Snowmorse1457

A Dutch cohort of 105 carefully selected limb girdle muscular dystrophy (LGMD) patients from 68 families has been subject to genetic testing over the last 20 years. After subsequent targeted gene analysis around two thirds (45/68) of the families had received a genetic diagnosis in 2013.

To describe the results of further genetic testing in the remaining undiagnosed limb girdle muscular dystrophy families in this cohort.

In the families of the cohort for whom no genetic diagnosis was established (n = 23) further testing using Sanger sequencing, next generation sequencing with gene panel analysis or whole-exome sequencing was performed. In one case DNA analysis for facioscapulohumeral dystrophy type 1 was carried out.

In eight families no additional genetic tests could be performed. In 12 of the remaining 15 families in which additional testing could be performed a genetic diagnosis was established two LGMDR1 calpain3-related families with CAPN3 mutations, one LGMDR2 dysferlin-related family with DYSF mutations, three sarcoglycanopathy families (LGMDR3-5 α-, β- and γ-sarcoglycan-related) with SGCA/SGCB/SGCG mutations, one LGMDR8 TRIM 32-related family with TRIM32 mutations, two LGMDR19 GMPPB-related families with GMPPB mutations, one family with MICU1-related myopathy, one family with FLNC-related myopathy and one family with facioscapulohumeral dystrophy type 1. At this moment a genetic diagnosis has been made in 57 of the 60 families of which DNA was available (95%).

A genetic diagnosis is obtained in 95% of the families of the original Dutch LGMD cohort of which DNA was available.

A genetic diagnosis is obtained in 95% of the families of the original Dutch LGMD cohort of which DNA was available.We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60-80 years) diagnosed with subjective cognitive decline and APOEɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Screening Library supplier Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer's disease should be further evaluated.

The early cellular stresses leading to Alzheimer's disease (AD) remain poorly understood because we cannot access living, asymptomatic human AD brains for detailed molecular analyses. Sortilin-related receptor 1 (SORL1) encodes a multi-domain receptor protein genetically associated with both rare, early-onset familial AD (EOfAD) and common, sporadic, late-onset AD (LOAD). SORL1 protein has been shown to act in the trafficking of the amyloid β A4 precursor protein (AβPP) that is proteolysed to form one of the pathological hallmarks of AD, amyloid-β (Aβ) peptide. However, other functions of SORL1 in AD are less well understood.

To investigate the effects of heterozygosity for an EOfAD-like mutation in SORL1 on the brain transcriptome of young-adult mutation carriers using zebrafish as a model organism.

We performed targeted mutagenesis to generate an EOfAD-like mutation in the zebrafish orthologue of SORL1 and performed RNA-sequencing on mRNA isolated from the young adult brains of siblings in a family of fish either wild type (non-mutant) or heterozygous for the EOfAD-like mutation.

We identified subtle differences in gene expression indicating changes in mitochondrial and ribosomal function in the mutant fish. These changes appear to be independent of changes in mitochondrial content or the expression of AβPP-related proteins in zebrafish.

These findings provided evidence supporting that EOfAD mutations in SORL1 affect mitochondrial and ribosomal function and provide the basis for future investigation elucidating the nature of these effects.

These findings provided evidence supporting that EOfAD mutations in SORL1 affect mitochondrial and ribosomal function and provide the basis for future investigation elucidating the nature of these effects.

Neuropsychological feedback is an important part of the neuropsychological assessment process. However, patients have difficulties remembering this information.

The aim of this study was to develop a web-based visual tool to improve the understanding of neuropsychological results, information retention, and psychologist-patient communication.

The visual tool was developed and optimized using an iterative three-phase stepwise approach to determine its usability, technology acceptance, and feasibility in a memory clinic population. Feedback from different user perspectives (patients, family members, and psychologists) was obtained in each phase using a multimethod approach (e.g. a multidisciplinary brainstorm session, think-aloud sessions, focus groups). The prototype was subsequently tested in a pilot study.

The first phases offered insights that led to optimization of the prototype. On a scale ranging from 0 to 100, psychologists evaluated the usability as high [88.1±7.6,70-87]. During the pilot study, both patients and significant others gave positive feedback, but information retention in patients remained low. All participants thought the benefits of the visual tool included seeing cognitive strengths and weaknesses with a translation to daily life all at one glance and receiving feedback on paper to take home. Important barriers were mentioned by psychologists, such as a limited set of tests included and no integration with hospital systems.

Overall, patients, family members, and psychologists reported that a visual display of the cognitive profile with insights into daily life had added value to clinical practice. Feedback from the pilot study was adopted in the tool for future implementation purposes.

Overall, patients, family members, and psychologists reported that a visual display of the cognitive profile with insights into daily life had added value to clinical practice. Feedback from the pilot study was adopted in the tool for future implementation purposes.