Clara Trompeta

Objectives: Social Cognition (SC) can be impaired in Parkinson’s Disease (PD), yet its longitudinal evolution relative to cognitive status is unclear. This study examined whether SC deficits in PD patients suffers different changes based on baseline cognitive status and cognitive progression. Methods: In this observational study 48 non‐demented PD patients (32 with normal cognition [PD‐CN], 16 with mild cognitive impairment [PD‐MCI]), and 22 healthy controls (HC) were assessed at baseline and after three years. SC was assessed for facial emotion recognition (FER), affective and cognitive Theory of Mind (ToM), and social behavior. A comprehensive neuropsychological battery provided domain-specific z-scores. Cognitive classification followed MDS Level II criteria. Adjusted linear mixed models examined SC changes. Delta scores for SC tasks and z-score changes were correlated. Results: At baseline, PD-MCI patients scored lower on cognitive ToM than PD-CN and HC, with no significant group differences in affective ToM, FER, or social behavior. Over three years, PD-MCI patients experienced a significant decline in cognitive ToM compared to PD-CN and HC, while affective ToM and emotion recognition declined only relative to HC. The converters (n = 16) to a worse cognitive state (PD-CN to PD-MCI or PD-MCI to PDD) showed lower baseline cognitive ToM and steeper decline than stable patients. All SC changes correlated with visuospatial ability; affective ToM also correlated with memory, language and attention, and FER with memory and executive function. Conclusions: Cognitive ToM declines in parallel with cognitive deterioration in PD, while remaining stable in PD-CN. SC measures may help identify patients at higher risk of cognitive decline.

Background: Apathy, defined as a quantitative reduction in goal-directed activity, is a non-motor manifestation that can be present in Parkinson's disease (PD). It seems to be a risk factor for conversion to dementia (PDD) in this population. Amyloid-β deposition also predicts progression to PDD. Objective: We aimed to investigate whether PD patients with apathy showed higher amyloid burden than those without, as well as how these features may influence the rate of progression to dementia. Methods: We conducted an observational cross-sectional and longitudinal study. Forty-eight PD patients were recruited, including 20 with apathy and 28 without it according to the Starkstein Apathy Scale. They underwent clinical and cognitive evaluations and [ ¹⁸ F]-Flutemetamol PET. The neuropsychological assessment was repeated after 3 years. The predictive value of apathy and amyloid burden for conversion was assessed via logistic regression. Longitudinal trajectories across neuropsychological tests were modeled with linear mixed-effects. Results: Patients with apathy showed worse performance on several cognitive domains. Using disease duration and global cognition Z-score as covariates, amyloid burden was higher in apathetic vs. non-apathetic patients, mainly in the frontal and temporal cortices. Non-apathetic patients did not have regions with higher amyloid burden in comparison with apathetic patients. After 3 years’ follow-up, the conversion rate to worse cognitive state was significantly higher in apathetic (47.4%) vs. non-apathetic (12.0%) patients (p < 0.05). Logistic regression showed that amyloid burden, but not apathy, predicted 3-year cognitive conversion (χ² = 9.95, p < 0.05). Conclusions: Apathetic patients exhibit greater amyloid burden and higher cognitive deterioration over time than their non-apathetic counterparts.

Mild cognitive impairment (MCI) is a relevant non-motor feature in Parkinson’s disease (PD). Social cognition (SC) is a cognitive domain that refers to the ability to decode others’ intentions and to guide behavior in social contexts. We aimed to compare SC performance in mid-stage PD patients compared to a healthy population and according to their cognitive state. Fifty-two PD patients were classified as being cognitively normal (PD-CN) or having mild cognitive impairment (PD-MCI) following the Movement Disorder Society (MDS) Level II criteria. SC assessment included facial emotion recognition (FER), affective and cognitive theory of mind (ToM), and self-monitoring (RSMS test). Twenty-seven age-matched healthy controls (HC) were enrolled. PD-MCI patients scored worse than HC on affective and cognitive ToM task scores. Only cognitive ToM scores were significantly lower when compared with the PD-MCI and PD-CN groups. We found no differences in FER or self-monitoring performance. There were significant correlations between cognitive ToM and executive functions, memory, language, and attention, whereas FER and affective ToM correlated with memory. Our findings indicates that SC is normal in cognitively unimpaired and non-depressed mid-stage PD patients, whereas a decline in affective and cognitive ToM is linked to the presence of MCI.

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.