Background Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood–brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD. Objective Here, we report a prospective, single‐arm, nonrandomized, proof‐of‐concept, phase I clinical trial (NCT03608553 amended) in PD with dementia to test the safety and feasibility of striatal BBB opening in PD patients. Methods Seven PD patients with cognitive impairment were treated for BBB opening in the posterior putamen. This was performed in two sessions separated by 2 to 4 weeks, where the second session included bilateral putamina opening in 3 patients. Primary outcome measures included safety and feasibility of focal striatal BBB opening. Changes in motor and cognitive functions, magnetic resonance imaging (MRI), 18F‐fluorodopa (FDOPA), and β‐amyloid PET (positron emission tomography) images were determined. Results The procedure was feasible and well tolerated, with no serious adverse events. No neurologically relevant change in motor and cognitive (battery of neuropsychological tests) functions was recognized at follow‐up. MRI revealed putamen BBB closing shortly after treatment (24 hours to 14 days) and ruled out hemorrhagic and ischemic lesions. There was a discrete but significant reduction in β‐amyloid uptake in the targeted region and no change in FDOPA PET. Conclusions These initial results indicate that FUS‐mediated striatal BBB opening is feasible and safe and therefore could become an effective tool to facilitate the delivery of putative neurorestorative molecules in PD. © 2022 International Parkinson and Movement Disorder Society.

Theory of mind (ToM) is a social cognitive skill that involves the ability to attribute mental states to self and others (what they think (cognitive ToM) and feel (affective ToM)). We aim to provide an overview of previous knowledge of ToM in Parkinson’s disease (PD). In the last few years more attention has been paid to the study of this construct as a non-motor manifestation of PD. In advanced stages, both components of ToM (cognitive and affective) are commonly impaired, although in early PD results remain controversial. Executive dysfunction correlates with ToM deficits and other cognitive domains such as language and visuospatial function have also been related to ToM. Recent studies have demonstrated that PD patients with mild cognitive impairment show ToM deficits more frequently in comparison with cognitively normal PD patients. In addition to the heterogeneity of ToM tests administered in different studies, depression and dopaminergic medication may also be acting as confounding factors, but there are still insufficient data to support this. Neuroimaging studies conducted to understand the underlying networks of cognitive and affective ToM deficits in PD are lacking. The study of ToM deficit in PD continues to be important, as this may worsen quality of life and favor social stigma. Future studies should be considered, including assessment of the patients’ cognitive state, associated mood disorders, and the role of dopaminergic deficit.