**Author details**

studies focusing on motor cortical excitability measures, a particularly consistent and important finding is the significant reduction of SAI in AD patients. Abnormal SAI has also been reported in DLB [29] a form of dementia that responds to cholinergic medications [90]. In contrast, SAI was found to be normal in FTD [30], a non-cholinergic form of dementia. Therefore, SAI testing can be used as a non-invasive test for the assessment of cholinergic pathways in patients with dementia and may represent a useful additional tool in the differential diagnosis between the cholinergic and the non-cholinergic forms of dementia. Furthermore, TMS can thus be used to monitor AD progression and response to treatment [64]. It remains relatively unclear, how early in the course of the disease neurochemical and neuropathological alterations occur. However, neurobiological changes should be examined earlier in the disease process, when presumably they are more relevant for the pathogenesis of AD. Therefore, the findings that SAI abnormalities can be observed in patients with early diagnosis of AD [41] and even in patients with amnestic MCI-multiple domain may have potential diagnostic and therapeutic implications. Identification of SAI abnormalities that occur early in the course of the disease will allow earlier treatment with cholinergic drugs, and may be useful in identify-

The second most frequent cause of dementia following AD is VD. It was suggested that cholinergic mechanisms play a role also in the pathogenesis of VD; however, the role of the cholinergic system in the development of cognitive impairment is still under discussion in VD, also because previous studies failed to found significant SAI abnormalities in most VD patients. Interestingly, the cumulative effect of micro bleeds (MBs) on cognition appears to be independent of coexisting ischemic cerebrovascular disease, in particular of the severity of ischemic subcortical VD as assessed by magnetic resonance imaging (MRI) white matter changes [68].


The combination of TMS and EEG also enables the exploration of neural plasticity and connectivity across different neural networks. Encouraging findings, showing impaired cortical plasticity and functional connectivity between motor and non-motor brain regions in AD, have been obtained. This method may provide a novel tool for examining the degree and

Overall, several issues should be more carefully addressed in future studies. The impact of TMS depends on the distance between targeted cortex and scalp, as the magnetic field decreases with distance [91]. Since regional cortical thinning has been observed in AD [92], brain atrophy can substantially alter the effect of TMS [81]. Volumetric studies of white matter volume and cortical thinning should thus be included in future studies in order to ameliorate the interpretation of TMS results in patients with cerebral atrophy and dementing illnesses. On the other hand, the motor cortex does not seem the best cortical area to assess in AD patients, especially in the earlier stages of the disease. In fact, neuropathologic and neuroimaging

ing MCI individuals at increased risk of conversion to AD.

14 Transcranial Magnetic Stimulation in Neuropsychiatry

T2\*

ferent forms of dementia.

progression of dementia.

Stefan Martin Golaszewski1,3\* and Raffaele Nardone1,2

\*Address all correspondence to: s.golaszewski@salk.at

1 Department of Neurology and Neuroscience Institute, Paracelsus Medical University Salzburg, Austria

2 Department of Neurology, "F. Tappeiner" Hospital, Merano, Italy

3 Karl Landsteiner Institute of Neurorehabilitation and Space Neurology, Salzburg, Austria
