Meta-analysis shows PD-MCI patients have significant atrophy in hippocampus, thalamus, putamen, amygdala and right-lateralized globus pallidus compared with cognitively normal PD, while caudate volumes are preserved.

Identifies a reproducible subcortical imaging signature that could serve as a biomarker for early cognitive decline and trial enrichment in PD, but offers limited direct mechanistic or therapeutic leads for drug discovery.

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).