P 94. Influence of transcranial direct current stimulation on cortical plasticity and on cholinergic cortical activity in Alzheimer’s disease

Abstract

Introduction In patients with Alzheimer’s disease (AD) long-term potentiation (LTP)-like cortical plasticity as well as central cholinergic activity has been shown to be decreased ( Battaglia et al., 2007 , Bierer et al., 1995 ). In humans, LTP-like cortical plasticity can be assessed by paired associative stimulation (PAS), a widely established protocol combining peripheral electrical stimulation and subsequent transcranial magnetic stimulation (TMS) ( Stefan et al., 2000 ). The central cholinergic activity can be investigated non-invasively via the short-latency afferent inhibition (SAI). Previous studies suggested that the ability to induce LTP-like plasticity, as well as central cholinergic activity, can be improved by anodal transcranial direct current stimulation (atDCS) in healthy subjects ( Kasa et al., 1997 , Scelzo et al., 2011 ). The influence of tDCS on LTP-like cortical plasticity and the central cholinergic activity has not been investigated in patients with AD so far. Objective To assess the influence of atDCS on LTP-like cortical plasticity and central cholinergic activity in AD. Methods In this ongoing study 4 patients (mean age 75 ± 4 years, all male) with mild to moderate dementia due to AD (probable AD) were included. Subjects underwent 2 sessions of atDCS in a randomized and double blinded order (atDCS/sham, 20 min). LTP-like cortical plasticity was induced by the rapid-rate PAS (rPAS) protocol (2 min of 5 Hz rPAS, Quartarone et al., 2006 ), comparing motor evoked potentials (MEP) before, and 0, 15 and 30 min after rPAS. Central cholinergic cortical activity was measured by SAI, with interstimulus-intervals of 10 ms, 20 ms and 30 ms in a randomized order, before and after atDCS/sham, and after rPAS. (see Fig. 1 for experimental time-line). Results All patients tolerated the procedure well. Mean rMT was 46% of maximal stimulator output (range 37–59%). After sham, no increase in MEP amplitude due to rPAS was noted. Following atDCS, rPAS induced an increase in MEP amplitude in all four patients at all three timepoints (largest increase immediately after rPAS, range from 1.3 to 2.8-fold of baseline MEP) No changes of SAI were seen following atDCS, as compared to sham. Discussion Our results point towards an increase of LTP-like cortical plasticity after atDCS in patients with AD, indicating a possible role of atDCS in improving cognitive functions in AD, in line with previous studies on atDCS and recognition memory ( Ferrucci et al., 2008 ). Currently, we are recruiting more subjects to substantiate these preliminary findings, and to further assess possible effects of atDCS on central cholinergic activity (SAI) as well as learning ability in the motor domain, to be assessed in two sessions (anodal vs. sham) of a motor learning task.