Connecting genomic and proteomic signatures of amyloid burden in the brain.

Background: Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease.

Methods: We performed a meta-analysis of GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n=2,076).

Influence of daily life and health profile in subtle cognitive decline of women residing in Spanish religious communities: DeCo religious orders study.

Background: Prior to the onset of dementia, individuals commonly undergo a phase marked by subtle cognitive changes, known as subtle cognitive decline. Recognizing these early cognitive alterations is crucial, as they can serve as indicators of an impending decline in cognitive function, warranting timely intervention and support.

Objectives: To determine the incidence of subtle cognitive decline in a population of Spanish women and establish the relationship with possible protective and/or risk factors such as cognitive reserve, cardiovascular risk factors, medication consumption and psychosocial factors.

Special Issue "Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease".

We are pleased to present the first and second editions of this Special Issue, titled "Molecular and Genetic Aspects of SARS-CoV-2 Infection and COVID-19 Disease", of the [...

Erratum: Cumulative Genetic Score and C9orf72 Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.

[This corrects the article DOI: 10.1212/NXG.0000000000200079.

Relationship between COVID-19 Pandemic Confinement and Worsening or Onset of Depressive Disorders.

Several studies indicate that the pandemic and associated confinement measures may have had an impact on mental health, producing the onset or persistence of symptoms such as stress, anxiety, depression, and fear. This systematic review aims to identify the factors influencing the onset or worsening of depressive symptoms during COVID-19-related confinement. Our systematic search produced 451 articles from selected databases, 398 of which were excluded based on established criteria, while 53 were selected for review.

Cumulative Genetic Score and Repeat Status Independently Contribute to Amyotrophic Lateral Sclerosis Risk in 2 Case-Control Studies.

Background And Objectives: Most patients with amyotrophic lateral sclerosis (ALS) lack a monogenic mutation. This study evaluates ALS cumulative genetic risk in an independent Michigan and Spanish replication cohort using polygenic scores.

Methods: Participant samples from University of Michigan were genotyped and assayed for the chromosome 9 open reading frame 72 hexanucleotide expansion.

Changes in Liver Lipidomic Profile in G2019S- Mouse Model of Parkinson's Disease.

The identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis.

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of , , or in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L).

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

CRIDECO Anticholinergic Load Scale: An Updated Anticholinergic Burden Scale. Comparison with the ACB Scale in Spanish Individuals with Subjective Memory Complaints.

The increase in life expectancy has also been accompanied by an increase in the use of medication to treat chronic diseases. Polypharmacy is associated with medication-related problems such as the increase in the anticholinergic burden. Older people are more susceptible to anticholinergic effects on the central nervous system and this, in turn, may be related to cognitive impairment.

Presenilin-1 Mutations Are a Cause of Primary Lateral Sclerosis-Like Syndrome.

Background And Purpose: Primary lateral sclerosis (PLS) is a progressive upper motor neuron (UMN) disorder. It is debated whether PLS is part of the amyotrophic lateral sclerosis (ALS) spectrum, or a syndrome encompassing different neurodegenerative diseases. Recently, new diagnostic criteria for PLS have been proposed.

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene).

Pharmacist-Physician Interprofessional Collaboration to Promote Early Detection of Cognitive Impairment: Increasing Diagnosis Rate.

The increased pressure on primary care makes it important for other health care providers, such as community pharmacists, to collaborate with general practitioners in activities related to chronic disease care. Therefore, the objective of the present project was to develop a protocol of action that allows close pharmacist-physician collaboration to carry out a coordinated action for very early detection of cognitive impairment (CI). A comparative study to promote early detection of CI was conducted in 19 community pharmacies divided into two groups: one group with interprofessional collaboration (IPC) and one group without interprofessional collaboration (NonIPC).

Epigenome-wide association study of COVID-19 severity with respiratory failure.

Background: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the coronavirus disease 2019 (COVID-19), exhibit a wide spectrum of disease behaviour. Since DNA methylation has been implicated in the regulation of viral infections and the immune system, we performed an epigenome-wide association study (EWAS) to identify candidate loci regulated by this epigenetic mark that could be involved in the onset of COVID-19 in patients without comorbidities.

Methods: Peripheral blood samples were obtained from 407 confirmed COVID-19 patients ≤ 61 years of age and without comorbidities, 194 (47.

Epigenetic Study in Parkinson's Disease: A Pilot Analysis of DNA Methylation in Candidate Genes in Brain.

Efforts have been made to understand the pathophysiology of Parkinson's disease (PD). A significant number of studies have focused on genetics, despite the fact that the described pathogenic mutations have been observed only in around 10% of patients; this observation supports the fact that PD is a multifactorial disorder. Lately, differences in miRNA expression, histone modification, and DNA methylation levels have been described, highlighting the importance of epigenetic factors in PD etiology.

The width of the third ventricle associates with cognition and behaviour in motor neuron disease.

Objectives: An enlarged width of the third ventricle (WTV) has been described in amyotrophic lateral sclerosis (ALS) patients, although its clinical meaning is unknown. The aims of this study were to evaluate the contribution of demographical, clinical and genetic factors to the WTV in different motor neuron disease (MND) phenotypes and to assess its brain structural correlates.

Materials And Methods: The WTV was measured by transcranial ultrasound in 107 MND patients (82 diagnosed with classical ALS, 16 with progressive muscular atrophy and 9 with primary lateral sclerosis) and 25 controls.