The DTI-ALPS index and dBOLD-CSF coupling amplitude did not show significant differences between narcolepsy and controls, nor significant relations with the severity of excessive daytime sleepiness. We found a significant correlation between dBOLD-CSF coupling and sleep efficiency, as well as a significant correlation between the DTI-ALPS index and dBOLD-CSF coupling. The hypothesis of altered brain clearance in narcolepsy type 1 is not supported by evidence from the current study. The two surrogates correlated with each other, suggesting that both offer different perspectives from the same underlying physiology. Yet, the suitability of the surrogates as brain clearance markers remains debatable. Whereas DTI is not exclusively sensitive to perivascular fluid, dBOLD-CSF coupling is reflecting large-scale CSF motion. Future work should explore other surrogate markers, preferably during sleep, to better understand the possible role of altered brain clearance in narcolepsy type 1 symptomatology.