Observational cohort study of 100 patients presenting with functional visual loss: clinical characteristics and comparison with other functional neurologic disorders.

OBJECTIVE: Recent research has helped to develop a more detailed understanding of many functional neurologic disorders. The aim of this study was to increase our knowledge of functional visual loss and to compare the findings with those of other functional syndromes. DESIGN: Prospective and retrospective observational cohort study. METHODS: This study took place at neuro-ophthalmology clinics at 3 major hospitals in London, United Kingdom, over a 12-month period. The study population consisted of 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. All participants had their diagnosis confirmed with a full neuro-ophthalmic examination, neuroimaging, and visual electrophysiology. A full assessment of all participants' medical history was obtained from their general practitioner, and all participants completed a series of questionnaires assessing relevant associations. RESULTS: Data were obtained on 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. Participants with functional visual loss were typically female (74%) with a mean age at vision loss of 40.0 ± 16 years. Sixty-four percent of participants had bilateral vision loss; the remainder, unilateral loss. Twenty-six percent of the total cohort had organic visual loss with functional overlay. Fifty percent of participants with functional visual loss had a preexisting psychiatric diagnosis, the most common being a depressive disorder. Sixty-two percent of participants had an ocular history, and 87% had a previously diagnosed medical illness, most commonly neurologic (45%). Thirty-five percent of participants self-reported at least 1 additional functional symptom. CONCLUSIONS: Our population of functional visual loss subjects shares many similarities with the majority of patients with other functional neurologic disorders. They are generally young and female and have a greater than expected rate of psychiatric, medical, and coexisting ocular conditions. We found increased rates of precipitating stressors, clinical depression, and organic eye problems in subjects with functional visual loss.

Observations on the Clinical Features of the Wernicke-Korsakoff Syndrome.

This paper begins with a short case report of florid, spontaneous confabulation in a 61-year-old man with an alcohol-induced Wernicke-Korsakoff syndrome. His confabulation extended across episodic and personal semantic memory, as well as orientation in time and place, as measured on Dalla Barba's Confabulation Battery. Five other brief case summaries will then be presented, followed by a summary of the clinical, neurological, and background neuropsychological findings in three earlier series of Korsakoff patients. These observations will be considered in light of Wijnia's recent and my own, earlier reviews of the Korsakoff syndrome. Taken together, they indicate the need for a multi-faceted approach (clinical, neurological, neuropsychological, and neuroimaging) to the assessment and diagnosis of the disorder.

What is the Korsakoff syndrome? - a paper in tribute to Prof Alwyn Lishman.

INTRODUCTION: Alwyn Lishman was interested in how memory research could be applied to clinical psychiatry. After a brief review of his major contributions, this paper will focus on his research on the alcoholic Korsakoff syndrome. It will consider how his findings relate to contemporary debates, particularly on how the syndrome should be defined, and its relationship to broader alcohol-induced cognitive impairments. METHODS: A review of the contribution of Alwyn Lishman, Robin Jacobson and colleagues to our knowledge of Korsakoff's syndrome, together with a review of the pertinent recent literature. RESULTS: Lishman and colleagues followed earlier authors in defining the Korsakoff syndrome in terms of disproportionate memory impairment, but they also noted a variable degree of IQ, frontal-executive, and timed visuo-spatial impairment in their cases. More recent authors have included such features in their definitions of the syndrome. Lishman also argued for a specific "alcoholic dementia". The present paper argues that recent definitions of the Korsakoff syndrome confound its core and associated features, and also fail to recognise the multifactorial basis of alcohol-related brain damage. CONCLUSIONS: Korsakoff's syndrome is best defined in terms of disproportionate memory impairment, and more widespread cognitive impairment is best encompassed within "alcohol-related brain damage".

Autobiographical memory loss in Alzheimer's disease: The role of the reminiscence bump.

Research on autobiographical memory loss in Alzheimer's disease (AD) is characterized by conflicting findings concerning a possible sparing of older memories. The literature shows evidence for both a negative temporal gradient, a flat gradient and a reminiscence bump - that is, a disproportionally high frequency of memories from early adulthood relative to surrounding periods. Here, we expanded the number of lifetime periods of the Autobiographical Memory Interview (AMI; Kopelman, Wilson & Baddeley, 1989, 1990) from the standard three to seven in order to increase the sensitivity of the test to variations in the temporal distribution of autobiographical memories across the life span. Twenty-five older adults diagnosed with AD (MMMSE = 21.16, SD = 5.08) and a matched sample of 30 healthy, older adults were assessed. The temporal distribution for personal semantic information in AD showed a temporal gradient steadily decreasing from middle childhood to present life, consistent with predictions derived from consolidation theories. In comparison, the temporal distribution of incidents/episodic memories produced by AD patients in response to the expanded AMI showed a predominance of autobiographical memories from age 6 to 30, followed by a steep drop in memory referring to events that had occurred after age 30. This distribution challenges standard theories of retrograde amnesia in AD by showing neither a temporal gradient, decreasing progressively from early to later life, nor a flat gradient. In contrast, the distribution is consistent with the reminiscence bump identified in autobiographical memory research. Schematization and retrieval support provided by cultural life scripts are discussed.

Accelerated forgetting in temporal lobe epilepsy: When does it occur?

OBJECTIVE: The main goal of the study was to analyse differences in the forgetting rates of Temporal Lobe Epilepsy (TLE) patients at different intervals (30 sec, 10 min, 1 day and 1 week) compared with those of healthy controls. A secondary aim of this research was to provide an assessment of the relationship between clinical epilepsy-related variables and forgetting rates in TLE patients. METHOD: The sample was composed of 14 TLE patients and 14 healthy matched controls. All participants underwent a full standardised neuropsychological assessment including general intelligence, executive functioning, memory, language and other variables, such as depression, anxiety or everyday memory failures. Two specific memory tasks, consisting of cued recall of 4 short stories and 4 routes, were carried out at four different intervals. RESULTS: There was a significant difference between groups at 10-min interval on the stories task, with the TLE group displaying greater forgetting than healthy controls. None of the other intervals on either task showed significant group differences. No differences were found when controlling for clinical epilepsy-related variables. CONCLUSION: Forgetting of verbal information at 10 min was greater in patients with TLE compared with controls, but accelerated longer term forgetting was not found. This study suggests that a late consolidation process is not necessarily impaired in TLE patients.

A prospective study of the cognitive and psychiatric effects of pituitary tumours and their treatments.

Neurocognitive complaints are common in patients with pituitary tumours, particularly in memory and concentration. Past studies have shown impairments in executive function and memory, but it is not clear whether these result from direct effects of the tumour (pressure or hormonal secretion), incidental damage from radiotherapy or surgical treatments, and/or mediating psychiatric factors. This study assessed cognitive function and psychiatric state of 86 pituitary tumour patients and 18 healthy controls, pre and post-treatment, to examine the effects of tumour aetiology and treatment type. No significant cognitive impairments were found, except on verbal recognition memory. Patients with Cushing's disease showed lower verbal recognition memory than the other groups pre-treatment, but improved at follow-up. This was (at least partially) accounted for by an improvement in depression scores. Patients who were treated with surgery showed poorer verbal recognition memory than controls across all (pre- and post-treatment) time-points. Overall findings of minimal cognitive impairment in patients with pituitary tumours may reflect improved diagnostic and treatment techniques in recent years. We suggest that the verbal memory impairments identified in the Cushing's group may result from increased cortisol (directly, or mediated by depression). In the surgical groups, verbal memory impairments appeared to pre-date treatment. This may relate to treatment selection factors, rather than harmful effects of surgery itself.

Factors associated with self- and informant ratings of quality of life, well-being and life satisfaction in people with mild-to-moderate dementia: results from the Improving the experience of Dementia and Enhancing Active Life programme.

BACKGROUND: a large number of studies have explored factors related to self- and informant ratings of quality of life in people with dementia, but many studies have had relatively small sample sizes and mainly focused on health conditions and dementia symptoms. The aim of this study is to compare self- and informant-rated quality of life, life satisfaction and well-being, and investigate the relationships of the two different rating methods with various social, psychological and health factors, using a large cohort study of community-dwelling people with dementia and carers in Great Britain. METHODS: this study included 1,283 dyads of people with mild-to-moderate dementia and their primary carers in the Improving the experience of Dementia and Enhancing Active Life study. Multivariate modelling was used to investigate associations of self- and informant-rated quality of life, life satisfaction and well-being with factors in five domains: psychological characteristics and health; social location; capitals, assets and resources; physical fitness and health; and managing everyday life with dementia. RESULTS: people with dementia rated their quality of life, life satisfaction and well-being more highly than did the informants. Despite these differences, the two approaches had similar relationships with social, psychological and physical health factors in the five domains. CONCLUSION: although self- and informant ratings differ, they display similar results when focusing on factors associated with quality of life, life satisfaction and well-being. Either self- or informant ratings may offer a reasonable source of information about people with dementia in terms of understanding associated factors.

Psychological predictors of 'living well' with dementia: findings from the IDEAL study.

Objectives: Increasingly, research has explored how psychological resources enable adaptation to illness. However, it is unclear whether psychological resources protect against the potential negative effects on living well with a progressive and life-limiting condition such as dementia. This paper examines the association between psychological resources and the ability to 'live well' with dementia.Method: Data from 1547 people with mild-to-moderate dementia in the Improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort were used. Multivariate linear regression was employed to examine the association between self-reported measures of psychological resources (self-efficacy, optimism and self-esteem) and indices of capability to 'live well' (quality of life, well-being and life satisfaction).Results: All three measures of psychological resources had positive and independent associations with indices of living well and the effect sizes were similar. Effect sizes reduced when accounting for shared variance between psychological resources, showing some overlap in these constructs.Conclusion: Self-efficacy, optimism and self-esteem were each associated with capability to 'live well'. Overlap between these three resources is evident and when combined they may provide greater resilience when dealing with the challenges of living with dementia. Interventions for people with dementia could seek to improve levels of these potentially-modifiable psychological resources.

Use and costs of services and unpaid care for people with mild-to-moderate dementia: Baseline results from the IDEAL cohort study.

INTRODUCTION: We examined 3-month service use and costs of care for people with mild-to-moderate dementia in Great Britain. METHODS: We analyzed Improving the experience of Dementia and Enhancing Active Life cohort study baseline data on paid care, out-of-pocket expenditure, and unpaid care from participants with dementia (N = 1547) and their carers (N = 1283). In regression analyses, we estimated per-group mean costs of diagnostic and sociodemographic subgroups. RESULTS: Use of services apart from primary and outpatient hospital care was low. Unpaid care accounted for three-quarters of total costs (mean, £4008 [standard error, £130] per participant). Most participants (87%) received unpaid care equating to 36 hours weekly. Estimated costs for people with Parkinson's dementia were £8609, £4359 for participants with mixed dementia, and £3484 for those with Alzheimer's disease. Total costs were lower for participants with dementia living alone than living with others (£2484 vs. £4360); costs were lower for female than for male participants (£3607 vs. £4272). DISCUSSION: Costs varied by dementia subtype, carer status, and living arrangement. Policy makers should recognize the high costs of unpaid care for people with dementia, who do not always get the support that they need or would like to receive.

Anomalies of Autobiographical Memory.

OBJECTIVES: In this paper, I review three 'anomalies' or disorders in autobiographical memory: neurological retrograde amnesia (RA), spontaneous confabulation, and psychogenic amnesia. METHODS: Existing theories are reviewed, their limitations considered, some of my own empirical findings briefly described, and possible interpretations proposed and interspersed with illustrative case-reports. RESULTS: In RA, there may be an important retrieval component to the deficit, and factors at encoding may give rise to the relative preservation of early memories (and the reminiscence bump) which manifests as a temporal gradient. Spontaneous confabulation appears to be associated with a damaged 'filter' in orbitofrontal and ventromedial frontal regions. Consistent with this, an empirical study has shown that both the initial severity of confabulation and its subsequent decline are associated with changes in the executive function (especially in cognitive estimate errors) and inversely with the quantity of accurate autobiographical memories retrieved. Psychogenic amnesia can be 'global' or 'situation-specific'. The former is associated with a precipitating stress, depressed mood, and (often) a past history of a transient neurological amnesia. In these circumstances, frontal control mechanisms can inhibit retrieval of autobiographical memories, and even the sense of 'self' (identity), while compromised medial temporal function prevents subsequent retrieval of what occurred during a 'fugue'. An empirical investigation of psychogenic amnesia and some recent imaging studies have provided findings consistent with this view. CONCLUSIONS: Taken together, these various observations point to the importance of frontal 'control' systems (in interaction with medial temporal/hippocampal systems) in the retrieval and, more particularly, the disrupted retrieval of 'old' memories.

Clinical and neuroimaging correlates of cognition in HIV.

This study investigated whether HIV-positive participants, stable on combined antiretroviral therapy (cART), showed cognitive impairments relative to HIV-negative controls; and whether clinical and neuroimaging factors correlated with cognitive function in the HIV-positive participants. One hundred and twenty-six white men who have sex with men, of whom 78 were HIV-positive and stable on cART and 48 were HIV negative, were recruited to this cross-sectional study. The median age of HIV-positive participants in this study was 47. They underwent clinical and neuropsychological evaluation and magnetic resonance imaging of the brain, including diffusion tensor imaging (DTI). Cognitive scores for both groups were compared, and regression models were run to explore the influence of clinical, psychiatric, lifestyle, and neuroimaging variables on cognition. The prevalence of neurocognitive impairment, using the multivariate normative comparison criteria, was 28% in HIV-positive participants and 5% in HIV-negative participants. After covarying for age, years of education, and non-English speaking background, there were significant differences between the HIV group and the controls across four cognitive domains. The HIV group showed significantly higher mean diffusivity (MD) and lower fractional anisotropy (FA) than the control group on DTI. Although anxiety levels were clinically low, anxiety and DTI measures were the only variables to show significant correlations with cognitive function. In the HIV group, poorer cognitive performance was associated with higher MD and lower FA on DTI and higher (albeit clinically mild) levels of anxiety. Our findings suggest that white matter changes and subtle anxiety levels contribute independently to cognitive impairment in HIV.

A Comprehensive Model of Factors Associated With Capability to "Live Well" for Family Caregivers of People Living With Mild-to-Moderate Dementia: Findings From the IDEAL Study.

INTRODUCTION: Understanding key influences on outcomes for caregivers of people with dementia is hampered by inconsistent conceptualization and measurement of outcomes and limited evidence about the relative impact of different variables. We aimed to address these issues. METHODS: We analyzed data from 1283 caregivers of community-dwelling individuals with mild-to-moderate dementia in the Improving the experience of Dementia and Enhancing Active Life cohort study. We generated a "living well" latent factor from measures of quality of life, satisfaction with life, and well-being. We used structural equation modelling to derive latent variables for 7 domains reflecting caregivers' perceptions of their personal resources and experiences, and to examine the associations with caregivers' perceptions of their capability to "live well." RESULTS: The domain of psychological characteristics and psychological health was most strongly related to living well [2.53; 95% confidence interval (CI), 2.08-2.97], followed by physical fitness and physical health (1.48; 95% CI, 1.04-1.91) and experiencing caregiving (1.34; 95% CI, 0.99-1.70). Social capitals, assets and resources (0.68; 95% CI, 0.35-1.00) and relationship with the person with dementia (-0.22; 95% CI, -0.41 to -0.03) had smaller, significant associations. Social location (0.28; 95% CI, -0.33 to 0.89) and managing everyday life with dementia (0.06; 95% CI, -0.15 to 0.28) were not significantly associated with living well. DISCUSSION: These findings demonstrate the importance of supporting caregivers' psychological and physical health and their ability to develop and maintain positive coping strategies, as well as enabling them to maintain vital social capitals, assets and resources.

A Comprehensive Model of Factors Associated With Subjective Perceptions of "Living Well" With Dementia: Findings From the IDEAL Study.

INTRODUCTION: We aimed to better understand what predicts the capability to "live well" with dementia by identifying the relative contribution of life domains associated with the subjective experience of living well. METHODS: We analyzed data from 1547 individuals with mild-to-moderate dementia in the IDEAL cohort. We generated a "living well" latent factor from measures of quality of life, satisfaction with life, and well-being. We used multivariate modeling to identify variables related to living well measures and structural equation modeling to derive latent variables for 5 life domains and to examine the associations of these domains with living well. RESULTS: All 5 domains were individually associated with living well. When modeled together, the psychological characteristics and psychological health domain was the only independent predictor of living well [effect size, 3.55; 95% confidence interval (CI): 2.93-4.17], and effect sizes were smaller for physical fitness and physical health (1.23, 95% CI: -0.10 to 2.58), social capitals, assets and resources (0.67; 95% CI: -0.04 to 1.38), managing everyday life with dementia (0.33; 95% CI: -0.06 to 0.71), and social location (0.08; 95% CI: -2.10 to 2.26). DISCUSSION: Psychological resources, and the social, environmental, and physical factors that underpin positive psychological states, are potentially important targets for interventions and initiatives that aim to improve the experience of living with dementia.

The impact of co-morbidity on the quality of life of people with dementia: findings from the IDEAL study.

BACKGROUND: The aim was to investigate the co-morbidity profile of people with dementia and examine the associations between severity of co-morbidity, health-related quality of life (HRQoL) and quality of life (QoL). METHODS: The improving the experience of Dementia and Enhancing Active Life (IDEAL) cohort consisted of 1,547 people diagnosed with dementia who provided information on the number and type of co-morbid conditions. Participants also provided ratings of their health-related and dementia-specific QoL. RESULTS: The majority of the sample were living with more than one chronic condition. Hypertension was commonly reported and frequently combined with connective tissue disease, diabetes and depression. The number of co-morbid conditions was associated with low QoL scores, and those with severe co-morbidity (≥5 conditions) showed the greatest impact on their well-being. CONCLUSIONS: Co-morbidity is an important risk factor for poor QoL and health status in people with dementia. Greater recognition of the nature and impact of co-morbidity is needed to inform support and interventions for people with dementia and a multidisciplinary approach to care provision is recommended.

Have we forgotten about forgetting? A critical review of 'accelerated long-term forgetting' in temporal lobe epilepsy.

Forgetting has been researched for over a century. This literature highlighted how forgetting rates can vary dependent on factors in the design and method. Recent interest in forgetting revived with evidence suggesting that seizures experienced almost immediately after matched learning could accelerate forgetting. This was followed by a growth in forgetting studies in patients with temporal lobe epilepsy (TLE), including a subset of those with transient epileptic amnesia (TEA). These patients have been described as expressing concerns about memory, yet often perform within 'normal' ranges on standard neuropsychological memory assessments. It was argued that such patients were experiencing a phenomenon termed 'accelerated long-term forgetting': apparently normal learning and initial retention with abnormal forgetting over days to weeks after learning. In this review, we critically evaluate aspects of this definition, namely whether learning and initial retention is, in fact, 'normal' at first, and further what this means in relation to 'when' abnormal forgetting starts. We propose a shift in the understanding of accelerated forgetting in TLE from an emphasis on late-onset forgetting to greater focus on early-onset, progressively greater forgetting. We argue that most evidence from studies to date could be conceptualized within the latter framework, with differences in forgetting patterns reflective of a continuum of severity and/or sensitivity.

Spatial navigation deficits in amnestic mild cognitive impairment with neuropsychiatric comorbidity.

AIMS: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI). METHODS: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly participants (HE, n = 22). They completed the Mini-Mental State Examination and a virtual Hidden Goal Task in egocentric, allocentric, and delayed recall subtests. RESULTS: In allocentric navigation, aMCI and comMCI performed significantly worse than HE and similarly to each other. Although aMCI performed significantly worse at egocentric navigation than HE, they performed significantly better than patients with comMCI. CONCLUSIONS: Despite the growing burden of dementia and the prevalence of neuropsychiatric symptoms in the elderly population, comMCI remains under-studied. Since trials often assess "pure" aMCI, we may underestimate patients' navigation and other deficits. This finding emphasizes the importance of taking account of the cognitive effects of psychiatric disorders in aMCI.

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch's and Kopelman's models of psychogenic amnesia, and with respect to Anderson's neuroimaging findings in memory inhibition.