Cerebrovascular–CSF coupling measured by broadband near-infrared spectroscopy as a physiological marker of brain aging and Alzheimer’s disease

Introduction Alzheimer’s disease (AD) is strongly associated with cerebrovascular dysfunction and impaired glymphatic clearance. These dysfunctions may precede, contribute to, and interact bidirectionally with AD pathology, highlighting the importance of identifying physiological markers for the early detection of AD. Noninvasive approaches for assessing these processes and identifying early biomarkers remain limited. Cerebrospinal fluid (CSF) plays a central role in clearing neurotoxins from the brain, but current methods for quantifying CSF dynamics are invasive, costly, and not well suited for early detection of AD. Methods Broadband near-infrared spectroscopy (bbNIRS) provides a promising alternative by enabling noninvasive measurement of total hemoglobin concentration (HbT) and CSF-related free-water fluctuations in the prefrontal cortex (PFC). In this study, we quantified cerebrovascular–CSF coupling using two-channel bbNIRS (2bbNIRS) in three groups: healthy young adults (YA; n = 26), healthy older adults (OA; n = 27), and early-stage AD patients ( n = 16). Time series data of 7-min Δ[HbT] and CSF-related Δ[H 2 O] free dynamics were extracted and analyzed within three distinct infraslow oscillatory frequency (endogenic, neurogenic, and myogenic) bands. Linear correlation coefficients and slopes between Δ[HbT] and Δ[H 2 O] free signals were computed to quantify HbT-CSF coupling at each frequency band for each of the three groups, followed by statistical comparisons after Fisher transformation and ANOVA with Bonferroni correction. Results The results showed that (1) HbT-CSF coupling was significantly stronger in the AD group than in healthy OA across all frequency bands, and (2) coupling exhibited clear age dependence, with YA showing the weakest prefrontal HbT-CSF coupling. Discussion These trends may reflect age- and disease-related reductions in cerebrovascular elasticity and intracranial compliance. Enhanced coupling in the AD group may represent an early compensatory response to impaired CSF transport. Overall, this work demonstrates that 2bbNIRS offers a noninvasive, low-cost method for quantifying cerebrovascular-CSF interactions in the human PFC, with promising potential as a physiological marker of brain aging and early AD.