Simon F. Crowe

Cognitive effects of long-term benzodiazepine use: A meta-analysis

AbstractIntroduction: While benzodiazepines are the most widely used psychotropic drugs, there are relatively few studies that have examined deficits in cognitive functioning after long-term use. The literature that is available is difficult to interpret due to conflicting results as well as a variety of methodological flaws. Objective: To systematically evaluate and integrate the available research findings to determine the effect of long-term benzodiazepine use on cognitive functioning using meta-analytical techniques. Methods: Thirteen research studies that employed neuropsychological tests to evaluate cognitive performance after long-term use of benzodiazepine medication met inclusion criteria. The neuropsychological tests employed in these 13 studies were each categorised as measuring one of 12 cognitive domains. Separate effect sizes were calculated for each of the 12 cognitive categories. Each study was only allowed to contribute one effect size to each cognitive category by averaging together the effect sizes from the same study if more than one type of test was used to measure a particular category. This strategy resulted in equal weight being given to each study per category, regardless of the number of tests in that category. Results: The overall mean number of patients who were benzodiazepine users was 33.5 (SD ± 28.9) and the mean number of controls was 27.9 (SD ± 19.6). The duration of benzodiazepine use ranged from 1 to 34 (mean 9.9) years. Long-term benzodiazepine users were consistently more impaired than controls across all cognitive categories examined, with effect sizes ranging in magnitude from −1.30 to −0.42. The mean weighted effect size was −0.74 (SD ± 0.25). None of the effect sizes had 95% CIs that spanned zero and, therefore, all of these effects were significant and different to zero. Conclusion: Moderate-to-large weighted effect sizes were found for all cognitive domains suggesting that long-term benzodiazepine users were significantly impaired, compared with controls, in all of the areas that were assessed. However, this study has several limitations, one being that it includes a relatively small number of studies. Further studies need to be conducted; ideally, well designed, controlled studies that thoroughly investigate certain areas of cognitive functioning and present data in such a way so as to be amenable to inclusion in a meta-analysis. Incorporating the information from these studies into a larger meta-analysis would allow for a more thorough and statistically sound investigation of the effects of moderator variables. The observation that long-term benzodiazepine use leads to a generalised effect on cognition has numerous implications for the informed and responsible prescription of these drugs.

The differential contribution of mental tracking, cognitive flexibility, visual search, and motor speed to performance on parts A and B of the trail making test

Ninety-eight undergraduate students were subjected to the TMT as well as a series of derived measures from the TMT with a view to ascertaining the nature of the contribution of each to the performance. Performance on the TMT(A) was uniquely contributed to by visual search and motor speed measures, whereas the performance on TMT(B) was uniquely contributed to by the visual search and cognitive alternation measures. After controlling for the effects of TMT(A) on TMT(B), further variance in the score on TMT(B) was contributed to, in order of effect, by lowered reading level, poor skill in visual search, poor ability to mentally maintain two simultaneous sequences, as well as decrease in attention and working memory functions. The analysis indicates that, in a nonclinical sample, the TMT measures a number of different functions and the observation of impaired performance must be further investigated to ascertain the specific nature of these deficits in order to guide rehabilitation and management planning.

Persistence of cognitive effects after withdrawal from long-term benzodiazepine use: A meta-analysis

Despite the widespread prescribing of benzodiazepines, uncertainty still surrounds the potential for cognitive impairment following their long-term use. Furthermore, the degree of recovery that may take place after withdrawal or the level of residual impairment, if any, that is maintained in long-term benzodiazepine users is also unclear. The current paper employed meta-analytic techniques to address two questions: (1) Does the cognitive function of long-term benzodiazepine users improve following withdrawal? (2) Are previous long-term benzodiazepine users still impaired at follow-up compared to controls or normative data? Results of the meta-analyses indicated that long-term benzodiazepine users do show recovery of function in many areas after withdrawal. However, there remains a significant impairment in most areas of cognition in comparison to controls or normative data. The findings of this study highlight the problems associated with long-term benzodiazepine therapy and suggest that previous benzodiazepine users would be likely to experience the benefit of improved cognitive functioning after withdrawal. However, the reviewed data did not support full restitution of function, at least in the first 6 months following cessation and suggest that there may be some permanent deficits or deficits that take longer than 6 months to completely recover.

Psychological distress and family satisfaction following traumatic brain injury: injured individuals and their primary, secondary, and tertiary carers.

Objective: To assess family psychosocial outcome following traumatic brain injury (TBI) in all family members, including relatives more peripheral to the person with the injury. Design: A cross-sectional design was used to gather outcome data from individuals with TBI and primary, secondary, and tertiary carers, 19.3 months posttrauma. Multivariate analyses of variance (ANOVAs) ascertained differences in levels of psychological distress and family satisfaction within families. Setting and participants: Seventy-nine families (65 individuals with TBI, 72 primary carers, 43 secondary carers, and 22 tertiary carers) were drawn from a sample of outpatients of three metropolitan, acute rehabilitation hospitals over a 12-month period. Outcome measures: In addition to using the Family Satisfaction Scale (FSS), measures of psychological distress included the Beck Depression Inventory (BDI), State Anxiety Inventory (SAI), and Profile of Mood States (POMS). Results: Although it was noted that a significant proportion of family members were not psychologically distressed and reported good family satisfaction, people with TBI remain at greater risk of poor psychosocial outcome than do their relatives. Of other family members, primary carers—particularly wives—are at greatest risk of poor psychosocial outcome, and a number of secondary and tertiary carers also displayed high levels of psychological distress. Conclusions: Male relatives (the majority of whom were secondary or tertiary carers) may report their distress in terms of anger and fatigue, rather than as depression and anxiety. Future research could develop TBI-specific measures of anger and fatigue as screening instruments to identify peripheral family members requiring assistance in adapting to TBI. Many families—despite their initial traumatic experience—eventually cope well, encouraging researchers and clinicians to focus future research efforts on those families who have made good adjustments to TBI.

Coping Strategies and Emotional Outcome following Traumatic Brain Injury: A Comparison with Orthopedic Patients

Objectives: To investigate coping strategies in relation to emotional adjustment in individuals with traumatic brain injury (TBI) 1–5 years postinjury and to compare these with a group of 40 participants who sustained serious orthopedic injuries. Design: Participants completed measures of handicap and coping strategies, and rated their levels of depression, anxiety, and self-esteem on standardized questionnaires. Setting: Participants had received inpatient rehabilitation at Bethesda Hospital 1–5 years prior to completing questionnaires. They were recruited from a list of consecutive admissions. Participants: 88 TBI individuals were compared with 40 participants who had sustained serious orthopedic injuries without damage to the central nervous system. They had all been involved in motor vehicle or work-related accidents. Outcome Measures: Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). Results: Consistent with previous studies; a significant proportion of the current sample displayed high levels of emotional distress. Results showed few differences between the TBI and orthopedic groups. Coping strategies characterized by worry, wishful thinking, and self-blame were associated with higher levels of depression and anxiety in both groups. Strategies focusing on problem solving and having a positive outlook were related to lower anxiety levels, but to a lesser degree. Conclusions: This study has provided further evidence that coping strategies are associated with emotional outcome in TBI individuals. There is now a growing empirical basis on which preliminary interventions can be based.

Dissociation of two frontal lobe syndromes by a test of verbal fluency

Numerous researchers have attempted to localise the behavioural manifestations of frontal pathology to the regions of the frontal lobe. Three prinicpal syndromes have been identified; the disinhibited syndrome associated with damage to the orbital area, the apathetic syndrome associated with damage to the frontal convexity, and the akinetic syndrome associated with damage to medial structures. This study attempted to determine if two of these syndromes could be dissociated from each other on the basis of a test of verbal fluency. This study used some commonly occurring clinical entities as the treatment groups. The orbitally lesioned individuals produced higher levels of disinhibited responding on the test than did non-orbitally lesioned subjects. However, all pathological groups produced lower overall levels of responding than did normals on the fluency component of the test. A number of suggestions are made as to why this may have been the case, and some guidelines for the clinical interpretation of response patterns on the fluency test are suggested.

Does the Letter Number Sequencing Task Measure Anything More Than Digit Span

A total of 102 undergraduate students performed the Letter Number Sequencing (LNS) task in addition to a series of other measures of reading, working memory, motor execution, visuo-spatial memory, and executive functions. Performance on the LNS was uniquely contributed to by reading level, digit span forward and backward, arithmetic, visual spatial learning, and by performance on the Symbol Search subtest of the WAISIII. The results indicate that while much of the variance on the LNS task is explained by performance on the traditional measures of digit span, additional unique contributions to prediction of LNS performance are provided by measures of processing speed and visual spatial working memory.

Neuropsychological dimensions of the fragile X syndrome: Support for a non-dominant hemisphere dysfunction hypothesis

This study contends that males with the fragile X syndrome feature problems in the visuospatial sphere as compared with Down syndrome males matched on vocabulary ability. Fragile X males suffer impairments of constructional functions, as demonstrated by their poor performance on block construction tests and on drawing tasks. These problems exist in association with visuoperceptive impairments, including the inability to reliably estimate angular relationships (Judgement of Line Orientation). They have shortened Digit and Corsi spans, and may feature some deficits in left hand co-ordination. The observation of a pervasive non-verbal deficit may also apply to carrier females, who despite functioning at an overall higher level, feature a similar pattern of deficits. It is possible that the deficit in non-dominant hemisphere functioning may be a pathognomonic feature of the chromosomal abnormality.

Memory formation processes in weakly reinforced learning.

Day-old chicks trained on a single-trail passive avoidance learning task, with varying concentrations of the aversive stimulus (methyl anthranilate), truncated retention functions for low concentrations. The retention function for a 20% v/v dilution of methyl anthranilate in absolute ethanol yielded high retention levels until approximately 40 to 45 minutes following learning. This retention function appears to consist of only the short-term and intermediate (phase A) memory stages of Gibbs and Ngs three-stage model of memory formation, with the short-term stage susceptible to inhibition by monosodium glutamate, and the intermediate stage by ouabain and dinitrophenol. The results suggest that processing of memory into the relatively permanent long-term stage may depend on the strength of the reinforcer in aversive learning.

Inhibitory processes in covert orienting in patients with Alzheimer's disease.

Previous studies of covert orienting in Alzheimers disease (AD) have investigated exogenous and endogenous processes separately. We aimed to investigate how the 2 modes of orienting interact to control attention in healthy older participants and patients with AD. The covert orienting of visual attention task (COVAT) with abrupt onset cues was used in all experiments. In Experiments 1 and 2, predictive information was added to cues to initiate an endogenous orienting response. Results showed that healthy older participants were able to use endogenous processes to inhibit exogenous orienting. In contrast, patients with AD were unable to inhibit exogenous orienting to cues even when targets rarely appeared there. Experiment 3 investigated inhibition of return (IOR) in patients with AD. Both healthy older controls and patients with AD showed a normal IOR, suggesting that exogenous orienting processes are relatively unaffected by the normal aging process or in patients with AD. A model of covert orienting in which exogenous and endogenous orienting processes interact to control attentional behaviors is discussed.