Long-term cognitive and psychiatric outcomes of acute respiratory distress syndrome managed with Extracorporeal Membrane Oxygenation.

BACKGROUND: Cognitive dysfunction is often reported in patients who have experienced acute respiratory distress syndrome (ARDS). Extra Corporeal Membrane Oxygenation (ECMO) therapy is increasingly used to manage ARDS patients in ICU, transforming survival rates. However, few studies have examined cognitive outcomes. METHODS: We examined self-reported cognitive complaints, psychiatric outcomes and neuropsychological test performance in survivors of severe hypoxaemia managed with VV-ECMO, at 18-24 month follow-up, compared with a group of healthy controls. RESULTS: Over 70% of ECMO-treated patients (N = 46) complained of difficulty in at least one aspect of cognition on self-report measures (study 1). However, a much lower frequency of cognitive impairment was found on formal neuropsychological testing (study 2). Mean neuropsychological test scores of the ECMO group (N = 24) did not significantly differ from healthy controls (N = 23) after controlling for depression. Less than 30% of ECMO-treated patients showed impairments in anterograde memory, and deficits on general IQ or executive function were seen in <17% of patients. However, we observed high levels of self-reported anxiety and depression in the ECMO-treated patients. CONCLUSIONS: Cognitive outcomes in ECMO-treated patients were generally good, with preserved neuropsychological function in the majority of patients, despite severe hypoxaemia and high rates of self-reported difficulties. However, we saw high levels of mental health symptoms in these patients, highlighting a need for psychological support.

HIV: ageing, cognition and neuroimaging at 4-year follow-up.

OBJECTIVES: The aim of the study was to investigate the hypothesis of accelerated cognitive ageing in HIV-positive individuals using longitudinal assessment of cognitive performance and quantitative magnetic resonance imaging (MRI). METHODS: We assessed a broad cognitive battery and quantitative MRI metrics [voxel-based morphometry (VBM) and diffusion tensor imaging (DTI)] in asymptomatic HIV-positive men who have sex with men (15 aged 20-40 years and 15 aged ≥ 50 years), and HIV-seronegative matched controls (nine aged 20-40 years and 16 aged ≥ 50 years). RESULTS: Being HIV positive was associated with greater decreases in executive function and global cognition. Additionally, using DTI, we found that the HIV-positive group had a greater increase in mean diffusivity, but we did not find group differences in volume change using VBM. With respect to the HIV status by age group interaction, this was statistically significant for change in global cognition, with older HIV-positive individuals showing greater global cognitive decline, but there were no significant interaction effects on other measures. Lastly, change in cognitive performance was correlated with change in the DTI measures, and this effect was stronger for the HIV-positive participants. CONCLUSIONS: In the present study, we found some evidence for accelerated ageing in HIV-positive individuals, with a statistically significant HIV status by age group interaction in global cognition, although this interaction could not be explained by the imaging findings. Moreover, we also found that change in cognitive performance was correlated with change in the DTI measures, and this effect was stronger for the HIV-positive participants. This will need replication in larger studies using a similarly lengthy follow-up period.

Psychologic/functional forms of memory disorder.

In this chapter, we discuss the wide variety of patients who may attend a memory clinic or other health services presenting with memory symptoms but who do not have dementia. These diagnoses may include a wide range of neurologic and neuropsychiatric disorders; in this chapter we will focus on other causes of memory symptoms which may be labeled psychologic or functional, or be more obviously part of an established psychiatric disorder. We describe the differential categorization recently posited by Stone et al. (2015), and consider important aspects of assessment and management in these cases.

Investigating virtual reality navigation in amnestic mild cognitive impairment using fMRI.

Spatial navigation requires a well-established network of brain regions, including the hippocampus, caudate nucleus, and retrosplenial cortex. Amnestic Mild Cognitive Impairment (aMCI) is a condition with predominantly memory impairment, conferring a high predictive risk factor for dementia. aMCI is associated with hippocampal atrophy and subtle deficits in spatial navigation. We present the first use of a functional Magnetic Resonance Imaging (fMRI) navigation task in aMCI, using a virtual reality analog of the Radial Arm Maze. Compared with controls, aMCI patients showed reduced activity in the hippocampus bilaterally, retrosplenial cortex, and left dorsolateral prefrontal cortex. Reduced activation in key areas for successful navigation, as well as additional regions, was found alongside relatively normal task performance. Results also revealed increased activity in the right dorsolateral prefrontal cortex in aMCI patients, which may reflect compensation for reduced activations elsewhere. These data support suggestions that fMRI spatial navigation tasks may be useful for staging of progression in MCI.

Alterations in working memory networks in amnestic mild cognitive impairment.

Patients with amnestic mild cognitive impairment (aMCI) show preserved or mildly impaired working memory, despite their deficits in episodic memory. We aimed to identify performance and/or neural differences between aMCI patients and matched controls on a standard working memory fMRI task. Neuropsychological assessment demonstrated aMCI impairments in verbal and visual episodic long-term memory, with intact IQ and executive function. Participants completed a standard three-level N-back task where patients were unimpaired. Functional activations in the control group were found in expected areas, including the inferior parietal lobule and dorsolateral prefrontal cortex. Group differences were found in the insula and lingual gyrus and, in a region of interest analysis, in the hippocampus. In all cases, these were caused by an absence of task-related deactivations in the aMCI group. The results are consistent with reports of failure in task-related deacivations in aMCI and could be early indications of pathology.

On remembering and forgetting our autobiographical pasts: retrograde amnesia and Andrew Mayes's contribution to neuropsychological method.

Andrew Mayes's contribution to the neuropsychology of memory has consisted in steadily teasing out the nature of the memory deficit in the amnesic syndrome. This has been done with careful attention to matters of method at all stages. This particularly applies to his investigations of forgetting rates in amnesia and to his studies of retrograde amnesia. Following a brief outline of his work, the main current theories of retrograde amnesia are considered: consolidation theory, episodic-to-semantic shift theory, and multiple trace theory. Findings across the main studies in Alzheimer dementia are reviewed to illustrate what appears to be consistently found, and what is much more inconsistent. A number of problems and issues in current theories are then highlighted--including the nature of the temporal gradient, correlations with the extent of temporal lobe damage, what we would expect 'normal' remote memory curves to look like, how they would appear in focal retrograde amnesia, and whether we can pinpoint retrograde amnesia to hippocampal/medial temporal damage on the basis of existing studies. A recent study of retrograde amnesia is re-analysed to demonstrate temporal gradients on recollected episodic memories in hippocampal/medial temporal patients. It is concluded that there are two requirements for better understanding of the nature of retrograde amnesia: (i) a tighter, Mayesian attention to method in terms of both the neuropsychology and neuroimaging in investigations of retrograde amnesia; and (ii) acknowledging that there may be multiple factors underlying a temporal gradient, and that episodic and semantic memory show important interdependencies at both encoding and retrieval. Such factors may be critical to understanding what is remembered and what is forgotten from our autobiographical pasts.

A psychiatric perspective on the therapy of psychosis in systemic lupus erythematosus.

A brief description of psychosis in the general psychiatric setting and its treatment using antipsychotic agents including 'atypical' drugs. A review of the prevalence of neuropsychiatric syndromes in lupus (using The American College of Rheumatology standardized definitions) from recent studies showing wide variation in reported rates. Underlying pathophysiologic mechanisms postulated for neuropsychiatric manifestations of lupus are reviewed with implications for treatment. The use and success of intravenous pulsed cyclophosphamide (singly and in combination with methylprednisiolone) for severe neuropsychiatric psychosis is reviewed.

Hypocretin (orexin) deficiency in narcolepsy and primary hypersomnia.

The discovery that hypocretins are involved in narcolepsy, a disorder associated with excessive daytime sleepiness, cataplexy, and unusually rapid transitions to rapid eye movement sleep, opens a new field of investigation in the area of disorders of sleep and activation. Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) (also called orexin-A and orexin-B) are newly discovered neuropeptides processed from a common precursor. Hypocretin containing cells are located exclusively in the lateral hypothalamus, with widespread projections within the central nervous system. The role of the hypocretin system in other disorders causing excessive daytime sleepiness is more uncertain. This study reports the findings of a prospective study measuring cerebrospinal fluid concentrations of hypocretin-1 and hypocretin-2 in HLA DQB1*0602 positive narcolepsy with cataplexy, monosymptomatic narcolepsy, and primary hypersomnia. The results confirmed the previous observations, that hcrt-1 is deficient in narcolepsy and for the first time report very low levels of hcrt-1 in primary hypersomnia. It is also reported for the first time that there is a generalised defect in hcrt-2 transmission in all three of these clinical entities compared with controls.

Lost for words or loss of memories? Autobiographical memory in semantic dementia.

Recent reports have suggested that patients with semantic dementia show a loss of early (remote) auto-biographical memories with pronounced sparing of recent memories (Graham & Hodges, 1997; Snowden, Griffiths, & Neary, 1996), i.e., a 'reversed' temporal gradient or 'Ribot effect'. At first sight, these findings suggest that the deficits in 'semantic' dementia go beyond the semantic domain, involving aspects of autobiographical (episodic) memory. It has also been proposed that there is a 'step-like' function with personal memories preserved for 18 months to 2 years in the immediate past. This view is consistent with the theory that the hippocampal complex/medial temporal lobe (relatively intact in semantic dementia) plays a time-limited role in the acquisition and storage of memories, while the temporal neocortex (damaged in semantic dementia) is required for long-term storage and retrieval. In this study we ask whether (a) previous tests have underestimated the integrity of remote memory in semantic dementia as a result of not allowing for these patients' comprehension and language production difficulties, and (b) whether a recency effect, if obtained, is genuinely step-like or more graded. We used a cued autobiographical memory interview with semantic dementia patient, IH, to examine the effect of providing increasingly specific lexical cues to probe salient events throughout his lifespan. Results demonstrated that the provision of specific cues enabled IH to access and express memories from his childhood and early adulthood as well as from more recent times. There was a gentle recency effect only for intermediate levels of cueing, indicating that recent memories were easier to retrieve and/or express in the absence of specific cues, but this effect was graded, with no evidence of a step-like cut-off at 18 months or 2 years before testing. In brief, our findings are consistent with the view that the deficits in semantic dementia are predominantly or exclusively semantic, rather than involving the storage of autobiographical memories per se.

Retrograde amnesia and the volume of critical brain structures.

There are many controversies concerning the structural basis of retrograde amnesia (RA). One view is that memories are held briefly within a medial temporal store ("hippocampal complex") before being "consolidated" or reorganised within temporal neocortex and/or networks more widely distributed within the cerebral cortex. An alternative view is that the medial temporal lobes are always involved in the storage and retrieval (reactivation) of autobiographical memories (multiple trace theory). The present study used quantitative magnetic resonance imaging (MRI) in 40 patients with focal pathology/volume loss in different sites, to examine the correlates of impairment on three different measures of RA. The findings supported the view that widespread neural networks are involved in the storage and retrieval of autobiographical and other remote memories. Brain volume measures in critical structures could account for 60% of variance on autobiographical memory measures (for incidents and facts) in diencephalic patients and for 60-68% of variance in patients with frontal lesions. Significant correlations with medial temporal lobe volume were found only in the diencephalic group, in whom they were thought to reflect thalamic changes, but not in patients with herpes encephalitis or hypoxia in whom the temporal lobes were particularly implicated. The latter finding fails to support one of the main predictions of multiple trace theory, as presently expounded.

Amnesic syndrome and severe ataxia following the recreational use of 3,4-methylene-dioxymethamphetamine (MDMA, 'ecstasy') and other substances.

A 26-year-old woman suffered disseminated intravascular coagulation (DIC) and a brief respiratory arrest following recreational use of 3,4-methylene-dioxymethamphetamine (MDMA; 'ecstasy'), together with amyl nitrate, lysergic acid (LSD), cannabis and alcohol. She was left with residual cognitive and physical deficits, particularly severe anterograde memory disorder, mental slowness, severe ataxia and dysarthria. Follow-up investigations have shown that these have persisted, although there has been some improvement in verbal recognition memory and in social functioning. Magnetic resonance imaging and quantified positron emission tomography investigations have revealed: (i) severe cerebellar atrophy and hypometabolism accounting for the ataxia and dysarthria; (ii) thalamic, retrosplenial and left medial temporal hypometabolism to which the anterograde amnesia can be attributed; and (iii) some degree of fronto-temporal-parietal hypometabolism, possibly accounting for the cognitive slowness. The putative relationship of these abnormalities to the direct and indirect effects of MDMA toxicity, hypoxia and ischaemia is considered.

The loss of episodic memories in retrograde amnesia: single-case and group studies.

Retrograde amnesia in neurological disorders is a perplexing and fascinating research topic. The severity of retrograde amnesia is not well correlated with that of anterograde amnesia, and there can be disproportionate impairments of either. Within retrograde amnesia, there are various dissociations which have been claimed-for example, between the more autobiographical (episodic) and more semantic components of memory. However, the associations of different types of retrograde amnesia are also important, and clarification of these issues is confounded by the fact that retrograde amnesia seems to be particularly vulnerable to psychogenic factors. Large frontal and temporal lobe lesions have been postulated as critical in producing retrograde amnesia. Theories of retrograde amnesia have encompassed storage versus access disruption, physiological processes of 'consolidation', the progressive transformation of episodic memories into a more 'semantic' form, and multiple-trace theory. Single-case investigations, group studies and various forms of neuroimaging can all contribute to the resolution of these controversies.

Learning and memory: recent findings.

Recent findings from neuroimaging, event-related potential and lesion investigations reflect a rapidly emerging view that the memory system is widely distributed throughout the cortex. It is clear that the pattern of cortical involvement during encoding and retrieval of memories is critically dependent on the nature and complexity of task demands. This has implications, both for existing models of memory function, and in the methodology of future investigations and the issues they address. No consensus has yet been reached on a number of issues, perhaps most notably the role of the hippocampus in retrieval, but advances in measurement techniques should enable some of these matters to be resolved. Further work must address the complex dynamics of the memory system, the extent to which the same regions underlie different functions, and how different regions interact and reflect common functions.

Structural MRI volumetric analysis in patients with organic amnesia, 2: correlations with anterograde memory and executive tests in 40 patients.

BACKGROUND: Cognitive-MRI correlations have often been studied in disorders in which there are multiple cognitive deficits and widespread cortical atrophy, such as Alzheimer's dementia. In such circumstances, the interpretation of any single cognitive-structural correlation is equivocal. Only by measuring differing cognitive functions and a wide range of brain structures in patients with a varying distribution of lesions or atrophy can specific brain-cognitive relations be determined in neurological disorder. METHOD: In the present study, a clear set of anatomical criteria and detailed MRI segmentation procedures were applied to measure whole brain, and left and right frontal, temporal lobe, anterolateral and medial temporal volumes, as well as thalamic cross sectional areas in 40 patients with organic amnesia (from various diseases) and 10 healthy controls. RESULTS: Within the total patient group, anterograde memory measures correlated significantly with medial temporal, hippocampal, and thalamic measurements. A spatial memory measure correlated significantly with hippocampal volume, and temporal context memory with frontal volume. After a factor analysis of the cognitive measures, the association between anterograde memory and hippocampal volume was corroborated. Forgetting rates and subjective memory evaluations did not show any significant MR correlations and, of executive tests employed, only card sorting categories correlated significantly with frontal volume. CONCLUSION: Loss of volume in key brain structures (for example, hippocampus, thalamus) is detectable on quantitative MRI, and this loss of volume correlates significantly with impaired performance on measures of anterograde memory function. Correlations with hippocampal volume did not indicate a specific role in either recall or verbal memory, as opposed to recognition or visual memory.

Structural MRI volumetric analysis in patients with organic amnesia, 1: methods and comparative findings across diagnostic groups.

BACKGROUND: If they are to be replicable, MRI volume measurements require explicit definitions of structures and of criteria for delineating these structures on MRI. Previously published volumes in healthy subjects show considerable differences in measurements across different studies, including a fourfold variation in estimates of hippocampal volume. Previous neuroimaging reports in patients with Korsakoff syndrome have generally found widespread or non-specific change, whereas in patients with herpes encephalitis the extent of pathological involvement reported beyond the temporal lobes has varied. METHOD: In the present study, a clear set of anatomical criteria and detailed MRI segmentation procedures were applied to measure whole brain, frontal and temporal lobe, and anterolateral and medial temporal volumes, as well as thalamic areas in patients with organic amnesia (from Korsakoff's syndrome, herpes encephalitis, and focal frontal lesions) as well as healthy controls. RESULTS: Patients with Korsakoff's syndrome showed decreased thalamic measurements but no significant changes in the medial temporal lobes, whereas patients with herpes encephalitis showed severe medial temporal but not thalamic atrophy. In the patients with known frontal lobe lesions, quantitative analysis on MRI showed reduced frontal lobe volume but no significant temporal lobe or thalamic atrophy. CONCLUSION: Quantified MRI can be a useful technique with which to examine brain-cognitive relations, provided that detailed techniques are explicitly described. In particular, specific patterns of volume change can be found in vivo in patients with Korsakoff's syndrome and those with herpes encephalitis.

Rapid eye movement sleep behaviour disorder, depression and cognitive impairment. Case study.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder is a relatively new diagnostic category. It has never before been associated with a treatable depressive condition. AIMS: To report on a 74-year-old man with a history of depression and REM sleep behaviour disorder, associated with mild cognitive impairment. METHOD: Assessment using brain CT, MRI, PET, electroencephalography, neuropsychological testing and nocturnal polysomnography. RESULTS: Depression was treated with sertraline. Sleep laboratory studies supported a diagnosis of REM sleep behaviour disorder, which was treated with clonazepam. Sleep apnoea, revealed later, was treated with nasal continuous positive airways pressure. Brain MRI showed mild atrophy, but neuropsychological testing indicated no progressive cognitive deterioration. CONCLUSIONS: This case draws attention to REM sleep behaviour disorder and its potential interaction with depression and cognitive impairment, producing symptoms which can be mistaken for early dementia. The diagnosis of REM sleep behaviour disorder is easily missed, and it requires careful history-taking and sleep investigation in all suspected sufferers. Associated neurological, sleep and psychiatric conditions (including depression and cognitive impairment) may confound the diagnosis.