Brain network connectivity and dementia risk: a bidirectional Mendelian randomisation perspective.

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Dementia is associated with disruptions in resting-state functional brain networks.
• The precise relationships between these network disruptions and dementia subtypes are not fully understood.

Purpose of the Study:

• To investigate associations between resting-state functional MRI (rs-fMRI) phenotypes and various dementia subtypes.
• To explore bidirectional relationships using Mendelian randomization.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) analyses were performed.
• Summary statistics from 191 rs-fMRI phenotypes and five dementia types were utilized.
• Forward MR assessed rs-fMRI effects on dementia risk; reverse MR evaluated dementia impact on rs-fMRI.

Main Results:

• Forward MR identified seven rs-fMRI phenotypes associated with dementia risk.
• Enhanced default mode network connectivity correlated with reduced Alzheimer's disease risk.
• Increased default mode and central executive network connectivity linked to lower vascular dementia risk.
• Reverse MR showed dementia subtypes influencing rs-fMRI phenotypes, including limbic and default mode network alterations.

Conclusions:

• Functional network connectivity patterns are associated with dementia risk.
• Findings may inform biomarker discovery and preventive strategies for dementia.
• Further validation in longitudinal and experimental studies is needed to confirm clinical relevance.