Serum α-Synuclein Associated With Impaired Executive Function in Patients With Obesity, T1D

A study published in the International Journal of Obesity found that α-synuclein could have a role in the impairment of executive function (EF) in children with obesity and those with type 1 diabetes (T1D). Diastolic blood pressure and waist to hip ratio were also parameters associated with an increase in α-synuclein.

A link among obesity, diabetes, and cognitive decline has previously been found, with some studies finding an association among obesity, diabetes, and risk of Alzheimer disease and Parkinson disease. The aim of the current study was to determine if the level of serum α-synuclein in children with obesity or T1D was a biomarker when compared with healthy controls and if it had an association with neurocognitive skills, particularly EF.

Children were recruited from the pediatric hospital Ain Shams University if they were regular attendees of the pediatric diabetes unit and the pediatric obesity clinic. Diagnosis of diabetes was based on the International Society of Pediatric and Adolescent Diabetes 2018 criteria, and obesity was defined as a body mass index (BMI) greater than the 95th percentile for age and gender.

Patients were excluded if they were obese children with T1D, if they had a comorbid neuropsychiatric illness like autism or epilepsy, or had other types of diabetes.

All patients recorded their sociodemographic information and clinical history. Children with T1D were asked about disease duration, insulin therapy, median self-monitoring of blood glucose per week, and history of acute complications. BMI was assessed using World Health Organization recommendations and blood pressure was measured manually.

Serum α-synuclein measurement was obtained with a human enzyme-linked immunosorbent assay kit. Blood samples were collected in the morning after an overnight fast. Estimated glucose disposal rate (eGDR) was used to assess insulin resistance in children with T1D. General intelligence quota was measured using the Stanford-Binet Scale 4th edition, which provides a full-scale IQ. The Barkley Deficits in Executive Functioning Scale–Children and Adolescents was used to assess the deficits in EF with daily life activities.

There were 120 children who participated in this study, with 40 controls, 40 children with obesity, and 40 children with T1D. The mean (SD) age of the control group was 13.3 (2.2) years, 12.7 (3.1) years in the children with obesity, and 13.6 (2.5) years in the children with T1D. The median (IQR) BMI of the children with obesity was 3.25 (2.76-4.31). The mean (SD) eGDR of the children with T1D was 9.4 (1.6). Blood pressure, fasting cholesterol, triglycerides, and low-density lipoprotein were highest in the children with obesity.

Total EF summary score percentile and its subscales were impaired in the groups with obesity and T1D compared with the control group, with the highest score coming from the group with obesity; the self-regulation of emotions score, however, was highest in the group with T1D. The level of serum α-synuclein corresponded with the increased EF summary score percentile, as serum α-synuclein was highest in the group with obesity. Children with T1D had a significantly lower IQ compared with the controls.

There was a positive correlation between serum α-synuclein and total EF percentile and EF symptom count percentile in children with obesity and T1D, respectively. There was also a negative correlation between α-synuclein and total IQ, with children who had higher α-synuclein receiving a lower IQ score.

Serum α-synuclein was also positively correlated with diastolic blood pressure and waist to hip ratio in children with obesity, whereas serum α-synuclein was correlated with duration of disease in children with T1D.

There were some limitations to this study. Causal inferences could not be made due to the cross-sectional design of the study. Generalizability may be limited due to the small number of patients enrolled in the study. Detection of α-synuclein differs from body fluid vs solid tissue.

The researchers concluded that children with obesity and T1D had an increased amount of serum α-synuclein when compared with controls, which is correlated with an impairment in executive function. Serum α-synuclein is a potential biomarker for cognitive affection and neurodegeneration in children with obesity and T1D.

Reference

Salah NY, Taha SI, Hassan S, Abdeen MSE, Hashim MA, Mahmoud R. Metabolism and memory: α-synuclein level in children with obesity and children with type 1 diabetes; relation to glucotoxicity, lipotoxicity and executive functions. Int J Obes. 2022;46:2040-2049. doi:10.1038/s41366-022-01222-z