Saccades in Alzheimer’s disease: an MRI study.

Abstract

The body of work described in this thesis used saccades (fast eye movements) and MRI measures to characterise an Alzheimer’s disease (AD) group. Saccades are served by a network of cortical and subcortical regions, and abnormalities of impaired inhibitory responses and prolonged step reflexive saccade latency in AD are known. There has been a sole prior study using fMRI in AD.

The present study utilised a comprehensive battery of saccadic tasks (step reflexive, gap reflexive, predictive and antisaccades) and neuropsychological testing to probe the integrity of the saccadic system in 15 subjects with mild to moderate AD and 16 healthy older control subjects using fMRI. Saccadic performance was impaired in the AD group, and correlated with the degree of cognitive impairment. The saccadic abnormalities exhibited were prolonged step reflexive saccade latency, impaired procedural learning in the predictive task, prolonged latency of correctly performed antisaccades and an increased error rate of antisaccades. There was increased activity in the middle temporal gyri in the AD group when performing step reflexive saccades, due to compensatory recruitment, as reduced resources were available in the posterior parietal processing complex. The impairment of procedural learning of the predictive task in the AD group was reflected by increased activity in the temporo-parietal cortices, as a slower transition from reflexive saccades to predictive saccades occurred. The cognitively challenging antisaccade tasks lead to the non-selective recruitment of alternative neural networks in the temporo-occipital cortex. Overall, the AD group demonstrated reduced activity during all tasks compared to controls and regions as a ‘resource ceiling’ of available neurons was reached. An AD-related perfusion network was derived that separated AD from controls in an unbiased fashion, with regions of both reduced and preserved cerebral perfusion. The saccadic, fMR and perfusion profiles from single cases of other dementias – posterior cortical atrophy and corticobasal syndrome – compared to AD were reported.

In AD the substantial underlying structural changes limit the ability to engage the extra neuronal ‘scaffolding’ required to adequately perform a sensorimotor task. This link between structure and function in AD manifests as altered fMRI activity while performing saccades. This first comprehensive study into the performance of saccades in AD using fMRI, has shown robust differences between AD and controls, and the underlying structural damage to brain regions appear to alter saccadic performance.