In MCI subjects, it seems that the motor cortex excitability has not yet increased although the cellular loss has already begun, as indicated by the strong negative correlation between cortical thickness and EFMT, especially on the sensorimotor cortex. It has been postulated that cholinergic neural circuits in the motor cortex may be relatively normal in MCI Selumetinib MEK inhibitor subjects since short afferent inhibition is still normal whereas in AD subjects, reduced SAI has been observed. A recent follow-up study examined the cortical excitability after long-term AChEI therapy in AD patients. TMS was established as an objective tool to follow the biological progression of AD. Furthermore, AChEI medication seemed to stabilize both the brain hyperexcitability pattern as well as the cognitive performance of the AD patients. Therefore, the difference in cortical excitability between the MCI and AD patients could be more pronounced if the AD patients were not under AChEI medication. Since the majority of the AD patients in our study were under AChEI medication, the observed differences between the MCI and AD patients cannot thus be explained merely by changes in cholinergic activity. It has been shown that the motor areas are the last regions to undergo degeneration in AD, whereas cuneus and precuneus cortices are affected at a rather early stage of the disease. In our study, the cortical thickness of both precuneus and cuneus was thinnest in the AD group, although the difference was not statistically significant in our small groups of participants. Furthermore, the cortical thickness of both of these areas had a strong negative correlation with the EFMT in AD subjects. Therefore, it seems that a similar compensatory hyperexcitability for neuronal loss as encountered on the sensorimotor cortex does not occur on the precuneus or the cuneus. In MCI subjects, the thickness of the precuneus correlated with the EFMT implying that some pathophysiological changes might already have occurred on the precuneus. Previous studies have shown that the cortical thickness of the precuneus is lower in multiple-domain MCI subjects, i.e. subjects with both memory impairment and other cognitive deficits, compared to MCI subjects with only memory dysfunction, or when compared to controls. It has been postulated that the atrophy of the precuneus is responsible for the multiple cognitive impairments experienced by MCI subjects. This clear role of the precuneus in neurodegenerative diseases was observed in our results since the negative correlation between the cortical thickness of the precuneus and EFMT was significant both in AD and MCI subjects. A previous study of low-frequency blood oxygenation-level-dependent fluctuations detected decreased coherence in the precuneus in AD patients and this correlated with their MMSE scores. The decrease in the coherence was hypothesized to be related to the resting hypometabolism. In addition, it was found that there is increased coherence in the cuneus in AD subjects suggesting this region might act as a compensatory area for the impaired precuneus.