Moderating effects of uric acid and sex on cognition and psychiatric symptoms in asymmetric Parkinson's disease.

BACKGROUND: Non-motor symptoms are an important early feature of Parkinson's disease (PD), encompassing a variety of cognitive and psychiatric symptoms that seem to manifest differently depending on motor symptom asymmetry. Different factors, such as uric acid (UA) and sex, seem to influence cognitive and psychiatric expression in PD, however their interplay remains to be better understood. METHODS: Participants taking part in the Parkinson's Progression Marker Initiative were studied based on the side of motor symptom asymmetry and sex. Three-way interaction modeling was used to examine the moderating effects of sex and UA on cognitive functions and psychiatric symptoms. RESULTS: Significant three-way interactions were highlighted at 1-year follow-up between motor symptom asymmetry, UA and sex for immediate and long-term memory in female patients exhibiting predominantly left-sided motor symptoms, and for processing speed and sleepiness in female patients exhibiting predominantly right-sided motor symptoms. No significant interactions were observed for male patients. Moreover, female patients exhibiting predominantly right-sided motor symptoms demonstrated lower serum UA concentrations and had overall better outcomes, while male patients with predominantly right-sided motor symptoms demonstrated particularly poor outcomes. CONCLUSIONS: These findings suggest that in the earliest stages of the disease, UA and sex moderate cognitive functions and psychiatric symptoms differently depending on motor asymmetry, holding important clinical implications for symptom management in patients.

Parkinson's disease is characterized by motor symptoms that usually manifest in an asymmetrical fashion. Given this motor symptom asymmetry, it is possible to distinguish patients that exhibit predominantly right-sided motor symptoms from those that exhibit predominantly left-sided motor symptoms. Patients also often develop non-motor symptoms, such as cognitive and psychiatric complaints. Recent studies have found that non-motor symptoms can manifest differently depending on motor symptom asymmetry. Furthermore, different factors, such as uric acid, a natural antioxidant in the human body, and the patient's sex seem to influence cognitive and psychiatric manifestations, however their interplay remains to be better understood. The present study aimed to examine the interactions between motor symptom asymmetry, serum uric acid and patient's sex on the manifestation of cognitive and psychiatric symptoms. Using regression models, it was found that at 1 year from diagnosis, uric acid and sex moderated cognitive and psychiatric symptoms differently according to motor symptom asymmetry. Indeed, female patients with predominantly left-sided motor symptoms had better memory performances with lower concentrations of serum uric acid, whereas female patients with predominantly right-sided symptoms presented better psychomotor speed and less sleepiness with higher concentrations of uric acid. Moreover, female patients with predominantly right-sided motor symptoms had overall better outcomes, while male patients with predominantly right-sided motor symptoms demonstrated particularly poor clinical outcomes. These findings suggest that in the earliest stages of the disease, uric acid and sex moderate cognitive and psychiatric symptoms differently depending on motor asymmetry, holding important clinical implications for symptom management in patients.

Biomarkers and non-motor symptoms as a function of motor symptom asymmetry in early Parkinson's disease.

INTRODUCTION: The longitudinal trajectories of cognitive-neuropsychiatric symptoms from the early stages of Parkinson's disease, as a function of motor symptom asymmetry at the onset of the disease, remain to be fully explored. Moreover, the relationship to biomarkers warrants further investigation. METHODOLOGY: Non-motor and biospecimen data from 413 patients with Parkinson's disease, dissociating predominantly left-sided motor symptoms patients (n = 179), predominantly right-sided motor symptoms patients (n = 234), and matched healthy controls (n = 196), were extracted from the Parkinson's Progression Marker Initiative database during a 3-Year follow-up. Non-parametric and conservative corrections for multivariate comparisons were carried out on neuropsychiatric and biomarker data. RESULTS: A decline for global cognitive efficiency scores in predominantly right-sided motor symptoms patients was observed, whereas depressive and anxiety symptoms were greater overtime for predominantly left-sided motor symptoms patients. Biomarker analysis revealed that predominantly right-sided patients expressed decreased levels of total-tau and phospho-tau over time, while left-sided patients didn't differ from healthy controls. CONCLUSION: From the early course of the disease, the existence of different clinical phenotypes is proposed, associated to emerging evidences of distinct pathological pathways and a left-hemispheric vulnerability for cognitive decline.

Impacts of an Interdisciplinary Developmental Follow-Up Program on Neurodevelopment in Congenital Heart Disease: The CINC Study.

Objectives: This study investigates the impact of an early systematic interdisciplinary developmental follow-up and individualized intervention program on the neurodevelopment of children with complex congenital heart disease (CHD) who required cardiac surgery. Study Design: We prospectively enrolled 80 children with CHD: 41 were already followed at our neurocardiac developmental follow-up clinic from the age of 4 months, while 39 were born before the establishment of the program and therefore received standard health care. We conducted cognitive, motor, and behavioral assessments at 3 years of age. We used one-way multivariate analyses of variance to compare the neurodevelopmental outcome of both groups. Results: Between-group analyses revealed a distinct neurodevelopmental profile with clinically significant effect size (P < 0.001, partial η2 = 0.366). Children followed at our clinic demonstrated better receptive language performances (P = 0.048) and tended to show higher scores on visuo-constructive tasks (P = 0.080). Children who received standard health care exhibited greater performances in working memory tasks (P = 0.032). We found no group differences on global intellectual functioning, gross and fine motor skills, and behaviors. Referral rates for specific remedial services were higher in patients followed at our neurocardiac clinic compared to the historical cohort (P < 0.005). Conclusions: Overall, the impact of the developmental follow-up and individualized intervention program on neurodevelopmental outcomes remains subtle. Nevertheless, results, although limited by several factors, point toward an advantage for the children who took part in the program regarding receptive language skills over children who received standard health care. We hypothesize that group differences may be greater with growing age. Further research involving larger cohorts is needed to clearly assess the effectiveness of neurocardiac developmental follow-up programs at school age.