Neurophysiological Hallmarks of Neurodegenerative Cognitive Decline: The Study of Brain Connectivity as A Biomarker of Early Dementia.

Paolo Maria Rossini,Riccardo Di Iorio,Francesco Iodice,Francesca Alù,Francesca Miraglia,Florinda Ferreri,Maria Cotelli,Fabrizio Vecchio

doi:10.3390/jpm10020034

Abstract

Neurodegenerative processes of various types of dementia start years before symptoms, but the presence of a “neural reserve”, which continuously feeds and supports neuroplastic mechanisms, helps the aging brain to preserve most of its functions within the “normality” frame. Mild cognitive impairment (MCI) is an intermediate stage between dementia and normal brain aging. About 50% of MCI subjects are already in a stage that is prodromal-to-dementia and during the following 3 to 5 years will develop clinically evident symptoms, while the other 50% remains at MCI or returns to normal. If the risk factors favoring degenerative mechanisms are modified during early stages (i.e., in the prodromal), the degenerative process and the loss of abilities in daily living activities will be delayed. It is therefore extremely important to have biomarkers able to identify—in association with neuropsychological tests—prodromal-to-dementia MCI subjects as early as possible. MCI is a large (i.e., several million in EU) and substantially healthy population; therefore, biomarkers should be financially affordable, largely available and non-invasive, but still accurate in their diagnostic prediction. Neurodegeneration initially affects synaptic transmission and brain connectivity; methods exploring them would represent a 1st line screening. Neurophysiological techniques able to evaluate mechanisms of synaptic function and brain connectivity are attracting general interest and are described here. Results are quite encouraging and suggest that by the application of artificial intelligence (i.e., learning-machine), neurophysiological techniques represent valid biomarkers for screening campaigns of the MCI population.

Highlights

Dementias are of several types; the most frequent and diffusely known by the public opinion is Alzheimer’s disease (AD), which is characterized by a progressive loss of memory and deterioration of other cognitive functions that significantly interfere with daily life activities [1]
In all the studies reported below, the diagnosis of AD was reached with neuropsychological tests eventually combined with other biomarkers dealing with brain metabolism and analysis of beta-amyloid and tau protein metabolites (i.e., fluorodeoxyglucose positron emission tomography (PET–FDG), PET–radioligands, and cerebrospinal fluid (CSF) analysis)
mild cognitive impairment (MCI) patients display a significant decrease of α power compared to Nold [33]

Summary

Introduction

MCI is typically characterized by evidence of an objective impairment of memory and/or of other cognitive domains on neuropsychological testing, but not yet encompassing the standards for dementia diagnosis It represents an intermediate condition in the elderly between normal cognition and dementia and includes a consistent percentage of subjects (about 50%) in a stage that is prodromal to different types of dementia, including AD (MCI prodromal-to-dementia or prodromal-to-AD). In order to plan optimal and early therapeutic, organizational, and rehabilitative interventions, MCI diagnosis should be combined with the most reliable prognosis on the likelihood and time of eventual progression to dementia In other words, those MCI subjects who are already in a prodromal-to-dementia condition should be intercepted as early as possible. This goal can nowadays be achieved by combining biomarkers reflecting ongoing neurodegenerative phenomena with the results of neuropsychological tests

Methods

Results

Conclusion