Cognitive Effects of Montelukast: A Pharmaco-EEG Study.

Montelukast is a well-established antiasthmatic drug with little side effects. It is a leukotriene receptor antagonist and recent research suggests cognitive benefits from its anti-inflammatory actions on the central nervous system. However, changes in brain activity were not directly shown so far in humans. This study aims to document changes in brain activity that are associated with cognitive improvement during treatment with Montelukast. We recorded EEG and conducted neuropsychological tests in 12 asthma-patients aged 38-73 years before and after 8 weeks of treatment with Montelukast. We found no significant changes on neuropsychological scales for memory, attention, and mood. In the EEG, we found decreased entropy at follow up during rest (p < 0.005). During episodic memory acquisition we found decreased entropy (p < 0.01) and acceleration of the background rhythm (p < 0.05). During visual attention performance, we detected an increase in gamma power (p < 0.005) and slowing of the background rhythm (p < 0.05). The study is limited by its small sample size, young age and absence of baseline cognitive impairment of the participants. Unspecific changes in brain activity were not accompanied by cognitive improvement. Future studies should examine elderly patients with cognitive impairment in a double-blind study with longer-term treatment by Montelukast.

Prediction of Cognitive Decline in Temporal Lobe Epilepsy and Mild Cognitive Impairment by EEG, MRI, and Neuropsychology.

Cognitive decline is a severe concern of patients with mild cognitive impairment. Also, in patients with temporal lobe epilepsy, memory problems are a frequently encountered problem with potential progression. On the background of a unifying hypothesis for cognitive decline, we merged knowledge from dementia and epilepsy research in order to identify biomarkers with a high predictive value for cognitive decline across and beyond these groups that can be fed into intelligent systems. We prospectively assessed patients with temporal lobe epilepsy (N = 9), mild cognitive impairment (N = 19), and subjective cognitive complaints (N = 4) and healthy controls (N = 18). All had structural cerebral MRI, EEG at rest and during declarative verbal memory performance, and a neuropsychological assessment which was repeated after 18 months. Cognitive decline was defined as significant change on neuropsychological subscales. We extracted volumetric and shape features from MRI and brain network measures from EEG and fed these features alongside a baseline testing in neuropsychology into a machine learning framework with feature subset selection and 5-fold cross validation. Out of 50 patients, 27 had a decline over time in executive functions, 23 in visual-verbal memory, 23 in divided attention, and 7 patients had an increase in depression scores. The best sensitivity/specificity for decline was 72%/82% for executive functions based on a feature combination from MRI volumetry and EEG partial coherence during recall of memories; 95%/74% for visual-verbal memory by combination of MRI-wavelet features and neuropsychology; 84%/76% for divided attention by combination of MRI-wavelet features and neuropsychology; and 81%/90% for increase of depression by combination of EEG partial directed coherence factor at rest and neuropsychology. Combining information from EEG, MRI, and neuropsychology in order to predict neuropsychological changes in a heterogeneous population could create a more general model of cognitive performance decline.

A virtual reality paradigm to assess episodic memory: Validation-dataset for six parallel versions and a structured behavioral assessment.

In the epilepsy monitoring unit of the Department of Neurology at the University Clinic of Salzburg 20 adult patients were recruited to participate in a validation of 6 parallel versions of the virtual reality test for episodic memory. Patients were tested up to 7 times, i.e. twice a day, in the morning and evening, beginning on Monday evening. Each session consisted of learning a new town and immediate recall for this town. All sessions but the first one included also delayed recall of the previously learned town and a recognition test. Recall included the sub-scales what, details, when, egocentric where and allocentric where. Recognition memory was tested by presenting the patients 30 sentences of which 15 were true and 15 were false. While not all patients completed the full testing schedule, at immediate recall for 9 patients a full data set (7 sessions) is available. All patients were free of antiepileptic medication (N = 19) or medication was kept constant across the week (N = 1). This data can be used to demonstrate the feasibility to use the virtual reality test in the epilepsy monitoring unit e.g. to monitor effects of seizures or medication on episodic memory.

Effects of Antiepileptic Drug Tapering on Episodic Memory as Measured by Virtual Reality Tests.

Antiepileptic drugs impair episodic memory in patients with epilepsy, but this effect has so far only been examined with tests that do not provide first-person experience-an aspect that is crucial for episodic memory. Virtual reality techniques facilitate the development of ecologically valid tests. In the present study, we measure the effect of antiepileptic drug changes in a within-subject design using a virtual reality test in order to provide direct evidence for effects of antiepileptic drugs on episodic memory. Among 106 recruited patients, 97 participated in a virtual reality test up to six times during a 4-day hospitalization, and 78 patients underwent changes in drug load during this period. There were six parallel versions of a virtual town test, with immediate recall and delayed recall after about 12 h. The test requires recall of elements, details, sequence of experience, and egocentric and allocentric spatial memory. We determined drug load by defined daily dose, and compared test performance at lowest antiepileptic drug load to highest antiepileptic drug load. Across the six towns, performance was lower in delayed compared to immediate recall. There was an overall effect of medication when comparing patients taking vs. not taking antiepileptic drugs and/or psychoactive drugs (p = 0.005). Furthermore, there was a within-subject effect of antiepileptic drug load (p = 0.01), indicating lower test performance at higher drug load. There was no effect of gender, daytime, circadian type, depression, seizures, lesions, and epilepsy. For patients with temporal lobe epilepsy, there was no effect of lateralization. The present study provides direct evidence for episodic memory impairment due to antiepileptic drugs, suggesting that a small change in drug load can matter. This study can serve as a proof of principle for the methodology, but a larger sample is needed to examine the differential effects of individual antiepileptic drugs.