Resting-state functional connectivity alterations in dementia with Lewy bodies: a systematic review and activation likelihood estimation meta-analysis

Dementia with Lewy Bodies is a neurodegenerative disease characterized by fluctuating cognition, visual hallucinations and parkinsonian features. Resting-state functional MRI has been increasingly used to investigate functional connectivity alterations in this disease, though findings have been inconsistent. This systematic review and meta-analysis aim to comprehensively synthesize existing evidence on connectivity changes in this condition to clarify underlying networks dysfunctions and provide future research directions. We analyzed studies from EMBASE, PubMed and Scopus. Thirteen eligible studies were categorized by methods: seed-based, ROI-to-ROI or Independent Component Analysis. To maintain consistency, we conducted an Activation Likelihood Estimation meta-analysis using the whole-brain Independent Component Analysis studies. Thirteen studies included 730 patients (343 diseased, 387 controls). Widespread connectivity alterations were present across multiple networks, with decreased connectivity in the sensorimotor, temporal, frontoparietal and salience networks. Decreased internetwork connectivity was observed between the default-mode and sensorimotor networks, across left and right visual networks, and between the frontoparietal and other networks. Increased connectivity was also reported within the default-mode network, basal ganglia and thalamus, although findings were mixed. Coordinate-based meta-analysis demonstrated decreased connectivity in the insula, cingulate gyrus, middle frontal gyrus, caudate, lentiform nucleus and putamen (p < 0.001), while no significant clusters were found for increased connectivity. Dementia with Lewy Bodies shows widespread and heterogeneous connectivity disruptions, particularly in motor and attention networks. While the meta-analysis confirmed decreases in select regions, findings of increased connectivity were inconsistent. These findings highlight the need for larger, standardized studies to validate resting-state functional MRI as a biomarker for this disorder.