Invited review EEG dynamics in patients with Alzheimer’s disease Jaeseung Jeong * Center for Neurodynamics and the Department of Physics, Korea University, Sungbuk-gu, Anham-dong 5-1, Seoul 136-701, South Korea Accepted 6 January 2004 Available online 21 February 2004 Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by cognitive and intellectual deficits and behavior disturbance. The electroencephalogram (EEG) has been used as a tool for diagnosing AD for several decades. The hallmark of EEG abnormalities in AD patients is a shift of the power spectrum to lower frequencies and a decrease in coherence of fast rhythms. These abnormalities are thought to be associated with functional disconnections among cortical areas resulting from death of cortical neurons, axonal pathology, cholinergic deficits, etc. This article reviews main findings of EEG abnormalities in AD patients obtained from conventional spectral analysis and nonlinear dynamical methods. In particular, nonlinear alterations in the EEG of AD patients, i.e. a decreased complexity of EEG patterns and reduced information transmission among cortical areas, and their clinical implications are discussed. For future studies, improvement of the accuracy of differential diagnosis and early detection of AD based on multimodal approaches, longitudinal studies on nonlinear dynamics of the EEG, drug effects on the EEG dynamics, and linear and nonlinear functional connectivity among cortical regions in AD are proposed to be investigated. EEG abnormalities of AD patients are characterized by slowed mean frequency, less complex activity, and reduced coherences among cortical regions. These abnormalities suggest that the EEG has utility as a valuable tool for differential and early diagnosis of AD. q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Alzheimer’s disease; Electroencephalography; Linear; Nonlinear; Complexity; Diagnosis; Clinical neurophysiology 1. Introduction Dementia is one of the most common disorders among the elderly population. The prevalence rate of dementia in persons aged 65 years or over has been reported to be about 3.6–10.3% in Western countries and 1.8–10.8% in Asian countries since the mid-1980s (Lee et al., 2002, and the references therein). The prevalence increases markedly with age, so that dementia affects up to 50% of all Americans over the age of 80 (Vicioso, 2002). Among several subtypes of dementia, Alzheimer’s disease (AD) is the most frequent cause of dementia. Approximately 50 – 60% of patients with dementia over 65 years are clinically related to AD. In 2002, 4.3 million individuals are estimated to be with AD in the United States (Lahiri et al., 2002). This number is projected to increase to 15 million by 2050, and consequently the personal and social ramifications of the disease will be more significant. Thus, early diagnosis and effective treatment of AD are critical issues in dementia research. The neuropathology of AD is characterized by wide- spread neuronal cell loss, neurofibrillary tangles, and senile plaques in the hippocampus, entorhinal cortex, neocortex and other brain regions (DeCarli, 2001; Selkoe, 1994). Senile plaques are extracellular aggregates of amyloid b-peptides, and neurofibrillary tangles are the aggregation of tau proteins. Hyperphosphorylated tau, produced by an imbalance between protein phosphorylation and depho- sphorylation due to a decrease in the activity of protein phosphatase-2A which regulates the activities of tau kinases, is the major protein subunit of neurofibrillary tangles (Iqbal et al., 2002; Smith et al., 2002). Tangles are found mainly in the limbic structures, particularly hippo- campal and parahippocampal regions, whereas extensive diffuse and neuritic amyloid plaques form preferentially throughout the neocortex (Price and Morris, 1999; Price et al., 2001). Reduced brain weight, cortical atrophy, and ventricular enlargement are also prominent in the brains of AD patients. The size of the hippocampus and of the temporal horn of the lateral ventricle is associated with the number of neurofibrillary tangles in the hippocampus (DeCarli et al., 1990), whereas cortical atrophy is correlated Clinical Neurophysiology 115 (2004) 1490–1505 www.elsevier.com/locate/clinph 1388-2457/$30.00 q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.01.001 * Tel.: þ 82-2-3290-4288; fax: þ82-2-3290-3534. E-mail address: jsjeong@complex.korea.ac.kr (J. Jeong).