Alterations in cholesterol homeostasis influence the risk for Alzheimer's disease (AD). Apolipoprotein A1 is the major apolipoprotein of the high-density lipoprotein and is involved in reverse cholesterol transport. Variation in the apolipoprotein A1 gene (APOA1) might influence the function of the protein, and thus brain cholesterol metabolism, leading to an increased risk for AD. Two polymorphisms of APOA1, a G/A substitution at position -75bp and a C/T and G/A base substitution at position +83bp or +84bp, or both, in the APOA1 promoter, have been described. We investigated the effect of these polymorphisms on the risk for AD in 427 AD patients and 500 healthy control subjects of German and English descent. The A allele of the APOA1 -75bp G/A polymorphism was associated with an increased risk for AD in subjects with an age at onset of 66 years or younger. Further data analysis indicated that AD patients homozygous for the A allele at position -75bp presented with disease onset 8 years earlier than carriers of at least one G allele. No influence of the +83/84bp polymorphism on the risk for AD was observed. These results suggest that variants of APOA1 might influence the onset and the risk for AD.

Our study suggests that poor sleep quality is associated with increased HbA1c in adolescents with type 1 diabetes and that higher levels of circadian misalignment are associated with increased insulin requirements. If replicated, our results indicate a clinical relevance of sleep habits in adolescents with type 1 diabetes.

As result of the investigation of early childhood BMI trajectories in this pediatric cohort with monogenic obesity we suggest that BMI values >27.0 kg/m or %BMI > 140% at the age of 2 years and BMI values >33.0 kg/m or %BMI> 184% at the age of 5 years may be useful cut points to identify children who should undergo genetic screening for monogenic obesity due to functionally relevant mutations in the leptin gene or leptin receptor gene.

Background: A limited number of published case reports suggest a positive effect of dextroamphetamine, an adrenergic agonist affecting both the central nervous system (CNS) and peripheral nervous system, on physical activity and weight in patients with hypothalamic obesity (intractable obesity following CNS insult). Here, we present our clinical experience with dextroamphetamine treatment for hypothalamic obesity. Methods: The clinical course of all patients started on dextroamphetamine treatment for severe hypothalamic obesity at our institution between 2010 and 2013 is reported. Dextroamphetamine administration was initiated at a single dose of 5 mg per day and titrated to effect up to a dose of 20 mg/day. BMI z-score velocity was calculated as change in BMI z-score over standardized intervals of 12 months. Parameters of treatment success and adverse events were assessed in a standardized fashion. Results: Seven patients (2 males; mean age 17.6 years [range 12.9–24.5]) underwent individual treatment attempts with dextroamphetamine between 2010 and 2013. The primary diagnoses were craniopharyngioma (n = 4), ganglioglioma WHO I (n = 1), astrocytoma (n = 1), and neonatal meningitis (n = 1). Time from initial CNS insult to initiation of dextroamphetamine treatment averaged 5.2 years (range 2.4 months to 16.5 years). All patients demonstrated a steady increase in BMI z-score from the time of initial diagnosis until initiation of dextroamphetamine treatment. Mean baseline BMI z-score was +3.17 ± 0.93 (+1.9 to +4.4). Mean BMI z-score velocity decelerated to –0.18 ± 0.12 per year during the first year of treatment and stabilized at +0.05 ± 0.32 per year during the second year of treatment. No significant adverse events were reported. Conclusion: Dextroamphetamine treatment led to stabilization or reduction of BMI z-score in a cohort of 7 patients with hypothalamic obesity, with no adverse effects. Considering the projected increase in BMI z-score according to the natural course of the disease, these findings are promising and warrant further study.

The observed prevalence of mutations causing impaired receptor function in this large cohort is comparable to other pediatric cohorts. MC4R deficiency tends to lead to a taller stature, confirming previous clinical reports. The association of MC4R mutations with a distinct phenotype concerning metabolic characteristics remains questionable.