The coupling of global brain activity and cerebrospinal fluid flow as a potential predictive marker of brain amyloid-β accumulation

Area of Science:

• Neuroscience
• Biomarkers
• Neuroimaging

Background:

• Impaired cerebrospinal fluid (CSF) clearance is linked to amyloid-β (Aβ) buildup in Alzheimer's disease (AD).
• Global brain activity-CSF flow coupling (gBOLD-CSF coupling), assessed via resting-state fMRI, quantifies CSF clearance capacity, with higher values signifying weaker coupling.
• The predictive value of gBOLD-CSF coupling for Aβ accumulation is not well-established.

Purpose of the Study:

• To investigate if reduced gBOLD-CSF coupling precedes Aβ accumulation in individuals who are cognitively normal and Aβ-negative.
• To evaluate the potential of gBOLD-CSF coupling as a predictive marker for conversion to Aβ positivity.

Main Methods:

• A longitudinal observational study utilizing data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
• Analysis included 16 cognitively normal, initially Aβ-negative participants (7 fast-converters, 9 slow-converters).
• gBOLD-CSF coupling was computed using Pearson correlation between global BOLD and CSF inflow signals; correlations with Aβ biomarkers and cognitive scores were examined.

Main Results:

• Fast-converters exhibited significantly higher gBOLD-CSF coupling values, indicating weaker CSF clearance (Cohen's d = 1.76, p = 0.012).
• gBOLD-CSF coupling positively correlated with annual increases in Aβ-PET SUVR (r = 0.594, p = 0.054).
• Weaker coupling negatively correlated with Montreal Cognitive Assessment (MoCA) scores (r = -0.654, p = 0.021).

Conclusions:

• Diminished gBOLD-CSF coupling precedes the accumulation of Aβ in the brain.
• This metric shows promise as an early predictive marker for amyloid conversion in Alzheimer's disease.
• Further research is recommended to establish clinical thresholds for early intervention strategies in AD prevention.