Structural Volumetric Alterations in Parkinson's Disease With Mild Cognitive Impairment

Parkinson's disease with mild cognitive impairment (PD-MCI) is a critical dementia prodrome, but its structural neuropathology remains incompletely defined. While hippocampal atrophy is established, volumetric changes in other subcortical structures are poorly characterized.

To perform the first comprehensive meta-analysis quantifying gray matter volume alterations across six subcortical regions in PD-MCI.

A systematic search of PubMed, Web of Science, Embase, and Cochrane (inception-June 2025) for studies reporting MRI volumetric data comparing PD-MCI and cognitively normal PD (PD-NC) was done. Random-effects models calculated pooled weighted mean differences (WMDs) with 95% confidence intervals (CIs). Heterogeneity (I²), publication bias, sensitivity analyses, and meta-regression were assessed.

PD-MCI showed significant bilateral atrophy versus PD-NC in the hippocampus (total WMD = -0.65 cm³), thalamus, putamen, and amygdala, alongside right-lateralized globus pallidus atrophy (WMD = -0.08 cm³). Bilateral caudate nuclei volumes were preserved. Sensitivity analyses confirmed robustness. Meta-regression identified segmentation tools and country as sources of left hippocampal heterogeneity (p < 0.05). No publication bias was detected.

PD-MCI exhibits a distinct subcortical atrophy signature involving limbic-striato-thalamic networks, with right globus pallidus atrophy as a novel lateralized biomarker. Network-based imaging paradigms are advocated, requiring standardized protocols and longitudinal validation.

Identifier PROSPERO (CRD420251051275).