Diagnostic dynamic contrast-enhanced magnetic resonance imaging blood-brain barrier assessment combined with plasma biomarkers for mild cognitive impairment.

Abstract

Background: The role of cerebral microvascular dysfunction in early cognitive impairment and dementia has become increasingly recognized. Furthermore, pathological changes in both Alzheimer's disease and vascular dementia are almost always associated with cerebral hemodynamic deficits.

Aim: To investigate the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) assessment of the blood-brain barrier (BBB) in combination with relevant plasma biomarkers for mild cognitive impairment (MCI).

Methods: This study selected 50 patients with non-amnestic MCI (na-MCI group), 52 patients with amnestic MCI (a-MCI group), and 55 healthy elderly controls (control group). The Chinese version of the Montreal cognitive assessment (MoCA), auditory verbal learning test (AVLT), Hamilton anxiety/depression scale (HAMA/HAMD), and activity of daily living (ADL) scales were used to analyze the characteristics of mental and behavioral symptoms of patients with MCI. The DCE-MRI technique was used to assess the contrast enhancement kinetics. The Patlak model was utilized to analyze the BBB permeability (volume transfer constants). Further, fasting blood was was used to quantify plasma homocysteine (Hcy), β-amyloid protein (Aβ) 40, Aβ42, human phosphorylated tau-181 protein (p-tau181), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) levels, as well as serum neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) concentrations.

Results: The na-MCI and a-MCI groups demonstrated significantly lower MoCA and AVLT-Huashan version scores, and statistically higher HAMA, HAMD, and ADL scores compared to the control group. Moreover, the a-MCI group showed notably higher HAMA, HAMD, and ADL scores compared to the na-MCI group. Cranial MRI results revealed significant disparities in cerebral blood flow in the left and right frontal lobes, temporal lobes, hippocampi, cuneus, precuneus, parietal lobes, basal ganglia, and occipital lobes between the a-MCI and na-MCI groups. Compared to healthy controls, patients with MCI demonstrated a smaller amplitude of hippocampal contrast enhancement kinetics and a slower decay rate, indicating smaller vascular volume and increased BBB permeability. Further, Hcy, p-tau181, ICAM-1, VCAM-1, PAI-1, and NFL levels were substantially higher in the a-MCI group than in the na-MCI group, whereas the Aβ42 level was significantly lower. We did not observe any significant differences in Aβ40 and GFAP levels.

Conclusion: Patients with MCI may have experienced cerebrovascular system changes in the hippocampal region. Disorders associated with changes in cerebral blood supply may begin before pathophysiological changes are visible by imaging, which provides references for the assessment and treatment of patients with cognitive disorders. Further, DCE-MRI provides a noninvasive approach to diagnose subtle BBB leakage associated with cerebrovascular pathology.