The Global Deterioration Scale for Down Syndrome Population (GDS-DS): A Rating Scale to Assess the Progression of Alzheimer’s Disease

Global deterioration scale; Down syndrome; Alzheimer’s diseaseEscala de deteriorament global; Síndrome de Down; Malaltia d'AlzheimerEscala de deterioro global; Síndrome de Down; Enfermedad de AlzheimerThe 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

An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader–Willi Syndrome

D2:D4; Prader–Willi syndrome; EpigeneticD2:D4; Síndrome de Prader-Willi; EpigenèticaD2:D4; Síndrome de Prader-Willi; EpigenéticaPrader-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)

Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader-Willi Syndrome

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 < 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)

Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?

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 00 , 300 , 600 and 1200 . 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

High Incidence of Copy Number Variants in Adults with Intellectual Disability and Co-morbid Psychiatric Disorders

Altres ajuts: Financial support was received from "Fundació Parc Taulí Institut d'Investigació i Innovació Parc Taulí I3PT" (Grant Nos. CIR2009/33, CIR2010/034) and "Fundació Barnola-Vallribera 2011".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

A common cognitive, psychiatric, and dysmorphic phenotype in carriers of NRXN1 deletion

Altres ajuts: Fundació Parc Taulí - Institut Universitari UAB CIR2009/33 i CIR2010/034Deletions 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

Neuropsicología del trastorno del desarrollo intelectual con y sin origen genético

El trastorno del desarrollo intelectual (TDI) es un estado particular de funcionamiento que comienza en la infancia en el que coexisten limitaciones del funcionamiento intelectual y de las habilidades adaptativas. No existen en nuestro entorno demasiados instrumentos creados y/o adaptados y validados para personas adultas con TDI. Tampoco existen perfiles cognitivos realizados sobre los estándares de su población normativa de referencia. Generalmente las investigaciones utilizan como grupo normativo, población emparejada por edad mental o cronológica. Los sesgos que comporta utilizar una u otra opción son importantes a la hora de interpretar los resultados y enfocar las intervenciones. Un test neuropsicológico debe ser sensible a variables propias del individuo (edad y escolaridad) y otros relacionados con la lesión, como la causa genética de su TDI. La detección de diferencias en función de nivel de DI, es también un indicador de buena sensibilidad. Las personas con Síndrome de Down (SD) presentan un envejecimiento precoz y una alta prevalencia de aparición de deterioro cognitivo leve (DCL) y Enfermedad de Alzheimer (EA). El infradiagnóstico en ambas patologías es elevado, todo ello muy asociado a la inexistencia de una definición de los criterios diagnósticos de DCL basados en perfiles cognitivos estandarizados, y a la inexistencia de señales que puedan advertir la aparición de EA en estadio precoz. Por último y con respecto a la población con Síndrome de Prader-Willi (SWP), los estudios realizados son heterogéneos, tanto a la hora de definir su nivel de DI como a la hora de reportar diferencias en función del subgrupo genético. No existe unanimidad en la descripción de un perfil cognitivo específico para la población adulta. Los objetivos de esta tesis son: Elaborar una versión del Test Barcelona para personas con TDI (TB-DI) de grado leve y moderado, al mismo tiempo que se estudian sus propiedades psicométricas y se crean datos normativos (Estudio 1). Estudiar el perfil cognitivo de personas con SD envejecidas en comparación con su grupo normativo con TDI. Observar las diferencias a nivel cognitivo entre el grupo SD envejecido y el grupo DCL, y entre DCL y EA. Establecer el porcentaje de personas con DCL y EA y los índices de conversión anuales (Estudio 2). Elaborar el perfil cognitivo de las personas con SPW y comprobar si existen diferencias significativas entre las distintas etiologías genéticas (Estudio 3). Para todo ello, en primer lugar se creó el TB-DI y se administró a una muestra de personas con TDI (n = 170) estudiando sus características psicométricas. Posteriormente se aplicó a una población con SD > 40 años (n = 94) una batería neuropsicológica compuesta por diversos tests, en el momento L0 y L1. Paralelamente se aplicó el protocolo a personas con SPW (n = 30). A todos los individuos de las muestras se le realizó el estudio genético correspondiente. Los principales resultados del trabajo indican que el TB-DI presenta unas buenas propiedades psicométricas, aportando datos normativos para población con TDI sin etiología genética en función del nivel de DI, la edad y la competencia curricular adquirida. Esto ha permitido constatar cómo las personas con SD presentan tres perfiles cognitivos diferenciados en función del grupo diagnóstico (envejecidos/DCL/EA). Por otra parte tanto el infradiagnóstico como el porcentaje de conversión anual son altos. Los resultados obtenidos permiten establecer una propuesta de criterios diagnósticos DCL-SD. Por último y a tenor de los resultados, se comprueba que las personas con SPW presentan un perfil heterogéneo, con una marcada apraxia no referenciada anteriormente en la literatura y con una excelente capacidad visuo-constructiva. Las diferencias cognitivas halladas en función del subtipo genético son pocas.Intellectual disability (ID) is a particular state of functioning that begins in childhood and in which limitations in intellectual and adaptive skills coexist. In our environment, there are few instruments created and validated for adults with ID. In addition, no cognitive profiles are made about the standards of their reference normative population. Generally, research studies have used population matched by mental or chronological age as a control group. The bias that involves using either option is important in interpreting the results and focusing interventions. A neuropsychological test should be sensitive to the individual's own variables (e.g., age and years of education) and other variables, such as the genetic cause of the ID. Detecting differences in terms of level of ID is also a good indicator of the test sensitivity. On the on hand, people with Down Syndrome (DS) show premature aging and a high prevalence of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The underdiagnosis in both pathologies is high. This is related to the absence of a definition of the diagnostic criteria of MCI based on standardized cognitive profiles, as well as the absence of signs that may warn of the onset of AD in early stages. On the other hand, and with respect to the population with Prader-Willi Syndrome (PWS), studies are heterogeneous, not only in defining the level of ID but also in establishing differences based on genetic subgroups. There is no consensus when it comes to describe the presence of a specific cognitive profile for adults. The aims of this thesis are: To develop a version of the BT-ID for people with mild and moderate ID, as well as to study its psychometric properties and provide normative data (Study 1). To study the cognitive profile of old people with DS compared to their normative ID group, and to observe the differences between aged, MCI and AD DS groups. Finally, an additional aim was to establish the percentage of people with MCI and AD and the annual conversion rates (Study 2). To determine the cognitive profile of people with PWS and check if there are significant differences between different genetic aetiologies (Study 3). To achieve these aims, the BT-ID was created and administered to a sample of individuals with ID (n = 170); and the psychometric properties of this test were studied. Secondly a complete neuropsychological battery composed of different tests, was applied to a DS population aged > 40 (n = 94) in the L0 and L1 time. In parallel, the protocol was applied to a sample of individuals with PWS (n = 30). All individuals of the samples underwent the corresponding genetic study. The main results of the thesis show that BT-ID has good psychometric properties, providing normative data for population with non-genetic ID aetiology based on ID level, age and years of curricular competence. DS people showed three distinct cognitive profiles depending on the diagnostic group (old/MCI/AD). Moreover, both underdiagnosis and percentage of annual conversion are high. The obtained results allow to suggest diagnostic criteria of MCI-AD. Finally, it is found that people with PWS have a heterogeneous profile, with a marked general apraxia, not referenced previously in the literature, and an exc

Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader–Willi Syndrome

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)

Cognitive training in adults with intellectual disability: pilot study applying a cognitive tele-rehabilitation program

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.Depto. de Psicología Social, del Trabajo y DiferencialFac. de PsicologíaTRUEpu