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.

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.

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.

Non-verbal, short-term forgetting in the alcoholic Korsakoff syndrome and Alzheimer-type dementia.

On a non-verbal, short-term forgetting task, Alzheimer patients showed a severe impairment and Korsakoff patients a more moderate impairment. At block span, less demanding of information-processing resources. Alzheimer patients were impaired and Korsakoff patients intact. The pattern of results suggested that the impairment resulted from diminished processing resources and/or an encoding or retrieval deficit, rather than from accelerated decay of the memory trace, although this latter possibility could not be completely excluded. The impairment involved memory for location or position, and there was no evidence that "short-term" memory for sequence was disproportionately affected. The deficit correlated with the degree of general, cortical atrophy evident on a CT scan and with a measure of right hemisphere dysfunction (picture arrangement errors). Together, these findings suggest that right hemisphere atrophy may underlie the deficit in non-verbal, "short-term" tests. The results are compared with those obtained in previous studies employing a verbal, short-term forgetting (Brown-Peterson) task.

Rates of forgetting in Alzheimer-type dementia and Korsakoff's syndrome.

After initial learning had been equated as closely as possible, 16 Alzheimer-type dementing patients showed the same rate of forgetting on a picture recognition test administered at intervals over the course of a week as 16 Korsakoff patients and 16 healthy controls. This suggested that the anterograde amnesic deficit in both Alzheimer's disease and Korsakoff's syndrome is primarily an acquisition or learning deficit. The Alzheimer patients differed from both the Korsakoff patients and the healthy controls in showing diminished digit span and severely impaired performance at the Brown-Peterson test, implicating a deficit of short-term (or working) memory. The variability of performance within groups on the principal tests employed was also examined; and the Alzheimer results are discussed with respect to the underlying neuropathology, and the implication for pharmacotherapy.

Remote and autobiographical memory, temporal context memory and frontal atrophy in Korsakoff and Alzheimer patients.

Korsakoff and Alzheimer patients were assessed on tests of remote, autobiographical, and temporal context memory. On the remote memory tests, both groups showed a temporal gradient across all the measures used, although the gradient was significantly steeper in the Korsakoff group. Both groups also showed a marked improvement in performance on recognition testing. Correlations with an anterograde "memory quotient" were relatively low, and in the Korsakoff group, there was evidence of partial independence between memory for personal events/facts and memory for public events/facts. Better performance within the Korsakoff group in the recall of early memories was correlated with higher intelligence, whereas worse performance for recent memories was associated with a longer duration of the disorder. Both patient groups were impaired at tests of retrospective and anterograde temporal context memory, but there was no association with a neuroradiological measure of frontal atrophy and only a very weak correlation with tests of frontal function. It is concluded that both patient groups show a retrieval deficit in remote memory, that a superimposed anterograde impairment produces the steeper temporal gradient in Korsakoff patients, and that the deficit in temporal context memory is unlikely to be related to frontal atrophy or frontal dysfunction.

Recall and recognition memory in patients with focal frontal, temporal lobe and diencephalic lesions.

Patients with frontal, temporal lobe, or diencephalic lesions were compared with healthy controls on measures of recall and recognition memory for word lists. Exposure times were titrated to match recognition memory scores 30 s after the end of word-list presentation as closely as possible. Using this technique, we failed to find a disproportionate impairment in recall memory in either the frontal lobe lesion patients or in the amnesic (temporal lobe and diencephalic) patients, compared with healthy controls. Consistent with this finding, performance on these tasks showed highly significant correlations with anterograde memory quotients (despite the titration procedure), but not with executive/frontal function tasks. On the other hand, the frontal lobe lesion group showed disproportionate benefit in the recall of semantically categorised words, compared with unrelated words. This may indicate an impairment in retrieval or access, compared with the amnesic (temporal lobe and diencephalic) patients, and/or an inability to organise their learning of unrelated words spontaneously, compared with healthy controls.

Rates of forgetting in normal ageing: a comparison with dementia.

This paper examines the effect of normal ageing on the forgetting rate of visuo-spatial material in a sample of 74 subjects, aged between 16 and 83. It finds that normal ageing produces a mild acquisition deficit as well as a significant increase in the forgetting rate; and it demonstrates that the relatively rapid rate of forgetting in the elderly cannot be accounted for by differences in the initial level of acquisition. The present result is contrasted with that obtained in studies of dementia and the Korsakoff syndrome, which have demonstrated a profound acquisition deficit but a normal forgetting rate once initial learning has been accomplished. Possible explanations of these differing patterns of results are briefly considered.

Frequency judgements of abstract designs by patients with diencephalic, temporal lobe or frontal lobe lesions.

Patients with diencephalic, temporal lobe or frontal lobe lesions were compared with healthy controls on a frequency judgement task. The three patient groups were disproportionately impaired at estimating how often a series of abstract designs had been presented relative to controls. Diencephalic and temporal lobe patients did not differ from each other. It is argued that the results may reflect a 'core' memory deficit in the temporal lobe patients. The impairment in the frontal patients may reflect their difficulty in making an organised search in memory for multiple traces of an item, while the deficit shown by the diencephalic patients (particularly those with Korsakoff syndrome) may be due to the combined effects of a generally poor memory and superimposed frontal pathology.

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions.

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.

Retrograde amnesia in patients with diencephalic, temporal lobe or frontal lesions.

Patients with focal diencephalic, temporal lobe, or frontal lobe lesions were examined on various measures of remote memory. Korsakoff patients showed a severe impairment with a characteristic 'temporal gradient', whereas two patients with focal diencephalic damage (and anterograde amnesia) were virtually unimpaired on remote memory measures. Patients with frontal lobe pathology were severely impaired in the recall of autobiographical incidents and famous news events. Patients with temporal lobe pathology showed severe impairment but a relatively 'flat' temporal gradient, largely attributable to herpes encephalitis patients. From recognition and cued recall tasks, it is argued that there is an important retrieval component to the remote memory deficit across all the lesion groups. In general, the pattern of performance by the frontal lobe and temporal lobe groups was closely similar, and there was no evidence of any major access/storage difference between them. However, laterality comparisons across these groups indicated that the right temporal and frontal lobe regions may make a greater contribution to the retrieval of past episodic (incident and event) memories, whereas the left temporal region is more closely involved in the lexical-semantic labelling of remote memories.

The great escape: a neuropsychological study of psychogenic amnesia.

This paper describes the neuropsychological test performance of a patient who experienced a "fugue" episode (functional retrograde amnesia) lasting 7 days, but who continued to complain of a virtually complete loss of autobiographical memory for well over a year. Subsequent evidence revealed that she had been at least partially simulating her amnesia during this prolonged period. Neuropsychological testing took place soon after admission to hospital, at intervals thereafter, and after an Amytal abreaction, which produced a substantial recovery of her memories. On various anterograde tests, designed to detect simulation, the patient's performance was unimpaired, including recognition memory tasks, word-stem completion priming for "neutral" word-lists and for post-onset autobiographical material, and some aspects of semantic memory. However, her pattern of performance on an autobiographical and a remote News Event test differentiated her from patients with organic amnesia, because she showed a grossly disproportionate autobiographical memory loss and an extreme recency effect. In addition, a rating scale, on which she showed impaired feelings-of-knowing for items from her autobiographical memory, suggested simulation. On a word-completion task for pre-onset autobiographical material, she showed absent "priming" relative to "baseline" material. However, following the Amytal abreaction, there was a substantial improvement on this task, relative to recognition and cued recall performance. This finding has been interpreted within an hierarchical model of awareness in memory, derived from studies of normal memory and organic amnesia; and it is suggested that patients with "psychogenic amnesia" may manifest different levels of awareness for differing memories.

Rates of forgetting in Alzheimer dementia.

Patients diagnosed with Alzheimer's disease (AD) were compared with healthy controls on a picture recognition task, a forced choice word recognition task, a forced choice design recognition task, a picture recall task and a stem completion task. Performance on recognition and word stem completion was assessed at 1, 10 and 20 min after exposure to experimental stimuli, as these are delays across which previous studies had suggested there might be differing forgetting rates. AD patients did not show significantly faster rates of forgetting relative to controls on picture recognition, design recognition, word recognition or stem completion, after levels of learning had been matched as closely as possible. Moreover, once initial learning was equated in a small number of subjects, there were no qualitative differences between AD patients and controls following inclusion and exclusion instructions on the stem completion task. In particular, those AD patients who were matched to controls for initial levels of "recollection" showed comparable forgetting rates in recollection (or cued recall). Although matching was more difficult for a picture recall task, both the main analysis and subgroup analysis indicated faster forgetting in the AD group than controls, suggesting a difference between "free recall" and recognition or cued recall measures, comparable with the finding in a parallel study of organic amnesia.

Rates of forgetting in organic amnesia following temporal lobe, diencephalic, or frontal lobe lesions.

Forgetting rates were examined in patients with diencephalic, temporal lobe, or frontal lesions. No significant differences were found in short-term forgetting of verbal and nonverbal material; in recognition memory for pictures, words, or designs over delays between 1 min and 20 or 30 min; or on a measure of explicit cued recall for words, calculated in terms of the process dissociation procedure. Significantly faster forgetting was found in the diencephalic and the temporal lobe groups in the free recall of pictures of objects, although there was no difference between these 2 groups. It is concluded that the major deficit in amnesic patients' memory processes is in the initial acquisition of information but that there is a subtler deficit in retention over specific delays, detectable only on measures of free recall.

Subjective memory evaluations in patients with focal frontal, diencephalic, and temporal lobe lesion.

This paper examines subjective memory evaluations and their correlates in patients with focal frontal, diencephalic, or temporal lobe lesions. Although all patient groups showed significantly lower subjective memory evaluations than healthy subjects, the temporal lobe group rated themselves significantly lower than the frontal lobe or diencephalic groups despite comparable severity of amnesia, implying more severely impaired 'insight' in the latter two groups. There was a 'temporal gradient' such that patients rated their memory for 'old' (premorbid) items better than their memory for 'new' (recent) or prospective items. As in previous studies, subjective memory evaluations were not correlated with measures of 'objective' anterograde memory performance, but the present study suggests that subjective evaluations are not randomly determined. It seemed to be the site of lesion (frontal and/or diencephalic), rather than underlying aetiology, which produced a particularly severe loss of 'insight'. Whether the earliest remote or autobiographical memories were preserved or not appeared to be an important correlate of current subjective memory evaluations, and patients who had been memory-disordered for longer were more likely to evaluate their memory as poor than those with a more recent onset.

Does the sedation resulting from sleep deprivation and lorazepam cause similar cognitive deficits?

It is notoriously difficult to assess the contribution of the sedative effects of benzodiazepines to the cognitive impairments that they produce. The purpose of the present experiment was to determine whether a similar pattern of cognitive impairment would be seen in conditions when subjects felt equally sleepy as the result of sleep deprivation. The effects of a sedative dose of lorazepam (2.5 mg) in healthy volunteers was therefore compared with the effects of acute sleep deprivation (a night on-call) in a group of junior doctors and the effects of chronically disturbed sleep due to snoring. Lorazepam, acute sleep deprivation, and chronic sleep disturbance all significantly increased subjective sedation. In addition, lorazepam significantly impaired performance in two tests of psychomotor speed and caused significant anterograde amnesia. Semantic and short-term memory were not impaired by lorazepam, nor was there any impairment in executive function. The only deficit found following acute sleep deprivation was in a test of semantic memory, generating examples from a difficult category. The only significant deficit in the group suffering from chronically disturbed sleep, compared with age-matched controls, was in executive function, and there was a nearly significant impairment in sustained attention. These results suggest that, despite the common factor of increased subjective sedation, the profile of cognitive impairment in the two sleep deprivation groups are neither similar to each other nor to that seen following an acute dose of lorazepam.

Recall of anomalous sentences in dementia and amnesia.

Alzheimer-type dementing patients were compared with amnesic (Korsakoff) patients, depressed patients, and healthy controls in the immediate recall of semantically anomalous sentences. It was found that the dementing (Alzheimer) patients were severely impaired in their recall of these sentences, but that the amnesic (Korsakoff) patients were not. Alzheimer patients have a severe impairment of short-term memory, and it is argued that this deficit may make Alzheimer patients especially dependent upon the presence of semantic cues in immediate verbal recall--hence, the removal or reversibility of these cues results in a collapse of their performance. Other research has indicated that Alzheimer patients also show impaired semantic processing, and the possible interaction of their short-term memory and semantic processing deficits is briefly discussed.