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

BACKGROUND

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.

OBJECTIVE

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

METHODS

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.

RESULTS

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.

CONCLUSION

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.

SYSTEMATIC REVIEW REGISTRATION: Identifier PROSPERO (CRD420251051275).