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Global deterioration scale; Down syndrome; Alzheimer’s disease Escala de deteriorament global; Síndrome de Down; Malaltia d'Alzheimer Escala de deterioro global; Síndrome de Down; Enfermedad de Alzheimer 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. This research was funded by the Spanish Government, grant number PI12/02019, PSI-2014-53524-P. The APC was funded by S.E.-C,’s SESMDI research start-up funds.

D2:D4; Prader–Willi syndrome; Epigenetic D2:D4; Síndrome de Prader-Willi; Epigenètica D2:D4; Síndrome de Prader-Willi; Epigenética Prader-Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11-13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the 'social brain' during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance-as measured using the Social Responsiveness Scale (SRS)-and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls. Support of the Spanish Ministry of Science and Innovation/ISCIII/FEDER (PI21/01148); and J.C. thanks the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement of the Generalitat de Catalunya (2017 SGR 1412); the CERCA program of the I3PT; the Instituto de Salud Carlos III; and the CIBER of Mental Health (CIBERSAM).

BACKGROUND Despite presenting higher risk of dementia, mild cognitive impairment (MCI) is not well defined in Down syndrome population. OBJECTIVE We aimed to describe cognitive and neuropsychological patterns associated with MCI in Down syndrome individuals. METHOD Two groups of adults with Down syndrome (control and prodromal) were studied throughout 3 years. Two linear mixed models and a model including the variables that best predicted group membership were built. RESULTS Behavioural Regulation Index (BRI) (Behaviour Rating Inventory of Executive Function test) and the model composed of BRI, abstraction and delayed verbal memory were the variable and model best predicting group membership, respectively. CONCLUSION Suggest a diagnosis of MCI when BRI is the earliest change perceived by caregivers and this is combined with low scores in abstract thinking, and when an amnesic pattern in delayed verbal memory is observed, but adaptive skills are preserved.

INTRODUCTION: This pilot study analyzes the effect of a cognitive training program in adults with intellectual disability (ID). METHOD: Twenty subjects (mean age 52.7 ± 9.77 years) with mild and moderate ID were divided in control and experimental group. Only the experimental group received the training program. This program was applied through the GNPT® (Guttmann, NeuroPersonalTrainer®) platform for people with ID. RESULTS: The results revealed a significant improvement in the Kaufman Brief Intelligence Test-2 scores (Matrices subtest) in the experimental group [Z = 2.12; p = .03] after the intervention, indicating an enhancement in fluid ability due to effect of cognitive training program. CONCLUSION: Findings provide evidence of the importance of applying these programs in a systematized way in adults with ID.

Altres ajuts: Fundació Parc Taulí CIR2020/022 We compared body composition, biochemical parameters, motor function, and brain neural activation in 27 adults with Prader-Willi syndrome and growth-hormone deficiency versus age-and sex-matched controls and baseline versus posttreatment values of these parameters after one year of recombinant human growth hormone (rhGH) treatment. To study body composition, we analyzed percentage of fat mass, percentage of lean mass, and muscle-mass surrogate variables from dual X-ray absorptiometry. Biochemical parameters analyzed included IGF-I, glucose metabolism, and myokines (myostatin, irisin, and IL6). To explore muscle function, we used dynamometer-measured handgrip strength, the Timed Up and Go (TUG) test, and the Berg Balance Scale (BBS). To study brain activation, we acquired functional magnetic resonance images during three motor tasks of varying complexity. After one year of treatment, we observed an increase in lean mass and its surrogates, a decrease in fat mass, improvements in TUG test and BBS scores, and increased neural activation in certain cerebellar areas. The treatment did not significantly worsen glucose metabolism, and no side-effects were reported. Our findings support the benefits of rhGH treatment in adults with Prader-Willi syndrome and growth-hormone deficiency on body composition and suggest that it may also improve balance and brain neural activation.

Although various studies have investigated symptoms of autism spectrum disorder (ASD) in Prader–Willi syndrome (PWS), little is known about the consequences of these symptoms, especially in psychosocial function. We aimed to explore ASD symptoms in adults with PWS with special attention to psychosocial functionality. This cross-sectional study included 26 adults (15 women) with PWS who attended a reference unit for rare diseases. Participants’ primary caregivers completed the Social Responsiveness Scale (SRS), and clinicians assessed multidimensional functioning with the Personal and Social Performance Scale (PSP). Impaired social responsiveness was identified in 20 (76.9%) participants, and manifest to marked difficulties in social functioning were identified in 13 (50%). Participants with impaired social responsiveness (SRS ≥ 60) had significantly worse scores in functionality measured with the PSP (U = 12.5; p = 0.009) and with three of the four PSP main areas. Moreover, scores for the Social Cognition domain of the SRS correlated positively with the Socially useful activities (p < 0.05) and Personal and social relationships (p < 0.01) main areas of the PSP. These results suggest that difficulties in social skills should be assessed in all psychosocial evaluations of patients with PWS.

Obesity and growth hormone (GH)-deficiency are consistent features of Prader–Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5–156.8) pg/mL vs. 141.96 (113.9–165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3–139.0) pg/mL), plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80–67.10) ng/mL vs. 33.10 (20.50–67.30) ng/mL, respectively, p = 0.152) and higher (p &lt, 0.001) than in healthy subjects (14.80 (11.37–67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2–153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range).

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.

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 char...

Objective:To explore motor praxis in adults with Prader–Willi syndrome (PWS) in comparison with a control group of people with intellectual disability (ID) and to examine the relationship with brain structural measurements.Method:Thirty adult participants with PWS and 132 with ID of nongenetic etiology (matched by age, sex, and ID level) were assessed using a comprehensive evaluation of the praxis function, which included pantomime of tool use, imitation of meaningful and meaningless gestures, motor sequencing, and constructional praxis.Results:Results support specific praxis difficulties in PWS, with worse performance in the imitation of motor actions and better performance in constructional praxis than ID peers. Compared with both control groups, PWS showed increased gray matter volume in sensorimotor and subcortical regions. However, we found no obvious association between these alterations and praxis performance. Instead, praxis scores correlated with regional volume measures in distributed apparently normal brain areas.Conclusions:Our findings are consistent in showing significant impairment in gesture imitation abilities in PWS and, otherwise, further indicate that the visuospatial praxis domain is relatively preserved. Praxis disability in PWS was not associated with a specific, focal alteration of brain anatomy. Altered imitation gestures could, therefore, be a consequence of widespread brain dysfunction. However, the specific contribution of key brain structures (e.g., areas containing mirror neurons) should be more finely tested in future research.

Hyperphagia is one of the main problems of patients with Prader-Willi syndrome (PWS) to cope with everyday life. The underlying mechanisms are not yet well understood. Gut-brain hormones are an interrelated network that may be at least partially involved. We aimed to study the hormonal profile of PWS patients in comparison with obese and healthy controls. Thirty adult PWS patients (15 men, age 27.5 ± 8.02 years, BMI 32.4 ± 8.14 kg/m2), 30 obese and 30 healthy controls were studied before and after eating a hypercaloric liquid diet. Plasma brain-derived neurotrophic factor (BDNF), leptin, total and active ghrelin, peptide YY (PYY), pancreatic polypeptide (PP), Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and amylin were determined at times 0′, 30′, 60′ and 120′. Cluster analysis was used. When considering all peptides together, two clusters were established according to fasting hormonal standardized concentrations. Cluster 1 encompassed most of obese (25/30) and healthy controls (28/30). By contrast, the majority of patients with PWS were located in Cluster 2 (23/27) and presented a similar fasting profile with hyperghrelinemia, high levels of leptin, PYY, GIP and GLP-1, compared to Cluster 1, that may reflect a dysfunction of these hunger/satiety hormones. When peptide behavior over the time was considered, PP concentrations were not sustained postprandially from 60 min onwards in Cluster 2. BDNF and amylin did not help to differentiate the two clusters. Thus, cluster analysis could be a good tool to distinguish and characterize the differences in hormone responses between PWS and obese or healthy controls.

Resumen Introduccion La escala Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) fue creada para evaluar de forma breve el funcionamiento de las personas con trastorno de desarrollo intelectual y problemas de salud mental/trastornos de conducta. El objetivo del presente trabajo fue estudiar las evidencias sobre la validez de las puntuaciones obtenidas con la escala HoNOS-LD traducida al castellano. Material y metodos La muestra estaba formada por 111 participantes que fueron evaluados con la HoNOS-LD traducida al castellano y otros cuestionarios relacionados. Para estudiar la fiabilidad entre examinadores y la fiabilidad test-retest, 33 participantes fueron evaluados por 2 examinadores y reevaluados al cabo de 7 dias. Resultados De acuerdo con criterios clinicos y conceptuales, y con el resultado del analisis paralelo, se selecciono una solucion factorial con unico factor. La consistencia interna fue buena (coeficiente omega de 0,87). Las fiabilidades entre examinadores y test-retest fueron excelentes (coeficientes de correlacion intraclase de 0,95 y 0,98, respectivamente). Las correlaciones entre secciones de la HoNOS-LD y los instrumentos relacionados fueron en el sentido esperado y altamente significativas ( p Conclusiones La version en castellano de la HoNOS-LD representa un instrumento breve, valido y fiable, que permitira la evaluacion rutinaria del funcionamiento con distintas finalidades, incluyendo el diagnostico y la intervencion.

A genetic analysis of unexplained mild-moderate intellectual disability and co-morbid psychiatric or behavioural disorders is not systematically conducted in adults. A cohort of 100 adult patients affected by both phenotypes were analysed in order to identify the presence of copy number variants (CNVs) responsible for their condition identifying a yield of 12.8% of pathogenic CNVs (19% when including clinically recognizable microdeletion syndromes). Moreover, there is a detailed clinical description of an additional 11% of the patients harbouring possible pathogenic CNVs—including a 7q31 deletion (IMMP2L) in two unrelated patients and duplications in 3q29, 9p24.2p24.1 and 15q14q15.1—providing new evidence of its contribution to the phenotype. This study adds further proof of including chromosomal microarray analysis (CMA) as a mandatory test to improve the diagnosis in the adult patients in psychiatric services. Electronic supplementary material The online version of this article (10.1007/s10519-018-9902-6) contains supplementary material, which is available to authorized users.

Compulsions are among the most typical behaviors in Prader-Willi syndrome (PWS). The most frequent causes of PWS are deletion of the genes located in the segment 15q11-q13 of the paternal allele and maternal uniparental disomy of cromosome 15. The aim of the present work was to study compulsive behavior in a sample of adults with PWS and analyze potential differences as a function of the genetic cause/subtype.In the 27 study participants, existence of type I deletion (n=7), type II deletion (n=13), and maternal disomy (n=7) was determined by means of genetic tests. The Yale-Brown Obsessive Compulsive Scale, the Compulsive Behavior Checklist, and the Repetitive Behavior Questionnaire were used to assess occurrence and severity of compulsions.Most of the participants showed compulsive behavior, the most frequent compulsions were those of inappropriate grooming (skin picking) and order (hoarding). The occurrence of compulsions was less frequent in the maternal disomy group than in the deletion groups. Severe compulsions were more frequent in those participants with type II deletion than in the other groups.Differences in occurrence and severity of compulsions exist as a function of PWS genetic subtype. Our results support the idea that individuals with maternal disomy are less affected by compulsive behavior. More research on the severity of compulsions as a function of deletion type should be done, as the studies conducted so far have shown contradictory results.

Down syndrome (DS) has been considered a unique model for the investigation of Alzheimer's disease (AD) but intermediate stages in the continuum are poorly defined. Considering this, we investigated the neurophysiological (i.e., magnetoencephalography [MEG]) and neuropsychological patterns of mild cognitive impairment (MCI) and AD in middle-aged adults with DS. The sample was composed of four groups: Control-DS (n = 14, mean age 44.64 ± 3.30 years), MCI-DS (n = 14, 51.64 ± 3.95 years), AD-DS (n = 13, 53.54 ± 6.58 years), and Control-no-DS (healthy controls, n = 14, 45.21 ± 4.39 years). DS individuals were studied with neuropsychological tests and MEG, whereas the Control-no-DS group completed only the MEG session. Our results showed that the AD-DS group exhibited a significantly poorer performance as compared with the Control-DS group in all tests. Furthermore, this effect was crucially evident in AD-DS individuals when compared with the MCI-DS group in verbal and working memory abilities. In the neurophysiological domain, the Control-DS group showed a widespread increase of theta activity when compared with the Control-no-DS group. With disease progression, this increased theta was substituted by an augmented delta, accompanied with a reduction of alpha activity. Such spectral pattern—specifically observed in occipital, posterior temporal, cuneus, and precuneus regions—correlated with the performance in cognitive tests. This is the first MEG study in the field incorporating both neuropsychological and neurophysiological information, and demonstrating that this combination of markers is sensitive enough to characterize different stages along the AD continuum in DS.

Objective 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). Methods 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. Results 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. Conclusions 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., Highlights • We report an abnormal pattern of brain response to images of disgusting food in PWS. • The activation demonstrated by PWS patients was restricted to the cerebral cortex. • Higher subjective disgust ratings were associated with greater insula activation. • In contrast, the neural response was almost absent in deep subcortical structures. • Disgusting signals may not adequately reach a main brain system for appetite control.

Despite how important it is to assess executive functioning in persons with Intellectual Disability (ID), instruments adapted and validated for this population are scarce. This study’s primary goal was to find evidence for the validity of the ID version of the Tower of London (TOLDXtm) test in persons with mild (IDMi) and moderate (IDMo) levels of ID with Down Syndrome (DS). A multicenter study was carried out. Subjects (n= 63, ≥ 39 years old) had DS with mild (n= 39) or moderate ID (n= 24) with no minor neurocognitive disorder or Alzheimer’s disease. Assessment protocol: TOLDXtmfor ID, Kaufman Brief Intelligence Test Second Edition (K-BIT II), Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS), Weigl’s Color-Form Sorting Test (WCFST), Barcelona Test for Intellectual Disability (BT-ID), and the Behavior Rating Inventory of Executive Function (BRIEF-P). The internal consistency (IDMiand IDMo), factor structure of the different subscales, and relationship between TOLDXtmsubscales and other cognitive measures (BT-ID, WCFST, and BRIEF-P) were analyzed. A normative data table with ID population quartiles is provided. TOLDXtmfor ID showed a robust one factor structure and coherentassociations with other, related neuropsychological instruments. Significant differences between IDMiand IDMoon movement-related variables likeCorrect (Corr; p = .002)andMoves (Mov; p = .042)were observed, along with good internal consistency values, Corr (α = .75), Mov (α = .52). Regarding internal consistency, no between-groups differences were observed (allp-value > 0.05). The TOLDXtmfor ID is thus an instrument, supported by good validity evidence, to evaluate problem-solving and planning in ID. It distinguishes between individuals with mild and moderate ID, and is highly associated with other measures of executive functioning.

Background Rare Copy Number Variants (CNVs) are known to be important risk factors for Neurodevelopmental Disorders (NDDs). Pathogenic CNVs identified to date confer moderate to large effect sizes (OR 1.5 - 50 or higher) and have important clinical implications for affected individuals and at-risk family members. Several studies have investigated pathogenic CNVs in paediatric cohorts with Intellectual Disabilities (ID), or in schizophrenia/Autism Spectrum Disorders (ASD) only samples. However, adult populations – in particular those who exhibit ID and co-morbid psychiatric diagnoses – are less well characterised. Methods We undertook Chromosomal Microarray Analysis (CMA) and clinical phenotyping in 599 adults with ID and co-morbid psychiatric disorders recruited from three European research sites (Catalonia, Spain; Leuven, Belgium; and England, UK). We compared the carrier frequency of 63 established NDD CNV risk loci to reported frequencies in healthy controls, schizophrenia and ID/ASD populations. We determine the clinical diagnostic yield of CMA in our sample and describe likely pathogenic CNVs affecting NDD candidate genes. Results We identified 58 carriers of NDD risk CNVs at 23 of the 63 risk loci investigated. The five most frequent CNVs were: 22q11.2 deletion (N=7, 1.2%), 15q11.2 (Prader-Willi syndrome/Angelman syndrome region) duplication (N=6, 1%), 16p11.2 duplication (N=5, 0.8%), 15q13.3 deletion (N=5, 0.8%) and 16p12.1 deletion (N=4, 0.7%). The frequency of NDD risk CNVs was significantly higher in our cohort (10%), compared to healthy controls (1.2%, p Discussion There is a paucity of research on CNVs in adults with ID and co-morbid psychiatric diagnoses. This poses a challenge for genetic counselling of rare CNVs, as descriptions of later-life phenotypes are largely unavailable. In our sample, the largest multi-population sample of its kind to date, we find a significantly higher rate of NDD risk CNVs compared to schizophrenia and ID/ASD only cohorts. Our high diagnostic yield of 13% pathogenic CNVs demonstrates the diagnostic utility of CMA in this patient group. We also find a high yield of likely pathogenic CNVs (21.5%), which enables us to phenotypically characterise rare recurrent CNVs. Increased clinical testing and research in this population should be a priority for both clinicians and researchers in the field of psychiatric genetics.

Background Neural tissue alterations in Down syndrome are fully expressed at relatively late developmental stages. In addition, there is an early presence of neurodegenerative changes in the late life stages. Objective The aims of this study were both to characterize white matter abnormalities in the brain of adult Down syndrome patients using diffusion tensor imaging (DTI) and to investigate whether degenerative alterations in white matter structure are detectable before dementia is clinically evident. Methods Forty-five adult non-demented Down syndrome patients showing a wide age range (18-52 years) and a matched 45-subject control group were assessed. DTI fractional anisotropy (FA) brain maps were generated and selected cognitive tests were administered. Results Compared with healthy controls, non-demented Down syndrome patients showed lower DTI FA in white matter involving the major pathways, but with more severe alterations in the frontal-subcortical circuits. White matter FA decreased with age at a similar rate in both DS and control groups. Conclusions Our results contribute to characterizing the expression of white matter structural alterations in adult Down syndrome. However, an accelerated aging effect was not demonstrated, which may suggest that the FA measurements used are not sufficiently sensitive or, alternatively, age-related white matter neurodegeneration is not obvious prior to overt clinical dementia.

Context: Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis. Objectives: To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS. Design: Experimental study. Setting: University hospital. Subjects: 90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls. Interventions: Subjects ingested a liquid meal after fasting ≥10 hours. Main Outcome Measures: Leptin and BDNF levels in plasma extracted before ingestion and 30’, 60’, and 120’ after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60’ and 120’ after ingestion. Results: Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p

Prader Willi syndrome is a genetic disorder with a behavioural expression characterized by the presence of obsessive-compulsive phenomena ranging from elaborate obsessive eating behaviour to repetitive skin picking. Obsessive-compulsive disorder (OCD) has been recently associated with abnormal functional coupling between the frontal cortex and basal ganglia. We have tested the potential association of functional connectivity anomalies in basal ganglia circuits with obsessive-compulsive behaviour in patients with Prader Willi syndrome.We analyzed resting-state functional MRI in adult patients and healthy controls. Whole-brain functional connectivity maps were generated for the dorsal and ventral aspects of the caudate nucleus and putamen. A selected obsessive-compulsive behaviour assessment included typical OCD compulsions, self picking and obsessive eating behaviour.We included 24 adults with Prader Willi syndrome and 29 controls in our study. Patients with Prader Willi syndrome showed abnormal functional connectivity between the prefrontal cortex and basal ganglia and within subcortical structures that correlated with the presence and severity of obsessive-compulsive behaviours. In addition, abnormally heightened functional connectivity was identified in the primary sensorimotor cortex-putamen loop, which was strongly associated with self picking. Finally, obsessive eating behaviour correlated with abnormal functional connectivity both within the basal ganglia loops and between the striatum and the hypothalamus and the amygdala.Limitations of the study include the difficulty in evaluating the nature of content of obsessions in patients with Prader Willi Syndrome and the risk of excessive head motion artifact on brain imaging.Patients with Prader Willi syndrome showed broad functional connectivity anomalies combining prefrontal loop alterations characteristic of OCD with 1) enhanced coupling in the primary sensorimotor loop that correlated with the most impulsive aspects of the behaviour and 2) reduced coupling of the ventral striatum with limbic structures for basic internal homeostasis that correlated with the obsession to eat.

Most individuals with Down syndrome (DS) reach an advanced age which gives rise to specific seniorcitizen needs. These must be considered and addressed, through anticipation and prevention. Difficulties are already emerging in services responsible for this population, as well as for the individuals concerned and their relatives. The inadequacy and unsuitability of policy planning and lack of adequate services are made apparent whenever a person with DS begins to develop cognitive deterioration or dementia. The World Health Organization (WHO) has drawn up, in conjunction with the International Association for the Scientific Study of Intellectual Disabilities (IASSID) and Inclusion International, a report on the social and health care needs of aging persons with intellectual disabilities, including those with DS. This working document highlights as a priority the need for each country in the European Union to implement “Projects for Healthy Aging” that are naturally conducive to social inclusion while improving support and training for both formal and informal caregivers. The present article provides a rough outline for potential future programs targeting individuals with DS and cognitive deterioration or dementia.

Resumen La mayoria de las personas con sindrome de Down (SD) llegan a una edad en que, como ciudadanos seniors , tienen una serie de necesidades que deben ser consideradas y atendidas, obligando a unas intervenciones de anticipacion y prevencion. Esta realidad ya esta generando dificultades en los servicios que tienen la responsabilidad de atenderlos, a sus propias familias y a los propios afectados. Cuando una persona con SD inicia un proceso de deterioro cognitivo o demencia, se hace evidente la inadecuada y escasa planificacion de politicas y, al mismo tiempo, la falta de provision de servicios. La Organizacion Mundial de la Salud (OMS) en colaboracion con la Asociacion Internacional para el Estudio Cientifico de Discapacidades Intelectuales (IASSID) y de Inclusion Internacional ha desarrollado un informe que recoge las necesidades sociales y sanitarias de las personas con discapacidad intelectual en proceso de envejecimiento, entre ellos las personas con SD. En el mismo documento de trabajo se senala como prioritaria la necesidad de que cada pais de la Union Europea desarrolle «Proyectos para el envejecimiento saludable» que conduzcan a la inclusion social de forma natural mejorando el soporte y la formacion de los cuidadores formales e informales. Se presenta a continuacion una primera aproximacion a la posible creacion de programas para personas con SD y deterioro-cognitivo/demencia.

Altres ajuts: Fundació Parc Taulí - Institut Universitari UAB CIR2009/33 i CIR2010/034 Deletions in the 2p16.3 region that includes the neurexin (NRXN1) gene are associated with intellectual disability and various psychiatric disorders, in particular, autism and schizophrenia. We present three unrelated patients, two adults and one child, in whom we identified an intragenic 2p16.3 deletion within the NRXN1 gene using an oligonucleotide comparative genomic hybridization array. The three patients presented dual diagnosis that consisted of mild intellectual disability and autism and bipolar disorder. Also, they all shared a dysmorphic phenotype characterized by a long face, deep set eyes, and prominent premaxilla. Genetic analysis of family members showed two inherited deletions. A comprehensive neuropsychological examination of the 2p16.3 deletion carriers revealed the same phenotype, characterized by anxiety disorder, borderline intelligence, and dysexecutive syndrome. The cognitive pattern of dysexecutive syndrome with poor working memory and reduced attention switching, mental flexibility, and verbal fluency was the same than those of the adult probands. We suggest that in addition to intellectual disability and psychiatric disease, NRXN1 deletion is a risk factor for a characteristic cognitive and dysmorphic profile. The new cognitive phenotype found in the 2p16.3 deletion carriers suggests that 2p16.3 deletions might have a wide variable expressivity instead of incomplete penetrance.

Dementia caused by Alzheimer's disease commonly affects the adult population with Down's syndrome. This population presents two characteristic clinical features: a semiologic pattern that differs from the typical Alzheimer's disease, and previous intellectual deficits that may confound the clinical diagnosis. There is a clear need to validate specific instruments adapted to Spanish population.To adapt and to validate CAMDEX-DS (Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities) in Spanish population.146 patients with intellectual disability (mild to moderate) were recruited and assessed with CAMDEX-DS, K-BIT I and DMR tests. Test-retest reliability, inter-rater concordance and validity statistic were performed between CAMDEX-DS and clinical diagnosis. This is an observational, multicenter, cross-sectional and validation study.Test-retest and inter-rater reliability achieved kappa coefficient values of 0.92 and 0.91, respectively. Agreement (kappa index) for CAMDEX-DS on clinical diagnosis compared to other clinical criteria was high: CAMDEX-DS vs DSM-IV (kappa = 0.95; p0,001); CAMDEX-DS vs ICD-10 (kappa = 0.97; p0.001). All item-test correlations ranged between 0,31 and 0,69. Internal reliability-calculated using Chronbach's alpha scored 0.93.The Spanish version of CAMDEX-DS is a valid instrument with high applicability for people with intellectual disability. It shows good psychometric properties. The Cambridge Cognitive Examination for Older Adults with Down's Syndrome (CAMCOG-DS) can set two key points by the level of intellectual disability on the suspicion of cognitive impairment in people with Down's syndrome.Adaptacion y validacion del Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) en poblacion española con discapacidad intelectual.Introduccion. La demencia causada por la enfermedad de Alzheimer afecta comunmente a la poblacion adulta con sindrome de Down. Esta poblacion presenta dos rasgos clinicos caracteristicos: la presencia de demencia con semiologia distinta a la enfermedad de Alzheimer tipica y deficits intelectuales previos que pueden confundir el diagnostico clinico. Existe una evidente necesidad de validar instrumentos especificos en castellano adaptados a esta poblacion. Objetivo. Adaptar y validar el Cambridge Examination for Mental Disorders of Older People with Down's Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) en poblacion española. Pacientes y metodos. Se consideraron 146 pacientes con discapacidad intelectual (leve-moderada). Se realizo un estudio de validacion de tipo observacional, transversal y multicentrico. Se administraron los siguientes tests: CAMDEX-DS, test breve de inteligencia de Kaufman y Dementia Questionnaire for Persons with Mental Retardation. Se calculo la fiabilidad test-retest, la fiabilidad interjueces, la concordancia del CAMDEX-DS para el diagnostico clinico y la validez. Resultados. La fiabilidad test-retest e interjueces obtuvo un coeficiente kappa de 0,92 y 0,91, respectivamente. El indice kappa del CAMDEX-DS para el diagnostico clinico respecto al resto de los criterios clinicos utilizados fue alto: CAMDEX-DS frente a DSM-IV (kappa = 0,95; p0,001); CAMDEX-DS frente a Clasificacion Internacional de Enfermedades, decima revision (kappa = 0,97; p = 0,000). Todas las correlaciones item-test oscilaban entre 0,31 y 0,69. La fiabilidad interna calculada mediante el alfa de Cronbach fue de 0,93. Conclusiones. La version española del CAMDEX-DS es un instrumento valido, de alta aplicabilidad a personas con discapacidad intelectual, que muestra buenas propiedades psicometricas. El Cambridge Cognitive Examination for Older Adults with Down's Syndrome (CAMCOG-DS) permite establecer dos puntos de corte para la sospecha de deterioro cognitivo en el grupo de personas con sindrome de Down en funcion del nivel de discapacidad intelectual previo.

Introduccion. La evaluacion neuropsicologica en las personas con discapacidad intelectual es importante para determinar los deficits cognitivos especificos que subyacen a la afectacion cerebral, limitan el funcionamiento intelectual y afectan al comportamiento adaptativo. A pesar de ello, no existen baterias neuropsicologicas en castellano adaptadas y validadas para esta poblacion. Objetivo. Adaptar el programa integrado de exploracion neuropsicologica-test Barcelona y validar la nueva version, el test Barcelona para discapacidad intelectual (TB-DI), estableciendo datos normativos para el empleo clinico. Sujetos y metodos. A partir de los datos obtenidos en una muestra piloto de 65 personas con discapacidad intelectual, se realizaron cambios en el test original. Para estudiar las propiedades psicometricas del TB-DI, se administro a una muestra de 170 personas con discapacidad intelectual y a un grupo de 60 personas sin ella. Mediante modelos de regresion, se determino que variables eran importantes para la estratificacion de los datos normativos. Resultados. El TB-DI, compuesto de 67 subtests agrupados en ocho dominios cognitivos, muestra unas buenas propiedades psicometricas. Se crean datos normativos para cinco grupos en funcion del nivel de discapacidad intelectual, la edad y la competencia curricular. Estos datos se organizan en percentiles, lo que permite trazar perfiles cognitivos en el ambito clinico y experimental. Conclusion. El TB-DI es un instrumento de alta aplicabilidad para la poblacion con discapacidad intelectual, y muestra una validez y una fiabilidad adecuadas, y con buenas propiedades psicometricas. Los perfiles cognitivos determinados mediante el TB-DI proporcionaran informacion valiosa para el tratamiento integral de las personas adultas con discapacidad intelectual leve y moderada.

Introduccion. La demencia causada por la enfermedad de Alzheimer afecta comunmente a la poblacion adulta con sindrome de Down. Esta poblacion presenta dos rasgos clinicos caracteristicos: la presencia de demencia con semiologia distinta a la enfermedad de Alzheimer tipica y deficits intelectuales previos que pueden confundir el diagnostico clinico. Existe una evidente necesidad de validar instrumentos especificos en castellano adaptados a esta poblacion. Objetivo. Adaptar y validar el Cambridge Examination for Mental Disorders of Older People with Down´s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) en poblacion espanola. Pacientes y metodos. Se consideraron 146 pacientes con discapacidad intelectual (leve-moderada). Se realizo un estudio de validacion de tipo observacional, transversal y multicentrico. Se administraron los siguientes tests: CAMDEX-DS, test breve de inteligencia de Kaufman y Dementia Questionnaire for Persons with Mental Retardation. Se calculo la fiabilidad test-retest, la fiabilidad interjueces, la concordancia del CAMDEX-DS para el diagnostico clinico y la validez. Resultados. La fiabilidad test-retest e interjueces obtuvo un coeficiente kappa de 0,92 y 0,91, respectivamente. El indice kappa del CAMDEX-DS para el diagnostico clinico respecto al resto de los criterios clinicos utilizados fue alto: CAMDEX-DS frente a DSM-IV (kappa = 0,95; p < 0,001); CAMDEX-DS frente a Clasificacion Internacional de Enfermedades, decima revision (kappa = 0,97; p = 0,000). Todas las correlaciones item-test oscilaban entre 0,31 y 0,69. La fiabilidad interna calculada mediante el alfa de Cronbach fue de 0,93. Conclusiones. La version espanola del CAMDEX-DS es un instrumento valido, de alta aplicabilidad a personas con discapacidad intelectual, que muestra buenas propiedades psicometricas. El Cambridge Cognitive Examination for Older Adults with Down´s Syndrome (CAMCOG-DS) permite establecer dos puntos de corte para la sospecha de deterioro cognitivo en el grupo de personas con sindrome de Down en funcion del nivel de discapacidad intelectual previo.