SAGE-Hindawi Access to Research International Journal of Alzheimer’s Disease Volume 2011, Article ID 654794, 9 pages doi:10.4061/2011/654794 Research Article Combining Transcranial Magnetic Stimulation and Electroencephalography May Contribute to Assess the Severity of Alzheimer’s Disease Petro Julkunen, 1 Anne M. Jauhiainen, 2 Mervi K¨ on¨ onen, 1, 3 Ari P¨ a¨ akk¨ onen, 1 Jari Karhu, 4, 5 and Hilkka Soininen 2, 6 1 Department of Clinical Neurophysiology, Kuopio University Hospital, POB 1777, 70211 Kuopio, Finland 2 Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland 3 Department of Clinical Radiology, Kuopio University Hospital, 70211 Kuopio, Finland 4 Nexstim Ltd, 00510 Helsinki, Finland 5 Department of Physiology, Institute of Biomedicine, University of Eastern Finland, 70211 Kuopio, Finland 6 Department of Neurology, Kuopio University Hospital, 70211 Kuopio, Finland Correspondence should be addressed to Petro Julkunen, petro.julkunen@kuh.fi Received 30 December 2010; Revised 3 March 2011; Accepted 13 March 2011 Academic Editor: Fabio Ferrarelli Copyright © 2011 Petro Julkunen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Alzheimer’s disease (AD) is the most common form of old age dementia, and mild cognitive impairment (MCI) often precedes AD. In our previous study (Julkunen et al. 2008), we found that the combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) was able to find distinct differences in AD and MCI patients as compared to controls. Here, we reanalyzed the small sample data from our previous study with the aim to test the sensitivity of the TMS-EEG characteristics to discriminate control subjects (n = 4) from MCI (n = 5) and AD (n = 5) subjects. Furthermore, we investigated how the TMS-EEG response characteristics related to the scores of the dementia rating scales used to evaluate the severity of cognitive decline in these subjects. We found that the TMS-EEG response P30 amplitude correlated with cognitive decline and showed good specificity and sensitivity in identifying healthy subjects from those with MCI or AD. Given the small sample size, further studies may be needed to confirm the results. 1. Introduction Alzheimer’s disease (AD) is a neurodegenerative disorder which leads to dementia through a progressive cognitive decline. In Europe, AD affects over 5% of population aged above 70 years [1]. This makes it the most common cause of dementia in old age. It has been postulated that the impair- ment of the lateral cholinergic pathway originating from the Meynert’s nucleus would characterize AD and contributes to its typical symptom of memory loss [2, 3]. AD-related pathology leads to the degeneration of the large cortical pyramidal neurons [4], and subsequently impairment of functional connectivity takes place [5]. Before the diagnosis of AD can be set, subjects often suffer from impaired episodic memory [6]. The stage characterised by mild memory or other cognitive loss is called mild cognitive impairment (MCI), and it has been proposed as a prodromal state of AD. Thus, subjects with MCI have an increased risk to develop AD [7–9]. Understanding the pathophysiology of MCI would be essential for predicting and possibly in the future preventing the development of AD. It is possible that altered functional connectivity precedes structural changes, and therefore, a sensitive method to detect those early functional changes would be useful in the diagnostics of MCI and AD. Early identification of AD would be desirable, as it could help aiming the current treatment to the appropriate subjects. With the prospects of obtaining treatments that modify the course of AD, accurate identification of subjects who will develop AD is essential. Earlier it has been shown that the primary motor cortex experiences changes during the development of AD, which also relate to the severity of the disease [10]. Structural