Increased risk of incident dementia following use of anticholinergic agents: A systematic literature review and meta-analysis

Background/rationale: Long-term treatment with anticholinergic agents may increase the risk of cognitive impairment or dementia. This systematic literature review and meta-analysis aimed to assess the impact of ≥3 months of exposure to anticholinergics as a class on the risk of dementia, mild cognitive impairment, and change in cognitive function. The impact of anticholinergic agents specifically used to treat overactive bladder was also evaluated. Materials and Methods: A systematic literature review was conducted to identify English language articles evaluating the impact of anticholinergic use for ≥3 months on dementia or cognitive function in adult patients. Databases searched included PubMed, Embase, and the Cochrane Library. Meta-analyses were conducted using random-effects models; 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were reported. Results: A total of 2122 records were identified. Out of those, 21 studies underwent qualitative synthesis and 6 reported endpoints relevant for inclusion in a meta-analysis assessing the risk of incident dementia. The overall rate ratio for incident dementia was 1.46 (95% CI: 1.17–1.81; 95% PI: 0.70–3.04; n = 6). The risk of incident dementia increased with increasing exposure (n = 3). In addition, two studies from the meta-analysis reported an increased risk of dementia with ≥3 months of use of bladder antimuscarinics (adjusted odds ratios ranged from 1.21 to 1.65, depending on exposure category). Conclusion: Anticholinergic use for ≥3 months increased the risk of dementia on average by an estimated 46% versus nonuse. This relationship was consistent in studies assessing overactive bladder medications. The risk of developing dementia should be carefully considered in the context of potential benefit before prescribing anticholinergics

Intermittent catheterisation after botulinum toxin injections : the time to reassess our practice

INTRODUCTION AND HYPOTHESIS Botulinum toxin has become a widely adopted treatment for patients with recalcitrant overactive bladder (OAB) symptoms. Some recommend clean intermittent self-catheterisation (CISC) if a postvoid residual (PVR) >200 ml posttreatment, but there is no evidence for this recommendation. The aim of this study was to identify whether abstinence from CISC as a routine strategy for patients with a PVR following intradetrusor botulinum toxin injections is associated with any measurable adversity. METHODS This was a cohort observation study. Patients with lower urinary tract symptoms (LUTS) attending a medical urology centre were observed before and after botulinum toxin treatment. Intradetrusal botulinum toxin injections were administered in the day-treatment centre at a medical urology centre in London, UK. Patients were reviewed at follow-up consultations to measure PVR. RESULTS Of the 240 patients studied, 215 were women and 25 were men, of whom, 196 (82%) received botulinum toxin injections and were not managed with CISC; 18% were using CISC prior to injections and continued. None of the 196 patients developed acute retention or significant voiding symptoms. CONCLUSIONS Our study indicates that routine administration of CISC based on an arbitrary PVR volume is unlikely to confer benefit. In order to avoid patients being deterred from botulinum treatment, we recommend that CISC be reserved for those who have troublesome voiding symptoms as well as a raised PVR. It is unlikely that CISC, initiated on the basis of an arbitrary PVR volume, would benefit the patient

What is the role of the film viewer? The effects of narrative comprehension and viewing task on gaze control in film

Film is ubiquitous, but the processes that guide viewers' attention while viewing film narratives are poorly understood. In fact, many film theorists and practitioners disagree on whether the film stimulus (bottom-up) or the viewer (top-down) is more important in determining how we watch movies. Reading research has shown a strong connection between eye movements and comprehension, and scene perception studies have shown strong effects of viewing tasks on eye movements, but such idiosyncratic top-down control of gaze in film would be anathema to the universal control mainstream filmmakers typically aim for. Thus, in two experiments we tested whether the eye movements and comprehension relationship similarly held in a classic film example, the famous opening scene of Orson Welles' Touch of Evil (Welles & Zugsmith, Touch of Evil, 1958). Comprehension differences were compared with more volitionally controlled task-based effects on eye movements. To investigate the effects of comprehension on eye movements during film viewing, we manipulated viewers' comprehension by starting participants at different points in a film, and then tracked their eyes. Overall, the manipulation created large differences in comprehension, but only produced modest differences in eye movements. To amplify top-down effects on eye movements, a task manipulation was designed to prioritize peripheral scene features: a map task. This task manipulation created large differences in eye movements when compared to participants freely viewing the clip for comprehension. Thus, to allow for strong, volitional top-down control of eye movements in film, task manipulations need to make features that are important to narrative comprehension irrelevant to the viewing task. The evidence provided by this experimental case study suggests that filmmakers' belief in their ability to create systematic gaze behavior across viewers is confirmed, but that this does not indicate universally similar comprehension of the film narrative

Basic mechanisms of urgency: roles and benefits of pharmacotherapy

Introduction Since urgency is key to the overactive bladder syndrome, we have reviewed the mechanisms underlying how bladder filling and urgency are sensed, what causes urgency and how this relates to medical therapy. Materials and methods Review of published literature. Results As urgency can only be assessed in cognitively intact humans, mechanistic studies of urgency often rely on proxy or surrogate parameters, such as detrusor overactivity, but these may not necessarily be reliable. There is an increasing evidence base to suggest that the sensation of ‘urgency’ differs from the normal physiological urge to void upon bladder filling. While the relative roles of alterations in afferent processes, central nervous processing, efferent mechanisms and in intrinsic bladder smooth muscle function remain unclear, and not necessarily mutually exclusive, several lines of evidence support an important role for the latter. Conclusions A better understanding of urgency and its causes may help to develop more effective treatments for voiding dysfunction