To investigate, based on a putative abnormal neural processing of disgusting signals in Prader Willi syndrome (PWS) patients, the brain response to visual representations of disgusting food in PWS using functional MRI (fMRI). Twenty-one genetically-confirmed PWS patients, 30 age- and sex-matched and 28 BMI-matched control subjects viewed a movie depicting disgusting food-related scenes interspersed with scenes of appetizing food while fMRI was acquired. Brain activation maps were compared between groups and correlated with disgust and hunger ratings. At the cortical level, the response to disgusting food representations in PWS patients was qualitatively similar to that of control subjects, albeit less extensive, and engaged brain regions typically related to visually-evoked disgust, such as the anterior insula/frontal operculum, the lateral frontal cortex and visual areas. By contrast, activation was almost absent in limbic structures directly concerned with the regulation of instinctive behavior robustly activated in control subjects, such as the hypothalamus, amygdala/hippocampus and periaqueductal gray. Our study provides novel insights into the neural substrates of appetite control in a genetically-mediated cause of obesity. The presence of significant cortical changes further indicates that PWS patients consciously process disgusting stimuli, but the virtual absence of response in deep, limbic structures suggests that disgusting signals do not adequately reach the primary brain system for the appetite control.

Introduction: The majority of individuals with Down syndrome (DS) show signs of Alzheimer's disease (AD) neuropathology in their fourth decade. However, there is a lack of specific markers for characterizing the disease stages while considering this population's differential features. Methods: Forty-one DS individuals participated in the study, and were classified into three groups according to their clinical status: Alzheimer's disease (AD-DS), mild cognitive impairment (MCI-DS), and controls (CN-DS). We performed an exhaustive neuropsychological evaluation and assessed brain functional connectivity (FC) from magnetoencephalographic recordings. Results: Compared with CN-DS, both MCI-DS and AD-DS showed a pattern of increased FC within the high alpha band. The neuropsychological assessment showed a generalized cognitive impairment, especially affecting mnestic functions, in MCI-DS and, more pronouncedly, in AD-DS. Discussion: These findings might help to characterize the AD-continuum in DS. In addition, they support the role of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD. Impact statement: The pattern of functional connectivity (FC) hypersynchronization found in this study resembles the largely reported Alzheimer's disease (AD) FC evolution pattern in population with typical development. This study supports the hypothesis of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD, and its conclusions could help in the characterization and prediction of Down syndrome individuals with a greater likelihood of converting to dementia.

There are no studies about insight or awareness of illness in patients with Prader-Willi Syndrome (PWS). The objective of this study was to explore the level of awareness of the disorder, of the need for medication, and of the social consequences of the disease, as well as of its main symptoms in PWS. We also aimed to explore relationships between awareness and sociodemographic and clinical characteristics, and to compare all data with a matched sample of patients with psychosis. Insight was assessed by an Adapted version of the Scale of Unawareness of Mental Disorder in a cross-sectional pilot study at a University Hospital. Thirty-six individuals with PWS (58.3% women) were included. Results showed that PWS patients had a good awareness of the illness and of the effects of medication, in contrast to a lack of awareness of illness’ social consequences. Awareness of obesity/overweight was excellent, as was the awareness of excessive appetite. Awareness of excessive food intake was only mild. Insight correlated with age and functionality, but not with BMI. PWS patients showed a better insight into the illness but a similar awareness of the effects of the medication and of the social consequences of the disease as compared to schizophrenia-spectrum patients. This profile of insight may have relevant clinical implications.

The aim of this study is to adapt and validate the global deterioration scale (GDS) for the systematic tracking of Alzheimer’s disease (AD) progression in a population with Down syndrome (DS). A retrospective dual-center cohort study was conducted with 83 participants with DS (46.65 ± 5.08 years) who formed the primary diagnosis (PD) group: cognitive stability (n = 48), mild cognitive impairment (n = 24), and Alzheimer’s disease (n = 11). The proposed scale for adults with DS (GDS-DS) comprises six stages, from cognitive and/or behavioral stability to advanced AD. Two neuropsychologists placed the participants of the PD group in each stage of the GDS-DS according to cognitive, behavioral and daily living skills data. Inter-rater reliability in staging with the GDS-DS was excellent (ICC = 0.86; CI: 0.80–0.93), and the agreement with the diagnosis categories of the PD group ranged from substantial to excellent with κ values of 0.82 (95% CI: 0.73–0.92) and 0.85 (95% CI: 0.72, 0.99). Performance with regard to the CAMCOG-DS total score and orientation subtest of the Barcelona test for intellectual disability showed a slight progressive decline across all the GDS-DS stages. The GDS-DS scale is a sensitive tool for staging the progression of AD in the DS population, with special relevance in daily clinical practice.