P 25. Comparing brain reactivity and plasticity in medicated Alzheimer’s patients and healthy elderly

Abstract

Alterations in neuroplasticity and synaptic functions in Alzheimer’s disease (AD) have been previously demonstrated. Transcranial magnetic stimulation (TMS) measures can be used to explore these alterations. A recent study using TMS measures found significant differences in active motor threshold and plasticity measures in non-medicated AD patients as compared to healthy controls (HC) (Koch et al., 2012) . However, little is known about the possible impact of anticholinesterase medications on such measures. Evaluate the effect of pharmacological treatment on TMS measures of cortical reactivity and plasticity in patients with AD. We compared brain reactivity and plasticity measures in medicated patients with AD and age-matched elderly subjects. All AD patients were treated with acetylcholinesterase inhibitors (AChE-inh). Intermittent theta-burst stimulation (iTBS) was applied over the left motor cortex at 80% of active motor threshold. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle (FDI) with single-pulse TMS at 120% of resting motor threshold before and at different time-points (T5, 10, 20, 30) after iTBS. Brain reactivity was defined as the amplitude of MEPs at baseline. Plasticity was defined as the ratio of post-iTBS MEPs to baseline MEPs. Intracortical facilitation (ICF) as well as short-interval and long-interval intracortical inhibition (SICI, LICI) were explored with paired-pulse TMS. We found that patients with AD on AChE-inh showed significantly smaller MEP amplitudes at baseline and up to 30 min post-iTBS as compared to HC ( Fig. 1 A). Plasticity measures were marginally reduced at T5/T10 ( Fig. 1 B). LICI was significantly reduced, while SICI and ICF were comparable in both groups ( Fig. 2 ). We found no significant differences in resting and active motor threshold. Here we show that alterations in cortical reactivity and plasticity persist in patients with AD despite treatment with AChE-inh. Thus, pharmacological treatment does not lead to normalization of aberrant plasticity in AD. TMS can be used to identify changes in brain reactivity and plasticity and assess the impact of medication on these measures. We thank Catarina Freitas, Léonie Asboth, Edward Gold, Christina Carbone, and Ilya Vidrin for their assistance with data collection. Nexstim, Neuronix, Harvard Catalyst, National Institute of Health (NIH).