An explorative approach to understanding individual differences in driving performance and neurocognition in long-term benzodiazepine users.

OBJECTIVE: Previous research reported cognitive and psychomotor impairments in long-term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and clinical complaints. METHODS: Neurocognitive and on-road driving performance of 19 long-term (≥6 months) regular (≥twice weekly) BZRA users with estimated plasma concentrations, based on self-reported use, exceeding the therapeutic threshold (CBZRA +), and 31 long-term regular BZRA users below (CBZRA -), was compared to that of 76 controls. RESULTS: BZRA users performed worse on tasks of response speed, processing speed, and sustained attention. Age, but not CBZRA or self-reported clinical complaints, was a significant covariate. Road-tracking performance was explained by CBZRA only. The CBZRA  + group exhibited increased mean standard deviation of lateral position comparable to that at blood-alcohol concentrations of 0.5 g/L. CONCLUSIONS: Functional impairments in long-term BZRA users are not attributable to self-reported clinical complaints or estimated BZRA concentrations, except for road-tracking, which was impaired in CBZRA + users. Limitations to address are the lack of assessment of objective clinical complaints, acute task related stress, and actual BZRA plasma concentrations. In conclusion, the results confirm previous findings that demonstrate inferior performance across several psychomotor and neurocognitive domains in long-term BZRA users.

On-the-road driving performance the morning after bedtime administration of lemborexant in healthy adult and elderly volunteers.

STUDY OBJECTIVES: To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers. METHODS: Randomized, double-blind, double-dummy, placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23-78 years old. Participants were treated at bedtime for eight consecutive nights with two of three dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last night with placebo on intervening nights), or placebo. Driving performance was assessed in the morning on days 2 and 9 using a standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment. RESULTS: Mean drug-placebo differences in SDLP following lemborexant 2.5, 5, and 10 mg on days 2 and 9 were 0.74 cm or less. The upper bound of the 95% confidence intervals (CIs) for lemborexant treatment groups were all below 2.4 cm and the 95% CIs included zero, indicating that the effects were neither clinically meaningful nor statistically significant. Symmetry analysis further supported the lack of clinically meaningful impairment with lemborexant. CONCLUSIONS: When assessed starting ~9 h after lemborexant administration at bedtime the previous night, there was no statistically significant or clinically meaningful effect on driving performance in healthy adults and elderly, as assessed by either mean differences in SDLP relative to placebo or symmetry analysis. In this study, lemborexant at doses up to 10 mg was well-tolerated. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT02583451. https://clinicaltrials.gov/ct2/show/NCT02583451.

Single- and dual-task performance during on-the-road driving at a low and moderate dose of alcohol: A comparison between young novice and more experienced drivers.

Driving experience and alcohol are two factors associated with a higher risk of crash involvement in young novice drivers. Driving a car is a complex task involving multiple tasks leading to dividing attention. The aim of this study was to compare the single and combined effects of a low and moderate dose of alcohol on single- and dual-task performance between young novice and more experienced young drivers during actual driving. Nine healthy novice drivers were compared with 9 more experienced drivers in a three-way, placebo-controlled, cross-over study design. Driving performance was measured in actual traffic, with standard deviation of lateral position as the primary outcome variable. Secondary task performance was measured with an auditory word learning test during driving. Results showed that standard deviation of lateral position increased dose-dependently at a blood alcohol concentration (BAC) of 0.2 and 0.5 g/L in both novice and experienced drivers. Secondary task performance was impaired in both groups at a BAC of 0.5 g/L. Furthermore, it was found that driving performance in novice drivers was already impaired at a BAC of 0.2 g/L during dual-task performance. The findings suggest that young inexperienced drivers are especially vulnerable to increased mental load while under the influence of alcohol.

Nicotine deprivation elevates neural representation of smoking-related cues in object-sensitive visual cortex: a proof of concept study.

OBJECTIVE: In the current study, we use functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA) to investigate whether tobacco addiction biases basic visual processing in favour of smoking-related images. We hypothesize that the neural representation of smoking-related stimuli in the lateral occipital complex (LOC) is elevated after a period of nicotine deprivation compared to a satiated state, but that this is not the case for object categories unrelated to smoking. METHODS: Current smokers (≥10 cigarettes a day) underwent two fMRI scanning sessions: one after 10 h of nicotine abstinence and the other one after smoking ad libitum. Regional blood oxygenated level-dependent (BOLD) response was measured while participants were presented with 24 blocks of 8 colour-matched pictures of cigarettes, pencils or chairs. The functional data of 10 participants were analysed through a pattern classification approach. RESULTS: In bilateral LOC clusters, the classifier was able to discriminate between patterns of activity elicited by visually similar smoking-related (cigarettes) and neutral objects (pencils) above empirically estimated chance levels only during deprivation (mean = 61.0%, chance (permutations) = 50.0%, p = .01) but not during satiation (mean = 53.5%, chance (permutations) = 49.9%, ns.). For all other stimulus contrasts, there was no difference in discriminability between the deprived and satiated conditions. CONCLUSION: The discriminability between smoking and non-smoking visual objects was elevated in object-selective brain region LOC after a period of nicotine abstinence. This indicates that attention bias likely affects basic visual object processing.

Effect of chronic opioid therapy on actual driving performance in non-cancer pain patients.

RATIONALE: Chronic non-cancer pain (CNCP) is a major health problem. Patients are increasingly treated with chronic opioid therapy (COT). Several laboratory studies have demonstrated that long-term use of opioids does not generally impair driving related skills. But there is still a lack of studies investigating on-the-road driving performance in actual traffic. OBJECTIVES: The present study assessed the impact of COT on road-tracking and car-following performance in CNCP patients. METHODS: Twenty CNCP patients, long-term treated with stable doses of opioid analgesics, and 19 healthy controls conducted standardized on-the-road driving tests in normal traffic. Performance of controls with a blood alcohol concentration (BAC) of 0.5 g/L was used as a reference to define clinically relevant changes in driving performance. RESULTS: Standard Deviation of Lateral Position (SDLP), a measure of road-tracking control, was 2.57 cm greater in CNCP patients than in sober controls. This difference failed to reach statistical significance in a superiority test. Equivalence testing indicated that the 95% CI around the mean SDLP change was equivalent to the SDLP change seen in controls with a BAC of 0.5 g/L and did not include zero. When corrected for age differences between groups the 95% CI widened to include both the alcohol reference criterion and zero. No difference was found in car-following performance. CONCLUSIONS: Driving performance of CNCP patients did not significantly differ from that of controls due to large inter-individual variations. Hence in clinical practice determination of fitness to drive of CNCP patients who receive opioid treatments should be based on an individual assessment.

On-the-road driving performance the morning after bedtime use of suvorexant 15 and 30 mg in healthy elderly.

RATIONALE: Suvorexant is a first-in-class orexin receptor antagonist for treating insomnia. There is a general concern that hypnotics may impair next-morning driving ability. OBJECTIVE: The objective of this study was to evaluate next-morning driving performance in older adults after single and repeated doses of suvorexant. METHODS: Double-blind, randomized, placebo-controlled, 4-period crossover study in 24 healthy volunteers (10 females), aged 65-80 years. Subjects were treated with suvorexant (15 and 30 mg) for eight consecutive nights, zopiclone 7.5 mg nightly on days 1 and 8, and placebo. Driving performance was assessed on days 2 and 9 (9 h after dosing) using a 1-h standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment. RESULTS: Driving performance as measured by SDLP was not impaired following suvorexant. Mean drug-placebo differences in SDLP following suvorexant 15 and 30 mg on day 2 and 9 were 0.6 cm or less. Their 90 % CIs were all below the threshold of 2.4 cm for clinical relevance and included zero, indicating effects were not clinically meaningful or statistically significant. Symmetry analysis showed no significant differences between the number of participants who had SDLP differences >2.4 cm and those who had SDLP differences <-2.4 cm following suvorexant. CONCLUSIONS: There was no clinically meaningful residual effect of suvorexant 15 and 30 mg on next-morning driving (9 h after bedtime dosing) in healthy older adults, as assessed by mean changes in SDLP and by the number of participants on drug versus placebo that exceeded a predetermined threshold for clinically meaningful impairment.

On-the-Road Driving Performance the Morning after Bedtime Use of Suvorexant 20 and 40 mg: A Study in Non-Elderly Healthy Volunteers.

STUDY OBJECTIVE: To evaluate next-morning driving performance in adults younger than 65 years, after single and repeated doses of suvorexant 20 and 40 mg. DESIGN: Double-blind, placebo-controlled, 4-period crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: 28 healthy volunteers (15 females), aged 23 to 64 years. INTERVENTIONS: Suvorexant (20 and 40 mg) for 8 consecutive nights; zopiclone 7.5 mg nightly on day 1 and 8; placebo. MEASUREMENTS: Performance on day 2 and 9 (9 h after dosing) using a one-hour standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo changes in SDLP > 2.4 cm were considered to reflect meaningful driving impairment. RESULTS: Mean drug-placebo changes in SDLP following suvorexant 20 and 40 mg were 1.01 and 1.66 cm on day 2, and 0.48 and 1.31 cm on Day 9, respectively. The 90% CIs of these changes were all below 2.4 cm. Symmetry analysis showed that more subjects had SDLP changes > 2.4 cm than < -2.4 cm following suvorexant 20 and 40 mg on day 2, and following suvorexant 40 mg on day 9. Four female subjects requested that a total of 5 driving tests--all following suvorexant--stop prematurely due to self-reported somnolence. CONCLUSIONS: As assessed by mean changes in standard deviation of lateral position (SDLP), there was no clinically meaningful residual effect of suvorexant in doses of 20 and 40 mg on next-morning driving (9 h after bedtime dosing) in healthy subjects < 65 years old. There may be some individuals who experience next-day effects, as suggested by individual changes in SDLP and prematurely stopped tests. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01311882.

Sensitivity and validity of psychometric tests for assessing driving impairment: effects of sleep deprivation.

OBJECTIVE: To assess drug induced driving impairment, initial screening is needed. However, no consensus has been reached about which initial screening tools have to be used. The present study aims to determine the ability of a battery of psychometric tests to detect performance impairing effects of clinically relevant levels of drowsiness as induced by one night of sleep deprivation. METHODS: Twenty four healthy volunteers participated in a 2-period crossover study in which the highway driving test was conducted twice: once after normal sleep and once after one night of sleep deprivation. The psychometric tests were conducted on 4 occasions: once after normal sleep (at 11 am) and three times during a single night of sleep deprivation (at 1 am, 5 am, and 11 am). RESULTS: On-the-road driving performance was significantly impaired after sleep deprivation, as measured by an increase in Standard Deviation of Lateral Position (SDLP) of 3.1 cm compared to performance after a normal night of sleep. At 5 am, performance in most psychometric tests showed significant impairment. As expected, largest effect sizes were found on performance in the Psychomotor Vigilance Test (PVT). Large effects sizes were also found in the Divided Attention Test (DAT), the Attention Network Test (ANT), and the test for Useful Field of View (UFOV) at 5 and 11 am during sleep deprivation. Effects of sleep deprivation on SDLP correlated significantly with performance changes in the PVT and the DAT, but not with performance changes in the UFOV. CONCLUSION: From the psychometric tests used in this study, the PVT and DAT seem most promising for initial evaluation of drug impairment based on sensitivity and correlations with driving impairment. Further studies are needed to assess the sensitivity and validity of these psychometric tests after benchmark sedative drug use.

Treatment with a nicotine vaccine does not lead to changes in brain activity during smoking cue exposure or a working memory task.

AIMS: To assess whether immunization attenuates nicotinic stimulation of the brain and elucidate brain and behavioural responses during exposure to smoking cues and a working memory task. DESIGN: Randomized, placebo-controlled parallel-group, repeated-measures design. SETTING: Maastricht University, the Netherlands. PARTICIPANTS: Forty-eight male smokers were randomized to receive five injections with either 400 µg/ml of the 3'-aminomethylnicotine Pseudomonas aeruginosa r-Exoprotein-conjugated vaccine or placebo. Subjects were tested on two occasions, once after a nicotine challenge and once after a placebo challenge, and were asked to refrain from smoking 10 hours before testing. MEASUREMENTS: Reaction-times and accuracies were recorded during an n-back task. Moreover, regional blood oxygenated level-dependent (BOLD) response was measured during this task and during smoking cue exposure. FINDINGS: Greater activation was found in response to smoking cues compared to neutral cues in bilateral trans-occipital sulcus (P < 0.005); however, this effect did not survive correction for multiple comparisons. There was no difference in brain activity to smoking cues between the treatment groups and no effects of acute nicotine challenge were established. For the n-back task we found working memory load-sensitive increases in brain activity in several frontal and parietal areas (P < 0.0025). However, no effects of immunization or nicotine challenge were observed. CONCLUSION: No significant effects of immunization on brain activity in response to a nicotine challenge were established. Therefore this vaccine is not likely to be an effective aid in smoking cessation.

Residual effects of low-dose sublingual zolpidem on highway driving performance the morning after middle-of-the-night use.

STUDY OBJECTIVE: To evaluate next-morning driving performance after middle-of-the-night use of zolpidem 3.5 mg in a buffered sublingual formulation (ZST). DESIGN: Single-center, four-period, randomized, double-blind, placebo-controlled, crossover study. SETTING: Maastricht University, The Netherlands. PARTICIPANTS: Forty healthy volunteers (20 females). INTERVENTIONS: Single dose of ZST administered in the middle of the night at 3 and 4 h before driving, zopiclone 7.5 mg at bedtime 9 h before driving, and placebo. MEASUREMENTS: Performance in a 100-km standardized highway driving test in normal traffic measuring standard deviation of lateral position (SDLP) - an index of weaving. Drug-placebo changes in SDLP > 2.5 cm were considered to reflect clinically relevant driving impairment. RESULT: For ZST, Max McNemar symmetry analyses showed that the proportion of drivers classified as impaired was increased 3 h after dosing (P < 0.012), but not 4 h after dosing. Mean increases in SDLP from placebo, although statistically significant, were small (1.46 cm [P < 0.0001] at 3 h and 0.83 cm [P = 0.0174] at 4 h). The morning after zopiclone, 45% of the drivers were classified as impaired with a mean increase in SDLP of 2.46 cm (P < 0.0001). There were no significant sex differences in effects of ZST and zopiclone. CONCLUSION: Zolpidem 3.5 mg in a buffered sublingual formulation has a minimal risk of impairing driving performance in the morning ≥ 4 hours after middle-of-the night use. When taken 3 hours before driving, the drug may have impairing effects so caution should be exercised if medication is taken other than as indicated. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01106859; Trial Name: Driving Performance After Middle of the Night Administration of 3.5 mg Zolpidem Tartrate Sublingual Tablet; http://clinicaltrials.gov/ct2/show/NCT01106859.

Alcohol calibration of tests measuring skills related to car driving.

RATIONALE: Medication and illicit drugs can have detrimental side effects which impair driving performance. A drug's impairing potential should be determined by well-validated, reliable, and sensitive tests and ideally be calibrated by benchmark drugs and doses. To date, no consensus has been reached on the issue of which psychometric tests are best suited for initial screening of a drug's driving impairment potential. OBJECTIVE: The aim of this alcohol calibration study is to determine which performance tests are useful to measure drug-induced impairment. The effects of alcohol are used to compare the psychometric quality between tests and as benchmark to quantify performance changes in each test associated with potentially impairing drug effects. METHODS: Twenty-four healthy volunteers participated in a double-blind, four-way crossover study. Treatments were placebo and three different doses of alcohol leading to blood alcohol concentrations (BACs) of 0.2, 0.5, and 0.8 g/L. RESULTS: Main effects of alcohol were found in most tests. Compared with placebo, performance in the Divided Attention Test (DAT) was significantly impaired after all alcohol doses and performance in the Psychomotor Vigilance Test (PVT) and the Balance Test was impaired with a BAC of 0.5 and 0.8 g/L. The largest effect sizes were found on postural balance with eyes open and mean reaction time in the divided attention and the psychomotor vigilance test. CONCLUSIONS: The preferable tests for initial screening are the DAT and the PVT, as these tests were most sensitive to the impairing effects of alcohol and being considerably valid in assessing potential driving impairment.

Contingent negative variation as a dopaminergic biomarker: evidence from dose-related effects of methylphenidate.

RATIONALE: The basal ganglia play an important role in motor control, which is dependent on dopaminergic input. Preparation of a motor response has been associated with dopamine release in the basal ganglia, and response readiness may therefore serve as a pharmacodynamic marker of dopamine activity. METHODS: We measured response readiness using the amplitude of the contingent negative variation (CNV), a slow negative shift in the electroencephalogram. The CNV is evoked in a paradigm in which a warning stimulus (S1) signals the occurrence of the imperative stimulus (S2) 4 s later, to which the participant has to respond. CNV was assessed in healthy volunteers after administration of placebo or 10, 20 or 40 mg of methylphenidate, a catecholamine re-uptake blocker which primarily enhances the synaptic concentration of dopamine and to a lesser extent also noradrenaline. In addition, participants filled out two visual analogue scales measuring subjective ratings of mood and alertness: Profile of Mood States and Bond and Lader. RESULTS: Methylphenidate dose dependently increased CNV amplitude and decreased reaction times. Furthermore, participants reported improved mood, feeling more alert, vigorous and content and less angry and tired after methylphenidate. CONCLUSIONS: These results indicate that dopamine availability increases response readiness as measured by the CNV paradigm. The CNV appears to be a good candidate biomarker for assessing changes in dopaminergic function by treatments that either directly or indirectly target the dopaminergic system.

Aging does not affect gray matter asymmetry.

Previous research has shown that asymmetry of brain activity is decreased in older adults. This study investigates whether cortical gray matter asymmetry also shows age-related differences, and whether gray matter asymmetry differs between cognitively stable persons and persons who have shown profound age-related declines in cognitive functioning. In addition, we have examined whether prodromal dementia affects the study outcome. The gray matter volumes of seven prefrontal and temporal regions of interest were delineated on T1-weighted MRI scans in 70 adults aged between 52 and 84 years. Statistical analyses were conducted with and without participants who developed dementia within 6 years after the MRI scan session. It was found that asymmetry did not differ over the age range of 52-84 years of age. This result did not change when data from participants who were diagnosed with dementia within 6 years after MRI assessment were excluded from the analysis. In addition, no gray matter asymmetry differences were found between cognitively stable participants and participants who showed cognitive decline. We conclude that alterations in gray matter asymmetry may not be part of the healthy aging process.

A time-saving and facilitating approach for segmentation of anatomically defined cortical regions: MRI volumetry.

In this study, we present an accurate, reliable, robust, and time-efficient technique for a semi-automatic segmentation of neuroanatomically defined cortical structures in Magnetic Resonance Imaging (MRI) scans. It involves manual drawing of the border of a region of interest (ROI), supported by three-dimensional (3D) visualization techniques (rendering), and a subsequent automatic tracing of the gray matter voxels inside the ROI by means of an automatic tissue classifier. The approach has been evaluated on a set of MRI scans of 75 participants selected from the Maastricht Aging Study (MAAS) and applied to cortical brain structures for both the left and right hemispheres, viz., the inferior prefrontal cortex (PFC); the orbital PFC; the dorsolateral PFC; the anterior cingulate cortex; and the posterior cingulate cortex. The use of a 3D surface-rendered brain can be rotated in any direction was invaluable in identifying anatomical landmarks on the basis of gyral and sulcal topography. This resulted in a high accuracy (anatomical correctness) and reliability: the intra-rater intra-class correlation coefficient (ICC) was between 0.96 and 0.99. Furthermore, the obtained time savings were substantial, i.e., up to a factor of 7.5 compared with fully manual segmentations.

The use of faces as stimuli in neuroimaging and psychological experiments: a procedure to standardize stimulus features.

In psychological experiments involving facial stimuli, it is of great importance that the basic perceptual or psychological characteristics that are investigated are not confounded by factors such as brightness and contrast, head size, hair cut and color, skin color, and the presence of glasses and earrings. Standardization of facial stimulus materials reduces the effect of these confounding factors. We therefore employed a set of basic image processing techniques to deal with this issue. The processed images depict the faces in grayscale, all at the same size, brightness, and contrast, and confined to an oval mask revealing only the basic features such as the eyes, nose, and mouth. The standardization was successfully applied to four different face databases, consisting of male and female faces and including neutral as well as happy facial expressions. An important advantage of the proposed standardization is that featural as well as configurational information is retained. We also consider the procedure to be a major contribution to the development of a de facto standard for the use of facial stimuli in psychological experiments. Such methodological standardization would allow a better comparison of the results of these studies.

The prevalence of cortical gray matter atrophy may be overestimated in the healthy aging brain.

Prevailing opinion holds that normal brain aging is characterized by substantial atrophy of cortical gray matter. However, this conclusion is based on earlier studies whose findings may be influenced by the inclusion of subjects with subclinical cognitive disorders like preclinical dementia. The present magnetic resonance imaging study tested this hypothesis. Cognitively healthy subjects (mean age 72 years, range 52-82) who remained cognitively stable over a 3-year period were compared to subjects with significant cognitive decline. Subjects who developed dementia within 6 years after the scan session were excluded. The gray matter volumes of seven cortical regions were delineated on T1-weighted magnetic resonance imaging scans. Participants without cognitive decline did not exhibit an age effect on the gray matter volume. Conversely, participants with cognitive decline exhibited a significant age effect in all the seven areas. These results suggest that cortical gray matter atrophy may have been overestimated in studies on healthy aging, since most studies were unable to exclude participants with a substantial atypical cognitive decline or preclinical dementia. Our results underscore the importance of establishing stringent inclusion criteria for future studies on normal aging.

Lack of effects between rupatadine 10 mg and placebo on actual driving performance of healthy volunteers.

INTRODUCTION: Rupatadine fumarate is a potent, selective, histamine H(1)-receptor antagonist and PAF inhibitor with demonstrated efficacy for the relief of allergic rhinitis. Rupatadine does not easily cross the blood-brain barrier and is believed to be non-sedating at therapeutic doses. Consequently, rupatadine should show no impairment on car driving. OBJECTIVE: This study compared the acute effects of rupatadine, relative to placebo and hydroxyzine (as an active control), on healthy subjects' driving performance. METHODS: Twenty subjects received a single dose of rupatadine 10 mg, hydroxyzine 50 mg, or placebo in each period of this randomized, double-blind, three-way crossover study. Two hours postdosing, subjects operated a specially instrumented vehicle in tests designed to measure their driving ability. Before and after the driving tests ratings of sedation were recorded. RESULTS: There was no significant difference between rupatadine and placebo in the primary outcome variable: standard deviation of lateral position (SDLP); however, hydroxyzine treatment significantly increased SDLP (p < 0.001 for both comparisons). Objective (Stanford sleepiness scale) and subjective sedation ratings (Visual Analogue Scales) showed similar results: subjects reported negative effects after hydroxyzine but not after rupatadine. CONCLUSION: Rupatadine 10 mg is not sedating and does not impair driving performance.

The irrelevant speech effect and the level of interference in aging.

In general, no disproportionate detrimental effects of irrelevant background speech on cognition are found in aging individuals, although this is predicted by the inhibitory view of aging. This may be due to the nature of the primary task (most studies involve a verbal learning task) or the cognitive level at which irrelevant speech interferes with this task. In this study, the irrelevant speech effect on a numeric working memory task was investigated among 20 young (M = 21.8 years) and 20 older (M = 68.1 years) native Dutch individuals. Level of interference (LOI) was manipulated by presenting white noise (no interference), Russian words (low interference), Dutch words (phonological interference), and Dutch numbers (semantic interference) in the background. Results showed that reaction time increases as a function of LOI relative to silence, whereas accuracy remains unaffected. However, no interaction between LOI and age group was found, which suggests that the elderly were not disproportionately affected by an increased level of interference. These results are discussed in the light of the inhibitory view of aging.