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Patients with Alzheimer's disease have an impairment of inhibitory control for reasons that are currently unclear. Using an eye-tracking task (the gapoverlap paradigm), we examined whether the uncorrected errors relate to the task of attentional disengagement in preparation for action. Alternatively, the difficulty in correcting for errors may be caused by the working memory representation of the task. A major aim of this study was to distinguish between the effects of healthy aging and neurodegenerative disease on the voluntary control of saccadic eye movements. Using the antisaccade task (AST) and pro-saccade task (PST) with the 'gap' and 'overlap' procedures, we obtained detailed eye-tracking measures in patients, with 18 patients with probable Alzheimer's disease, 25 patients with Parkinson's disease and 17 healthy young and 18 old participants. Uncorrected errors in the AST were selectively increased in Alzheimer's disease, but not in Parkinson's disease compared to the control groups. These uncorrected errors were strongly correlated with spatial working memory. There was an increase in the saccade reaction times to targets that were presented simultaneously with the fixation stimulus, compared to the removal of fixation. This 'gap' effect (i.e. overlap-gap) saccade reaction time was elevated in the older groups compared to young group, which yielded a strong effect of aging and no specific effect of neurodegenerative disease. Healthy aging, rather than neurodegenerative disease, accounted for the increase in the saccade reaction times to the target that are presented simultaneously with a fixation stimulus. These results suggest that the impairment of inhibitory control in the AST may provide a convenient and putative mark of working memory dysfunction in Alzheimer's disease.

Introduction: Eye tracking provides a convenient and promising biological marker of cognitive impairment in patients with neurodegenerative disease. Here we report a longitudinal study of saccadic eye movements in a sample of patients with Alzheimer's disease and elderly control participants who were assessed at the start of the study and followed up 12-months later.Methods: Eye movements were measured in the standard gap and overlap paradigms, to examine the longitudinal trends in the ability to disengage attention from a visual target.Results: Overall patients with Alzheimer's disease had slower reaction times than the control group. However, after 12-months, both groups showed faster and comparable reductions in reaction times to the gap, compared to the overlap stimulus. Interestingly, there was a general improvement for both groups with more accurately directed saccades and speeding of reaction times after 12-months.Conclusions: These findings point to the value of longer-term studies and follow-up assessment to ascertain the effects of dementia on oculomotor control.

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Dementia (most notably, Alzheimer's Disease) is often associated with impairments of both working memory and inhibitory control. However, it is unclear whether these are functionally distinct impairments. We addressed the issue of whether working memory and inhibitory control can be dissociated, using data from a sample of patients who were recruited in a longitudinal study (Crawford et al., 2013, 2015). The first case revealed a preserved working memory capacity together with poor inhibitory control in the anti-saccade task. A longitudinal follow-up revealed that the defective inhibitory control emerged 12-months before the dementia was evident on the mini-mental state examination assessment. A second case revealed a poor working memory together with a well-preserved level of inhibitory control. The dissociation of working memory and inhibitory control was confirmed statistically in 7 additional cases. These findings yield converging evidence that working memory and inhibitory control are distinct cognitive operations and challenges the Kimberg and Farah (2000) cognitive model of working memory.

A series of experiments were conducted to examine the inhibitory effect of a visual distracter on saccadic eye movements. Participants were presented with a sequence of two critical displays. In one display a red target was presented together with a green distracter. This was followed by a display with a new red target presented in isolation at one of three locations with respect to the previous display. The lone target was presented either at the location of the recent target, the location of the recent distracter, or a new location. Participants were instructed to fixate the target in both displays and to ignore the green distracter. Experiment 1 revealed a significant increase in saccadic reaction times (SRTs) when the target was presented at the location of the recent distracter. Experiment 2 revealed that SRTs increased only in the conditions where the new target was presented at the location of the recent distracter, irrespective of its colour. Experiment 3 found that the inhibitory effect lasted for at least 2 s. In Experiment 4 the inhibitory effect was abolished when a lone distracter (i.e., anti-target) was presented without a target. Experiments 5 and 6 revealed that inhibition at the location of the recent target ('inhibition-of-return') also emerged with a shorter inter-display interval and when the distracter was removed from the recent display. These results distinguished between inhibition of a recent distracter and 'inhibition-of-return' and are consistent with models of competitive interactions which generate inhibitory effects on the spatial representation of a distracter.

When human observers are presented with a double target display, a saccadic eye movement is triggered to an intermediate position close to the 'centre-of-gravity' of the configuration. This study examined the saccadic eye movements of dyslexic and normal readers in response to displays of single and double targets. Eye movement analyses revealed no differences in the spatial position of saccadic eye movements of dyslexic and normal readers in response to single targets presented at 5 degrees or 10 degrees. However, when presented with two targets simultaneously at 5 degrees AND 10 degrees, in contrast to normal readers who generated saccades to an intermediate position between the two targets (towards the 'centre-of gravity'), dyslexics generated saccades that landed close to the near target eccentricity. These findings suggest that dyslexia is associated with a deficit in the processing of global spatial information for the control of saccadic eye movements.

Conducting ethical research in vulnerable client groups demands that many factors are addressed to safeguard both patients and carers. A checklist of practical and ethical considerations when conducting research in people with dementia is suggested.