White Matter Microstructural Underpinnings of Mild Behavioral Impairment in Parkinson's Disease

Abstract Background Patients with Parkinson's disease (PD) experience changes in behavior, personality, and cognition that can manifest even in the initial stages of the disease. Previous studies have suggested that mild behavioral impairment (MBI) should be considered an early marker of cognitive decline. However, the precise neurostructural underpinnings of MBI in early‐ to mid‐stage PD remain poorly understood. Objective The aim was to explore the changes in white matter microstructure linked to MBI and mild cognitive impairment (MCI) in early‐ to mid‐stage PD using diffusion magnetic resonance imaging (dMRI). Methods A total of 91 PD patients and 36 healthy participants were recruited and underwent anatomical MRI and dMRI, a comprehensive neuropsychological battery, and the completion of the Mild Behavioral Impairment‐Checklist. Metrics of white matter integrity included tissue fractional anisotropy (FAt) and radial diffusivity (RDt), free water (FW), and fixel‐based apparent fiber density (AFD). Results The connection between the left amygdala and the putamen was disrupted when comparing PD patients with MBI (PD‐MBI) to PD‐non‐MBI, as evidenced by increased RDt ( η 2 = 0.09, P = 0.004) and both decreased AFD ( η 2 = 0.05, P = 0.048) and FAt ( η 2 = 0.12, P = 0.014). Compared to controls, PD patients with both MBI and MCI demonstrated increased FW for the connection between the left orbitofrontal gyrus (OrG) and the hippocampus ( η 2 = 0.22, P = 0.008), augmented RDt between the right OrG and the amygdala ( η 2 = 0.14, P = 0.008), and increased RDt ( η 2 = 0.25, P = 0.028) with decreased AFD ( η 2 = 0.10, P = 0.046) between the right OrG and the caudate nucleus. Conclusion MBI is associated with abnormal microstructure of connections involving the orbitofrontal cortex, putamen, and amygdala. To our knowledge, this is the first assessment of the white matter microstructure in PD‐MBI using dMRI. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.