Body mass index, systemic inflammation and cognitive performance in adolescents: A cross-sectional study.

BACKGROUND: Excessive body weight has been related to lower cognitive performance. One of the mechanisms through which excess body weight may affect cognition is inflammation. HYPOTHESIS: Our hypothesis is that both body mass index (BMI) and circulating levels of inflammatory biomarkers will be negatively related to cognitive performance. DESIGN: Cross-sectional study. SETTING: Users of the public health centres of the Consorci Sanitari de Terrassa (Terrassa, Spain) between 2010 and 2017 aged 12-21 years. PARTICIPANTS: One hundred and five adolescents (46 normoweight, 18 overweight, 41 obese). MEASUREMENTS: Levels of high sensitivity C-reactive protein, interleukin 6, tumour necrosis factor α (TNFα) and fibrinogen were determined from blood samples. Cognitive performance was evaluated and six cognitive composites were obtained: working memory, cognitive flexibility, inhibitory control, decision-making, verbal memory, and fine motor speed. A single multivariate general lineal model was used to assess the influence of the four inflammatory biomarkers, as well as participants' BMI, sex, and age on the 6 cognitive indexes. RESULTS: An inverse relationship between BMI and inhibitory control (F = 5.688, p = .019; ß = -0.212, p = .031), verbal memory (F = 5.404, p = .022; ß = -0.255, p = .009) and fine motor speed (F = 9.038, p = .003; ß = -0.319, p = .001) was observed. Levels of TNFα and fibrinogen were inversely related to inhibitory control (F = 5.055, p = .027; ß = -0.226, p = .021) and verbal memory (F = 4.732, p = .032; ß = -0.274, p = .005), respectively. LIMITATIONS: The cross-sectional nature of the study, the use of cognitive tests designed for clinical purposes, and the use of BMI as a proxy for adiposity are limitations of our study that must be taken into account when interpreting results. CONCLUSIONS: Our data indicate that some components of executive functions, together with verbal memory, are sensitive to specific obesity-related inflammatory agents at early ages.

Heterozygous aggrecan variants are associated with short stature and brachydactyly: Description of 16 probands and a review of the literature.

OBJECTIVE: Mutations in the aggrecan gene (ACAN) have been identified in two autosomal dominant skeletal dysplasias, spondyloepiphyseal dysplasia, Kimberley type (SEDK), and osteochondritis dissecans, as well as in a severe recessive dysplasia, spondyloepimetaphyseal dysplasia, aggrecan type. Next-generation sequencing (NGS) has aided the identification of heterozygous ACAN mutations in individuals with short stature, minor skeletal defects and mild facial dysmorphisms, some of whom have advanced bone age (BA), poor pubertal spurt and early growth cessation as well as precocious osteoarthritis. DESIGN AND METHODS: This study involves clinical and genetic characterization of 16 probands with heterozygous ACAN variants, 14 with short stature and mild skeletal defects (group 1) and two with SEDK (group 2). Subsequently, we reviewed the literature to determine the frequency of the different clinical characteristics in ACAN-positive individuals. RESULTS: A total of 16 ACAN variants were located throughout the gene, six pathogenic mutations and 10 variants of unknown significance (VUS). Interestingly, brachydactyly was observed in all probands. Probands from group 1 with a pathogenic mutation tended to be shorter, and 60% had an advanced BA compared to 0% in those with a VUS. A higher incidence of coxa valga was observed in individuals with a VUS (37% vs 0%). Nevertheless, other features were present at similar frequencies. CONCLUSIONS: ACAN should be considered as a candidate gene in patients with short stature and minor skeletal defects, particularly those with brachydactyly, and in patients with spondyloepiphyseal dysplasia. It is also important to note that advanced BA and osteoarticular complications are not obligatory conditions for aggrecanopathies/aggrecan-associated dysplasias.