P 170. Characterization of brain plasticity in Diabetes Type II and Alzheimer’s disease supports link between both diseases

Introduction Increased incidence of Alzheimer’s disease (AD) in individuals with Diabetes Type II (DM2) suggests a possible pathophysiologic link. Support for such a link comes from several experimental animal models. Insulin deficiency and resistance are major factors in the pathogenesis of DM2 and appear to be involved in the neurodegenerative processes of AD by altering synaptic brain plasticity. Transcranial magnetic stimulation (TMS) can be used to examine mechanisms of plasticity, and may thus reveal abnormalities in patients with DM2 that might resemble those in patients with AD. Objectives Evaluate cortical plasticity mechanisms in subjects with DM2 and compare them with those in patients with AD as assessed by TMS measures. Explore possible similarities in abnormal brain plasticity in order to investigate the link between DM2 and AD. Materials and methods To evaluate cortical brain plasticity we applied intermittent theta burst stimulation (iTBS) at 80% of active motor threshold (aMT) over the left primary motor cortex (M1) in patients with mild to moderate AD, DM2 and in healthy individuals. iTBS consisted of a total of 600 pulses divided into 20 trains, each including bursts of 3 pulses at 50 Hz repeated at 5 Hz for 2 s and with an 8 s interval between trains. Motor evoked potentials (MEPs) of the right first dorsal interosseus muscle (FDI) were triggered by neuronavigated single pulse transcranial magnetic stimulation (spTMS) over left M1 at 120% of resting motor threshold (rMT) before and after iTBS. Changes in MEP amplitudes after iTBS were examined as measures of long term potentiation (LTP) like plasticity. Results Within the first 20 min following iTBS baseline corrected MEPs were significantly larger for healthy subjects (1.32 ± 0.21 mV) compared to patients with AD (0.92 ± 0.08 mV; p = 0.023) and DM2 (0.69 ± 0.15 mV; p = 0.007) (Fig. 1). There was no significant difference between AD and DM2 (p = 0.63). Interestingly, while iTBS had almost no effect on AD patients it tended to have a paradoxically inhibitory effect in patients with DM2. Conclusion The iTBS-induced modulation of corticospinal excitability is impaired in both AD and DM2. This finding supports the notion of aberrant LTP-like mechanisms of plasticity in DM2 and AD, and suggests a pathophysiologic link between the two diseases. This link may account for the epidemiologically increased risk for patients with DM2 to develop AD. Further studies and longitudinal assessments are needed to explore such a link further, but in this context, TMS-methods appear promising and may become a valuable early biomarker for AD and individuals at risk. Acknowledgements The study was sponsored and supported by the Harvard Catalyst, Nexstim, Neuronix Ltd., the National Institutes of Health, and the Berenson-Allen Foundation. Download : Download high-res image (60KB) Download : Download full-size image