Sex-specific age-related differences in cerebrospinal fluid clearance assessed by resting-state functional magnetic resonance imaging

Cerebrospinal fluid (CSF) flow may assist the clearance of brain wastes, such as amyloid-β (Aβ) and tau, and thus play an important role in aging and dementias. However, a lack of non-invasive tools to assess the CSF dynamics-related clearance in humans hindered the understanding of the relevant changes in healthy aging. The global infra-slow (<0.1 Hz) brain activity measured by the global mean resting-state fMRI signal (gBOLD) was recently found to be coupled by large CSF movements. This coupling has been found to correlate with various pathologies of Alzheimer's disease (AD), particularly Aβ pathology, linking it to waste clearance. Using resting-state fMRI data from a group of 719 healthy aging participants, we examined the sex-specific differences of the gBOLD-CSF coupling over a wide age range between 36–100 years of age. We found that this coupling index remains stable before around age 55 and then starts to decline afterward, particularly in females. Menopause may contribute to the accelerated decline in females.