Objective: To identify sex-specific white-matter (WM) correlates of neuropsychological measures in Parkinson’s disease (PD) with mild cognitive impairment (MCI).

Background: Neuropsychological measures of executive function and processing speed are poorer in PD-males than in PD-females. Furthermore, higher-order diffusion MRI (dMRI) measures such as Diffusion kurtosis imaging (DKI) model have revealed sex-specific WM disorganization in PD. However, whether there is a sex-specific correlation between neuropsychological scores and DKI-derived measures is yet unknown. Establishing the correlation between neuropsychological scores and MRI measures might help to understand the neuroanatomical basis of poorer sex-specific functional scores in PD.

Method: Forty healthy controls (HC) and 37 PD patients were recruited of which 22 PD patients were diagnosed with MCI based on results of a comprehensive neuropsychological test battery. Isotropic (1.5mm³) 71-directions dMRI was acquired at 3-shells (b=500s/mm², 1000s/mm², and 2500s/mm²) with a 3T Siemens scanner. DKI model was fitted for every participant, and respective DKI-derived measures were estimated. WM skeleton was derived using tract-based-spatial-statistics. Each group was split into male and female before statistical comparisons. Nonparametric statistical comparisons using permutation analysis of linear models with age, education, and handedness as confounding variables were conducted for observing the correlation between DKI-derived measures and neuropsychological scores testing for executive functions (Trails Making Test-B (TMT-B)) and processing speed (Trails Making Test-A (TMT-A)). Significance was established at family-wise-error-corrected (p_corr) <0.05.

Results: Handedness and all cognitive assessments revealed a statistically significant difference between the groups (Table.1). TMT-A in HC, RAVLT in PD-MCI, and TMT-B in PD-NC revealed sex-specific differences (Table.2). A significantly higher correlation in PD-MCI-Males as compared to PD-MCI-Females was obtained between BVMT and axonal kurtosis (AK); as well as mean kurtosis (MK) and axonal water fraction (AWF), respectively. PD-MCI-Females also showed a significantly positive correlation between BVMT, and AK; as well as MK and AWF, respectively.

Conclusion: DKI model is sensitive to understand the neuroanatomical underpinnings of sex-specific neuropsychological scores in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/sex-specific-white-matter-correlates-of-neuropsychological-measures-in-parkinsons-disease-with-mild-cognitive-impairment/