Preventing the spread of COVID-19 in long-term care homes is critical for the health of residents who live in these institutions. As a result, broad policies restricting visits to these facilities were put in place internationally. While well meaning, these policies have exacerbated the ongoing social isolation crisis present in long-term care homes prior to the COVID-19 pandemic. This perspective highlights the dominant COVID-19 LTC policies from six countries, and proposes five strategies to address or mitigate social isolation during the COVID-19 pandemic that can also be applied in a post-pandemic world.

The Impact of COVID-19 on Social Isolation in Long-term Care Homes: Perspectives of Policies and Strategies from Six Countries.

Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

Some Candidate Drugs for Pharmacotherapy of Alzheimer's Disease.

Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are neurodevelopmental and neurodegenerative disorders affecting two opposite ends of life span, i.e., childhood and old age. Both disorders pose a cumulative threat to human health, with the rate of incidences increasing considerably worldwide. In the context of recent developments, we aimed to review correlated symptoms and genetics, and overlapping aspects in the mechanisms of the pathogenesis of ASD and AD. Dementia, insomnia, and weak neuromuscular interaction, as well as communicative and cognitive impairments, are shared symptoms. A number of genes and proteins linked with both disorders have been tabulated, including MECP2, ADNP, SCN2A, NLGN, SHANK, PTEN, RELN, and FMR1. Theories about the role of neuron development, processing, connectivity, and levels of neurotransmitters in both disorders have been discussed. Based on the recent literature, the roles of FMRP (Fragile X mental retardation protein), hnRNPC (heterogeneous ribonucleoprotein-C), IRP (Iron regulatory proteins), miRNAs (MicroRNAs), and α-, β0, and γ-secretases in the posttranscriptional regulation of cellular synthesis and processing of APP (amyloid-β precursor protein) have been elaborated to describe the parallel and overlapping routes and mechanisms of ASD and AD pathogenesis. However, the interactive role of genetic and environmental factors, oxidative and metal ion stress, mutations in the associated genes, and alterations in the related cellular pathways in the development of ASD and AD needs further investigation.

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer's Disease.

Creutzfeldt-Jakob disease (CJD) is a rare and fatal condition that leads to progressive neurodegeneration due to gliosis, vacuolation of central nervous system tissue, and loss of neurons. Microglia play a crucial role in maintaining Central Nervous System (CNS) homoeostasis, both in health and disease, through phagocytosis and cytokine production. In the context of CJD, the immunomodulatory function of microglia turns it into a cell of particular interest. Microglia would be activated by infectious prion proteins, initially acquiring a phagocytic and anti-inflammatory profile (M2), and producing cytokines such as IL-4, IL-10, and TGF-β. Therefore, microglia are seen as a key target for the development of new treatment approaches, with many emerging strategies to guide it towards a beneficial role upon neuroinflammation, by manipulating its metabolic pathways. In such a setting, many cellular targets in microglia that can be involved in phenotype modulation, such as membrane receptors, have been identified and pointed out as possible targets for further experiments and therapeutic approaches. In this article, we review the major findings about the role of microglia in CJD, including its relationship to some risk factors associated with the development of the disease. Furthermore, considering its central role in neural immunity, we explore microglial connection with other elements of the immune system and cell signalling, such as inflammasomes, the complement and purinergic systems, and the latest finding strategies to guide these cells from harmful to beneficial roles.

The role of microglia in prion diseases and possible therapeutic targets: a literature review.

RESUMO Atualmente não há tratamento curativo para as demências neurodegenerativas ou para a demência vascular, mas algumas intervenções farmacológicas e não farmacológicas podem contribuir para aliviar os sintomas, retardar a progressão da doença e melhorar a qualidade de vida. As abordagens terapêuticas atuais são baseadas na etiologia, no perfil dos sintomas e no estágio da demência. Neste artigo apresentamos recomendações sobre os tratamentos farmacológicos e não farmacológicos da demência devida à doença de Alzheimer, comprometimento cognitivo vascular, demência frontotemporal, demência da doença de Parkinson e demência com corpos de Lewy.

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Tratamento da demência: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

We assessed psychotropic prescribing patterns in the clinical treatment of agitation and aggressive behavior in patients with Alzheimer's disease (AD) treated at specialist outpatient clinics in the Federal District of Brazil. This was a naturalistic, observational, multicenter study of a convenience sample of patients with AD (according to DSM-5) who had behavioral symptoms of aggression and/or agitation at outpatient visits, as assessed by the Neuropsychiatric Inventory (NPI), and required pharmacologic intervention. Participants were recruited in 2018-2019 from 11 AD treatment centers. Sociodemographic and clinical data were collected during routine visits. The sample consisted of 369 older adults with a mean age of 82.3 (SD, 7.7) years. The medications most commonly used in patients with behavioral disorders were antidepressants (79.1%), antipsychotics (70.2%), benzodiazepines (10.6%), and mood stabilizers (9.5%). Quetiapine was the most frequently prescribed antipsychotic medication (48.5%), at a mean dose of 57.4 (SD, 40.7) mg. Citalopram was the most widely used antidepressant medication (32.0%), at a mean daily dose of 24.1 (SD, 8.1) mg. In this sample, two or more pharmacologic agents were frequently used together to control aggression and agitation. Benzodiazepine was not frequently used.

Use of psychotropic agents to treat agitation and aggression in Brazilian patients with Alzheimer's disease: A naturalistic and multicenter study

caused by a misfolded variant of the cellular prion protein (PrP) known as PrPSc. The clinical presentation of sCJD includes a wide range of neurological signs of cortical, subcortical, or cerebellar origin, either isolated or in various combinations. Due to this protean clinical presentation form, sCJD must be distinguished from other dementias. In this case report, we discuss the Heidenhain variant of Creutzfeldt-Jakob disease (HvCJD), a rare variant characterized by early visual symptoms and typical findings in imaging scans. Our patient presented rapidly progressive dementia and a history of visual hallucinations. As for other prion diseases, only symptomatic treatment is available for HvCJD. Thirty years of clinical investigation of patients with prion disease have resulted in little progress in either defining or evaluating potential treatments.

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Heidenhain Variant of Creutzfeldt-Jakob Disease in Brazil: a case report

ABSTRACT We present the case report of a 61-year-old male participant with chronic conduction aphasia and deep agraphia after ischemic stroke who received training on writing under dictation associated with transcranial direct current stimulation. The treatment consisted of five 50-minute dictation sessions with the application of 2 mA of anodal transcranial direct current stimulation for 20 minutes over the left occipitotemporal cortex. The participant improved his written production of pseudowords and regular low-frequency words, via the phonological route, in addition to a small improvement in the production of irregular words, via the lexical route. After training, there was also a small improvement in writing for untrained stimuli, suggesting generalization. In the assessment carried out 5 months after the end of the treatment, the benefit was maintained for stimuli processed via the phonological route. The results are promising given the severity and chronicity of the case and suggest that transcranial direct current stimulation associated with writing therapy represents a possible clinical alternative for patients with deep agraphia.

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Luciana Lilian Louzada Martini

Papers

Use of psychotropic agents to treat agitation and aggression in Brazilian patients with Alzheimer's disease: A naturalistic and multicenter study

Heidenhain Variant of Creutzfeldt-Jakob Disease in Brazil: a case report

Effects of Transcranial Direct Current Stimulation in writing: a case report of deep agraphia