Task-induced subjective fatigue and resting-state striatal connectivity following traumatic brain injury.

BACKGROUND: People with traumatic brain injury (TBI) often experience fatigue, but an understanding of the neural underpinnings of fatigue following TBI is still lacking. This study used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between functional connectivity (FC) changes and task-induced changes in subjective fatigue in people with moderate-severe TBI. METHODS: Sixteen people with moderate-severe TBI and 17 matched healthy controls (HC) performed an adaptive N-back task (working memory task) to induce cognitive fatigue. Before and after the task they rated their state fatigue level and underwent rs-fMRI. Seed-to-voxel analyses with seeds in areas involved in cognitive fatigue, namely the striatum and default mode network (DMN) including, medial prefrontal cortex and posterior cingulate cortex, were performed. RESULTS: The adaptive N-back task was effective in inducing fatigue in both groups. Subjective task-induced fatigue was positively associated with FC between striatum and precuneus in people with TBI, while there was a negative association in HC. In contrast, subjective task-induced fatigue was negatively associated with FC between striatum and cerebellum in the TBI group, while there was no association in HC. Similar associations between task-induced subjective fatigue and DMN FC were found across the groups. CONCLUSIONS: Our results suggest that the subjective experience of fatigue was linked to DMN connectivity in both groups and was differently associated with striatal connectivity in people with moderate-severe TBI compared to HC. Defining fatigue-induced neuronal network changes is pertinent to the development of treatments that target abnormal neuronal activity after TBI.

On-the-road driving performance of patients with central disorders of hypersomnolence.

INTRODUCTION: Excessive Daytime Sleepiness is a core symptom of narcolepsy and idiopathic hypersomnia, which impairs driving performance. Adequate treatment improves daytime alertness, but it is unclear whether driving performance completely normalizes. This study compares driving performance of patients with narcolepsy and idiopathic hypersomnia receiving treatment to that of healthy controls. METHODS: Patients diagnosed with narcolepsy type 1 (NT1, n = 33), narcolepsy type 2 (NT2, n = 7), or idiopathic hypersomnia (IH, n = 6) performed a standardized one-hour on-the-road driving test, measuring standard deviation of lateral position (SDLP). RESULTS: Results showed that mean SDLP in patients did not differ significantly from controls, but the 95%CI of the mean difference (+1.02 cm) was wide (-0.72 to +2.76 cm). Analysis of subgroups, however, showed that mean SDLP in NT1 patients was significantly increased by 1.90 cm as compared to controls, indicating impairment. Moreover, four NT1 patients requested to stop the test prematurely due to self-reported somnolence, and two NT1 patients were stopped by the driving instructor for similar complaints. CONCLUSION: Driving performance of NT1 patients may still be impaired, despite receiving treatment. No conclusions can be drawn for NT2 and IH patients due to the low sample sizes of these subgroups. In clinical practice, determination of fitness to drive for these patients should be based on an individual assessment in which also coping strategies are taken into account.

Validating lane drifts as a predictive measure of drug or sleepiness induced driving impairment.

BACKGROUND: Standard deviation of lateral position (SDLP) has been accepted as a reliable parameter for measuring driving impairment due to lowered vigilance caused by sleepiness or the use of sedating drugs. Recently, lane drifts were proposed as an additional outcome measure quantifying momentary lapses of attention. The purpose of this study was to validate lane drifts as outcome measure of driver impairment in a large data pool from two independent research centers. METHODS: Data from 11 placebo-controlled studies that assessed the impact of alcohol, hypnotics, and sleep deprivation on actual driving performance were pooled. In total, 717 on-the-road tests performed by 315 drivers were subjected to an automated algorithm to detect occurrences of lane drifts. Lane drifts were defined as deviations > 100 cm from the mean (LDmlp) and from the absolute lateral position (LDalp) for 8 s. RESULTS: The number of LDmlp was low and did not differ between treatments and baseline, i.e., 14 vs. 3 events, respectively. LDalp were frequent and significantly higher during treatment relative to baseline, i.e., 1646 vs. 470 events. The correlation between LDalp and SDLP in the treatment conditions was very high (rs = 0.77). The frequency of the occurrence of treatment-induced lane drifts however depended on baseline SDLP of drivers, whereas treatment-induced changes in SDLP occurred independent of baseline SDLP. CONCLUSION: LDmlp is not useful as an outcome measure of driver impairment due to its rare occurrence, even when treatment-induced increments in SDLP are evident. Treatment effects on LDalp and SDLP are closely related.

The MMSE should not be the sole indicator of fitness to drive in mild Alzheimer's dementia.

Since Alzheimer's disease may affect driving performance, patients with Alzheimer's disease are assessed on fitness to drive. On-road driving assessments are widely used, and attempts have also been made to develop strategies to assess fitness to drive in a clinical setting. Preferably, a first indication of fitness to drive is obtained quickly after diagnosis using a single test such as the Mini-Mental State Examination (MMSE). The aim of this study is to investigate whether the MMSE can be used to predict whether patients with Alzheimer's disease will pass or fail an on-road driving assessment. Patients with Alzheimer's disease (n = 81) participated in a comprehensive fitness-to-drive assessment which included the MMSE as well as an on-road driving assessment [PLoS One 11(2):e0149566, 2016]. MMSE cutoffs were applied as suggested by Versijpt and colleagues [Acta Neurol Belg 117(4):811-819, 2017]. All patients with Alzheimer's disease who scored below the lower cutoff (MMSE ≤ 19) failed the on-road driving assessment. However, a third of the patients with Alzheimer's disease who scored above the upper cutoff (MMSE ≥ 25) failed the on-road driving assessment as well. We conclude that the MMSE alone has insufficient predictive value to correctly identify fitness to drive in patients with very mild-to-mild Alzheimer's disease implicating the need for comprehensive assessments to determine fitness to drive in a clinical setting.

Comparing the effects of oxazepam and diazepam in actual highway driving and neurocognitive test performance: a validation study.

OBJECTIVE: Screening of drug-induced performance impairment is needed to provide meaningful information for users and prescribers regarding the impact of drugs on driving. The main objective was to assess the effects of oxazepam 10 mg (OXA10), oxazepam 30 mg (OXA30), and diazepam 10 mg (DIA10) on standard deviation of lateral position (SDLP) in a highway driving test in actual traffic and to determine the ability of eight neurocognitive tests to detect comparable effects. METHODS: Twenty-three healthy volunteers participated in a four-way double-blind, placebo-controlled, crossover study. The highway driving test was conducted between 4 and 5 h after drug intake. A range of neurocognitive tests was conducted before and after driving, 2 and 6 h post-treatment, respectively. RESULTS: Mean SDLP increased by 1.83, 3.03, and 7.57 cm after OXA10, DIA10, and OXA30, respectively. At 2 h post-treatment, all neurocognitive tests, except the useful field of view, showed performance impairment in all active treatments. Effect sizes (ES) were moderate for OXA10, large ES for DIA10, and largest ES for OXA30. Modest correlations were found between changes in SDLP and performance in the attention network test (ANT), the divided attention test (DAT), and the psychomotor vigilance test (PVT). CONCLUSION: OXA10 caused minor, DIA10 moderate, and OXA30 severe driving impairment. No neurocognitive test was both dose dependently sensitive and able to be associated with driving impairment. No neurocognitive test can replace the on-the-road highway driving test.

A pooled analysis of on-the-road highway driving studies in actual traffic measuring standard deviation of lateral position (i.e., "weaving") while driving at a blood alcohol concentration of 0.5 g/L.

INTRODUCTION: The on-the-road highway driving test is generally regarded as a gold standard for assessing drug-induced driving impairment. The primary outcome measure is the standard deviation of lateral position (SDLP), a measure of road tracking error or "weaving". The test has been calibrated for incremental doses of alcohol almost 30 years ago in order to define the impact of drug-induced impairment in terms of blood alcohol concentration (BAC) equivalents. Drug-induced changes in SDLP exceeding 2.4 cm have been evaluated as clinically relevant ever since. The present analysis was conducted to assess the robustness of the alcohol effect in a range of on-the-road driving studies which have been conducted since the initial alcohol calibration study. METHODS: The present study pooled data of 182 participants from nine placebo-controlled crossover studies who performed the highway driving test, while their BAC was at or just below the legal limit for drivers (i.e., 0.5 g/L). RESULTS: Overall, mean SDLP increased with 2.5 cm (95% CI 2.0-2.9 cm). Equivalence testing showed that the clinical relevance criterion value of 2.4 cm fell well within the 95% CI in each individual study. Gender did not affect alcohol-induced changes in SDLP. DISCUSSION: These results demonstrate the robustness and validity of the clinical relevance criterion for SDLP as measured during on-the-road driving.

Driving performance and EEG fluctuations during on-the-road driving following sleep deprivation.

The present study mainly aimed to assess whether and how sleepiness due to sleep deprivation interacts with Time on Task (ToT) effects both on electroencephalography (EEG) measures and driving performance in real driving conditions. Healthy participants performed a one hour on-the-road monotonous highway driving task while EEG was recorded continuously after one night of normal sleep and after one night of total sleep deprivation. The main outcome parameter in the highway driving test was the Standard Deviation of Lateral Position (SDLP). SDLP and EEG indices (i.e alpha and theta power spectra) increased after sleep deprivation and varied with ToT. The latter was more pronounced after sleep deprivation. Beta power spectra did not differ between conditions but increased with ToT. Changes in SDLP and EEG did not correlate significantly. We conclude that driving performance as well as fatigue and sleepiness fluctuations with ToT were more evident after sleep deprivation as compared to normal sleep.

On-the-road driving performance after use of the antihistamines mequitazine and l-mequitazine, alone and with alcohol.

OBJECTIVE: Previous studies demonstrated that mequitazine produces mild sedation after single doses. Its enantiomer, l-mequitazine, has a stronger potency for the H1 receptor. The aim of the current study was to assess the effects of l-mequitazine and mequitazine, alone and with alcohol, on driving. METHODS: Twenty-five healthy volunteers were treated with l-mequitazine 2.5, 5.0 and 10 mg, mequitazine 10 mg and placebo, alone and in combination with alcohol in a double-blind crossover design. Driving performance was assessed using the standardized highway driving test in normal traffic. Its primary measure is the Standard Deviation of the Lateral Position (SDLP). Secondary measures consisted of an auditory word learning test during driving, and subjective measures of driving performance. RESULTS: L-mequitazine 2.5 and 5.0 mg showed no effect on SDLP in the highway driving test, while SDLP significantly increased after l-mequitazine 10 mg (alone +1.59 cm; with alcohol +1.41 cm) and mequitazine 10 mg (with alcohol +1.17 cm). Alcohol significantly impaired all performance measures (SDLP +2.63 cm) but did not interact with the effects of treatment. Subjective measures indicated that participants were aware of the impairing effects of alcohol, but not of l-mequitazine and mequitazine. CONCLUSION: L-mequitazine can be considered safe to drive in dosages of 2.5 and 5.0 mg. L-mequitazine 10 mg led to mild driving impairment. Alcohol impaired all performance measures and added to the effects of l-mequitazine and mequitazine.

The sensitivity of laboratory tests assessing driving related skills to dose-related impairment of alcohol: A literature review.

Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity.

Electroencephalography during on-the-road driving in older untreated insomnia patients and normal sleepers.

Insomniacs report decreased performance in daily routines, which may have detrimental consequences for car driving. We compared changes over time in driving performance (measured as Standard Deviation of Lateral Position - SDLP) and background EEG between 20 untreated insomnia patients (52-70 years old) and 21 normal sleepers (54-73 years old) during a 1h on-the-road driving test after a normal night of sleep, in the morning. SDLP did not differ between groups and increased slightly over time to similar degrees in both groups. EEG alpha and beta power were lower in insomniacs as compared to normal sleepers. Alpha and beta power slightly reduced during driving in normal sleepers but remained at a constant low level in insomniacs. Changes in EEG power and SDLP were not related. It is concluded that on-the-road driving performance does not differ between older insomniacs and older normal sleepers and that changes in spectral EEG measures of cortical arousal and in driving performance are not related.

On-the-road driving performance and driving-related skills in older untreated insomnia patients and chronic users of hypnotics.

RATIONALE: Many older adults report sleep problems and use of hypnotics. Several studies have shown that hypnotics can have acute adverse effects on driving the next morning. It is unclear however whether driving of chronic hypnotic users is impaired. Therapeutic effects on insomnia and development of tolerance may reduce the residual effects on driving. OBJECTIVES: The present study aimed to compare actual driving performance and driving-related skills of chronic hypnotic users to good sleepers. To determine whether insomnia itself affects driving performance, driving and driving-related skills were compared between insomnia patients who do not or infrequently use hypnotics and good sleepers. METHODS: Twenty-two frequent users of hypnotics (using hypnotics ≥ 4 nights per week for more than 3 months), 20 infrequent users (using hypnotics ≤ 3 nights per week), and 21 healthy, age-matched controls participated in this study. On the night before testing, all subjects were hospitalized for an 8-h sleep recorded by polysomnography. Frequent hypnotic users used their regular medication at bedtime (2330 hours), while infrequent users and controls received no medication. Cognitive performance (word learning, digit span, tracking, divided attention, vigilance, and inhibitory control) was assessed 8.5 h and driving performance between 10 and 11 h after bedtime and dosing. RESULTS: Polysomnographic recordings did not significantly differ between the groups, but the insomnia patients, treated or untreated, still reported subjective sleep complaints. Results show no differences in driving performance and driving-related skills between both groups of insomnia patients and controls. CONCLUSIONS: Driving performance in chronic users of hypnotics and untreated insomnia patients is not impaired. For chronic users, this may be due to prescription of relatively safe drugs and low doses. For untreated insomniacs, this corroborates previous findings showing an absence of neuropsychological deficits in this group of patients.

Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study.

RATIONALE: Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs. OBJECTIVES: The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls). METHODS: The study was conducted according to a 3 × 2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test. RESULTS: Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls. CONCLUSIONS: The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.

Zopiclone's residual effects on actual driving performance in a standardized test: a pooled analysis of age and sex effects in 4 placebo-controlled studies.

BACKGROUND: In many European countries, Canada, and Japan, the nonbenzodiazepine zopiclone is now among the most frequently prescribed hypnotic drugs. This finding can be explained by the growing view among physicians that zopiclone is more effective and safer than conventional benzodiazepines. However, in 4 studies using similar procedures, it has been shown that zopiclone 7.5 mg causes moderate to severe impairment in driving performance. OBJECTIVE: The goal of the present article was to review these studies and analyze the pooled data to determine whether the severity of effects is modified by the sex and age of the subjects. METHODS: The driving data of the placebo and zopiclone 7.5 mg evening treatment periods from a total of 4 studies conducted at Maastricht University were included in this pooled analysis. All studies were conducted according to balanced double-blind, crossover designs. The effects on driving were always measured the next morning, between 10 and 11 hours after administration, by using a standardized highway driving test. A total of 101 healthy volunteers of both sexes in equal proportions (with no reports of insomnia) participated. Subjects comprised young volunteers (age range, 21-45 years) in 3 studies and older volunteers (age range, 55-75 years) in the fourth study. RESULTS: Results show that zopiclone 7.5 mg has significant and clinically relevant performance-impairing effects on driving in the morning, until 11 hours after bedtime ingestion. The effects did not differ between male and female subjects and did not increase with age, at least until 75 years. The effects of zopiclone 7.5 mg are comparable to the effects of a mean blood alcohol concentration between 0.5 and 0.8 mg/mL, which has been associated with a 2- to 3-fold increase in the risk of becoming involved in a traffic accident. CONCLUSIONS: We concluded that patients using an evening dose of zopiclone 7.5 mg should avoid activity in skilled work and participation in traffic the morning after intake. General practitioners' beliefs regarding the beneficial safety profile of zopiclone may need adjustment, and patients using zopiclone 7.5 mg should be warned accordingly. There is no need to differentiate warnings about zopiclone's residual impairing effects depending on the sex of the patient.

A randomized trial on the acute and steady-state effects of a new antidepressant, vortioxetine (Lu AA21004), on actual driving and cognition.

The aim of this study was to assess the effects of a novel antidepressant, vortioxetine 10 mg, on driving, cognitive, and psychomotor performance in 24 healthy subjects in a double-blind, placebo-controlled, three-way crossover design. Mirtazapine 30 mg was included as an active comparator. Drugs were administered in the evening of 15 consecutive days. Performance was measured in the morning of days 2 and 16, using standardized tests measuring on-the-road driving, memory, tracking, divided attention, and vigilance. The statistical analysis on the primary measure of driving, i.e., SD of lateral position showed noninferiority of vortioxetine on days 2 and 16, and inferiority for mirtazapine on day 2. Vortioxetine did not cause cognitive or psychomotor impairment. Mirtazapine, however, impaired cognitive and psychomotor performance on day 2. Most of these effects disappeared after multiple doses of mirtazapine. To conclude, vortioxetine did not impair driving, cognitive, or psychomotor performance after single or multiple doses.

Cognitive domains affected by histamine H(1)-antagonism in humans: a literature review.

The neurotransmitter histamine has been suggested to be involved in cognitive functioning. Generally, studies in animals have shown a decrease in performance after decreasing histamine neurotransmission and improved performance after increasing histamine neurotransmission. It is unclear, however, what role histamine plays in cognition in humans. Up until now, most data are derived from studies and reviews that aimed to assess the sedative potential of H(1)-antagonists and not the effects on cognition in particular. The objective of this paper is specifically to review which cognitive domains are affected by H(1)-antagonists. Taken together, 90 experimental studies on the performance effects of sedative H(1)-antagonists published between 1973 and 2009 were reviewed. Results showed that psychomotor skills and attention are most frequently impaired and memory the least. Tasks assessing memory that were affected usually required rapid responses. It was concluded that both the complexity of the task as well as the demand for information processing speed determines the sensitivity to the effects of central H(1)-antagonism. The importance of the sensitive cognitive domains to histaminergic dysfunction, as well as the relation between histamine related decrease in arousal and task performance deserve further research.

Histamine H1 receptor antagonist cetirizine impairs working memory processing speed, but not episodic memory.

BACKGROUND AND PURPOSE: The histaminergic neurotransmitter system is currently under investigation as a target for drug treatment of cognitive deficits in clinical disorders. The therapeutic potential of new drugs may initially be screened using a model of histaminergic dysfunction, for example, as associated with the use of centrally active antihistamines. Of the selective second generation antihistamines, cetirizine has been found to have central nervous system effects. The aim of the present study was to determine whether cetirizine can be used as a tool to model cognitive deficits associated with histaminergic hypofunction. EXPERIMENTAL APPROACH: The study was conducted according to a three-way, double-blind, cross-over design. Treatments were single oral doses of cetirizine 10 and 20 mg and placebo. Effects on cognition were assessed using tests of word learning, memory scanning, vigilance, divided attention, tracking and visual information processing speed. KEY RESULTS: Cetirizine 10 mg impaired tracking performance and both doses impaired memory scanning speed. None of the other measures indicated impaired performance. CONCLUSION AND IMPLICATIONS: Cetirizine affects information processing speed, but these effects were not sufficient to serve as a model for cognitive deficits in clinical disorders.

Memory in humans is unaffected by central H1-antagonism, while objectively and subjectively measured sedation is increased.

Animal literature suggests an important role for histamine in memory. In humans, this hypothesis has been scarcely tested and results from studies that have addressed this are conflicting. Second, impaired memory performance may be secondary to sedation. This study aimed to determine whether a centrally active antihistamine impairs memory performance and to dissociate such effects from sedation. Eighteen healthy volunteers received single oral doses of dexchlorpheniramine 4 mg, lorazepam 1mg and placebo in a 3-way, double blind, crossover designed study. The active control lorazepam impaired episodic- and working memory performance and increased sedation, while dexchlorpheniramine only increased sedation.

Effects of L-histidine depletion and L-tyrosine/L-phenylalanine depletion on sensory and motor processes in healthy volunteers.

BACKGROUND AND PURPOSE: Animal studies show that histamine plays a role in cognitive functioning and that histamine H3-receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H1-receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L-histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event-related-potentials) effects. EXPERIMENTAL APPROACH: Seventeen healthy volunteers completed a three-way, double-blind, crossover study with L-histidine depletion, L-tyrosine/L-phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed. KEY RESULTS: Measures of sedation and critical tracking task performance were not affected by treatment. L-histidine depletion was effective and enlarged the effect of response complexity as measured with the response-locked lateralized readiness potential onset latency. CONCLUSIONS AND IMPLICATIONS: L-histidine depletion affected response- but not stimulus-related processes, in contrast to the effects of H1-receptor antagonists which were previously found to affect primarily stimulus-related processes. L-histidine depletion is promising as a model for histamine-based cognitive impairment. However, these effects need to be confirmed by further studies.

Histamine H1 receptor blockade predominantly impairs sensory processes in human sensorimotor performance.

BACKGROUND AND PURPOSE: Centrally active antihistamines impair cognitive performance, particularly sensorimotor performance. The aim of the present study was to further elucidate the scarcely studied subprocesses involved in sensorimotor performance, which may be affected by H1 receptor blockade. Better knowledge about the cognitive deficits associated with histamine dysfunction can contribute to better treatment of clinical disorders in which histamine hypofunction may be a contributing factor, such as in schizophrenia. EXPERIMENTAL APPROACH: Interactions of dexchlorpheniramine with specific task manipulations in a choice reaction time task were studied. Task demands were increased at the level of sensory subprocesses by decreasing stimulus quality, and at the level of motor subprocesses by increasing response complexity. A total of 18 healthy volunteers (9 female) aged between 18 and 45 years participated in a three-way, double-blind, crossover design. Treatments were single oral doses of 4 mg dexchlorpheniramine, 1 mg lorazepam and placebo. Behavioural effects were assessed by measuring reaction times and effects on brain activity by event-related potentials. KEY RESULTS: Dexchlorpheniramine significantly slowed reaction times, but did not significantly interact with task manipulations. However, it did significantly interact with stimulus quality, as measured by event-related potentials. Lorazepam slowed reaction times and interacted with perceptual manipulations, as shown by effects on reaction times. CONCLUSIONS AND IMPLICATIONS: The results confirm that the histamine system is involved in sensory information processing and show that H1 blockade does not affect motoric information processing. Histamine hypofunction in clinical disorders may cause impaired sensory processing, which may be a drug target.

Disturbed cognitive functions after nasal provocation in patients with seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) reduces quality of life as a result of impaired psychological well-being and perceived impaired cognitive functioning. Few studies have measured cognitive functions objectively and it remains uncertain whether AR leads to an objective reduction in cognitive functions. OBJECTIVE: The present study investigated whether AR is associated with a decrement in several aspects of cognitive functioning. Furthermore, the study investigated whether AR patients invest more 'mental effort' in order to achieve the same cognitive performances as healthy controls. METHODS: Twenty five patients with seasonal allergic rhinitis (SAR) and 26 healthy controls, matched for age, education and sex, were tested on a battery of time-demanding and strenuous objective cognitive tests and subjective questionnaires, both before and after nasal provocation (NP). The cognitive functions assessed were sustained attention, short- and long-term memory and speed of information processing. Mental effort was assessed using visual rating scales. RESULTS: Sustained but not short cognitive performance was impaired in patients after NP. Patients showed an increased effort on short cognitive tests. CONCLUSION: SAR patients suffer from cognitive performance decrements that can be compensated by additional mental effort for short tasks only.