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Reduced DTI-ALPS Index Mediates Neuropsychiatric Symptoms in Coronary Artery Disease: Evidence for Cardiac-Glymphatic
Yanlin Tang1, Dong Lu2, Wen Sun3
1Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China (Y.T., L.R., J.Z., Y.L., P.W.).
Insights
Coronary artery disease patients show reduced brain glymphatic function, measured by DTI-ALPS, linked to cognitive and mood issues. This brain clearance pathway may partially explain cardiac-brain symptom associations.
Area of Science:
- Neuroimaging
- Cardiovascular Science
- Glymphatic System Research
Background:
- Coronary artery disease (CAD) is linked to cognitive and neuropsychiatric dysfunction, but underlying mechanisms are unclear.
- The glymphatic system, a brain waste clearance network influenced by cardiac function, may offer a mechanistic explanation.
- This study investigates the role of perivascular diffusivity in CAD-related neurological symptoms.
Purpose of the Study:
- To determine if perivascular diffusivity, assessed by Diffusion Tensor Imaging-based Analysis of Longitudinal/Perfusion-weighted Signals (DTI-ALPS), differs between CAD patients and controls.
- To examine the correlation between DTI-ALPS indices, CAD severity, and associated cognitive and neuropsychiatric symptoms.
- To evaluate the impact of revascularization on DTI-ALPS and symptoms.
Main Methods:
- A cross-sectional study involving 90 CAD patients and 90 matched controls, with a 7-day follow-up post-revascularization.
- Diffusion Tensor Imaging (DTI) MRI was used to calculate DTI-ALPS indices, measuring periventricular water diffusivity.
- Cognitive function, fatigue, depression, and cardiac disease severity were assessed using standardized scales and myocardial perfusion imaging.
Main Results:
- CAD patients exhibited significantly reduced DTI-ALPS indices compared to controls (P=0.001).
- Lower DTI-ALPS correlated with poorer cognitive screening performance and increased symptom severity (P<0.01).
- Reduced DTI-ALPS statistically accounted for 14.7-16.8% of the association between cardiac disease and symptoms. DTI-ALPS improved post-revascularization.
Conclusions:
- Reduced periventricular diffusivity (DTI-ALPS) is associated with CAD and neuropsychiatric symptoms.
- The glymphatic system represents a potential cardiac-brain pathway linking CAD to neurological dysfunction.
- Further prospective studies are needed to validate these findings and explore therapeutic implications.
Rationale And Objectives:
Coronary artery disease is associated with cognitive and neuropsychiatric dysfunction through mechanisms that remain poorly understood. The glymphatic system-a cardiac-driven brain clearance network-may provide a mechanistic link. This study examined whether perivascular diffusivity DTI-ALPS differs between coronary disease patients and controls, correlates with disease severity and symptoms, and responds to revascularization.
Methods:
This cross-sectional study with seven-day post-revascularization follow-up enrolled 90 coronary artery disease patients and 90 matched controls. DTI-ALPS indices were calculated from 3.0 T MRI to assess periventricular water diffusivity. Cognitive function (Mini-Mental State Examination, Montreal Cognitive Assessment), fatigue (Fatigue Severity Scale), and depression (Hamilton Depression Rating Scale) were evaluated. Cardiac disease severity was quantified using myocardial perfusion imaging. Bootstrap mediation analysis examined whether DTI-ALPS statistically accounted for cardiac-symptom associations.
Results:
Coronary artery disease patients demonstrated reduced DTI-ALPS indices compared to controls (1.28±0.21 vs 1.38±0.18, P=0.001, Cohen's d=0.52). DTI-ALPS correlated with cognitive screening performance (r=0.298-0.341, P<0.01) and symptom severity (r=-0.278 to -0.325, P<0.01). Mediation analysis revealed that reduced DTI-ALPS statistically accounted for 14.7-16.8% of cardiac-symptom associations (all bootstrap 95% confidence intervals excluded zero, P<0.05). DTI-ALPS demonstrated dose-response relationships with diseased vessels and myocardial perfusion deficits. Following revascularization, DTI-ALPS increased (P=0.013) alongside trends toward mood improvement, although neuropsychological screening measures did not reach statistical significance.
Conclusion:
Reduced periventricular diffusivity assessed by DTI-ALPS is associated with both coronary artery disease and neuropsychiatric symptoms, statistically accounting for a modest proportion of their association. These cross-sectional findings suggest potential cardiac-brain clearance pathway connections that require prospective validation.
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