Roflumilast and cognition enhancement: A translational perspective.

Cognitive impairment affiliated with neurological disorders has a severe impact on daily life functioning and the quality of life of patients. This is associated with a significant and long-lasting health, social and financial burden, not only for the patients, but also for families and the wider society. However, treatment for cognitive impairment is only available for the indication Alzheimer's disease (AD) and its prodromal stage Mild Cognitive Impairment (MCI), although with major adverse effects, i.

A mindful approach to controlling intrusive thoughts.

Intrusive thoughts of negative experiences can pose a threat to our well-being. To some extent, unwanted memories can be intentionally controlled via an executive control mechanism that downregulates the occurrence of intrusions. Mindfulness training can improve executive control.

Age Effects on Old/New Recognition Memory Involving Abstract Figures and Non-words.

Age-related memory problems posit a growing concern in our society. This study investigated the impact of age and memory strength on recognition memory of pre-experimentally unfamiliar abstract figures and non-words. We applied a three-phase old/new recognition memory paradigm and manipulated memory strength as a function of the Levels of Processing (deep vs.

The antimuscarinic agent biperiden selectively impairs recognition of abstract figures without affecting the processing of non-words.

Objectives: The present study investigated the effects of biperiden, a muscarinic type 1 antagonist, on the recognition performance of pre-experimentally unfamiliar abstract figures and non-words in healthy young volunteers. The aim was to examine whether 4 mg biperiden could model the recognition memory impairment seen in healthy aging.

Methods: A double-blind, placebo-controlled, two-way crossover study was conducted.

EEG Correlates of Old/New Discrimination Performance Involving Abstract Figures and Non-Words.

The processing of pre-experimentally unfamiliar stimuli such as abstract figures and non-words is poorly understood. Here, we considered the role of memory strength in the discrimination process of such stimuli using a three-phase old/new recognition memory paradigm. Memory strength was manipulated as a function of the levels of processing (deep vs.

Optimizing Behavioral Paradigms to Facilitate Development of New Treatments for Anhedonia and Reward Processing Deficits in Schizophrenia and Major Depressive Disorder: Study Protocol.

Behavioral tasks focusing on different subdomains of reward processing may provide more objective and quantifiable measures of anhedonia and impaired motivation compared with clinical scales. Typically, single tasks are used in relatively small studies to compare cases and controls in one indication, but they are rarely included in larger multisite trials. This is due to limited systematic standardization as well as the challenges of deployment in international studies and stringent adherence to the high regulatory requirements for data integrity.

Biperiden Selectively Impairs Verbal Episodic Memory in a Dose- and Time-Dependent Manner in Healthy Subjects.

Purpose/background: Biperiden is a muscarinic antagonist that produces memory impairments without impairing attention or motor functions in healthy subjects. It has been suggested that a biperiden-induced memory deficit could model age- and dementia-related memory impairments. The goal of the current study was to determine the dose- and time-dependent effects of biperiden on cognition in healthy volunteers.

Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals: a double-blind placebo-controlled study.

There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design.

No interaction between rivastigmine and citalopram on memory and novelty processing in healthy human volunteers.

Background: Animal literature suggests an interaction between acetylcholine and serotonin on cognitive functions.

Aims: The aim of the current study was to assess whether both neurotransmitters interact during memory and novelty processing in humans.

Methods: We tested the interaction between acetylcholine and serotonin on cognitive functions in healthy volunteers by means of treatment with rivastigmine and citalopram, respectively.

The effects of the soluble guanylate cyclase stimulator riociguat on memory performance in healthy volunteers with a biperiden-induced memory impairment.

Rationale: After stimulation with nitric oxide, soluble guanylate cyclase (sGC) produces cyclic guanosine monophosphate (cGMP), which stimulates an important signalling pathway for long-term potentiation (LTP). By upregulating cGMP, LTP could be stimulated and thereby enhancing memory processes. The present study investigated the effects of the sGC stimulator riociguat on cognition in healthy volunteers.

Acute administration of roflumilast enhances immediate recall of verbal word memory in healthy young adults.

The need for new and effective treatments for dementia remains indisputably high. Phosphodiesterase inhibitors (PDE-Is) have proven efficacy as cognitive enhancers based on their positive effects in numerous preclinical studies. Especially the PDE4 subfamily is of interest due to its expression in the hippocampus, the key structure for memory formation.

Acute administration of roflumilast enhances sensory gating in healthy young humans in a randomized trial.

Introduction: Sensory gating is a process involved in early information processing which prevents overstimulation of higher cortical areas by filtering sensory information. Research has shown that the process of sensory gating is disrupted in patients suffering from clinical disorders including attention deficit hyper activity disorder, schizophrenia, and Alzheimer's disease. Phosphodiesterase (PDE) inhibitors have received an increased interest as a tool to improve cognitive performance in both animals and man, including sensory gating.

Role of acetylcholine and serotonin in novelty processing using an oddball paradigm.

The processing of novel stimuli is known to take place in the hippocampus and frontal cortex, and is influenced by the cholinergic system. This ability is crucial to help detect changes in the environment and adapt behaviour accordingly. Previous research has shown that acetylcholine (ACh) can interact with serotonin (5-HT) at the hippocampal level, which may have consequences for cognitive functioning.

Effects of biperiden and acute tryptophan depletion and their combination on verbal word memory and EEG.

Background: Research on the neurobiological foundations of memory has shown that multiple neurotransmitters play an important role in memory processing. To study the interaction between neurotransmitters such as acetylcholine and serotonin, pharmacological models can be used. In this study, we tested the effects of the muscarinic M1 antagonist biperiden, acute tryptophan depletion (ATD), and the interaction between the two on episodic memory using the verbal learning task.

Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective.

Background: Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users.

The PDE4 inhibitor roflumilast improves memory in rodents at non-emetic doses.

Enhancement of central availability of the second messenger cAMP is a promising approach to improve cognitive function. Pharmacological inhibition of phosphodiesterase type 4 (PDE4), a group of cAMP hydrolyzing enzymes in the brain, has been shown to improve cognitive performances in rodents and monkeys. However, inhibition of PDE4 is generally associated with severe emetic side-effects.

Treatment of Cognitive Impairment in Schizophrenia: Potential Value of Phosphodiesterase Inhibitors in Prefrontal Dysfunction.

No pharmacological treatment is available to date that shows satisfactory effects on cognitive symptoms in patients diagnosed with schizophrenia. Phosphodiesterase inhibitors (PDE-Is) improve neurotransmitter signaling by interfering in intracellular second messenger cascades. By preventing the breakdown of cAMP and/or cGMP, central neurotransmitter activity is maintained.

The use of EEG parameters as predictors of drug effects on cognition.

It has been shown to be difficult to predict whether cognition-enhancing effects of drugs in animal studies have the same effect in humans. Various issues in translating findings from animal to human studies can be identified. Here we discuss whether EEG could be considered as a possible tool to translate the effects of cognition enhancers across species.

Biperiden selectively induces memory impairment in healthy volunteers: no interaction with citalopram.

Rationale: Traditionally, the non-selective muscarinic antagonist scopolamine has been used to induce episodic memory impairments as found in Alzheimer's disease (AD). However, it also impairs attention and induces drowsiness. Muscarinic antagonists more selective for the M1 receptor might, therefore, be preferred.

Rivastigmine but not vardenafil reverses cannabis-induced impairment of verbal memory in healthy humans.

Rationale: One of the most often reported cognitive deficits of acute cannabis administration is an impaired recall of previously learned information.

Objective: The aim of the present study was to determine whether cannabis-induced memory impairment in humans is mediated via glutamatergic or cholinergic pathways.

Methods: Fifteen occasional cannabis users participated in a double-blind, placebo-controlled, six-way cross-over study.

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies.

Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain.

Effects of remifentanil on processing of auditory stimuli: a combined MEG/EEG study.

Remifentanil (Ultiva(®)) is a potent ultra-short acting mu-opioid receptor agonist used for perioperative pain treatment and anaesthesia. So far, it is not known how sensitive the cognitive processing of auditory perception elicited by the mismatch negativity (MMN) paradigm is to opioids. The present exploratory study investigated how the opioid remifentanil modulates different stages of auditory processing as reflected in the MMN(m) and P3a(m).

Cognitive effects of methylphenidate and levodopa in healthy volunteers.

Our previous study showed enhanced declarative memory consolidation after acute methylphenidate (MPH) administration. The primary aim of the current study was to investigate the duration of this effect. Secondary, the dopaminergic contribution of MPH effects, the electrophysiological correlates of declarative memory, and the specificity of memory enhancing effects of MPH to declarative memory were assessed.