Basic Science and Pathogenesis

Area of Science:

• Neuroimaging
• Neurology
• Cerebrovascular diseases

Background:

• Cerebral amyloid angiopathy (CAA) involves amyloid-beta deposition in brain blood vessels, increasing hemorrhage and dementia risk, and is common in Alzheimer's disease (AD).
• Impaired glymphatic clearance and reduced cerebrovascular reactivity (CVR) are hypothesized contributors to amyloid-beta deposition.
• Previous studies have not investigated these factors concurrently in patients with CAA or AD.

Purpose of the Study:

• To investigate glymphatic function and CVR in patients with CAA and AD.
• To explore the relationship between glymphatic function and CVR in these patient groups.

Main Methods:

• MRI including diffusion tensor imaging along the perivascular space (DTI-ALPS) and BOLD imaging with hypercapnic challenge was performed on 43 CAA patients, 16 AD patients, and 53 healthy controls (HC).
• Glymphatic function was quantified using DTI-ALPS, and CVR was measured as the percentage change in BOLD signal per mmHg increase in end-tidal CO2.
• Statistical analyses adjusted for age, sex, and hypertension.

Main Results:

• Patients with CAA and AD exhibited significantly lower DTI-ALPS and CVR compared to HC (p < 0.001).
• No significant association was found between DTI-ALPS and grey matter, white matter, or global CVR in the studied groups.
• CAA and AD participants were predominantly male, older, and had higher hypertension rates than HC.

Conclusions:

• Reduced glymphatic function in CAA and AD is associated with cerebrovascular changes.
• Vascular contributions to impaired glymphatic function in CAA and AD may be linked to altered vasomotion and blood flow pulsatility, not solely dilation capacity.