Sex-specific age-related changes in glymphatic function assessed by resting-state functional magnetic resonance imaging

The glymphatic system that clears out brain wastes, such as amyloid-β (Aβ) and tau, through cerebrospinal fluid (CSF) flow may play an important role in aging and dementias. However, a lack of non-invasive tools to assess the glymphatic function in humans hindered the understanding of the glymphatic 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 used to measure the glymphatic process and found to correlate with various pathologies of Alzheimer’s disease (AD), including Aβ pathology. Using resting-state fMRI data from a large group of 719 healthy aging participants, we examined the sex-specific changes of the gBOLD-CSF coupling, as a measure of glymphatic function, over a wide age range between 36-100 years old. 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.