VISUOMOTOR INTEGRATION IN PRESYMPTOMATIC FAMILIAL ALZHEIMER’S DISEASE

Abstract

As we enter an era of prevention trials for Alzheimer's disease (AD), it is vital to have sensitive cognitive tests that can identify and track subtle cognitive decline in preclinical AD. A circle-tracing task has identified visuomotor integration deficits in presymptomatic mutation carriers for Huntington's disease. As there is some evidence that visuomotor integration is impaired in early AD, we tested for similar deficits in presymptomatic individuals carrying mutations for autosomal dominant familial AD (FAD). Thirty-one participants at risk of FAD were recruited: 19 presymptomatic mutation carriers (MC) and 12 non-carriers (NC). MC were on average 7.0 years from expected symptom onset and were well matched with NC for mean age and performance on standard cognitive tests (Table). Participants completed 12 45-second circle-tracing trials, half with serial-subtraction, using a stylus to trace as quickly and accurately as possible round an annulus on a tablet screen. Six trials were ‘direct’: participants could see their arm and their tracing path on the tablet. Six trials were ‘indirect’: the participant's arm was covered by a box, but they could view a copy of the annulus and their tracing path on a monitor positioned behind the tablet (Figure 1). Outcome variables were tracing speed (number of rotations) and error rate (number of deviations outside the annulus per rotation). GEE models were used to compare outcomes between groups after adjustment for age, gender and education. As expected, the indirect condition was more difficult than the direct condition, with slower tracing (p<0.001) and higher error rates (p<0.01). There was no evidence of an interaction between mutation status and task condition. Across both conditions, MC made more errors than NC (difference=0.297 (95% CI 0.062–0.532), p=0.013) (Figure 2); there was no significant difference in tracing speed. Within MC, error rate did not correlate with years to expected onset. Subtle deficits in visuomotor integration are an early feature of cognitive decline that can be detected in presymptomatic FAD. These deficits may appear at a similarly early stage to subtle memory decline. Computerised tasks measuring visuomotor integration may be suitable outcome measures in AD prevention trials. Set-up of the circle-tracing task (reprinted from Figure 1A in Say et al., Visuomotor integration deficits precede clinical onset in Huntington's disease. Neuropsychologia 2011, Vol. 49, No. 2, 264–270, Elsevier). In the indirect condition the participant's arm was covered by a box, not shown here. Comparison of mutation carriers and non-carriers for speed and accuracy on the Direct and Indirect conditions of the circle-tracing task. Error bars show 95% confidence intervals for the mean. Asterisk shows significant difference between the groups.