Alzheimer's disease (AD) is a neurodegenerative disorder that accounts for nearly 70% of the more than 46 million dementia cases estimated worldwide. Although there is no cure for AD, early diagnosis and an accurate characterization of the disease progression can improve the quality of life of AD patients and their caregivers. Currently, AD diagnosis is carried out using standardized mental status examinations, which are commonly assisted by expensive neuroimaging scans and invasive laboratory tests, thus rendering the diagnosis time consuming and costly. Notwithstanding, over the last decade, electroencephalography (EEG) has emerged as a noninvasive alternative technique for the study of AD, competing with more expensive neuroimaging tools, such as MRI and PET. This paper reports on the results of a systematic review on the utilization of resting-state EEG signals for AD diagnosis and progression assessment. Recent journal articles obtained from four major bibliographic databases were analyzed. A total of 112 journal articles published from January 2010 to February 2018 were meticulously reviewed, and relevant aspects of these papers were compared across articles to provide a general overview of the research on this noninvasive AD diagnosis technique. Finally, recommendations for future studies with resting-state EEG were presented to improve and facilitate the knowledge transfer among research groups.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the lifespan. Several lines of evidence suggest that modifications of risk-enhancing life styles and initiation of pharmacological and nonpharmacological treatments in the early stage of disease, although not able to modify its course, helps to maintain personal autonomy in daily activities and significantly reduces the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to prodromal stages of AD. Thus, the identification of markers of conversion from prodromal form to clinically AD may be crucial for developing strategies of early interventions. The current available markers, including volumetric MRI, PET, and CSF analysis are expensive, poorly available in community health facilities, and relatively invasive. Taking into account its low cost, widespread availability and non-invasiveness, EEG would represent a candidate for tracking the prodromal phases of cognitive decline in routine clinical settings eventually in combination with other markers. After providing a short overview of the epidemiology andmarkers in AD, this review aimed to explore whether advanced analysis of EEG rhythms exploring brain function has sufficient specificity/sensitivity/accuracy to screen out the risk of conversion from Mild cognitive Impairment (MCI, a condition which is prodromal to AD in a high percentage of cases) to AD as a first-level screening method. HIGHLIGHTSThis review describes an integrated and multidisciplinary approach for the "early" diagnosis of AD.An overview of epidemiology, genetic risk factors, and different biomarkers of AD is provided.Analysis of EEG rhythms could represent a valid screening tool to predict AD conversion.

There is not a specific test to diagnose Alzheimer's disease (AD). Its diagnosis should be based upon clinical history, neuropsychological and laboratory tests, neuroimaging and electroencephalography (EEG). Therefore, new approaches are necessary to enable earlier and more accurate diagnosis and to follow treatment results. In this study we used a Machine Learning (ML) technique, named Support Vector Machine (SVM), to search patterns in EEG epochs to differentiate AD patients from controls. As a result, we developed a quantitative EEG (qEEG) processing method for automatic differentiation of patients with AD from normal individuals, as a complement to the diagnosis of probable dementia. We studied EEGs from 19 normal subjects (14 females/5 males, mean age 71.6 years) and 16 probable mild to moderate symptoms AD patients (14 females/2 males, mean age 73.4 years. The results obtained from analysis of EEG epochs were accuracy 79.9% and sensitivity 83.2%. The analysis considering the diagnosis of each individual patient reached 87.0% accuracy and 91.7% sensitivity.

Changes in electroencephalography (EEG) amplitude modulations have recently been linked with early-stage Alzheimer’s disease (AD). Existing tools available to perform such analysis (e.g., detrended fluctuation analysis), however, provide limited gains in discriminability power over traditional spectral based EEG analysis. In this paper, we explore the use of an innovative EEG amplitude modulation analysis technique based on spectro-temporal signal processing. More specifically, full-band EEG signals are first decomposed into the five well-known frequency bands and the envelopes are then extracted via a Hilbert transform. Each of the five envelopes are further decomposed into four so-called modulation bands, which were chosen to coincide with the delta, theta, alpha and beta frequency bands. Experiments on a resting-awake EEG dataset collected from 76 participants (27 healthy controls, 27 diagnosed with mild-AD, and 22 with moderate-AD) showed significant differences in amplitude modulations between the three groups. Most notably, i) delta modulation of the beta frequency band disappeared with an increase in disease severity (from mild to moderate AD), ii) delta modulation of the theta band appeared with an increase in severity, and iii) delta modulation of the beta frequency band showed to be a reliable discriminant feature between healthy controls and mild-AD patients. Taken together, it is hoped that the developed tool can be used to assist clinicians not only with early detection of Alzheimer’s disease, but also to monitor its progression.

Recent experimental evidence has suggested a neuromodulatory deficit in Alzheimer's disease (AD). In this paper, we present a new electroencephalogram (EEG) based metric to quantitatively characterize neuromodulatory activity. More specifically, the short-term EEG amplitude modulation rate-of-change (i.e., modulation frequency) is computed for five EEG subband signals. To test the performance of the proposed metric, a classification task was performed on a database of 32 participants partitioned into three groups of approximately equal size: healthy controls, patients diagnosed with mild AD, and those with moderate-to-severe AD. To gauge the benefits of the proposed metric, performance results were compared with those obtained using EEG spectral peak parameters which were recently shown to outperform other conventional EEG measures. Using a simple feature selection algorithm based on area-under-the-curve maximization and a support vector machine classifier, the proposed parameters resulted in accuracy gains, relative to spectral peak parameters, of 21.3% when discriminating between the three groups and by 50% when mild and moderate-to-severe groups were merged into one. The preliminary findings reported herein provide promising insights that automated tools may be developed to assist physicians in very early diagnosis of AD as well as provide researchers with a tool to automatically characterize cross-frequency interactions and their changes with disease.

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Abstract-There is recent indication that Alzheimer's disease (AD) can be characterized by atypical modulation of electrophysiological brain activity caused by fibrillar amyloid deposition in specific regions of the brain, such as those related to cognition and memory. In this paper, we propose to objectively characterize EEG sub-band modulation in an attempt to develop an automated noninvasive AD diagnostics tool. First, multi-channel full-band EEG signals are decomposed into five well-known frequency sub-bands: delta, theta, alpha, beta, and gamma. The temporal amplitude envelope of each sub-band is then computed via a Hilbert transformation. The proposed 'spectro-temporal modulation energy' feature measures the rate with which each sub-band is modulated. Modulation energy features are computed for 19 referential EEG signals and seven bipolar signals. Salient features are then selected and used to train four different classifiers, namely, support vector machines, logistic regression, classification and regression trees, and neural networks. Experiments with a database of 34 participants, 22 of which have been clinically diagnosed with probable-AD, show a neural network classifier achieving over 91% accuracy, thus significantly outperforming a classifier trained with conventional spectral-based features.

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