Judy Haworth

Abnormal visual search in mild cognitive impairment and Alzheimer's disease

Our aim was to further characterize the clinical concept of mild cognitive impairment (MCI). We examined the status of visual attention-related processing in such patients in relation to healthy older adults and patients with Alzheimer’s disease (AD) by measuring performance on a computer-based visual search task. We tested 20 older adult control participants, 13 patients with amnestic mild cognitive impairment and 12 patients with AD. Patients with AD and with MCI exhibited a significant detriment in visual search performance compared to the older adult controls. The deficit in visual search was greater for the patients with AD than the patients with MCI. The pattern of results displayed by the MCI group indicates that patients who appear clinically to suffer only from a deficit in memory also display a deficit in visual attention-related processing, which although not as severe as those with AD, represents a significant detriment in such performance compared to that seen in healthy ageing. The authors would like to thank all the participants for taking part and Mr A. Hughes for statistical support. Sara Nelson is now at The Department of Experimental Psychology, University of Bristol, Bristol, UK

Abnormal spatial and non-spatial cueing effects in mild cognitive impairment and Alzheimer's disease

Our aim was to further characterize the clinical concept of mild cognitive impairment (MCI). We examined visual attention-related processing in 12 patients with amnestic MCI, 16 healthy older adults and 16 patients with Alzheimer’s disease (AD) by measuring performance on computer-based tests of attentional disengagement, alerting ability, and inhibition of return. Unlike the healthy older controls, the patients with AD and the patients with amnestic MCI exhibited a significant detriment in both the ability to disengage attention from an incorrectly cued location and the ability to use a visual cue to produce an alerting effect. The pattern of results displayed by the MCI group indicates that patients who only appear clinically to suffer from a deficit in memory also display a deficit in specific aspects of visual attention-related processing, which closely resemble the magnitude seen in AD. The authors would like to thank the Bristol Research Into Alzheimer’s and Care of the Elderly (BRACE) Charity [Registered Charity Number 297965] for financial support. The authors would also like to thank all the participants taking part and Mr A. Hughes for statistical support.

New insights into feature and conjunction search: I. Evidence from pupil size, eye movements and ageing

Differences in the processing mechanisms underlying visual feature and conjunction search are still under debate, one problem being a common emphasis on performance measures (speed and accuracy) which do not necessarily provide insights to the underlying processing principles. Here, eye movements and pupil dilation were used to investigate sampling strategy and processing load during performance of a conjunction and two feature-search tasks, with younger (18-27 years) and healthy older (61-83 years) age groups compared for evidence of differential age-related changes. The tasks involved equivalent processing time per item, were controlled in terms of target-distractor similarity, and did not allow perceptual grouping. Close matching of the key tasks was confirmed by patterns of fixation duration and an equal number of saccades required to find a target. Moreover, moment-to-moment pupillary dilation was indistinguishable across the tasks for both age groups, suggesting that all required the same total amount of effort or resources. Despite matching, subtle differences in eye movement patterns occurred between tasks: the conjunction task required more saccades to reach a target-absent decision and involved shorter saccade amplitudes than the feature tasks. General age-related changes were manifested in an increased number of saccades and longer fixation durations in older than younger participants. In addition, older people showed disproportionately longer and more variable fixation durations for the conjunction task specifically. These results suggest a fundamental difference between conjunction and feature search: accurate target identification in the conjunction context requires more conservative eye movement patterns, with these further adjusted in healthy ageing. The data also highlight the independence of eye movement and pupillometry measures and stress the importance of saccades and strategy for understanding the processing mechanisms driving different types of visual search.

Intra-individual reaction time variability in mild cognitive impairment and Alzheimer's disease: gender, processing load and speed factors.

Compared to cognitively healthy ageing (CH), intra-individual variability in reaction time (IIVRT), a behavioural marker of neurological integrity, is commonly reported to increase in both Alzheimer’s disease (AD) and mild cognitive impairment (MCI). It varies in MCI with respect to whether it represents the pro-dromal stages of dementia or not; being greatest in those most likely to convert. Abnormal IIVRT in MCI therefore represents a potential measure of underlying functional integrity that may serve to differentiate MCI from CH and to help identify those patients for whom MCI is the result of a progressive pathological process. As the clinical approach to MCI is increasingly stratified with respect to gender, we investigated whether this factor could influence study outcome. The influence of RTSPEED and processing load upon IIVRT was also examined. Under low processing load conditions, IIVRT was significantly increased in both MCI and AD compared to CH. However, correcting for an individual’s processing speed abolished this effect in MCI but not in AD, indicating that the increased IIVRT in MCI and AD may result from different factors. In MCI but not in CH, IIVRT was significantly greater for females. Increasing task processing load by adding distracting information, although increasing overall IIVRT, failed to improve the differentiation between CH and both MCI and AD, and in MCI resulted in a reduction in the influence of gender upon study outcome. The outcome of studies investigating IIVRT in MCI and AD compared to CH therefore appear influenced by the gender of the participants, by task-related processing load and processing speed.

Intra-Individual Reaction Time Variability in Amnestic Mild Cognitive Impairment: A Precursor to Dementia?

We used an exogenous target detection cueing paradigm to examine whether intra-individual reaction time variability (IIV) or phasic alerting varied significantly between patients with amnestic mild cognitive impairment (aMCI) (n = 45) and healthy older adult controls (n = 31) or between those with aMCI who, within a 2.5 year follow-up period, developed dementia (n = 13) and those who did not (n = 26). Neither IIV, nor simple reaction time, differentiated aMCI from healthy aging, indicating that raised IIV and overall response slowing are not general characteristics of aMCI. However, within the aMCI group, IIV did differentiate between those who converted to dementia and those who remained with a diagnosis of aMCI (non-converters), being significantly more variable in those who later developed dementia. Furthermore, there was no difference in IIV between non-converters and healthy controls. High IIV appears related to an increased probability that an individual with aMCI will become demented within 2.5 years, rather than to amnestic dysfunction per se. In contrast, phasic alerting performance significantly differentiated aMCI from healthy aging, but failed to discriminate those with aMCI who developed dementia from those who did not. In addition, those patients with aMCI who did not develop dementia still showed a significantly poorer phasic alerting effect compared to healthy aging. The phasic alerting abnormality in aMCI compared to healthy aging does not appear specifically related to the performance of those patients for whom aMCI represents the prodromal stages of dementia.

Early visual evoked potentials and mismatch negativity in Alzheimer's disease and mild cognitive impairment

BACKGROUND Cortical visual association areas are highly vulnerable to Alzheimers disease (AD) microscopic pathology. Visual evoked potentials (VEPs) provide the tools to examine the functional integrity of these areas and may provide useful indicators of early disease progression. OBJECTIVE To assess the functional integrity of visual association area processing in AD and amnestic mild cognitive impairment (aMCI) using VEPs. METHODS We investigated the visual processing of healthy older adults (n = 26), AD (n = 20), and aMCI (n = 25) patients in a visual oddball paradigm designed to elicit the visual P1, N1, and visual mismatch negativity (vMMN). RESULTS AD patients showed a significant reduction of P1 and N1 VEP amplitudes and aMCI patients showed a reduction in N1 amplitude compared to healthy older adults. P1 amplitude in response to deviant stimuli and vMMN amplitude were found to be associated with the degree of cognitive impairment as measured by the Mini-Mental State Examination. CONCLUSIONS Changes in VEPs in AD may be a consequence of the microscopic AD pathology typically found in the extrastriate cortex. Neural measures of visual processing may help to better characterize subgroups of aMCI patients likely to develop AD. Additionally, VEPs and vMMN may provide objective markers of cognitive decline.

Exogenous phasic alerting and spatial orienting in mild cognitive impairment compared to healthy ageing: Study outcome is related to target response ☆

Whether or not attentional mechanisms such as phasic alerting, spatial cueing and inhibition of return (IOR) remain intact in adults with Alzheimers disease (AD) and mild cognitive impairment (MCI) remains a matter of debate. This is possibly the result of inter-study outcome variation caused by the adoption of different methodological components by different research groups. Here we investigated the influence of methodological factors upon study outcome, using a Posner-type exogenous cueing paradigm with amnestic MCI patients and healthy older controls. Specifically, we compared results when the required response involved target discrimination with results for a simple target detection response, using cue-to-target intervals (CTIs) of 200msec and 800msec in each case and with the same participants completing all conditions. For both groups, the presence or absence of both alerting and spatial cue-related effects depended upon the combination of target response requirement and CTI. Moreover, differences between the groups were specific to certain task conditions. The MCI group showed the same alerting effects as healthy people with a discrimination response, but the alerting effect shown by controls with a 200msec CTI and target detection was absent in MCI. Patients and controls showed similar spatial cue validity effects at 200msec CTI, but group differences emerged at 800msec CTI: target discrimination evoked a validity effect in the MCI group only, while target detection evoked an IOR effect in the healthy group only. These data indicate that detection and discrimination responses may each activate different attentional mechanisms, which are themselves differentially vulnerable in MCI. Thus a seemingly arbitrary choice of response may directly influence whether attentional processing appears preserved or disrupted in MCI. Furthermore, these data provide further evidence in support of the existence of significant visual attention-related functional abnormalities in amnestic MCI.

Measuring Information Processing Speed in Mild Cognitive Impairment: Clinical Versus Research Dichotomy

A substantial body of research evidence is indicative of disproportionately slowed information processing speed in a wide range of multi-trial, computer-based, neuroimaging- and electroencephalography-based reaction time (RT) tests in Alzheimer’s disease and mild cognitive impairment (MCI). However, in what is arguably a dichotomy between research evidence and clinical practice, RT associated with different brain functions is rarely assessed as part of their diagnosis. Indeed, often only the time taken to perform a single, specific task, commonly the Trail making test (TMT), is measured. In clinical practice therefore, there can be a failure to assess adequately the integrity of the rapid, serial information processing and response, necessary for efficient, appropriate, and safe interaction with the environment. We examined whether a typical research-based RT task could at least match the TMT in differentiating amnestic MCI (aMCI) from cognitively healthy aging at group level. As aMCI is a heterogeneous group, typically containing only a proportion of individuals for whom aMCI represents the early stages of dementia, we examined the ability of each test to provide intra-group performance variation. The results indicate that as well as significant slowing in performance of the operations involved in TMT part B (but not part A), individuals with aMCI also experience significant slowing in RT compared to controls. The results also suggest that research-typical RT tests may be superior to the TMT in differentiating between cognitively healthy aging and aMCI at group level and in revealing the performance variability one would expect from an etiologically heterogeneous disorder such as aMCI.

Different trajectories of decline for global form and global motion processing in aging, mild cognitive impairment and Alzheimer's disease

The visual processing of complex motion is impaired in Alzheimers disease (AD). However, it is unclear whether these impairments are biased toward the motion stream or part of a general disruption of global visual processing, given some reports of impaired static form processing in AD. Here, for the first time, we directly compared the relative preservation of motion and form systems in AD, mild cognitive impairment, and healthy aging, by measuring coherence thresholds for well-established global rotational motion and static form stimuli known to be of equivalent complexity. Our data confirm a marked motion-processing deficit specific to some AD patients, and greater than any form-processing deficit for this group. In parallel, we identified a more gradual decline in static form recognition, with thresholds raised in mild cognitive impairment patients and slightly further in the AD group compared with controls. We conclude that complex motion processing is more vulnerable to decline in dementia than complex form processing, perhaps owing to greater reliance on long-range neural connections heavily targeted by AD pathology.

Do memory-impaired individuals report stable attitudes?

This research explored whether individuals diagnosed with probable Alzheimers disease report stable attitudes. Two groups of participants (16 memory-impaired individuals with dementia and 16 matched controls without memory impairment) were presented with photos of various common objects and asked to indicate their attitude towards each object. Participants completed this task on two occasions, separated by 1 week. The results of the experiment revealed that memory-impaired individuals showed significant stability across time in their attitudes, although their level of attitude stability was less pronounced than that demonstrated by the matched controls. Theoretical and applied implications of the results are discussed.