Exploring preclinical signs and markers for neurodegenerative diseases via indirect testing of blood-brain barrier stability

Mild cognitive impairment (MCI) arises from inflammation and internal damage occurring within the brain and its surrounding tissues. By the time the various MCI symptoms and systemic inflammation present clinically, significant damage to the blood-brain barrier (BBB) has already occurred. Given current understanding and treatment options, little can be done to reverse the damage; thus, treatment is primarily reactive. This study seeks to evaluate patients presenting with known dementia risk factors (i.e., medication history, relevant pre-existing medical conditions, genetics, etc.) and potential pre-clinical serum-based biomarkers (i.e., GFAP, NfL, IL-6, MMP-3, etc.) identified through a comprehensive literature review. Utilizing a combination of ultrasound (US) study of the brachial artery, arterial spin labeling magnetic resonance imaging (ASL MRI), and blood tests for common biomarkers of neurovascular unit degradation (i.e., astrocytic death, inflammation, neuronal death, etc.), this study aims to indirectly monitor the onset and progression of inflammatory and/or destructive processes at the BBB. We expect to find whether there is a correlation between decreased systemic arterial compliance and diminished glymphatic clearance, potentially revealing the efficacy of our methods in presymptomatic detection of neurodegenerative diseases in a clinical setting.