Charting the shared genetic architecture of Alzheimer's disease, cognition, and educational attainment, and associations with brain development.

The observation that the risk of developing Alzheimer's disease is reduced in individuals with high premorbid cognitive functioning, higher educational attainment, and occupational status has led to the 'cognitive reserve' hypothesis. This hypothesis suggests that individuals with greater cognitive reserve can tolerate a more significant burden of neuropathological changes before the onset of cognitive decline. The underpinnings of cognitive reserve remain poorly understood, although a shared genetic basis between measures of cognitive reserve and Alzheimer's disease has been suggested.

Dissecting the Shared Genetic Architecture of Common Epilepsies With Cortical Brain Morphology.

Background And Objectives: Epilepsies are associated with differences in cortical thickness (TH) and surface area (SA). However, the mechanisms underlying these relationships remain elusive. We investigated the extent to which these phenotypes share genetic influences.

Unraveling the shared genetics of common epilepsies and general cognitive ability.

Objective: Cognitive impairment is prevalent among individuals with epilepsy, and it is possible that genetic factors can underlie this relationship. Here, we investigated the potential shared genetic basis of common epilepsies and general cognitive ability (COG).

Methods: We applied linkage disequilibrium score (LDSC) regression, MiXeR and conjunctional false discovery rate (conjFDR) to analyze different aspects of genetic overlap between COG and epilepsies.

Linking sarcopenia, brain structure and cognitive performance: a large-scale UK Biobank study.

Sarcopenia refers to age-related loss of muscle mass and function and is related to impaired somatic and brain health, including cognitive decline and Alzheimer's disease. However, the relationships between sarcopenia, brain structure and cognition are poorly understood. Here, we investigate the associations between sarcopenic traits, brain structure and cognitive performance.

Dissecting the genetic overlap between three complex phenotypes with trivariate MiXeR.

Comorbidities are an increasing global health challenge. Accumulating evidence suggests overlapping genetic architectures underlying comorbid complex human traits and disorders. The bivariate causal mixture model (MiXeR) can quantify the polygenic overlap between complex phenotypes beyond global genetic correlation.

Shared genetic loci between Alzheimer's disease and multiple sclerosis: Crossroads between neurodegeneration and immune system.

Background: Neuroinflammation is involved in the pathophysiology of Alzheimer's disease (AD), including immune-linked genetic variants and molecular pathways, microglia and astrocytes. Multiple Sclerosis (MS) is a chronic, immune-mediated disease with genetic and environmental risk factors and neuropathological features. There are clinical and pathobiological similarities between AD and MS.

Associations Between Symptoms of Premenstrual Disorders and Polygenic Liability for Major Psychiatric Disorders.

Importance: Premenstrual disorders are heritable, clinically heterogenous, with a range of affective spectrum comorbidities. It is unclear whether genetic predispositions to affective spectrum disorders or other major psychiatric disorders are associated with symptoms of premenstrual disorders.

Objective: To assesss whether symptoms of premenstrual disorders are associated with the genetic liability for major psychiatric disorders, as indexed by polygenic risk scores (PRSs).

Improved multimodal prediction of progression from MCI to Alzheimer's disease combining genetics with quantitative brain MRI and cognitive measures.

Introduction: There is a pressing need for non-invasive, cost-effective tools for early detection of Alzheimer's disease (AD).

Methods: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), Cox proportional models were conducted to develop a multimodal hazard score (MHS) combining age, a polygenic hazard score (PHS), brain atrophy, and memory to predict conversion from mild cognitive impairment (MCI) to dementia. Power calculations estimated required clinical trial sample sizes after hypothetical enrichment using the MHS.

Identification of novel genomic risk loci shared between common epilepsies and psychiatric disorders.

Psychiatric disorders and common epilepsies are heritable disorders with a high comorbidity and overlapping symptoms. However, the causative mechanisms underlying this relationship are poorly understood. Here we aimed to identify overlapping genetic loci between epilepsy and psychiatric disorders to gain a better understanding of their comorbidity and shared clinical features.

Levamisole-associated multifocal inflammatory encephalopathy: clinical and MRI characteristics, and diagnostic algorithm.

Levamisole-associated multifocal inflammatory encephalopathy (LAMIE) is a devastating adverse effect of levamisole (LEV) treatment. In Russia, people often use LEV without a doctor's prescription for anthelmintic prophylaxis. LAMIE often misdiagnosed as the first episode of MS or acute disseminated encephalomyelitis (ADEM).

[Peripheral vertigo as onset of an immune-mediated disorder].

In this article we present a clinical case of a female patient, 45 years old, with autoimmune encephalitis with antibodies to glutamate decarboxylase (GAD) beginning clinically with vertigo. According to high frequency of vestibular symptoms at the beginning and high frequency of admission to otoneurologist GAD-associated pathology should be included in differential diagnosis in complicated clinical cases with vertigo. These patients should be sent to neurologist.

[Autoimmune encephalitis in psychiatric institution (clinical case)].

Currently there is a new concept of «molecular neuropsychiatry» which aim is identification of biomarkers and biological substrates for mental disorders. Autoimmune encephalitis can start with psychiatric symptoms in 60% of cases. In this article we described a clinical case of a patient, 31 years old, with GABAb-associated AE started with acute polymorphic psychosis.

[Acute disseminated encephalomyelitis].

Acute disseminated encephalomyelitis (AEM) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS), usually single-phase. In WREM, multiple lesions of the central nervous system of an inflammatory-demyelinating nature accompanied by extremely polymorphic neurological disorders develop acutely or subacutely. The review considers the issues of epidemiology, trigger factors of the inflammatory process, clinical manifestations, differential and molecular diagnostics of WECM, and outlines the ways for further study of this pathology.

Stress load and neurodegeneration after gastrostomy tube placement in amyotrophic lateral sclerosis patients.

Dysphagia and progressive swallowing problems due to motoneuron death is one of amyotrophic lateral sclerosis (ALS) symptoms. Malnutrition and body weight loss result in immunological disturbances, fatigability and increase risk of secondary complications in ALS patients, percutaneous endoscopic gastrostomy tube (PEG) placement representing a well-recognized method for malnutrition correction and potentially increasing life expectancy. However, despite nutritional correction, occasional rapid neurological deterioration may develop after PEG placement.

The epidemiology of amyotrophic lateral sclerosis in Moscow (Russia).

: To estimate the incidence of amyotrophic lateral sclerosis (ALS) in Moscow by investigating multiple sources of cases. Incidence rates from previous Russian studies ranged from 0.3 to 0.

[Clinical case of levamisole-induced multifocal inflammatory leukoencephalopathy].

Levamisole is an immunomodulatory drug which can trigger development of levamisole-induced multifocal inflammatory leukoencephalopathy (LIMIL) in patients treated for helminthic invasion, aphthous stomatitis, cancer, or cocaine users. LIMIL clinical case in patient 45 years old after single dose of levamisole (taken without any medical prescription) was described. We presented clinical history and clinical picture, MRI and laboratory data and treatment results during 1-year observation.

Neurosyphilis in the modern era: Literature review and case series.

The term of neurosyphilis (NS) refers to infection of central nervous system by Treponema pallidum. Classically, it has been divided into early (meningitis, meningovascular) and late forms (general paresis and tabes dorsalis). The availability of penicillin and high sensitivity of Treponema pallidum to this antibiotic has led to a widely held perception about rarity of syphilitic forms with central nervous system involvement.

Neuronal damage and neuroinflammation markers in patients with autoimmune encephalitis and multiple sclerosis.

Inflammatory diseases of the central nervous system (CNS) are a diagnostic challenge to clinicians. Autoimmune encephalitis (AE) is an important diagnostic consideration in patients with CNS inflammatory disorders; despite of a wide range of neuropsychiatric symptoms it should be diagnosed as soon as possible and the patient transferred to the neurologist. We studied a group of AE patients (n = 24) as compared to multiple sclerosis (MS, n = 61) and control (n = 19) groups.

CLIPPERS and its mimics: evaluation of new criteria for the diagnosis of CLIPPERS.

Objective: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

Methods: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria.

Results: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2).

[The Edinburgh Cognitive and Behavioral ALS Screen (ECAS): a Russian version.].

Aim: To translate into Russian and adapt the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) for patients with amyotrophic lateral sclerosis (ALS).

Material And Methods: Medical care for ALS patients requires participation of a multidisciplinary team. More than one third of patients with ALS suffer from cognitive and behavioral disturbances, and it influences decisions of the team, patients and family.

Interleukin-6, S-Nitrosothiols, and Neurodegeneration in Different Central Nervous System Demyelinating Disorders: Is There a Relationship?

Background And Purpose: A few groups have suggested that activated cytokines and nitrosative stress are closely involved in the pathogenesis of different demyelinating disorders induced by the neuroinflammatory destruction of neurons. The purpose of this study was to elucidate the associations of cytokines and S-nitrosothiols (RSNO) with the severity of neurodegeneration during relapse in demyelinating disorders of the central nervous system.

Methods: We measured levels of interleukin-6 (IL-6), erythropoietin, RSNO, and phosphorylated neurofilament heavy chain (pNfh) in cerebrospinal fluid (CSF) samples obtained from patients with different demyelinating disorders: multiple sclerosis (MS, n=52), acute disseminated encephalomyelitis (ADEM, n=9), and neuromyelitis optica spectrum disorders (NMOSD) with aquaporin-4 immunoglobulin G (AQP4-IgG, n=12).