Understanding recent advances in non-amyloid/non-tau (NANT) biomarkers and therapeutic targets in Alzheimer's disease.

Unlabelled: The Alzheimer's disease (AD) research community continues to make great strides in expanding approaches for early detection and treatment of the disease, including recent advances in our understanding of fundamental AD pathophysiology beyond the classical targets: beta-amyloid and tau. Recent clinical trial readouts implicate a variety of non-amyloid/non-tau (NANT) approaches that show promise in slowing cognitive decline for people with AD. The Alzheimer's Association Research Roundtable (AARR) meeting held on December 13-14, 2022, reviewed the current state of NANT targets on underlying AD pathophysiology and their contribution to cognitive decline, the current data on a diverse range of NANT biomarkers and therapeutic targets, and the integration of NANT concepts in clinical trial designs.

Vagus nerve stimulation for conservative therapy-refractive epilepsy and depression.

Numerous studies confirm that the vagus nerve stimulation (VNS) is an efficient, indirect neuromodulatory therapy with electrically induced current for epilepsy that cannot be treated by epilepsy surgery and is therapy-refractory and for drug therapy-refractory depression. VNS is an established, evidence-based and in the long-term cost-effective therapy in an interdisciplinary overall concept.Long-term data on the safety and tolerance of the method are available despite the heterogeneity of the patient populations.

[Results of vagus nerve stimulator implantation in children and adolescents with treatment-refractory epilepsy].

Vagus nerve stimulation (VNS) is a therapeutic procedure that can be applied in a palliative setting in patients with treatment-refractory epilepsy who are not suitable for epilepsy surgery. The mechanism of action of VNS is currently not completely understood but appears to depend on a modification of neurotransmitter metabolism. Data of 25 patients with treatment-refractory epilepsy who underwent implantation of a vagus nerve stimulator were retrospectively analyzed in a monocentric study.

Magnetic Imaging of Encapsulated Superparamagnetic Nanoparticles by Data Fusion of Magnetic Force Microscopy and Atomic Force Microscopy Signals for Correction of Topographic Crosstalk.

Encapsulated magnetic nanoparticles are of increasing interest for biomedical applications. However, up to now, it is still not possible to characterize their localized magnetic properties within the capsules. Magnetic Force Microscopy (MFM) has proved to be a suitable technique to image magnetic nanoparticles at ambient conditions revealing information about the spatial distribution and the magnetic properties of the nanoparticles simultaneously.

Influence of dielectric layer thickness and roughness on topographic effects in magnetic force microscopy.

Magnetic force microscopy (MFM) has become a widely used tool for the characterization of magnetic properties. However, the magnetic signal can be overlapped by additional forces acting on the tip such as electrostatic forces. In this work the possibility to reduce capacitive coupling effects between tip and substrate is discussed in relation to the thickness of a dielectric layer introduced in the system.

[Orbital complications].

A disease or symptom of disease spreading from the vicinity of the orbit to the internal structures of the orbit is referred to as an orbital complication. Orbital complications can have a traumatic, inflammatory, allergic, or autoimmunologic cause. They are more frequent in children than adults.

2D laser lithography on silicon substrates via photoinduced copper-mediated radical polymerization.

A 2D laser lithography protocol for controlled grafting of polymer brushes in a single-step is presented. A series of polyacrylates were grafted from silicon substrates via laser-induced copper-mediated radical polymerization. Film thicknesses up to 39 nm were reached within 125 μs of exposure to UV laser light (351 nm).

Organocatalyzed Photo-Atom Transfer Radical Polymerization of Methacrylic Acid in Continuous Flow and Surface Grafting.

The organocatalyzed photo-atom transfer radical polymerization (photoATRP) using 10-phenylphenothiazine as catalyst is studied toward its use in methacrylic acid (MAA) polymerization and surface grafting. The organocatalyzed photoATRP of methyl methacrylate (MMA) is first optimized for continuous flow synthesis in order to assess the livingness of the polymerization. MMA can be polymerized in batch and in flow; however, conversions are limited by the loss of bromine functionality and hence high conversions have to be traded in with increasing dispersities.

[Traumatic optic nerve neuropathy. Longterm results following microsurgical optic nerve decompression].

Background: Traumatic optic nerve neuropathy (TON) is defined as injury to the optic nerve with subsequent vision loss due to head or craniocerebral trauma. The treatment of this disease is the subject of controversial discussions. The purpose of the present study was to investigate pre- and immediate postoperative visual acuity in patients with unilateral TON and to compare the results with the time interval between trauma and surgical intervention.

Memantine in moderate to severe Alzheimer's disease: a meta-analysis of randomised clinical trials.

The efficacy of memantine in Alzheimer's disease (AD) has been investigated in multiple randomised, placebo-controlled phase III trials. Recently, the indication label for memantine in Europe was extended to cover patients with moderate to severe AD, i.e.

Neuroprotective and symptomatological action of memantine relevant for Alzheimer's disease--a unified glutamatergic hypothesis on the mechanism of action.

The involvement of glutamate mediated neurotoxicity in the pathogenesis of Alzheimer's disease is finding increasingly more acceptance in the scientific community. Central to this hypothesis is the assumption that in particular glutamate receptors of the N-methyl-D-aspartate (NMDA) type are overactivated in a tonic rather than a phasic manner. Such continuous mild activation leads under chronic conditions to neuronal damage.

A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease.

Background: This study is an extension of a 28-week, randomized, double-blind, placebo-controlled study of memantine in 252 patients with moderate to severe Alzheimer disease.

Objective: To evaluate long-term memantine treatment in moderate to severe Alzheimer disease.

Design, Setting, And Patients: Open-label, 24-week extension trial.

Memantine in vascular dementia.

The uncompetitive N-methyl-D-aspartate (NMDA) antagonist memantine was tested against placebo in two randomized controlled trials. In total, 900 patients suffering from mild-to-moderate "probable" VaD (according to NINDS-AIREN criteria) were included. In these prospective, 2-arm parallel, multicenter trials conducted in the United Kingdom (MMM500) and in France (MMM300), patients suffering from "probable" vascular dementia (according to NINDS-AIREN criteria) were recruited.

Ambulatory electrical cardioversion of atrial fibrillation.

Elective electrical cardioversion of atrial fibrillation is an effective and safe cardiac procedure in selected patients. It is most often performed during a short hospital stay or in an outpatient setting of a hospital. In a retrospective analysis, we report our experience on electrical cardioversions in private practice without a hospital stand-by performed by a cardiologist and an anesthesiologist in concert.

Effects of memantine on behavioural symptoms in Alzheimer's disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies.

Introduction: Behavioural symptoms are common in moderate to severe Alzheimer's disease (AD). We have analysed the databases of two randomised studies with regard to the effects of memantine treatment on behavioural symptoms, measured using the 12-item version of the Neuropsychiatric Inventory (NPI).

Subjects: The monotherapy study (memantine only) reported by Reisberg et al.

Memantine hydrochloride: pharmacological and clinical profile.

Memantine (Axura, Merz Pharmaceuticals GmbH; Ebixa, H. Lundbeck A/S, Namenda, Forest Laboratories, Inc.) is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with low to moderate affinity for the (+)MK-801 binding site.

Specific functional effects of memantine treatment in patients with moderate to severe Alzheimer's disease.

Treatment of Alzheimer's disease (AD) that combats progressive functional deterioration can improve the patient's quality of life and reduce caregiver burden. Memantine, a moderate affinity N-methyl-D-aspartate receptor antagonist, reduces global deterioration in AD patients and provides cognitive and functional benefits relative to placebo. Two previous studies reported statistically significant benefits of memantine for overall functional ability on the Alzheimer Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia (ADCS-ADL(19)), Functional Assessment Staging, and G2 scale.

Memantine: update on the current evidence.

Nine years after the initial approval of a cholinergic drug for the treatment of Alzheimer's Disease in the USA, a compound with a different pharmacological approach, namely the NMDA antagonist memantine, has been approved for the first time in Europe in 2002. This event led to an enhanced perception of a decade of basic research work on its mode of action. At the same time, additional preclinical data, e.

Memantine in moderate-to-severe Alzheimer's disease.

Background: Overstimulation of the N-methyl-D-aspartate (NMDA) receptor by glutamate is implicated in neurodegenerative disorders. Accordingly, we investigated memantine, an NMDA antagonist, for the treatment of Alzheimer's disease.

Methods: Patients with moderate-to-severe Alzheimer's disease were randomly assigned to receive placebo or 20 mg of memantine daily for 28 weeks.

Resource utilisation and cost analysis of memantine in patients with moderate to severe Alzheimer's disease.

Background: Alzheimer's disease (AD) is a devastating illness that causes enormous emotional stress to affected families and is associated with substantial medical and nonmedical costs.

Objective: To determine the effects of 28 weeks of memantine treatment for patients with AD on resource utilisation and costs.

Study Design And Methods: Multicentre, prospective, double-blind, randomised, placebo-controlled clinical trial performed in the US.

Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy.

Memantine, a moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be effective in dementia, including Alzheimer disease (AD). Therefore, its combination with acetylcholinesterase inhibitors (AChEIs) is anticipated. We report a postmarketing surveillance study conducted among German physicians who, during routine clinical practice, treated demented patients with memantine in combination with an AChEI.

Glutamate receptors as a target for Alzheimer's disease--are clinical results supporting the hope?

Several years after the introduction of cholinergic drugs in Alzheimer's disease therapy, other approaches for symptomatic and also disease-modifying pharmacotherapy are progressing in their development. Among these, the NMDA antagonist memantine represents the most advanced and promising agent, gifted with many years of clinical experience in Germany. This paper provides an overview of both, the novel pharmacological background and recent clinical evidence in dementia.

Measuring cognition in advanced Alzheimer's disease for clinical trials.

Measurement of cognitive dysfunction and treatment response in the early stages of Alzheimer's disease (AD) has used such scales as the Mini-Mental State Examination (MMSE) and the AD Assessment Scale (ADAS). With the exception of clinical rating scales, however, there are only a few objective measures of cognition for tracking progression in advanced AD. Given renewed interest in potential therapies for advanced AD, objective measures of cognition are important for the adequate evaluation of change due to AD progression or therapy.

A double-blind, placebo-controlled multicentre study of memantine in mild to moderate vascular dementia (MMM500).

The aim of the reported trial was to investigate the safety and efficacy of memantine in mild to moderate vascular dementia (VaD). This was a 28-week, double-blind, parallel, randomized controlled trial of memantine 20 mg daily versus placebo which was conducted in 54 centres in the UK. Memantine is a uncompetitive, moderate affinity N-methyl-D-aspartate receptor antagonist.

Efficacy and safety of memantine in patients with mild to moderate vascular dementia: a randomized, placebo-controlled trial (MMM 300).

Background And Purpose: Based on the hypothesis of glutamate-induced neurotoxicity (excitotoxicity) in cerebral ischemia, this study examined the efficacy and tolerability of memantine, an uncompetitive N-methyl-D-aspartate antagonist, in the treatment of mild to moderate vascular dementia.

Methods: In this multicenter, 28-week trial carried out in France, 321 patients received 10 mg/d memantine or placebo twice a day; 288 patients were valid for intent-to-treat analysis. Patients had to meet the criteria for probable vascular dementia and have a Mini-Mental State (MMSE) score between 12 and 20 at inclusion.