Association of the DTI-ALPS index with motor and non-motor symptoms in Parkinson’s disease with postural instability/gait difficulty: a diffusion tensor MRI study

To explore brain perivascular fluid diffusivity dynamics indirectly applying diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to elucidate its relationship between motor and non-motor symptoms in Parkinson’s disease with postural instability/gait difficulty (PIGD).

105 PD patients (categorized into PIGD and non-PIGD subgroups) and 51 healthy control participants (HCs) received brain MRI examinations with DTI and clinical evaluations. Statistical comparisons of DTI-ALPS indices were performed between groups. Associations involving DTI-ALPS indices, motor scores, cognitive function, and sleep quality were examined using partial correlation and mediation analyses.

Compared to HCs, PD subgroups exhibited notably reduced left-hemispheric DTI-ALPS index (PIGD: p = 0.006; non-PIGD: p = 0.013). A lower right-hemispheric index was observed exclusively within PIGD group relative to HCs (p = 0.040). With covariates adjusted, left DTI-ALPS index showed inverse association with Unified Parkinson’s Disease Rating Scale III (r=-0.347, p = 0.023, p-FDR = 0.046) and PIGD score (r=-0.451, p = 0.002, p-FDR = 0.008), and positive correlation with Frontal Assessment Battery (r = 0.451, p = 0.002, p-FDR = 0.008) scores. After adjustment for education, left ALPS index significantly mediated the association between PIGD score and FAB score, with a significant indirect effect (a*b=-0.140, 95% CI -0.278 to -0.032).

The results indicate that impaired perivascular diffusivity, is more pronounced in PIGD subtype and is markedly linked to motor symptoms intensity and cognitive abilities. DTI-ALPS index may present a possible neural substrate mediating the interplay between motor/non-motor manifestations in PIGD subtype.