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INTRODUCTION: Aducanumab selectively targets aggregated forms of amyloid beta (Aß), a neuropathological hallmark of Alzheimer's disease (AD). METHODS: PRIME was a Phase 1b, double-blind, randomized clinical trial of aducanumab. During the 12-month placebo-controlled period, participants with prodromal AD or mild AD dementia were randomized to receive aducanumab or placebo. At week 56, participants could enroll in a long-term extension (LTE), in which all participants received aducanumab. The primary endpoint was safety and tolerability. RESULTS: Amyloid-related imaging abnormalities-edema (ARIA-E) were the most common adverse event. Dose titration was associated with a decrease in the incidence of ARIA-E. Over 48 months, aducanumab decreased brain amyloid levels in a dose- and time-dependent manner. Exploratory endpoints suggested a continued benefit in the reduction of clinical decline over 48 months. DISCUSSION: The safety profile of aducanumab remained unchanged in the LTE of PRIME. Amyloid plaque levels continued to decrease in participants treated with aducanumab. HIGHLIGHTS: PRIME was a Phase 1b, double-blind, randomized clinical trial of aducanumab. We report cumulative safety and 48-month efficacy results from PRIME. Amyloid-related imaging abnormalities-edema (ARIA-E) were the most common adverse event (AE); 61% of participants with ARIA-E were asymptomatic. Dose titration was associated with a decrease in the incidence of ARIA-E. Aducanumab decreased levels of amyloid beta (Aß) in a dose- and time-dependent manner.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Anticuerpos Monoclonales Humanizados , Humanos , Método Doble Ciego , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Masculino , Femenino , Anciano , Péptidos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/patología , Resultado del Tratamiento , Placa Amiloide/tratamiento farmacológico , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND AND OBJECTIVES: Amyloid-related imaging abnormalities (ARIA) were the most common adverse events reported in the phase 3 ENGAGE and EMERGE trials of aducanumab, an anti-amyloid monoclonal antibody. APOE ε4 carrier status has been shown to increase risk of ARIA in prior trials of aducanumab and other anti-amyloid therapies; however, the remainder of the human genome has not been evaluated for ARIA risk factors. Therefore, we sought to determine in a hypothesis-free manner whether genetic variants beyond APOE influence risk of ARIA in aducanumab-treated patients. METHODS: We performed genome-wide association studies (GWAS) of ARIA in participants in the ENGAGE and EMERGE trials. Participants had mild cognitive impairment due to Alzheimer disease or mild Alzheimer disease dementia and were amyloid-positive on PET scans. All participants underwent regular MRI monitoring to detect and diagnose ARIA. RESULTS: Of the 3,285 participants in the intent-to-treat population, this analysis included 1,691 with genotyping array data who received at least one dose of aducanumab with at least one post-baseline MRI. All participants in the study cohort were of European ancestry; 51% were female. The mean age was 70.3 years. 31% had ARIA-E, 19% had ARIA-H microhemorrhage, and 14% had ARIA-H superficial siderosis. We identified one genome-wide significant (p < 5.0 × 10-8) association at the chromosome 19 locus encompassing APOE. The APOE association with ARIA was stronger in ε4/ε4 homozygotes (OR = 4.28, 4.58, 7.84; p < 2.9 × 10-14 for ARIA-E, ARIA-H microhemorrhage, and ARIA-H superficial siderosis, respectively) than in ε3/ε4 heterozygotes (OR = 1.74, 1.46, 3.14; p ≤ 0.03). We found greater odds of radiographically severe ARIA (OR = 7.04-24.64, p ≤ 2.72 × 10-5) than radiographically mild ARIA (OR = 3.19-5.00, p ≤ 1.37 × 10-5) among ε4/ε4 homozygotes. APOE ε4 was also significantly associated with both symptomatic (ε4/ε4 OR = 3.64-9.52; p < 0.004) and asymptomatic (ε4/ε4 OR = 4.20-7.94, p < 1.7 × 10-11) cases, although among ARIA cases, APOE did not appear to modulate symptomatic status. No other genome-wide significant associations were found. DISCUSSION: We identified a strong, genome-wide significant association between APOE and risk of ARIA. Future, larger studies may be better powered to detect associations beyond APOE. These findings indicate that APOE is the strongest genetic risk factor of ARIA incidence, with implications for patient management and risk-benefit treatment decisions. TRIAL REGISTRATION INFORMATION: Both trials (ENGAGE [221AD301]: NCT02477800 and EMERGE [221AD302]: NCT02484547) were registered in June 2015 at clinicaltrials.gov and enrolled patients from August 2015 to July 2018.
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Enfermedad de Alzheimer , Siderosis , Humanos , Femenino , Anciano , Masculino , Estudio de Asociación del Genoma Completo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Proteínas AmiloidogénicasRESUMEN
In Alzheimer's disease, the spread of aberrantly phosphorylated tau is an important criterion in the Braak staging of disease severity and correlates with disease symptomatology. Here, we report the results of TANGO ( NCT03352557 ), a randomized, double-blind, placebo-controlled, parallel-group and multiple-dose long-term trial of gosuranemab-a monoclonal antibody to N-terminal tau-in patients with early Alzheimer's disease. The primary objective was to assess the safety and tolerability of gosuranemab compared to placebo. The secondary objectives were to assess the efficacy of multiple doses of gosuranemab in slowing cognitive and functional impairment (using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores at week 78) and evaluate the immunogenicity of gosuranemab (using the incidence of anti-gosuranemab antibody responses). Participants were randomized (n = 654); received (n = 650) low-dose (125 mg once every 4 weeks (q4w), n = 58; 375 mg q12w, n = 58), intermediate-dose (600 mg q4w, n = 106) or high-dose (2,000 mg q4w, n = 214) gosuranemab or placebo (q4w, n = 214) intravenously for 78 weeks; and assigned to cerebrospinal fluid (n = 327) and/or tau positron emission tomography (n = 357) biomarker substudies. Gosuranemab had an acceptable safety profile and was generally well tolerated (incidence of serious adverse events: placebo, 12.1%; low dose, 10.3%; intermediate dose, 12.3%; high dose, 11.7%). The incidence of treatment-emergent gosuranemab antibody responses was low at all time points. No significant effects were identified in cognitive and functional tests as no dose resulted in a favorable change from the baseline CDR-SB score at week 78 compared to placebo control (adjusted mean change: placebo, 1.85; low dose, 2.20; intermediate dose, 2.24; high dose, 1.85). At week 76, all doses caused significant (P < 0.0001) reductions in the cerebrospinal fluid levels of unbound N-terminal tau compared to placebo.
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Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/efectos adversosRESUMEN
Two studies are reported that extend the evidence base for use of the Personal Stigma of Suicide Questionnaire (PSSQ). In the first study (N = 117), the Rosenberg Self-Esteem Scale, the WHO-5 measure of well-being, as well as measures of suicidality were examined in relation to the PSSQ. A self-selected sub-sample (N = 30) completed the PSSQ after an interval of two months. In line with the stigma internalization model, when demographic variables and suicidality were accounted for, the PSSQ self-blame subscale was the most significant predictor of self-esteem. As for well-being, the rejection subscale was involved as well as self-blame. The retest stability of the PSSQ for the sub-sample was 0.85 and coefficient alpha for the total sample was 0.95, indicating both good stability and internal consistency for the scale. In the second study (N = 140), PSSQ was studied in relation to intention to seek help from four sources in the case of suicidal ideation. The strongest relationship with PSSQ was with intention not to seek help from anyone (r = 0.35). When other variables were included in the prediction of help-seeking from a general medical practitioner, family or friends, or from nobody, the only significant PSSQ correlate was minimization. For help-seeking from a psychologist or psychiatrist, the most significant predictor was judged helpfulness of prior contact with them. The results from these studies strengthen previous findings of the construct validity of the PSSQ and point to its utility in understanding barriers to help-seeking among those experiencing suicidality.
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Suicidio , Humanos , Estigma Social , Ideación Suicida , Encuestas y Cuestionarios , Intención , Aceptación de la Atención de SaludRESUMEN
Two studies are reported examining the relation of self-control, as measured by self-report inventories, to indices of suicidal ideation and suicide attempts. In the first study (n = 113), self-control related significantly (p < 0.05) and negatively to both indices (r = -0.37 and r = -0.26), and, in a hierarchical regression analysis, added significantly to the variance in the suicidal ideation index accounted for by a measure of impulsivity. The second study (n = 223) replicated the findings of the bivariate correlations (r = -0.55 and r = -0.59) with the suicidality indices in the first study, both with the earlier measures and with alternative measures of self-control and impulsivity. Results indicated self-control added to the prediction of both indices and not just the ideation index. The second study also demonstrated that self-control acts as a moderator for perceived stress, a known risk factor for suicidality, such that, at low levels of perceived stress, there is little difference between those high and low in measured self-control, but that at high stress levels, those with high self-control had lower scores on suicidal ideation. The results are interpreted as showing that self-control is a protective factor for suicidality.
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Autocontrol , Intento de Suicidio , Humanos , Ideación Suicida , Conducta Impulsiva , Autoinforme , Factores de RiesgoRESUMEN
INTRODUCTION: Individuals with progressive supranuclear palsy (PSP) experience cognitive changes that are challenging to follow without a validated neuropsychological test battery to measure progression. This study describes a composite measure to evaluate cognition in individuals with PSP. METHODS: Baseline cognitive test data from 486 participants with PSP in the PASSPORT (NCT03068468) study included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Color Trails Test (CTT) parts 1 and 2, letter-number sequencing, and letter fluency. Data were analyzed using summary statistics and a matrix of Pearson correlations. A hypothetical factor structure was constructed and validated. RESULTS: Observed correlations were highest for scores between story memory and story recall (correlation coefficient = 0.78) and lowest for scores between letter fluency and picture naming (correlation coefficient = 0.11), and picture naming and figure copy (correlation coefficient = 0.12). After excluding picture naming and Color Trails Test (CTT) parts 1 and 2, a 3-factor structure was hypothesized for the remaining 13 tests. Confirmatory factor analysis demonstrated goodness of fit within acceptable limits (comparative fit index and Tucker-Lewis index = 0.98, standardized root-mean-square residual and root-mean-square error of approximation = 0.05-0.06). Mixed-model repeated-measures analysis of change from baseline to week 52 in RBANS and PSP cognitive composite score produced mean-to-standard-deviation ratios of 0.418 and 0.780, respectively. CONCLUSIONS: This novel composite endpoint, based on RBANS and designed to account for motor impairments in PSP, improves on current cognitive assessments PSP.
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Pruebas Neuropsicológicas/normas , Parálisis Supranuclear Progresiva/psicología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Cognición , Método Doble Ciego , Análisis Factorial , Femenino , Humanos , Masculino , Memoria , Pruebas de Memoria y Aprendizaje , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Reproducibilidad de los Resultados , Parálisis Supranuclear Progresiva/tratamiento farmacológico , Prueba de Secuencia Alfanumérica , Resultado del TratamientoRESUMEN
A randomized, double-blind, placebo-controlled, 52-week study (no. NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, in the treatment of progressive supranuclear palsy (PSP). In total, 486 participants dosed were assigned to either gosuranemab (n = 321) or placebo (n = 165). Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week 52 between gosuranemab and placebo (10.4 versus 10.6, P = 0.85, primary endpoint), or at secondary endpoints, resulting in discontinuation of the open-label, long-term extension. Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P < 0.0001). Incidences of adverse events and deaths were similar between groups. This well-powered study suggests that N-terminal tau neutralization does not translate into clinical efficacy.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Parálisis Supranuclear Progresiva/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Neumonía/etiología , Resultado del Tratamiento , Proteínas tau/inmunologíaRESUMEN
OBJECTIVE: The study sought to replicate, with a community sample and different measures of the critical variables, the finding of Chu et al. (Cognitive Therapy and Research, 2016, 40, 22) in a military sample that suicide attempts were more frequent for those reporting higher numbers of depressive episodes if acquired capability for suicide (ACS) was also high. METHOD: An online survey (N = 251) collected data on episodes and severity of depression, number of suicide attempts, and a questionnaire measure of ACS. RESULTS: The interaction effect reported by Chu et al. (Cognitive Therapy and Research, 2016, 40, 22) was replicated, but depended on using the Fearlessness of Death component of ACS and the number and not the severity of depressive episodes. CONCLUSION: The moderating effect of ACS on the relation between depression and suicide attempts can be demonstrated beyond a military and predominately male sample. Limitations of the study are noted.
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Depresión , Intento de Suicidio , Depresión/epidemiología , Humanos , Masculino , Ideación Suicida , Encuestas y CuestionariosRESUMEN
BACKGROUND: Progressive supranuclear palsy is a rare neurodegenerative disease associated with dysfunctional tau protein. BIIB092 is a humanised monoclonal antibody that binds to N-terminal tau and is thus being assessed as a potential novel treatment for progressive supranuclear palsy. We aimed to investigate the safety and tolerability of BIIB092 in individuals with progressive supranuclear palsy. METHODS: This 12-week, double-blind, randomised, placebo-controlled, multiple ascending dose, phase 1b trial was done at 13 outpatient sites in the USA. Participants aged 41-86 years with probable or possible progressive supranuclear palsy with a score of 20 or greater on the Mini-Mental State Examination (MMSE) were enrolled. Three BIIB092 dose escalation cohorts (150 mg, 700 mg, or 2100 mg; eight participants per cohort) were tested sequentially. For each dose cohort, the first two participants were randomly assigned by a computer-generated scheme to receive either BIIB092 or placebo intravenously every 4 weeks for 57 days. After 2 days, the six remaining participants in each cohort were randomly assigned (5:1) to receive BIIB092 or placebo for 57 days. An additional expansion panel of 24 patients was randomly assigned (3:1) to receive 2100 mg or placebo every 4 weeks for 57 days. All participants were followed up to day 85. The primary outcome was safety, which was analysed in the treated population (all enrolled participants who received at least one dose of the study drug). This trial is registered with ClinicalTrials.gov, NCT02460094. FINDINGS: Between Oct 2, 2015, and Oct 19, 2016, 48 participants were enrolled and randomly assigned to the BIIB092 (n=36) and placebo (n=12) groups. No apparent demographic differences were observed between the two groups at baseline. All 48 participants completed the treatment phase of the study. Adverse events were generally mild to moderate in severity; the most common in the placebo and BIIB092 groups were falls (in two [17%] of 12 patients and in ten [28%] of 36 patients), urinary tract infections (in one [8%] of 12 and in six [17%] of 36), contusions (in one [8%] of 12 and in five [14%] of 36), and headaches (in none and in five [14%] of 36). Four serious adverse events resulting in admission to hospital were reported in three participants who received BIIB092 2100 mg: two severe adverse events of urinary tract infection, one severe adverse event of change in mental status, and one moderate adverse event of aspiration pneumonia. None was considered to be related to the study drug, all were resolved, and no deaths were reported. INTERPRETATION: Repeated administration of the anti-tau monoclonal antibody BIIB092, at doses of up to 2100 mg, appears to be well tolerated in participants with progressive supranuclear palsy. Results of this phase 1b trial have informed the design of the ongoing phase 2 PASSPORT (NCT03068468) study to examine the efficacy and safety of BIIB092. FUNDING: Bristol-Myers Squibb, Biogen.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Parálisis Supranuclear Progresiva/tratamiento farmacológico , Tauopatías/tratamiento farmacológico , Proteínas tau/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Seguridad del Paciente , Parálisis Supranuclear Progresiva/psicología , Tauopatías/psicología , Resultado del TratamientoRESUMEN
Background: The detrimental consequences of stigma have been recognized in extensive research on mental illness stigma, but experiences of suicide-related stigmatization have not received sufficient research attention. The lack of a simple self-report assessment of personal suicide-related stigma led to the work reported here. Aim: To develop and assess the validity of the Personal Suicide Stigma Questionnaire (PSSQ). Method: The item pool for PSSQ was based on qualitative data and was tested in a community sample of 224 adults (mean age = 32.68 years, 83% female, 92.9% Caucasian) who reported lifetime suicidality. Factor analysis was used for item selection. The Self-Stigma of Mental Illness Scale - Short form (SSMIS-SF) and Suicide Behaviors Questionnaire - Revised (SBQ-R) were used to assess validity of the scale. Results: Following analysis, 16 items, forming three highly interrelated factors (Rejection, Minimization, and Self-blame), were selected for the PSSQ. The PSSQ scores showed predicted relationships with mental illness stigma and suicidality, suggesting its validity. Limitations: The validity of the scale still requires further research in clinical populations. Conclusion: The newly developed PSSQ can be used to assess the levels of suicide-related stigma experiences of suicidal individuals.
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Actitud Frente a la Salud , Autoimagen , Estereotipo , Ideación Suicida , Suicidio , Adolescente , Adulto , Australia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto JovenRESUMEN
SUV ratios (SUVRs) are commonly used to quantify tracer uptake in amyloid-ß PET. Here, we explore the impact of target and reference region-of-interest (ROI) selection on SUVR effect sizes using interventional data from the ongoing phase 1b PRIME study (NCT01677572) of aducanumab (BIIB037) in patients with prodromal or mild Alzheimer disease. Methods: The florbetapir PET SUVR was calculated at baseline (screening) and at weeks 26 and 54 for patients randomized to receive placebo and each of 4 aducanumab doses (1, 3, 6, and 10 mg/kg) using the whole cerebellum, cerebellar gray matter, cerebellar white matter, pons, and subcortical white matter as reference regions. In addition to the prespecified composite cortex target ROI, individual cerebral cortical ROIs were assessed as targets. Results: Of the reference regions used, subcortical white matter, cerebellar white matter, and the pons, alone or in combination, generated the largest effect sizes. The use of the anterior cingulate cortex as a target ROI resulted in larger effect sizes than the use of the composite cortex. SUVR calculations were not affected by correction for brain volume changes over time. Conclusion: Dose- and time-dependent reductions in the amyloid PET SUVR were consistently observed with aducanumab only in cortical regions prone to amyloid plaque deposition, regardless of the reference region used. These data support the hypothesis that florbetapir SUVR responses associated with aducanumab treatment are a result of specific dose- and time-dependent reductions in the amyloid burden in patients with Alzheimer disease.
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Amiloide/metabolismo , Anticuerpos Monoclonales Humanizados/metabolismo , Tomografía de Emisión de Positrones/normas , Adulto , Transporte Biológico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Estándares de ReferenciaRESUMEN
This corrects the article DOI: 10.1038/nature21361.
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This study examined the relationship between self-injurious behavior and intentions to seek help from professionals, family and friends, technology based support and from no-one. Participants were 679 young people aged 14-25 years drawn from a larger internet survey (N =1463) on the basis of their reported self-injury. A help-negation effect was found only in relation to intentions to seek help from family and friends. That is, a higher extent or severity of self-injury was independently associated with lower intentions to seek help from family and friends. This effect remained after controlling for psychological distress and suicidal ideation. Establishing avenues for early intervention and providing access to a range of potential avenues for help-seeking may assist young people to seek support in relation to self-injury.
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Conducta de Búsqueda de Ayuda , Aceptación de la Atención de Salud/psicología , Conducta Autodestructiva/psicología , Conducta Autodestructiva/terapia , Adolescente , Adulto , Femenino , Amigos/psicología , Humanos , Intención , Internet , Masculino , Conducta Autodestructiva/diagnóstico , Ideación Suicida , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Alzheimer's disease (AD) is characterized by deposition of amyloid-ß (Aß) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aß to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aß. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aß, and reduce soluble and insoluble Aß in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aß in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating-Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis.
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Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/antagonistas & inhibidores , Péptidos beta-Amiloides/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Placa Amiloide/tratamiento farmacológico , Placa Amiloide/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Amiloide/efectos de los fármacos , Amiloide/metabolismo , Péptidos beta-Amiloides/química , Animales , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/farmacocinética , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Ensayos Clínicos Fase III como Asunto , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Modelos Biológicos , Placa Amiloide/patología , Agregación Patológica de Proteínas/tratamiento farmacológico , SolubilidadRESUMEN
The study investigated, with an adult sample, the hypothesis that differences between subtypes of ADHD on neuropsychological tests contribute to the poor separation of ADHD and healthy groups on tests of this kind. Groups of ADHD inattentive (n=16) and combined (n=16) subtypes were carefully identified using DSM-IV criteria, and their performance on 14 measures of attention, memory, and executive function (EF) was compared between subtypes and between the two subtypes combined and a group of healthy controls (n=30). Multivariate analyses showed statistically significant differences between the two subtypes, and between the two subtypes combined and the healthy controls. Importantly for the hypothesis, where differences for neuropsychological tests in terms of effect sizes between subtypes were largest, the differences in effect sizes between the two groups combined and controls were smallest (r=-0.64, 95% CI [-0.15, -0.87]).
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Trastorno por Déficit de Atención con Hiperactividad/psicología , Atención , Función Ejecutiva , Memoria , Adulto , Trastorno por Déficit de Atención con Hiperactividad/clasificación , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas Neuropsicológicas , Desempeño Psicomotor , Prueba de Secuencia AlfanuméricaRESUMEN
The study sought to examine the role of frontal lobe functioning in focal prospective memory (PM) performance and its relation to PM deficit in older adults. PM and working memory (WM) differences were studied in younger aged (n = 21), older aged (n = 20), and frontal injury (n = 14) groups. An event-based focal PM task was employed and three measures of WM were administered. The younger aged group differed from the other two groups in showing significantly higher scores on PM and on one of the WM measures, but there were no differences at a statistically significant level between the older aged group and the frontal injury groups on any of the memory measures. There were, however, some differences in correlations with a WM measure between groups. It is concluded that there are similarities and differences in the deficits in PM between older adults and patients with frontal lobe injury on focal as well as nonfocal PM tasks.
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Envejecimiento/psicología , Lesiones Encefálicas/psicología , Lóbulo Frontal/lesiones , Trastornos de la Memoria/etiología , Memoria Episódica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Trastornos de la Memoria/fisiopatología , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
Three studies are reported on the development of a four-disc version of the Tower of London test of planning ability. The first (n = 138) involved the selection of items based on rational and empirical criteria to provide a short test of graded difficulty suitable for use with children and clinical populations. The second study (n = 480) checked the properties of the 10-item test on a new sample and in addition examined the internal consistency and factor structure of the test. The third study (n = 61) examined the test-retest reliability of the test over a period of 1 month. The difficulty level of the test remained relatively stable from sample to sample and was sensitive to linear trend in performance from age 5 years up to 30 years. Total score did not reflect the action of a single underlying construct but rather appeared to index a number of factors. Scores were reasonably stable over the 1-month period studied, at least for the children's sample employed. The four-disc version is a promising method of assessing planning in children and adolescents in clinical situations.
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Envejecimiento/psicología , Función Ejecutiva , Pruebas Neuropsicológicas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría/métodos , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Inconsistencies in the definition of impulsive suicide attempts hamper research integration. To expand the currently limited data on how this construct is used in clinical practice, researchers interviewed eight suicide attempters to create timelines of their suicide process, then had seven experienced clinicians review these timelines. Thematic analysis of the patient and clinician data revealed three themes: "thinking out," build-up, and unclear intentionality. The results imply that assessing build-up of agitation and exhaustion symptoms can contribute to understanding acuteness of suicide risk. In addition, uncertainty about one's intentions during the attempt should not be equated to low intent to die.
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Conducta Impulsiva/fisiología , Intención , Intento de Suicidio/psicología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Factores de Riesgo , Suicidio/psicología , Adulto JovenRESUMEN
The Interpersonal Psychological Theory of suicide proposes that the interaction between Thwarted Belongingness, Perceived Burdensomeness, and Acquired Capability for Suicide (ACS) predicts proximal risk of death by suicide. Instruments to assess all three constructs are available. However, research on the validity of one of them, the acquired capability for suicide scale (ACSS), has been limited, especially in terms of its clinical relevance. This study aimed to explore the utility of the different versions of the ACSS in clinical assessment. Three versions of the scale were investigated, the full 20-item version, a 7-item version and a single item version representing self-perceived capability for suicide. In a sample of patients recruited from a clinic specialising in the treatment of suicidality and in a community sample, all versions of the ACSS were found to show reasonable levels of reliability and to correlate as expected with reports of suicidal ideation, self-harm, and attempted suicide. The item assessing self-perceived acquired capacity for suicide showed highest correlations with all levels of suicidal behaviour. However, no version of the ACSS on its own showed a capacity to indicate suicide attempts in the combined sample. It is concluded that the versions of the scale have construct validity, but their clinical utility is limited. An assessment using a single item on self-perceived ACS outperforms the full and shortened versions of ACSS in clinical settings and can be recommended with caution for clinicians interested in assessing this characteristic.