Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease

Abstract

Frontotemporal lobar degeneration (FTLD) often overlaps clinically with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), both of which have prominent eye movement abnormalities. To investigate the ability of oculomotor performance to differentiate between FTLD, Alzheimer's disease, CBS and PSP, saccades and smooth pursuit were measured in three FTLD subtypes, including 24 individuals with frontotemporal dementia (FTD), 19 with semantic dementia (SD) and six with progressive non-fluent aphasia (PA), as compared to 28 individuals with Alzheimer's disease, 15 with CBS, 10 with PSP and 27 control subjects. Different combinations of oculomotor abnormalities were identified in all clinical syndromes except for SD, which had oculomotor performance that was indistinguishable from age-matched controls. Only PSP patients displayed abnormalities in saccade velocity, whereas abnormalities in saccade gain were observed in PSP > CBS > Alzheimer's disease subjects. All patient groups except those with SD were impaired on the anti-saccade task, however only the FTLD subjects and not Alzheimer's disease, CBS or PSP groups, were able to spontaneously self-correct anti-saccade errors as well as controls. Receiver operating characteristic statistics demonstrated that oculomotor findings were superior to neuropsychological tests in differentiating PSP from other disorders, and comparable to neuropsychological tests in differentiating the other patient groups. These data suggest that oculomotor assessment may aid in the diagnosis of FTLD and related disorders.

Distinctive features of microsaccades in Alzheimer’s disease and in mild cognitive impairment

“…4, Table 1). This finding is consistent with the lack of brainstem oculomotor function impairment in MCI or AD patients with mild to moderate severity of disease (Garbutt et al 2008;Yang et al 2011Yang et al , 2013; but see Simic et al 2009).…”

“…Antisaccades (i.e., volitional saccades with opposite direction to the target) in AD exhibit impaired inhibition towards the target, as well as impaired correction of errors, with the extent of the deficiencies being related to the severity of the disease (Hershey et al 1983;Fletcher and Sharpe 1986;Moser et al 1995;Shafiq-Antonacci et al 2003;Crawford et al 2005;Garbutt et al 2008). Prosaccades (i.e., saccades directed toward the target) in AD have abnormally long latencies (Hershey et al 1983;Fletcher and Sharpe 1986;Moser et al 1995;Shafiq-Antonacci et al 2003;Crawford et al 2005;Garbutt et al 2008), but see Hershey et al (1983) and Mosimann et al (2005). Saccadic gain and speed findings in AD are controversial: some studies found impairment (Fletcher and Sharpe 1986;Hotson and Steinke 1988;Shafiq-Antonacci et al 2003) whereas others did not (Moser et al 1995;Garbutt et al 2008).…”

“…Prosaccades (i.e., saccades directed toward the target) in AD have abnormally long latencies (Hershey et al 1983;Fletcher and Sharpe 1986;Moser et al 1995;Shafiq-Antonacci et al 2003;Crawford et al 2005;Garbutt et al 2008), but see Hershey et al (1983) and Mosimann et al (2005). Saccadic gain and speed findings in AD are controversial: some studies found impairment (Fletcher and Sharpe 1986;Hotson and Steinke 1988;Shafiq-Antonacci et al 2003) whereas others did not (Moser et al 1995;Garbutt et al 2008). Very few studies have examined saccadic eye movements in MCI (Yang et al 2011(Yang et al , 2013, and no research has examined the characteristics of microsaccades in either AD or MCI.…”

The role of working memory and attentional disengagement on inhibitory control: effects of aging and Alzheimer's disease

“…There was a marked reduction in the ability to generate a corrective eye movement, following a saccade that was incorrectly directed towards the target. This abnormality of uncorrected errors in AD has now been replicated (Boxer et al 2006;Garbutt et al 2008;Kaufman et al 2012). Crawford et al (2005) reported that the magnitude of the errors exceeded that in healthy aging, and there was a positive correlation with the dementia severity on the mini-mental state examination (MMSE).…”

“…The 'reverse' format requires the working memory processes of storage, inhibition and resequencing. We used the 'reverse' formats to estimate spatial and verbal working memory in common with previous clinical research ( Boxer et al 2006;Garbutt et al 2008). On the basis of previous studies, we predicted that the uncorrected errors would be strongly related to spatial working memory.…”