Measures of Resting State EEG Rhythms for Clinical Trials in Alzheimer’s Disease:Recommendations of an Expert Panel

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12Hz) and widespread delta (<4Hz) and theta (4-8Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes

What Electrophysiology Tells Us About Alzheimer’s Disease::A Window into the Synchronization and Connectivity of Brain Neurons

Electrophysiology provides a real-time readout of neural functions and network capability in different brain states, on temporal (fractions of milliseconds) and spatial (micro, meso, and macro) scales unmet by other methodologies. However, current international guidelines do not endorse the use of electroencephalographic (EEG)/magnetoencephalographic (MEG) biomarkers in clinical trials performed in patients with Alzheimer’s disease (AD), despite a surge in recent validated evidence. This Position Paper of the ISTAART Electrophysiology Professional Interest Area endorses consolidated and translational electrophysiological techniques applied to both experimental animal models of AD and patients, to probe the effects of AD neuropathology (i.e., brain amyloidosis, tauopathy, and neurodegeneration) on neurophysiological mechanisms underpinning neural excitation/inhibition and neurotransmission as well as brain network dynamics, synchronization, and functional connectivity reflecting thalamocortical and cortico-cortical residual capacity. Converging evidence shows relationships between abnormalities in EEG/MEG markers and cognitive deficits in groups of AD patients at different disease stages. The supporting evidence for the application of electrophysiology in AD clinical research as well as drug discovery pathways warrants an international initiative to include the use of EEG/MEG biomarkers in the main multicentric projects planned in AD patients, to produce conclusive findings challenging the present regulatory requirements and guidelines for AD studies

Innovations in Neurophysiology and Their Use in Neuropsychiatry

Many structural and functional tests are used to explore the nature of neurodevelopmental and neurodegenerative diseases. Cognitive involvement has become more and more remarkable in many neurological and psychiatric disorders. This condition evoked a paradigm shift, and today disorders are addressed from a neuroscientific perspective, including silent symptoms. The spatial resolution of structural studies is lacking and is combined with the unique temporal resolution of EEG methods. In our current clinical practice, EEG does not have definitive diagnostic value in psychiatric disorders, but it helps to make a correct diagnosis by excluding other neurological diseases. However, the use of EEG for research purposes is promising in both groups. In this review; there is up-to-date information on the use of electrophysiological examinations in neurological diseases, especially Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and psychiatric disorders such as schizophrenia, mood disorders, attention deficit and hyperactivity disorder, and obsessive-compulsive disorder, to define the point we have reached in our journey to understand these disorders

Behavioral Variant Frontotemporal Dementia

Frontotemporal dementia (FTD) is a sporadic or genetic neurodegenerative disease in which frontotemporal involvement is typically encountered. According to clinical features, three groups are distinguished as behavioral (bvFTD) and progressive aphasia variants; semantic dementia and progressive non-fluent aphasia. The most common type is bvFTD mimicking as disinhibition, apathy, loss of empathy, perseverative / compulsive behaviors, hyperorality, executive dysfunction and diagnosed with imaging, pathogenic mutation and histopathological evidence as well as clinical diagnosis. Brain magnetic resonance imaging (MRI) studies show atrophy especially in ventromedial frontal cortex, posterior orbital frontal regions, insula, anterior cingulate cortex and subcortical structures; the degeneration of these structures, known as the salience network, is held responsible for deterioration of the executive functions. In the early period, the presence of frontotemporal hypometabolism in positron emission tomography is more sensitive than MRI, parietal hypometabolism and amyloid deposition are not seen. Tau levels in cerebrospinal fluid may be low or high in FTD, but the tau / amyloid-beta ratio is found to be highly specific. More than 40% of bvFTD cases have family history and most autosomal dominant inheritance patterns are present. In FTD, cholinergic system is protected, cell loss in serotoninergic receptor and raphe nucleus is evident. Dopaminergic and cholinergic therapy has not been found to be useful and even worsening of behavioral symptoms with cholinesterase inhibitors has been reported. Selective serotonin reuptake inhibitors and trazodone are effective on behavioral symptoms and sleep problems. Pharmacological and non-pharmacological interventions, training and counseling services are important for the relatives of patients

Impaired digit span can predict further cognitive decline in older people with subjective memory complaint: A preliminary result

Subjective memory complaint (SMC) is common among elderly people, and is thought to be part of mild cognitive impairment (MCI). We evaluated whether impaired digit span (IDS) in older people with SMC can predict wider impairment in future neuropsychological tests that correspond to MCI. After a mean of 6.6 years from the initial assessment, we reevaluated 16 subjects with SMC and normal digit span (NDS) scores (mean age 57.6 +/- 8.1 years) and 28 subjects with SMC and IDS scores (mean age 59.7 +/- 9.9 years). The IDS group showed wider cognitive decline in tests of short-term verbal memory and category verbal fluency compared to the NDS group. IDS scores indicate an earlier step for conversion of SMC to MCI