Severe Hyperammonemia In Late-onset Ornithine Transcarbamylase Deficiency Triggered By Steroid Administration

Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked disorder of urea synthesis leading to hyperammonemia. Several late-onset cases have been reported. Undiagnosed and untreated patients are at the risk of death or suffering from irreversible sequelae. We describe a 56-year-old patient who presented with acute encephalopathy after steroid treatment. Hyperammonemia due to OTCD was diagnosed and a mutation was found. This allowed us to diagnose two other family members with unexplained encephalopathy who are now asymptomatic on a low-protein diet. OTCD should be considered in any patient with hyperammonemic encephalopathy and immediate treatment should be given to avoid a fatal outcome. We emphasize the need to examine other family members if the diagnosis is confirmed, in order to prevent further life-threatening episodes of encephalopathy or neonatal coma of newborn

The longitudinal association between a discrepancy measure of anosognosia in patients with dementia, caregiver burden and depression

Background: According to cross-sectional studies, there is an association between anosognosia in people with dementia and caregiver's burden and depression. Anosognosia in patients may be a cause of caregiver burden and depression. However, variability in caregiver anosognosia ratings may exist as caregivers with burden and depression may have a more pessimistic view of the patients' health. Objective: to assess the variability of caregiver anosognosia ratings of patients with dementia using a widely used anosognosia scale and its longitudinal relationship with caregiver burden and depression. Methods: A convenience cohort of 221 consecutive dementia outpatient and caregiver dyads was followed up at 12 and 24 months. The main instruments used were the Anosognosia Questionnaire-Dementia (AQ-D), Caregiver Burden Interview, and Geriatric Depression Scale. Linear mixed models were used including time as a factor in every model. Multivariate analyses controlled for caregiver's socio-demographic and possible confounding factors. Results: Attrition at 12 and 24 months was 24.9% and 42.5% respectively. Patients at baseline were on average 77.8 years of age, 63.3% were women, and 63.3% had <5 years of education. In the bivariate analyses, caregiver burden, depression, and gender were associated with caregiver ratings of total, cognitive, and personality AQ-D of the patient at different time points. Multivariate analyses revealed burden as the caregiver variable most consistently associated with total, cognitive, and personality caregiver AQ-D ratings of the patient. Conclusion: Some caregiver characteristics, especially burden, are associated with caregiver ratings of AQ-D with regard to the patient

Cognitive impairment in ALS patients and validation of the Spanish version of the ALS-CBS test

Our aim was to develop and validate the Spanish version of the Amyotrophic Lateral Sclerosis Cognitive Behavioural Screen (ALS-CBS) and investigate behavioural/cognitive impairment in our ALS patients. We enrolled 50 patients with definite or probable ALS, evaluated by the Motor Neuron Disease Unit (using El Escorial criteria) and Dementia Unit, and assessed with the Spanish ALS-CBS. The patients' cognitive/behavioural status was classified according to current criteria. Patients were classified into each diagnostic category: ALS-no impairment, 36%; ALS-mild cognitive impairment, 34%; ALS-mild behavioural impairment, 6%; ALS-mild cognitive/behavioural impairment, 12%; ALS-frontotemporal dementia, 12%. Cognitive impairment was more common in bulbar (90.9%) than spinal (48.7%) forms (p < 0.012). The Spanish ALS-CBS was validated. Performance to differentiate normal vs. impaired individuals was: 1) cognition (cut-off 15; AUC, 84.7%): sensitivity 86.2%, specificity 62%, positive predictive value 75.8%, negative predictive value 76.5%; 2) behaviour (cut-off 36; AUC, 83.3%): sensitivity 93.3%, specificity 74.3%, positive predictive value 61%, negative predictive value 96.3%. Performance to differentiate between patients with and without dementia: 1) cognition (cut-off 8; AUC, 87.3%): sensitivity 83.3%, specificity 75%, positive predictive value 31.3%, negative predictive value 97.1%; 2) behaviour (cut-off 35; AUC, 80.9%): sensitivity 83.3%, specificity 69%, positive predictive value 25%, negative predictive value 96.7%. In conclusion, cognitive impairment is common in ALS patients, particularly in bulbar forms. The Spanish version of the ALS-CBS is useful for screening cognitive/behavioural impairment in this population

Effects of anosognosia and neuropsychiatric symptoms on the quality of life of patients with alzheimer's disease: a 24-month follow-up study

Objectives: Neuropsychiatric symptoms and anosognosia are known to influence the perceived quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study analysed their impact on patient and caregiver ratings of QoL-p and how these ratings changed in relation to the severity of dementia. Methods: A baseline sample of 221 patients and caregivers was followed up over 24 months. Instruments: Neuropsychiatric Inventory (NPI), Anosognosia Questionnaire-Dementia (AQ-D), Quality of Life-Alzheimer's Disease (QoL-AD), and the Global Deterioration Scale (GDS). Longitudinal data were analysed using generalized linear models. Results: In the multivariate analysis, greater anosognosia was always associated with higher ratings of QoL-p among patients, especially at 24 months (p < 0.001), and with more negative ratings among caregivers, especially at baseline (p < 0.001). A higher total NPI score was associated with a more negative rating of QoL-p among caregivers (p < 0.001), and it also had a smaller negative effect on patients' self-ratings (p = 0.001). The neuropsychiatric symptoms (NPI) associated with a more negative view of QoL-p were depression, for patients' self-ratings, and apathy and agitation for caregiver ratings. The discrepancy between patient and caregiver ratings increased in line with the severity of dementia. Conclusion: Neuropsychiatric symptoms and anosognosia have differential effects on patient and caregiver ratings of the quality of life of patients with Alzheimer's disease. Key words: Alzheimer's disease, quality of life, anosognosia, neuropsychiatric symptoms, caregivers, patients

Kinship and cohabitation in relation to caregiver burden in the context of Alzheimer's disease: a 24-month longitudinal study

Objectives: The aims of the study were to identify the clinical characteristics of three groups of caregivers: spouses, live-in adult-child or non-live-in adult-child, and their relation to the degree of perceived burden (Caregiver Burden Interview). Methods: The sample comprised 275 Alzheimer's disease (AD) primary caregivers, with a follow-up of 24 months. Cognitive, functional and behavioural characteristics were evaluated in persons with AD (PwD), while socio-demographic data, use of socio-medical resources, physical and mental health, and self-perceived burden were assessed in caregivers. Generalized estimating equations (GEE) were used for longitudinal data analysis. Results: Spouse caregivers were 45.0% men, sole caregivers (> 80%), used few external resources, and had worse physical health. The number of female adult-child caregivers was higher (>75%). The live-in adult-child group, compared with the non-live-in adult-child group, were less likely to be married, had a lower level of education, were more commonly the sole caregiver, and used fewer external resources. The greatest burden was observed in live-in adult-child caregivers, and the lowest in the non-live-in adult-child group, with no significant variation in the follow-up for both groups. Spouses had an intermediate level of perceived burden, which rose significantly during follow-up (p <0.001). Conclusions: Kinship and cohabitation with the PwD were associated with different scores and evolution of the burden, with an increase in the follow-up of the spouses, and with more or less burden, depending on cohabitation, in the adult-child groups. Interventions to reduce the level of burden on caregivers should consider these differences

Severity of Dementia, Anosognosia, and Depression in Relation to the Quality of Life of Patients With Alzheimer Disease: Discrepancies Between Patients and Caregivers

Objective: To investigate the factors associated with discrepancies between patient and caregiver reports of the quality of life of patients (QoLp) with Alzheimer¿s disease (AD). Methods: Cross-sectional analytic study of 141 patients and their caregivers. The instruments used were the Quality of Life in AD (QoL-AD), the Global Deterioration Scale (GDS), the Geriatric Depression Scale (GDS-d) and the Anosognosia Questionnaire¿Dementia (AQ-D). Differences were analyzed according to GDS stage. A linear regression analysis was conducted using the difference between the absolute QoLp scores of patients and caregivers. A cluster analysis involving the patient variables was then performed. Results: The discrepancy between patient and caregiver QoLp ratings increased in line with GDS stages (χ2 (2) = 8.7, p = 0.013). In the regression model (F [7,133] = 16.6, p <0.001; R2 = 0.477), discrepancies in QoLp reports were associated with greater anosognosia, less depression and a better cognitive status in patients, as well as with female gender among caregivers. The cluster analysis showed that patients with the lowest ratings of QoLp had a better cognitive status, more depression and less anosognosia. Conversely, the highest ratings were given by patients with a poorer cognitive status, less depression and greater anosognosia. Conclusions: The factors associated with greater discrepancies between patient and caregiver ratings of QoLp were severity of dementia, anosognosia, depression and cognitive status in patients, and female gender in caregivers. In patients with advanced dementia, greater anosognosia leads to more positive ratings in QoLp and complementary observations are required

Síntomas depresivos y sobrecarga en los familiares cuidadores en la enfermedad de Alzheimer: un modelo de ecuaciones estructurales

Introducción. El cuidado de los pacientes con Enfermedad de Alzheimer (EA) incrementa la sobrecarga y depresión del cuidador principal (CP), aunque la relación entre ambas no está claramente definida. Objetivo. Explorar los factores asociados a la sintomatología depresiva y sobrecarga en el CP y aplicar un modelo de ecuaciones estructurales para identificar la relación entre ellas. Sujetos y métodos. La muestra estuvo formada por 127 cuidadores familiares de personas con EA, con un seguimiento de 24 meses. Se realizaron análisis de regresión multivariante para identificar las características de pacientes y cuidadores asociadas a la sobrecarga y depresión del CP, y se diseñó un modelo de ecuaciones estructurales para analizar la relación entre las variables. Resultados. En el modelo de ecuaciones estructurales, la sobrecarga tuvo un efecto directo sobre la depresión, tanto en la evaluación basal como a los 24 meses. Las variables asociadas a la sobrecarga fueron: la escolaridad y la menor salud mental del CP; y las alteraciones conductuales y la dependencia funcional del paciente. El menor nivel cognitivo del paciente y la menor salud mental del CP estuvieron asociadas a la depresión. La correlación entre sobrecarga y depresión aumentó desde la evaluación basal hasta los 2 años (r = 0,470 vs. 0,613). Conclusiones. El deterioro del paciente y la sobrecarga son factores de riesgo para la depresión en el CP. Serían necesarias intervenciones para reducir la carga y poder prevenir la depresión relacionada

Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease

Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer's disease (AD), and presents pathological and clinical overlap with both AD and Parkinson's disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD

Factors associated with the variability in caregiver assessments of the capacities of the patients with Alzheimer"s disease

Abstract Background: Several studies have identified certain caregiver factors that can produce variability in their assessments of the capacities of patients with Alzheimer"s disease (AD). Objectives: To identify the caregiver variables associated with variability in their ratings of patients" capacities. Methods: Consecutive sample of 221 out-patients with AD and their family caregivers. The capacities evaluated by caregivers were: the degree of functional disability, using the Disability Assessment for Dementia (DAD); psychological and behavioral symptoms, via the Neuropsychiatric Inventory (NPI); anosognosia, with the Anosognosia Questionnaire Dementia (AQ-D); and quality of life, using the Quality of Life in AD (QOL-AD). The relationship between these measures and caregiver gender, burden, depression, and health was analyzed by means of a bivariate analysis, calculating the effect size (Cohen"s d), and subsequently by a regression analysis, calculating the contribution coefficient (CC). Results: The greatest variability in caregiver assessments was observed in relation to patients with early-stage dementia, where caregiver burden was the main factor associated with a more negative evaluation (d = 1.02 to 1.25). Depression in the caregiver was associated with less variability and only in the assessments of patients with moderate dementia (d = 0.38 to 0.69). In the regression analysis, caregiver factors were associated with greater variance in scores on the NPI (CC = 37.4%) and QOL-AD (CC = 27.2%), and lower variance in AQ-D (CC = 21.6%) and DAD (CC = 10.3%) scores. Conclusions: Caregiver burden and depression were associated with more negative assessments of patients" psychological and behavioral symptoms and quality of life. Key words: Alzheimer"s disease, family caregivers, functional capacity, neuropsychiatric symptoms, anosognosia, quality of life