Brain health: Pathway to primary prevention of neurodegenerative disorders of environmental origin.

While rising global rates of neurodegenerative disease encourage early diagnosis and therapeutic intervention to block clinical expression (secondary prevention), a more powerful approach is to identify and remove environmental factors that trigger long-latencybrain disease (primary prevention) by acting on a susceptible genotype or acting alone. The latter is illustrated by the post-World War II decline and disappearance of Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC), a prototypical often-familial neurodegenerative disease formerly present in very high incidence on the island of Guam. Lessons learned from 75 years of investigation on the etiology of ALS/PDC include: the importance of focusing field research on the disease epicenter and patients with early-onset disease; soliciting exposure history from patients, family, and community to guide multidisciplinary biomedical investigation; recognition that disease phenotype may vary with exposure history, and that familial brain disease may have a primarily environmental origin.

A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer's disease.

Trial Registration: ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic.

Clinicaltrials: gov/ct2/show/NCT05821153.

Environmental neurology: Concepts and short history of an interdisciplinary approach to etiology, treatment and prevention.

Environmental Neurology (EN), a sub-discipline of Neurology and Neurological Sciences, favors an interdisciplinary collaboration allowing a holistic approach to understanding the impact of environmental factors on the nervous system and their relationship with neurological diseases. Several examples of diseases and conditions show the large scope of subjects addressed by EN. The EN sub-discipline focuses on both individual and population issues thus joining patient care and public health, respectively.

What does aducanumab treatment of Alzheimer's disease mean for research on vascular cognitive disorders?

•Controversial registration of aducanumab for Alzheimer's Disease•Aducanumab is the subject of post-licensing observational studies aiming to follow the effects of the drug•Given the high prevalence of cerebrovascular pathology it is important that these studies do not ignore vascular cognitive disorders•The studies may give detailed phenotyping data that may lead to knowledge of targets for treatments of patients with vascular cognitive disorders.

Pleural effusion and respiratory compromise from spontaneous migration of a ventriculoperitoneal shunt catheter in a patient with normal-pressure hydrocephalus.

Background: Ventriculoperitoneal shunt (VPS) insertion is one of the most common neurosurgical procedures done around the world to treat hydrocephalus. The occurrence of spontaneous migration of the peritoneal shunt catheter into the thoracic cavity is a very rare complication; we report here case number 27 of respiratory complications of a VPS in a patient with normal-pressure hydrocephalus (NPH).

Case Description: A 76-year-old woman with Alzheimer's disease and anosognosia was diagnosed idiopathic NPH treated surgically with a VPS.

The pericyte: A critical cell in the pathogenesis of CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease presenting with migraine, mood and cognitive disorders, focal neurological deficits, recurrent ischemic attacks, lacunar infarcts and brain white matter changes. As they age, CADASIL patients invariably develop cognitive impairment and subcortical dementia. CADASIL is caused by missense mutations in the gene resulting in a profound cerebral vasculopathy affecting primarily arterial vascular smooth muscle cells, which target the microcirculation and perfusion.

Clinical Phenotype and Mutation Spectrum of Alzheimer's Disease with Causative Genetic Mutation in a Chinese Cohort.

Background: Alzheimer's disease with a causative genetic mutation (AD-CGM) is an uncommon form, characterized by a heterogeneous clinical phenotype and variations in the genotype of racial groups affected.

Objective: We aimed to systemically describe the phenotype variance and mutation spectrum in the large sample size of the Peking Union Medical College Hospital (PUMCH) cohort, Beijing, China.

Methods: Next-generation sequencing (NGS) was carried out in 1108 patients diagnosed with dementia.

Acute Transverse Myelitis (ATM):Clinical Review of 43 Patients With COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse Events With the ChAdOx1 nCoV-19 Vaccine (AZD1222).

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic.

Neuroinflammation is highest in areas of disease progression in semantic dementia.

Despite epidemiological and genetic data linking semantic dementia to inflammation, the topography of neuroinflammation in semantic dementia, also known as the semantic variant of primary progressive aphasia, remains unclear. The pathology starts at the tip of the left temporal lobe where, in addition to cortical atrophy, a strong signal appears with the tau PET tracer 18F-flortaucipir, even though the disease is not typically associated with tau but with TDP-43 protein aggregates. Here, we characterized the topography of inflammation in semantic variant primary progressive aphasia using high-resolution PET and the tracer 11C-PBR28 as a marker of microglial activation.

The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries.

A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers.

, Vascular Risk Factors and Cognition in U.S. Older Adults.

Previous studies suggested that infection could be a risk factor for stroke, dementia, and Alzheimer's disease (AD). The authors examined data from participants, 60 years old and older in the Third National Health and Nutrition Examination Survey (NHANES-III) to assess the relation between infection and results of the Mini-Mental State Examination (n = 1860) using logistic regression analysis controlling for age, gender, race/ethnicity, education, poverty and history of medically diagnosed diabetes. Moreover, we examined performance on the digit-symbol substitution test (DSST) of 1031 participants in the 1999-2000 NHANES according to their infection status controlling for potential confounders using multiple linear regression analyses.

Gene Mutations Correlate with White Matter Disease Burden and Predict Cerebrovascular Disease and Dementia.

The incidence of dementia is on the rise and expected to continue to increase in the foreseeable future. Two of the most common subtypes of dementia are Alzheimer's subtype and vascular dementia. Hyperhomocysteinemia has been shown to serve as a risk factor for dementia due to an associated blood-brain barrier dysfunction and subsequent small-vessel disease pathology.

Multimodal F-AV-1451 and MRI Findings in Nonfluent Variant of Primary Progressive Aphasia: Possible Insights on Nodal Propagation of Tau Protein Across the Syntactic Network.

Although abnormally folded tau protein has been found to self-propagate from neuron to connected neuron, similar propagation through human brain networks has not been fully documented. We studied tau propagation in the left hemispheric syntactic network, which comprises an anterior frontal node and a posterior temporal node connected by the white matter of the left arcuate fasciculus. This network is affected in the nonfluent variant of primary progressive aphasia, a neurodegenerative disorder with tau accumulation.

Normal-pressure hydrocephalus: A critical review.

Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia and urinary incontinence. A critical review of the concept, pathophysiology, diagnosis, and treatment of both idiopathic and secondary NPH was conducted. We searched Medline and PubMed databases from January 2012 to December 2018 using the keywords "normal-pressure hydrocephalus" / "idiopathic normal-pressure hydrocephalus" / "secondary normal-pressure hydrocephalus" / "NPH" / "ventriculoperitoneal shunt".

Sleep-Disordered Breathing and Idiopathic Normal-Pressure Hydrocephalus: Recent Pathophysiological Advances.

Purpose Of Review: Idiopathic normal-pressure hydrocephalus (iNPH) is characterized clinically by ventriculomegaly, abnormal gait, falls, incontinence, and cognitive decline. This article reviews recent advances in the pathophysiology of iNPH concerning sleep-disordered breathing (SDB) and glymphatic circulation during deep sleep.

Recent Findings: The authors found iNPH frequently associated with obstructive sleep apnea (OSA).