Epidemiology of neural tube defects and folic acid

This review article combines four disparate observations about Neural Tube Defects (NTDs). They are the worldwide decline in the birth incidence that began prior to prenatal diagnosis; family recurrence risks; the effect of prenatal diagnosis and termination of affected pregnancies; and the effect of folic acid

A prospective follow-up study of first-episode acute transient psychotic disorder in Latvia

Background: Acute and transient psychotic disorder (ATPD) has been described as an acute psychosis with brief onset and polymorphous symptomatology (WHO, 1993). The study of ATPD is growing increasingly relevant as scientists start an active discussion of the possibility of changing the ATPD classification in the next International Classification of Diseases (ICD-11). The aims of this study were to describe the clinical features of the index episode of ATPD in patients in Latvia, to analyse the stability and longitudinal changes of the diagnosis, to explore potential correlations between the sociodemographic and disease characteristics and to describe stressful life events before the first ATPD episode.Methods: A prospective follow-up study of all first-time admitted patients from the Riga Centre of Psychiatry and Addiction Disorders who fulfilled the ICD-10 criteria for ATPD (WHO, 1993) during the 15-month period from 9 January 2010 to 30 March 2011 and followed up until 31 October 2012. Stressful life events, demographics and clinical features during the index episode were assessed.Results: One hundred two patients were admitted with first-episode ATPD. The majority were females (60.7%). Over an average 26.5-month follow-up period, 59.8% of the patients were not readmitted. The overall stability rate of ATPD diagnosis in our sample was 67.4% (p = 0.0001). In the subgroup of patients who were readmitted, 70.7% had their diagnosis converted to schizophrenia in subsequent visits. Stressful life events before the first episode were found in 49.0% of first-episode ATPD patients. Thought disorder was found to be the strongest statistically significant predictor of ATPD diagnosis conversation to schizophrenia (odds ratio 4.3), with high Wald's criterion (9.435) in binary logistic regression.Conclusions: ATPD is prevalent in Latvia, with rather high overall stability rate. Combining these data from first-episode ATPD patients in Latvia with data from other countries may help predict the development of the disease and provide a basis for potential changes to ICD-11.publishersversionPeer reviewe

Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults

This is the author accepted manuscript. the final version is available from Elsevier via the DOI in this recordObjective: Mild Behavioral Impairment (MBI) is a neurobehavioural syndrome characterized by later life emergent neuropsychiatric symptoms (NPS) which represent an at-risk state for incident cognitive decline and dementia in people with Mild Cognitive Impairment. We undertook a study to determine whether MBI was associated with progressive changes in neuropsychological performance in people without significant cognitive impairment. Methods: 9,931 older adults enrolled in the PROTECT study who did not have MCI or dementia undertook a comprehensive neuropsychological battery measuring attention, reasoning, executive function and working memory at baseline and one year. MBI was ascertained using self-administration of the MBI-C at one year, and participants grouped according to MBI status: no symptoms, intermediate neuropsychiatric symptoms and MBI. All assessments were completed online and data analyzed using MMRM ANOVA. Results: 949 (10%) people had MBI. These individuals had significantly worse cognitive performance at baseline and significantly greater decline over one year in the four composites cognitive scores measuring attentional intensity (F(2,8578)=3.97,p=0.019), sustained attention (F(2,8578)=18.63, p<.0001), attentional fluctuation (F(2,8578)=10.13, p=<.0001) and working memory F(2,9895)=13.1, p<.0001. Conclusions: Our novel findings show that MBI is associated with faster decline in attention and working memory in this cognitively normal sample. MBI may be an earlier marker of neurodegenerative disease than MCI, captured at the stage of SCD or before, raising the possibility that MBI represents a novel target for dementia clinical trials or prevention strategies.National Institute for Health Research (NIHR

Health Outcomes and Cost of Care Among Older Adults with Schizophrenia: A 10-Year Study Using Medical Records across the Continuum of Care

Objectives The population of older patients with schizophrenia is increasing. This study describes health outcomes, utilization, and costs over 10 years in a sample of older patients with schizophrenia compared to older patients without schizophrenia. Design, Setting, Participants An observational cohort study of 31,588 older adults (mean age 70.44 years) receiving care from an urban public health system, including a community mental health center, during 1999–2008. 1635 (5.2%) were diagnosed with schizophrenia and 757 (2.4%) had this diagnosis confirmed in the community mental health center. Patients’ electronic medical records were merged with Medicare claims, Medicaid claims, the Minimum Dataset, and the Outcome and Assessment Information Set. Information on medication use was not available. Measurements Rates of comorbid conditions, health care utilization, costs, and mortality. Results Patients with schizophrenia had significantly higher rates of congestive heart failure (45.05% v. 38.84%), chronic obstructive pulmonary disease (52.71% v. 41.41%), and hypothyroidism (36.72% v. 26.73%) than the patients without schizophrenia (p<0.001). They had significantly lower rates of cancer (30.78% v. 43.18%) and significantly higher rates of dementia (64.46% v. 32.13%). The patients with schizophrenia had significantly higher mortality risk (HR: 1.25, CI: 1.07–1.47) than the patients without schizophrenia. They also had significantly higher rates of health care utilization. The mean costs for Medicare and Medicaid were significantly higher for the patients with schizophrenia than for the patients without schizophrenia. Conclusions The management of older adult patients with schizophrenia is creating a serious burden for our health care system, requiring the development of integrated models of health care

Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare autosomal recessive sclerosing skeletal dysplasia. We report on a 34-year-old patient with sandwich vertebrae, platyspondyly, osteosclerosis of the tubular bones, pathologic fractures, and anemia. In the third decade, he developed osteonecrosis of the jaws, which was progressive in spite of repeated surgical treatment over a period of 11 years. An iliac crest bone biopsy revealed the presence of hypermineralized cartilage remnants, large multinucleated osteoclasts with abnormal morphology, and inadequate bone resorption typical for osteoclast-rich osteopetrosis. After exclusion of mutations in TCIRG1 and CLCN7 we performed trio-based exome sequencing. The novel homozygous splice-site mutation c.261G>A in the gene LRRK1 was found and co-segregated with the phenotype in the family. cDNA sequencing showed nearly complete skipping of exon 3 leading to a frameshift (p.Ala34Profs*33). Osteoclasts differentiated from the patient's peripheral blood monocytes were extremely large. Instead of resorption pits these cells were only capable of superficial erosion. Phosphorylation of L-plastin at position Ser5 was strongly reduced in patient-derived osteoclasts showing a loss of function of the mutated LRRK1 kinase protein. Our analysis indicates a strong overlap of LRRK1-related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption. Like in other osteoclast pathologies an increased risk for progressive osteonecrosis of the jaws should be considered in OSMD, an intermediate form of osteopetrosis

Depth of maximum of air-shower profiles at the Pierre Auger Observatory : II. Composition implications

Using the data taken at the Pierre Auger Observatory between December 2004 and December 2012, we have examined the implications of the distributions of depths of atmospheric shower maximum (Xmax), using a hybrid technique, for composition and hadronic interaction models. We do this by fitting the distributions with predictions from a variety of hadronic interaction models for variations in the composition of the primary cosmic rays and examining the quality of the fit. Regardless of what interaction model is assumed, we find that our data are not well described by a mix of protons and iron nuclei over most of the energy range. Acceptable fits can be obtained when intermediate masses are included, and when this is done consistent results for the proton and iron-nuclei contributions can be found using the available models. We observe a strong energy dependence of the resulting proton fractions, and find no support from any of the models for a significant contribution from iron nuclei. However, we also observe a significant disagreement between the models with respect to the relative contributions of the intermediate components.La lista completa de autores que integran el documento puede consultarse en el archivo.Facultad de Ciencias Exacta

Depth of maximum of air-shower profiles at the Pierre Auger Observatory : II. Composition implications

Using the data taken at the Pierre Auger Observatory between December 2004 and December 2012, we have examined the implications of the distributions of depths of atmospheric shower maximum (Xmax), using a hybrid technique, for composition and hadronic interaction models. We do this by fitting the distributions with predictions from a variety of hadronic interaction models for variations in the composition of the primary cosmic rays and examining the quality of the fit. Regardless of what interaction model is assumed, we find that our data are not well described by a mix of protons and iron nuclei over most of the energy range. Acceptable fits can be obtained when intermediate masses are included, and when this is done consistent results for the proton and iron-nuclei contributions can be found using the available models. We observe a strong energy dependence of the resulting proton fractions, and find no support from any of the models for a significant contribution from iron nuclei. However, we also observe a significant disagreement between the models with respect to the relative contributions of the intermediate components.La lista completa de autores que integran el documento puede consultarse en el archivo.Facultad de Ciencias Exacta

Psychiatric disorders and risk of subsequent dementia: Systematic review and meta-analysis of longitudinal studies

OBJECTIVES: Although psychiatric disorders have been found to be associated with increased risk of dementia, previous findings are mixed, and the nature of these relationships remains poorly understood. We examined longitudinal associations between depression, anxiety, post-traumatic stress disorders (PTSD), bipolar disorder (BPD), psychotic disorders and subsequent dementia. METHODS: We searched three databases for longitudinal, population-based studies investigating associations between psychiatric disorders and dementia (PROSPERO registration: CRD42020209638). We conducted narrative synthesis, and random-effects meta-analyses to obtain pooled estimates. We used meta-regression and stratified analyses to examine variation by sex, age-at-onset and follow-up time. RESULTS: Fifty-seven citations met eligibility criteria. Most studies focussed on depression (n = 33), which was associated with subsequent all-cause dementia (pooled relative risk [RR]: 1.96, 95% confidence interval [CI]: 1.59-2.43; I2  = 96.5%), Alzheimer's Disease (pooled RR: 1.9, 95% CI: 1.52-2.38; I2  = 85.5%), and Vascular Dementia (pooled RR: 2.71, 95% CI: 2.48-2.97; I2  = 0). Associations were stronger in studies with shorter follow-up periods and for severe and late-onset depression. Findings regarding anxiety were mixed, and we did not find evidence of an overall association (pooled RR: 1.18, 95% CI: 0.96-1.45; I2  = 52.2%, n = 5). Despite sparse evidence, psychotic disorders (pooled RR: 2.19, 95% CI: 1.44-3.31; I2  = 99%), PTSD and BPD were associated with subsequent dementia. CONCLUSIONS: People with psychiatric disorders represent high-risk groups for dementia, highlighting the importance of ongoing symptom monitoring in these groups. Findings regarding temporality and age-at-onset indicate that depression symptoms could reflect prodromal dementia for some individuals. Further longitudinal research is required to determine whether psychiatric disorders represent causal risk factors or early markers of dementia neuropathology

Late‐life onset psychotic symptoms and incident cognitive impairment in people without dementia: Modification by genetic risk for Alzheimer's disease

Supporting Information is available online at: https://doi.org/10.1002/trc2.12386 .Copyright © 2023 The Authors. Introduction: Late-life onset psychosis is associated with faster progression to dementia in cognitively normal people, but little is known about its relationship with cognitive impairment in advance of dementia. Methods: Clinical and genetic data from 2750 people ≥50 years of age without dementia were analyzed. Incident cognitive impairment was operationalized using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and psychosis was rated using the Mild Behavioral Impairment Checklist (henceforth MBI-psychosis). The whole sample was analyzed before stratification on apolipoprotein E (APOE) ε4 status. Results: In Cox proportional hazards models, MBI-psychosis had a higher hazard for cognitive impairment relative to the No Psychosis group (hazard ratio [HR]: 3.6, 95% confidence interval [CI]: 2.2–6, p < 0.0001). The hazard for MBI-psychosis was higher in APOE ε4 carriers and there was an interaction between the two (HR for interaction: 3.4, 95% CI: 1.2–9.8, p = 0.02). Discussion: Psychosis assessment in the MBI framework is associated with incident cognitive impairment in advance of dementia. These symptoms may be particularly important in the context of APOE genotype