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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.