Subjective Cognitive Dysfunction in Patients with Dizziness and Vertigo.

INTRODUCTION: Patients with vestibular disorders sometimes report cognitive difficulties, but there is no consensus about the type or degree of cognitive complaint. We therefore investigated subjective cognitive dysfunction in a well-defined sample of neuro-otology patients and used demographic factors and scores from a measure of depression, anxiety, and stress to control for potential confounding factors. METHODS: We asked 126 neuro-otology clinic outpatients whether they experienced difficulties with thinking, memory, or concentration as a result of dizziness or vertigo. They and 42 nonvertiginous control subjects also completed the Neuropsychological Vertigo Inventory (NVI, which measures cognitive, emotional, vision, and motor complaints), the Everyday Memory Questionnaire (EMQ), and Depression, Anxiety, and Stress Scales (DASS). RESULTS: In the initial interview questions, 60% of patients reported experiencing cognitive difficulties. Cognitive questionnaire scores were positively correlated with the overall DASS score and to a lesser extent with age and gender. Therefore, we compared patients and controls on the NVI and EMQ, using these mood and demographic variables as covariates. Linear regression analyses revealed that patients scored significantly worse on the total NVI, NVI cognitive composite, and 3 individual NVI cognition subscales (Attention, Space Perception, and Time Perception), but not the EMQ. Patients also scored significantly worse on the NVI Emotion and Motor subscales. CONCLUSIONS: Patients with dizziness and vertigo reported high levels of cognitive dysfunction, affecting attention, perceptions of space and time. Although perceptions of cognitive dysfunction were correlated with emotional distress, they were significantly elevated in patients over and above the impact of depression, anxiety, or stress.

How frequently is anxiety and depression identified and treated in hospital and community samples of adults with epilepsy?

While it is often stated that psychiatric co-morbidity in PWE is under-recognized and under-treated, little research has directly examined this assertion. The aims of this study were to understand the rates of confirmed diagnosis and treatment of depression and anxiety in people with epilepsy (PWE). Two samples were recruited: a hospital sample of 106 adult outpatients with epilepsy who underwent a structured psychiatric diagnostic interview and a community sample of 273 PWE who completed validated measures of depression and anxiety symptoms online. In the hospital sample, fewer participants who met criteria for an anxiety disorder had received a prior diagnosis compared to those with a depressive disorder (36% vs 67%). In the community sample, the rates of known diagnosis were comparable (65% vs. 69%). Approximately, one-third of PWE with an anxiety disorder (or clinically significant symptoms) were receiving current treatment compared to approximately half of those with depression. These findings confirm the high rates of psychiatric co-morbidity in PWE and indicate that a large proportion of anxiety diagnoses, in particular, are undetected and not receiving either pharmacological or psychological support. Future work is needed to improve the detection and management of psychiatric co-morbidity in PWE, especially for anxiety disorders.

Design and validation of two measures to detect anxiety disorders in epilepsy: The Epilepsy Anxiety Survey Instrument and its brief counterpart.

OBJECTIVE: The study objective was to develop and validate the first epilepsy-specific anxiety survey instrument (Epilepsy Anxiety Survey Instrument [EASI]) alongside a briefer screening instrument to detect anxiety disorders in routine clinical practice (brEASI). METHODS: The instruments were developed utilizing a mixed-methods approach in four related studies. Pilot items were developed following qualitative interviews with people with epilepsy (PWE; Study 1) and consultation with multidisciplinary experts in anxiety and epilepsy (Study 2). PWE (n = 314) then completed pilot items alongside existing measures of anxiety and depression (Study 3). Factor analysis was conducted to refine the scale and select well-performing items for a briefer diagnostic screener (brEASI). The brEASI was validated against a gold standard diagnostic interview in 106 PWE recruited from an outpatient epilepsy service (Study 4). Receiver operating characteristic analysis was conducted to determine the brEASI's diagnostic performance. RESULTS: Twenty-six pilot items were generated based on the findings of Studies 1 and 2. Analyses in Study 3 resulted in an 18-item EASI, and eight well-performing items were selected for the brEASI. The area under the curve (AUC) of brEASI was excellent (AUC = 0.89, 95% confidence interval = 0.82-0.94). At a cutoff of 7, it demonstrated a sensitivity of 76% and specificity of 84% for identifying Diagnostic and Statistical Manual of Mental Disorders, 5th edition anxiety disorders. SIGNIFICANCE: The EASI and brEASI represent the first valid and reliable epilepsy-specific anxiety instruments. The EASI has been designed to comprehensively assess anxiety in PWE, whereas the brEASI may be used within busy neurology settings to provide rapid information to aid diagnoses of anxiety disorders. Given the significant prevalence and burden of anxiety in PWE, these tools are important potential solutions to improve the understanding and detection of anxiety in epilepsy.

The impact of sleep characteristics and epilepsy variables on memory performance in patients with focal seizures.

Disturbed sleep can negatively affect overnight memory retention as well as new learning the subsequent day. In healthy participants, positive associations between memory performance and sleep characteristics (e.g., time spent in slow-wave sleep [SWS]) have been detected. In a previous study, we found that SWS was much reduced in patients with focal seizures, but when correlations between memory complaints and various sleep characteristics were considered, the only significant relationship was with the time to onset of rapid eye movement (REM) sleep (i.e., REM latency). In this study, we investigated the relationships between sleep, epilepsy, and objective memory performance variables. Twenty-five patients with focal seizures had their memory tested while undergoing a two-day ambulatory electroencephalography (EEG). The sleep variables of interest were the percentage of time spent in SWS (%SWS) and REM latency. Epilepsy variables included the presence of (1) seizures, (2) interictal epileptiform discharges, and/or (3) hippocampal lesions as well as site of seizure origin (temporal vs extratemporal). Overnight retention (of autobiographical events, a story, and a complex geometric figure) and the ability to learn a word list on day 2 were the measures of memory. A significant positive correlation was found between word-list learning and %SWS during the previous night. A significant negative correlation was observed between REM latency and overnight retention of autobiographical events. Overnight retention scores for the story and geometric figure were not related to sleep characteristics but were negatively affected by the presence of epileptiform activity. Story retention was also worse for temporal lobe epilepsy (TLE) than for patients with extratemporal epilepsy (ETE). Those with hippocampal lesions were more impaired than those without lesions on word-list learning, autobiographical events' retention, and story retention. When multiple contributing factors were entered into regression analyses, %SWS was found to be the best predictor of subsequent word-list learning, whereas the presence of a hippocampal lesion was the best predictor of overnight retention of autobiographical events and a story. These findings provide further evidence of the ways in which particular sleep characteristics are associated with memory and suggest that treatment of sleep disturbances in patients with epilepsy might be helpful for improving their performance.

A qualitative examination and theoretical model of anxiety in adults with epilepsy.

OBJECTIVE: There is an elevated prevalence of anxiety disorders among people with epilepsy, and the comorbidity of anxiety in epilepsy is associated with adverse medical and psychosocial outcomes. Despite its importance, little is known about what psychosocial or epilepsy factors may be associated with the development of anxiety. The aim of this qualitative study was to determine what factors may explain why some people with epilepsy develop anxiety disorders and others do not. METHODS: Adults with epilepsy were recruited from an outpatient epilepsy service. Semistructured interviews were conducted with 26 participants, 15 of whom reported clinically significant levels of anxiety. Grounded theory analysis was used to develop a theoretical model of anxiety development in the context of epilepsy. RESULTS: Qualitative analyses revealed a number of processes that appeared to account for the development of anxiety in the context of epilepsy. These included inflated estimates regarding epilepsy-specific risks and excessive attempts to avoid these risks. Such excessive avoidance often resulted in greater interference with participants' role functioning, thus risking ongoing quality of life. A number of premorbid and contextual factors also appear to be implicated in the development of anxiety. CONCLUSION: This investigation provides a comprehensive account for the development of anxiety in epilepsy, which is consistent with existing theories of anxiety development and maintenance. Importantly, this model provides a foundation for future research and appropriate treatment strategies to address anxiety in people with epilepsy.

Accelerated Long Term Forgetting in patients with focal seizures: Incidence rate and contributing factors.

BACKGROUND: Accelerated Long Term Forgetting (ALF) is usually defined as a memory impairment that is seen only at long delays (e.g., after days or weeks) and not at shorter delays (e.g., 30min) typically used in clinical settings. Research indicates that ALF occurs in some patients with epilepsy, but the incidence rates and underlying causes have not been established. In this study, we considered these issues. METHODS: Forty-four patients with a history of focal seizures were tested at 30min and 7day delays for material from the Rey Auditory Verbal Learning Test (RAVLT) and Aggie Figures Test. Recently published norms from a matched group of 60 control subjects (Miller et al., 2015 ) were used to determine whether patients demonstrated ALF, impairment at 30min or intact memory performance. RESULTS: The incidence of ALF in the epilepsy patients (18%) was >3 times higher than normal on the RAVLT, but no different (7%) from the incidence in normal subjects on the Aggie Figures. A different, but again significantly high, proportion of patients (36%) showed shorter-term memory deficits on at least one task. ALF was found mainly in patients with temporal-lobe epilepsy, but also occurred in one patient with an extratemporal seizure focus. Presence of a hippocampal lesion was the main predicting factor of ALF. CONCLUSIONS: Many patients with a focal seizure disorder show memory deficits after longer delays that are not evident on standard assessment. The present study explored the factors associated with this ALF memory profile. These new findings will enhance clinical practice, particularly the management of patients with memory complaints.

Perception of odor-induced tastes following insular cortex lesion.

Lesions of the insula can affect olfaction and gustation. Here, we examined the effect of insula lesions on taste and taste-like experiences generated via smelling (i.e., odor-induced tastes) in patients with focal insula lesions and intact olfaction. From a set of 16 patients with lesions to the insula, we found 7 (6 with right-sided lesions) who performed normally on various olfactory measures. These were compared to 42 normal control subjects on tests of gustatory and odor-induced taste perception as well as control measures. The patients were impaired relative to controls on most gustatory measures. They were also impaired on tests of odor-induced taste perception, primarily for stimuli presented on the left side. Examining cases individually revealed evidence of a dissociation: two patients exhibited no impairment in odor-induced taste perception in spite of gustatory deficits. Together, these findings suggest that the insula mediates taste recognition, hedonics, and intensity judgments as well as odor-induced taste perception. However, the areas responsible for aspects of taste perception and those responsible for odor-induced taste do not fully overlap each other and they are also independent of olfactory areas.

Disruption of learning and long-term retention of prose passages in patients with focal epilepsy.

Recent investigations of accelerated long-term forgetting, a condition in which newly acquired memory is normal initially but decays rapidly over days or weeks, indicate that multiple factors might influence whether this phenomenon is seen in patients with epilepsy. Test-based differences such as learning condition or type of memory measure (e.g., recall vs recognition) as well as epilepsy variables (e.g., side, site, or frequency of epileptiform activity) may be important. The present study sought to characterize factors affecting learning and memory for prose passages in patients with focal epilepsy. We enrolled 21 patients with temporal lobe epilepsy, with and without hippocampal lesions, 11 patients with extratemporal epilepsy (ETE), and 29 healthy controls. Two matched passages were used to compare effects of initial learning condition (one exposure versus learning-to-criterion) on subsequent patterns of retention. Recall and recognition were tested at different delays (i.e., immediately, 30min, 24h, and 4days). Regression analyses and one-way ANOVAs indicated that having a left-hemisphere epileptic focus had a negative impact on learning, whilst presence of a hippocampal lesion (irrespective of side) was associated with deterioration in recall for intervals up to 24h postencoding. Learning condition affected patterns of memory decay in that the ETE group showed significant decline in recall between 24h and 4days only when stories were learned to criterion. In contrast with recall, no changes over time were evident in recognition memory, as patients with hippocampal lesions were impaired from 30min onward. Epilepsy variables other than side and site of epilepsy/lesion did not influence performance. In conclusion, the left hemisphere is involved in learning of prose material, and the hippocampus is involved in the consolidation of this material mainly for the first 24h. After this, cortical regions outside the hippocampus become important for recall.

Old dogs with new tricks: Detecting accelerated long-term forgetting by extending traditional measures.

Accelerated long-term forgetting (ALF) is a condition in which normal memory performance is displayed after short delays, but significant memory loss is detected when memory is tested after several days or weeks. This condition has been reported in patients with epilepsy, but there are few normative scores available for its detection in clinical practice. In the present study, we assessed 60 healthy control subjects 18-60years of age on three memory measures [Rey Auditory Verbal Learning (RAVLT), Logical Memory (LM), and Aggie Figures] at delays of 30min and 7days. With these normative values, we determined cutoff scores to look for ALF and then categorized the performance of 15 patients with focal epilepsy on the same tasks. Seven of the patients showed ALF, and, in four of these, no other memory deficits (i.e., deficits at 30min on at least one task) were detected. Of the several demographic and epilepsy factors examined, only higher estimated IQ and older age predicted ALF (and only on one task: RAVLT). The findings provide a useful set of data to be applied in the clinic and some insight into the factors that influence retention within the first week.

Testing the effectiveness of group-based memory rehabilitation in chronic stroke patients.

Memory complaints are common after stroke, yet there have been very few studies of the outcome of memory rehabilitation in these patients. The present study evaluated the effectiveness of a new manualised, group-based memory training programme. Forty outpatients with a single-stroke history and ongoing memory complaints were enrolled. The six-week course involved education and strategy training and was evaluated using a wait-list crossover design, with three assessments conducted 12 weeks apart. Outcome measures included: tests of anterograde memory (Rey Auditory Verbal Learning Test: RAVLT; Complex Figure Test) and prospective memory (Royal Prince Alfred Prospective Memory Test); the Comprehensive Assessment of Prospective Memory (CAPM) questionnaire and self-report of number of strategies used. Significant training-related gains were found on RAVLT learning and delayed recall and on CAPM informant report. Lower baseline scores predicted greater gains for several outcome measures. Patients with higher IQ or level of education showed more gains in number of strategies used. Shorter time since onset was related to gains in prospective memory, but no other stroke-related variables influenced outcome. Our study provides evidence that a relatively brief, group-based training intervention can improve memory functioning in chronic stroke patients and clarified some of the baseline factors that influence outcome.

Examining factors related to accelerated long-term forgetting in epilepsy using ambulatory EEG monitoring.

PURPOSE: Some patients with epilepsy demonstrate normal memory when this is tested at relatively short intervals (e.g., 30 min), but substantial loss over longer delay periods (e.g., days or weeks) when compared to healthy control subjects. This pattern of "accelerated long-term forgetting" (ALF) affects the everyday lives of patients, yet goes undetected by standard neuropsychological memory tests, and its pathophysiologic basis is poorly understood. By testing memory over a period of concurrent ambulatory electroencephalography (EEG), the current study aimed to investigate possible factors contributing to ALF. METHODS: Thirty-nine patients diagnosed with epilepsy or probable epilepsy underwent 5 days of continuous ambulatory EEG: 18 had normal EEG studies, 10 had focal epileptic discharges, 5 had generalized epileptic discharges, and 6 had one or more seizures. Fifteen matched healthy control subjects also participated, but did not undergo EEG. Subjects were taught 13-item word and design lists to criterion, and recall was tested at 30 min, 24 h, and 4 days. Subjects also completed questionnaires pertaining to everyday memory and mood. KEY FINDINGS: Group analyses (excluding patients who experienced seizures during monitoring) indicated that patients who experienced generalized discharges during the 24-h to 4-day delay intervals showed higher rates of forgetting for nonverbal information. Those with focal discharges showed ALF between 30 min and 4 days for verbal information, whereas those with normal EEGs over the 4 days recording had no evidence of ALF. Surprisingly, mood and epilepsy variables (such as duration of disease or number of anticonvulsant medications) showed no significant correlation with ALF. Although no aspect of nighttime sleep architecture was found to be related to recall after the first 24 h, daytime naps were associated with better retention. Self-report of everyday memory functioning was related to recall at longer delays, but not at 30 min. SIGNIFICANCE: The present findings indicated that ALF in epilepsy is associated with subclinical discharges rather than antiepileptic drugs (AEDs), mood or sleep disturbance. Measures of longer-term recall can reveal correlations with subjective everyday memory complaints that are not evident when recall is only tested at a standard (30 min) delay interval. These findings have the potential to improve treatment strategies for patients who complain of memory difficulties.

Taste and odour-induced taste perception following unilateral lesions to the anteromedial temporal lobe and the orbitofrontal cortex.

Odour-induced tastes occur when smelling certain odours (e.g., sweet-smelling vanilla) and may represent a universal form of synaesthesia. If odour-induced tastes are perceptually akin to tastes generated by stimulating taste receptors on the tongue, as perceptual data imply, then these two forms of gustatory experience may also share common processing resources in the brain. In this study, we examine this hypothesis for two secondary gustatory processing areas--the orbitofrontal cortex (OFC) and amygdala. We compared nine patients with anteromedial temporal lobe (AMTL) resections that included the amygdala, and three patients with OFC damage, to a healthy comparison group (n = 42), on tests of olfactory, gustatory, and odour-induced taste perception. While AMTL patients had a range of generally small taste impairments, they were unimpaired on tests of odour-induced taste perception. Two of the three OFC cases had impairments in taste hedonics and discrimination. The case with the most profound gustatory deficit was also mildly impaired on tests of odour-induced taste perception. The OFC findings are consistent with overlaps in circuits supporting taste and odour-induced taste perception, especially those responsible for more perceptual aspects of processing.

Identifying cognitive and demographic variables that contribute to carer burden in dementia.

BACKGROUND/AIMS: Carer burden has been associated with other carer-reported factors (e.g. depression), but less is known about the influence of more independent variables. We aimed to determine the impact of cognitive deficits, demographic variables and dementia subtype on carer burden. METHODS: Patients with Alzheimer's dementia (n = 35) or frontotemporal lobar degeneration (n = 61) underwent assessment of anterograde memory, word generation, impulse control and emotion recognition. Age, sex, relationship type, disease duration and diagnosis were also considered. Carers completed the Zarit Burden Interview. RESULTS: In bivariate regression analyses, carer burden was related to age, diagnosis, memory, impulse control and emotion recognition. Stepwise multivariate regression revealed independent contributions by patient age, memory and emotion recognition, explaining 23% of the variance. CONCLUSION: The findings could help refine interventions and carer support.

Improving memory in outpatients with neurological disorders using a group-based training program.

Memory problems are common in patients with a range of neurological conditions, but there have been few attempts to provide and evaluate the usefulness of memory training for groups of neurological outpatients. We used a waitlist-controlled trial design to assess the effectiveness of a newly created, 6-session intervention, which involved training in the use of compensatory strategies as well as education regarding memory function, neurological damage, sleep and lifestyle factors that have an impact on memory. Fifty-six patients with neurological conditions (e.g., stroke, epilepsy) and memory complaints completed the training and assessments. Outcomes were evaluated in terms of reported strategy use as well as objective and subjective measures of anterograde and prospective memory. Training resulted in significant improvements on number of strategies used, scores on the Rey Auditory Verbal Learning Test (total learning and delayed recall) and self-report on the Comprehensive Assessment of Prospective Memory. Improvements were stable at 3-month follow-up. Better individual outcomes were related to lower baseline memory scores, fewer symptoms of depression and greater self-awareness of memory function. Overall the study provides encouraging results to indicate that patients with neurological conditions such as stroke and epilepsy can show improvements in memory after a relatively short group-based intervention.

The role of the mediodorsal thalamic nucleus in human olfaction.

Olfaction has a unique dual-route pathway to the neocortex - one being via the mediodorsal nucleus of the thalamus (MDNT). In this study we explored the role of the MDNT pathway, by comparing six patients with MDNT lesions, with 14 controls, on tests of general olfactory ability (i.e., odor acuity, discrimination, naming, recognition memory and hedonic judgement), visual control and neuropsychological tests, and tests of olfactory attention. The MDNT patients performed normally on most general olfactory tests but showed varying impairments on tests of olfactory attention. These findings suggest that the MDNT pathway is involved, either specifically or generically, in mediating human olfactory attention.

Visual paired-associate learning: in search of material-specific effects in adult patients who have undergone temporal lobectomy.

The mesial temporal lobes are important for learning arbitrary associations. It has previously been demonstrated that left mesial temporal structures are involved in learning word pairs, but it is not yet known whether comparable lesions in the right temporal lobe impair visually mediated associative learning. Patients who had undergone left (n=16) or right (n=18) temporal lobectomy for relief of intractable epilepsy and healthy controls (n=13) were administered two paired-associate learning tasks assessing their learning and memory of pairs of abstract designs or pairs of symbols in unique locations. Both patient groups had deficits in learning the designs, but only the right temporal group was impaired in recognition. For the symbol location task, differences were not found in learning, but again a recognition deficit was found for the right temporal group. The findings implicate the mesial temporal structures in relational learning. They support a material-specific effect for recognition but not for learning and recall of arbitrary visual and visual-spatial associative information.

Effective group-based memory training for patients with epilepsy.

Patients with epilepsy experience memory problems, but there have been few attempts to provide and evaluate the effectiveness of memory training. We designed a 6-week, group-based, psychoeducation and strategy course that was evaluated using a waitlist crossover design, with three assessments conducted 12 weeks apart. Thirty-one patients with a history of seizures participated. Significant gains were found on tests of anterograde (Rey Auditory Verbal Learning Test) and appointment memory. In addition, patients reported using more strategies and experiencing fewer prospective memory difficulties in daily life. Memory was more likely to improve in participants who were younger, less educated, and less depressed. Moreover, lower baseline memory, but better attention corresponded to better outcome. Of the clinical variables related to epilepsy, only number of anticonvulsant medications was found to be associated with outcome. Our study provides evidence that a relatively short intervention can improve memory functioning in patients with epilepsy.

The impact of mediodorsal thalamic lesions on olfactory attention and flavor perception.

Olfactory attention may be important in generating odor-induced tastes - an arguably universal form of synesthesia - by ensuring that the taste concurrent is captured by the nose and olfaction, not by the mouth and gustation (oral-capture). To examine the role of olfactory attention in generating odor-induced tastes and oral capture we tested a small sample (n=4) of participants with likely impairments in olfactory attention - individuals with mediodorsal thalamic nucleus (MDNT) lesions. These participants were compared to two sets of controls on tests of olfactory attention, oral capture, odor and flavor perception, and control tasks. MDNT participants demonstrated impaired olfactory attention and enhanced oral capture. Greater oral capture was associated with greater olfactory attentional impairment. These findings imply that olfactory attention may be important in attributing odor-induced tastes to the olfactory modality. However, unlike for visual binding and for the neurodevelopmental synesthesias, where attention may be necessary to demonstrate both phenomena, olfactory attention deficits did not impair flavor binding or the experience of odor-induced tastes.

Investigating the Effects of Seizures on Procedural Memory Performance in Patients with Epilepsy.

Memory complaints are frequently reported by patients with epilepsy and are associated with seizure occurrence. Yet, the direct effects of seizures on memory retention are difficult to assess given their unpredictability. Furthermore, previous investigations have predominantly assessed declarative memory. This study evaluated within-subject effects of seizure occurrence on retention and consolidation of a procedural motor sequence learning task in patients with epilepsy undergoing continuous monitoring for five consecutive days. Of the total sample of patients considered for analyses (N = 53, Mage = 32.92 ± 13.80 y, range = 18-66 y; 43% male), 15 patients experienced seizures and were used for within-patient analyses. Within-patient contrasts showed general improvements over seizure-free (day + night) and seizure-affected retention periods. Yet, exploratory within-subject contrasts for patients diagnosed with temporal lobe epilepsy (n = 10) showed that only seizure-free retention periods resulted in significant improvements, as no performance changes were observed following seizure-affected retention. These results indicate general performance improvements and offline consolidation of procedural memory during the day and night. Furthermore, these results suggest the relevance of healthy temporal lobe functioning for successful consolidation of procedural information, as well as the importance of seizure control for effective retention and consolidation of procedural memory.