Regional Cerebral Blood Flow and Cognition in Dementia of the Alzheimer Type

The studies described in this Thesis were designed to investigate the patterns of cerebral blood flow (CBF) deficits that occur in Dementia of the Alzheimer Type (DAT) and relate them to performance on a variety of cognitive tasks. Previous work investigating the relationship between CBF and cognition in DAT (Bonte et al. 1986; Burns et al., 1989; Hunter et al., 1989) has produced large numbers of non-specific associations which are difficult to interpret. It was hypothesised that more meaningful associations might be produced if the assessment of cognition involved more specific neuropsychological tests. Therefore these studies aimed to investigate the CBF-cognition relationship using a general cognitive test as well as a number of specific neuropsychological tasks. In recent years the focus of research in this field has shifted from the later to the earlier stages of DAT. This shift is reflected here with the investigations of rCBF and cognition not only in a moderate to severe DAT group, but also in a mild and a minimal group. Using a dedicated neuroimager (SME 810) and the relatively recently developed radiopharmaceutical, 99m-Technetium labelled Hexamethyl-propylenamine oxime (HMPAO). Single Photon Emission Computerised Tomography (SPECT) was carried out to measure regional cerebral blood flow in DAT patients and controls. SPECT images were obtained for two slices; a 'standard' slice containing medial and lateral frontal, temporal, posterior temporal, occipital, calcarine, thalamic and basal ganglia regions; and a 'high' slice containing high frontal and parietal regions. Measures of blood flow were obtained and expressed as proportions of calcarine activity for normalisation purposes. The patient populations were recruited from a psychiatric hospital (moderate and severe cases), and from a memory clinic (minimal and mild cases.) All patients were diagnosed as suffering from DAT according to the CAMDEX diagnostic criteria (Roth, Tym, Mountjoy et al., 1986) and severity was classified according to cognitive performance on the CAMCOG (Roth et al., 1986) a general cognitive assessment procedure. Further cognitive assessment involved recall and recognition memory performance on a Delayed Recognition Span Task (DRST) (Moss et al.,1986), performance on four established 'Frontal' tasks (word fluency, Wisconsin card sorting task, delayed alternation task, subject ordered pointing task) and performance on a standardised confrontational naming task (Graded Naming Test, McKenna & Warrington 1983). Performance of the DAT patients compared to controls was examined for both the memory and frontal investigations, while performance on the naming task was examined for the presence of highly specific subgroups within the DAT population itself. SPECT scanning was carried out within four weeks of neuropsychological assessment. Correlational analyses were performed in order to investigate the relationship between cognition and rCBF. In particular, correlations were carried out between CBF and performance on the GAMGOG (and its subscores) , GBF and performance on the Recognition Span Task and GBF and performance on the frontal tasks. The relationship between performance on the naming task and GBF was investigated quite differently. Subgroups of patients were selected on the basis of the types of naming error they made and their GBF patterns were examined to see whether they reflected their particular cognitive impairment. These studies found that a memory clinic provides a suitable method of recruiting cases of early DAT for research purposes and that the analysis of presenting symptoms may contribute to the difficult task of identifying very early cases of dementia. The results of the CBF studies support the view that deficits develop very early on in the degenerative process since the minimal group display a clear left temporal deficit. The increased severity of the mild DAT group is reflected in their CBF picture; this group display deficits in much of the cortex as well as the thalamic region. The moderate to severe group also displayed extensive CBF deficits reflecting severe damage to all cortical regions. The cognitive assessment of the patients with the CAMCOG revealed ceiling and floor effects suggesting that this type of task is more suitable for general cognitive monitoring rather than for the investigation of specific cognitive functions. The Recognition Span task illustrated very early deficits in both recall and recognition and demonstrated that recall scores distinguished the minimal DAT group from the control group. While recall scores drop to floor level by the moderate stage of DAT, performance on the recognition tasks shows that some recognition memory ability remains beyond this point. Performance on the frontal tasks was also shown to be impaired by DAT and related to overall severity. No outliers were found on any of these tasks therefore making it unlikely that a disproportionate frontal deficit exists in these patients. (Abstract shortened by ProQuest.)

Deconstructing the performance of everyday activities: a case in dementia

Background: The assessment of everyday functioning in dementia currently is very global and in most cases fails to provide an in-depth overview of specific areas of deficits. Every activity comprises different sub-tasks which may be impaired to different degrees. Performance of some sub-tasks might be maintained and could thus be the foundation for remaining independent for longer. Thus, the objective of this study was to explore the benefits of breaking down everyday activities into sub-tasks. Methods: A total of 183 family carers of people with mild dementia completed the revised Interview for Deteriorations in Daily Living Activities in Dementia 2 (R-IDDD2) rating their relative’s everyday functioning. Each of the 20 activities comprised three sub-tasks. Data were analysed using ANOVA with Bonferroni corrections, and sub-tasks were clustered in relation to different forms of cognition. Results: The majority of activities showed at least one major area of impairment. Sub-tasks could be clustered based on different types of cognition. Several sub-tasks had a focus on memory (forgetting it is time to do the cleaning; forgetting previously known telephone numbers), whereby short-term, long-term, and prospective memory could be distinguished further. Other sub-tasks were clustered into attention (getting more distracted when driving) and executive function (sorting out bills). Conclusions: The R-IDDD2 and its analysis of sub-task performance offers a novel platform to examine impairments comprehensively. This can help both in aiding timelier diagnosis by recognising subtle deficits, but also in care management planning, whereby family and paid carers should only care for those sub-tasks that are most impaired and thus encourage remaining independent for longer

Beneficial and detrimental effects of schema incongruence on memory for contextual events.

Mental schemas provide a framework into which new information can easily be integrated. In a series of experiments, we examined how incongruence that stems from a prediction error modulates memory for multicomponent events that instantiated preexisting schemas as noted in a previous study. Each event consisted of four stimulus pairs with overlapping components, presented in four blocks (A-B, B-C, C-D, D-A). A-B pairs elicited contextual expectations (A: Farm, B: Tractor) that were either met by a congruent C component (C: Farmer) or violated by an incongruent one (C: Lawyer). The baseline condition included unrelated pairs, where the C component was neither congruent nor incongruent. In experiment 2, events were presented in successive trials instead of blocks, and eye movements were recorded to analyze allocation of attention. Memory was tested through old-new item recognition followed by cued recall. Across experiments, recognition and recall performance for incongruent components was reduced compared to congruent components. Incongruent items were in some cases more accurately retrieved compared to unrelated ones, depending on task demands. Additionally, better recall was observed in the incongruent D-A pairs, compared to congruent and unrelated ones, because of reduced interference from C components. Eye-tracking revealed an increased number of fixations on C components in the incongruent and unrelated conditions. These results suggest that the integration of incongruent items into an episode is impaired, compared to congruent items, despite the contextual surprise and increased attention they elicited at encoding. However, there was a beneficial effect of prediction error on memory performance, compared to a baseline, depending on the task used

Information content best characterises the hemispheric selectivity of the inferior parietal lobe: a meta-analysis

From Springer Nature via Jisc Publications RouterHistory: received 2020-04-22, accepted 2020-08-21, registration 2020-08-28, pub-electronic 2020-09-15, online 2020-09-15, collection 2020-12Publication status: PublishedFunder: Engineering and Physical Sciences Research CouncilFunder: University of ManchesterAbstract: Our understanding of the inferior parietal lobe (IPL) remains challenged by inconsistencies between neuroimaging and neuropsychological perspectives. To date, others assume that hemispheric specialisation of the IPL is linked with the type of processing; attention processing in the right hemisphere; memory retrieval and semantic judgement in the left hemisphere. Here, we provide compelling evidence associating the type of information being processed with the recruitment of each hemisphere’s IPL. In a meta-analysis, we classify 121 previous fMRI reports of IPL activity arising from episodic memory retrieval, according to the type of information that characterises each fMRI contrast. We demonstrate that the left IPL is more consistently associated with retrieval of the semantic (95% of eligible contrasts) than perceptual aspects of memory (83%). In contrast, the right IPL is more consistently associated with the retrieval of perceptual (97%), than semantic aspects of memory (43%). This work revises assumptions of how the IPL contributes to healthy cognition and has major implications for IPL-related neuropsychological deficits

Pattern separation underpins expectation-modulated memory

Pattern separation and completion are fundamental hippocampal computations supporting memory encoding and retrieval. However, despite extensive exploration of these processes, it remains unclear whether and how top-down processes adaptively modulate the dynamics between these computations. Here we examine the role of expectation in shifting the hippocampus to perform pattern separation. In a behavioral task, 29 participants (7 males) learned a cue-object category contingency. Then, at encoding, one-third of the cues preceding the to-be-memorized objects, violated the studied rule. At test, participants performed a recognition task with old objects (targets) and a set of parametrically manipulated (very similar to dissimilar) foils for each object. Accuracy was found to be better for foils of high similarity to targets that were contextually unexpected at encoding compared with expected ones. Critically, there were no expectation-driven differences for targets and low similarity foils. To further explore these effects, we implemented a computational model of the hippocampus, performing the same task as the human participants. We used representational similarity analysis to examine how top-down expectation interacts with bottom-up perceptual input, in each layer. All subfields showed more dissimilar representations for unexpected items, with dentate gyrus (DG) and CA3 being more sensitive to expectation violation than CA1. Again, representational differences between expected and unexpected inputs were prominent for moderate to high levels of input similarity. This effect diminished when inputs from DG and CA3 into CA1 were lesioned. Overall, these novel findings strongly suggest that pattern separation in DG/CA3 underlies the effect that violation of expectation exerts on memory

Detection of scene-relative object movement and optic flow parsing across the adult lifespan

Moving around safely relies critically on our ability to detect object movement. This is made difficult because retinal motion can arise from object movement or our own movement. Here we investigate ability to detect scene-relative object movement using a neural mechanism called optic flow parsing. This mechanism acts to subtract retinal motion caused by self-movement. Because older observers exhibit marked changes in visual motion processing, we consider performance across a broad age range (N = 30, range: 20–76 years). In Experiment 1 we measured thresholds for reliably discriminating the scene-relative movement direction of a probe presented among three-dimensional objects moving onscreen to simulate observer movement. Performance in this task did not correlate with age, suggesting that ability to detect scene-relative object movement from retinal information is preserved in ageing. In Experiment 2 we investigated changes in the underlying optic flow parsing mechanism that supports this ability, using a well-established task that measures the magnitude of globally subtracted optic flow. We found strong evidence for a positive correlation between age and global flow subtraction. These data suggest that the ability to identify object movement during self-movement from visual information is preserved in ageing, but that there are changes in the flow parsing mechanism that underpins this ability. We suggest that these changes reflect compensatory processing required to counteract other impairments in the ageing visual system

The newly revised interview for deteriorations in daily living activities in dementia (R-IDDD2): distinguishing initiative from performance at assessment

Background: Minimal evidence exists on the detailed deficits in complex instrumental activities of daily living (IADLs) in mild dementia. The aim of this study was twofold, to validate a revised questionnaire focusing measuring the initiative and performance of IADLs in mild dementia and to explore the relationship between individual IADLs and patient and carer well-being. Methods: A total of 183 carers of people with mild dementia completed a further modified Revised Interview for Deterioration in Daily Living Activities 2 (R-IDDD2), which comprised new activities such as computer use, as well as sub-activities on the performance scale. Carers also completed questionnaires assessing patient quality of life (QoL-AD), carer quality of life (AC-QoL), and burden (GHQ-12). Results: Persons with dementia were significantly poorer initiating than performing cleaning, doing repair work, and preparing a hot or cold meal, whereas being poorer at performing dressing and following current affairs. Using the computer, preparing a hot meal, finance, and medication management were most impaired, whereas more basic activities of dressing, washing oneself, brushing hair or teeth, and preparing a hot drink were most preserved. Poor initiative and performance on nearly all activities were significantly related to reduced carer and patient well-being. Conclusions: The R-IDDD2 offers a platform to comprehensively assess everyday functioning. Deteriorations in initiative and performance need to be targeted separately in interventions, as the former requires effective triggering and the latter structured training and support. Most activities were significantly associated with well-being, particularly patient quality of life so that improving any activity should improve well-being

Diminished Neural and Cognitive Responses to Facial Expressions of Disgust in Patients with Psoriasis: A Functional Magnetic Resonance Imaging Study

Psoriasis produces significant psychosocial disability; however, little is understood about the neurocognitive mechanisms that mediate the adverse consequences of the social stigma associated with visible skin lesions, such as disgusted facial expressions of others. Both the feeling of disgust and the observation of disgust in others are known to activate the insula cortex. We investigated whether the social impact of psoriasis is associated with altered cognitive processing of disgust using (i) a covert recognition of faces task conducted using functional magnetic resonance imaging (fMRI) and (ii) the facial expression recognition task (FERT), a decision-making task, conducted outside the scanner to assess the ability to recognize overtly different intensities of disgust. Thirteen right-handed male patients with psoriasis and 13 age-matched male controls were included. In the fMRI study, psoriasis patients had significantly (P<0.005) smaller signal responses to disgusted faces in the bilateral insular cortex compared with healthy controls. These data were corroborated by FERT, in that patients were less able than controls to identify all intensities of disgust tested. We hypothesize that patients with psoriasis, in this case male patients, develop a coping mechanism to protect them from stressful emotional responses by blocking the processing of disgusted facial expressions