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

Siobhan Garbutt, Alisa Matlin, Joanna Hellmuth, Ana K Schenk, Julene K Johnson, Howard Rosen, David Dean, Joel Kramer, John Neuhaus, Bruce L Miller, Stephen G Lisberger, Adam L Boxer, Siobhan Garbutt, Alisa Matlin, Joanna Hellmuth, Ana K Schenk, Julene K Johnson, Howard Rosen, David Dean, Joel Kramer, John Neuhaus, Bruce L Miller, Stephen G Lisberger, Adam L Boxer

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.

Figures

Fig. 1
Fig. 1
Upward saccade examples. Eye position versus time traces showing three representative, successive 10° upward saccades in a control subject and a patient from each of the diagnostic groups.
Fig. 2
Fig. 2
Bar graphs summarizing the saccade behaviour under overlap conditions of controls (CON) and all the patient groups. Targets moved 10°. In all graphs, black and grey bars show responses to horizontal and vertical targets respectively. Error bars show standard errors across subjects within each group. Asterisks indicate effects that were statistically significant relative to controls (P < 0.05, ANOVA, Tukey post hoc). Double asterisks indicate P < 0.005 relative to controls. (A) Saccade latencies, (B) Saccade slope velocity, (C) First gain of saccades, (D) End gain of saccades.
Fig. 3
Fig. 3
Average vertical eye velocity traces for a control subject and a patient from each of the diagnostic groups. Target motion was 20°/s upward. Traces are an average of at least eight trials.
Fig. 4
Fig. 4
Bar graphs summarizing the pursuit behavior of controls (CON) and all the patient groups. Target velocity was 20°/s. In all graphs, black and grey bars show responses to horizontal and vertical targets respectively. Error bars show SEs across subjects within each group. Asterisks indicate effects that were statistically significant relative to controls (P < 0.05 ANOVA, Tukey post hoc). Double asterisks indicate P < 0.005 relative to controls. (A) Smooth pursuit latencies, (B) Initial eye acceleration of smooth pursuit, (C) Mean gain of smooth pursuit, (D) Peak gain of smooth pursuit.
Fig. 5
Fig. 5
Bar graphs summarizing the antisaccade behavior of controls (CON) and all the patient groups. In all graphs the bars show the responses to horizontal targets and the error bars show standard errors across subjects within each group. Asterisks indicate effects that were statistically significant relative to controls (P < 0.05, ANOVA, Tukey post hoc). Double asterisks indicate P < 0.005 relative to controls. (A) Percentage of correct antisaccades, (B) Percentage of errors that were corrected which was calculated by: number of trials that were corrected/number of error trials × 100.
Fig. 6
Fig. 6
Receiver operating characteristic (ROC) curves comparing best oculomotor and neuropsychological variables. (A) Comparison of the best oculomotor variable from the recursive partitioning analysis (upward saccade velocity) versus the best neuropsychological variable (time to complete the modified trails task) for differentiating PSP from all other patients. (B) Comparison of the best oculomotor variable (percentage correct antisaccade responses) versus best neuropsychological variable (number localization task from VOSP battery) for differentiating SD from AD group.

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