Exploring regional BOLD fluctuations to understand the pathophysiology of mild cognitive impairments in individuals with Parkinson's disease.

INTRODUCTION

This study investigated whether z-standardized fractional amplitude of low-frequency fluctuations (zfALFF) and z-standardized regional homogeneity (zKcc ReHo) capture functional brain alterations associated with mild cognitive impairment (MCI) in Parkinson's disease (PD) and their relationships with clinical and cognitive measures.

METHODS

Forty-seven participants (16 healthy controls [HC], 31 with PD) were recruited, with MCI identified using Litvan's criteria. After preprocessing, 45 participants were analyzed: HC (n = 15), PD with normal cognition (PD-NC, n = 12), and PD with MCI (PD-MCI, n = 18). Voxelwise zfALFF and zKcc ReHo maps were examined using nonparametric regression (PALM) for group differences and associations with disease duration, medication dose (LEDD), motor severity (UPDRS-III ON), and cognitive domains, adjusting for demographic and brain volume factors (FDR p < 0.05).

RESULTS

PD-MCI showed reduced zfALFF and zKcc ReHo in frontoparietal and midline regions linked to executive and default mode networks, while PD-NC exhibited increased activity and synchrony in subcortical-frontal and occipital areas. In PD-MCI, LEDD correlated positively with both metrics in frontostriatal and occipitotemporal regions; UPDRS-ON correlated positively with zKcc ReHo. In PD-NC, UPDRS-ON correlated positively with zfALFF in attention-related areas. Cognitive analyses indicated executive attention coupling in PD-NC and memory-related changes in PD-MCI.

CONCLUSIONS

zfALFF and zKcc ReHo reveal stage-specific alterations in neural activity and synchrony in PD that reflect disease severity and cognitive vulnerability, highlighting their promise as complementary neuroimaging biomarkers.