No abstract

Nonlinear analyses have shown that Alzheimer disease (AD) patients' brain activity is characterized by a reduced complexity and connectivity. The aim of this study is to define complexity patterns of mild cognitive impairment (MCI) patients. Whole-head magnetoencephalography recordings were obtained from 18 diagnosed AD patients, 18 MCI patients, and 18 healthy controls during resting conditions. Lempel-Ziv complexity (LZC) values were calculated. MCI patients exhibited intermediary LZC scores between AD patients and controls. A combination of age and posterior LZC scores allowed ADs-MCIs discrimination with 94.4% sensitivity and specificity, whereas no LZC score allowed MCIs---controls discrimination. AD patients and controls showed a parallel tendency to diminished LZC scores as a function of age, but MCI patients did not exhibit such "normal" tendency. Accordingly, anterior LZC scores allowed MCIs-controls discrimination for subjects below 75 years. MCIs exhibited a qualitatively distinct relationship between aging and complexity reduction, with scores higher than controls in older individuals. This fact might be considered a new example of compensatory mechanism in MCI before fully established dementia.

New diagnostic criteria for Alzheimer's disease (AD) stress the role of in vivo biomarkers. Neurophysiological markers are usually not considered as such criteria, although theoretical and practical reasons would justify them. In order to assess the value of neurophysiology as an AD biomarker, whole-head magnetoencephalographic (MEG) resting state recordings were obtained from 35 AD patients, 23 mild cognitive impairment (MCI) patients, and 24 healthy controls. The AD group was further split into two groups differing in severity according to the GDS/FAST criteria. A Minimum Norm Estimation procedure was utilized to estimate the cortical origin of slow brain oscillatory activity in the delta band (2-4 Hz). Eight regions of interest (ROIs) discriminated between AD patients and controls. Delta current density (DCD) in all ROIs showed a significant negative correlation with cognitive status (p < 0.001). DCD values in posterior parietal, occipital, prerolandic, and precuneus cortices distinguished reliably between MCI patients, AD patients with different severity scores, and controls. Importantly, an increase of DCD in right parietal cortex and precuneus indexed the transition from MCI to mild dementia and from mild to more severe dementia. MEG delta mapping might be a serious candidate for a "neural degeneration" marker of AD reflecting dysfunctional synaptic transmission. More importantly, the localization of DCD values is in line with functional imaging markers of AD. However, MEG delta mapping is a totally non-invasive technique that directly measures neural activity. We propose that individuals with enhanced DCD in posterior parietal and precuneus cortices are at risk of progression to full dementia.

It is now widely accepted that Alzheimer's disease is characterized by a functional disconnection between brain regions. The disease appears to begin up to decades prior to clinical diagnosis. Therefore, in the present study, we combined magnetoencephalography, a memory task, and functional connectivity analysis in mild cognitive impairment subjects in order to identify functional connectivity patterns that could characterize subjects who would eventually go on to develop the disease. We monitored 19 subjects and finally 5 of them developed Alzheimer's disease. These progressive patients showed a differential profile of functional connectivity values compared with those patients who remained stable over time. Specifically there were higher synchronization values over the parieto-occipital region in α and β frequency bands. The involvement of this brain region in amyloid-β accumulation and its possible association with hyper-synchronization are also discussed.

The brain magnetic activity patterns in a high load probe-letter (targets and distractors) memory task were examined in patients with Alzheimers's disease (AD) and elderly controls. Control subjects showed a higher number of activity sources over the temporal and parietal cortex between 400 and 700 ms after stimulus onset. However, AD patients showed a higher number of sources over the frontal motor areas, including Broca's and the insula. The number of activity sources on the left parietal areas in response to the target stimuli predicted the AD score oncognitive (MMSE, CAMCOG) and functional staging (FAST) scales. These results suggest that a high information load reveals a deficient functioning of phonological store and reduced task-related activity in temporal and parietal areas, manifesting in a rapid information trace decay. The increased levels of activity in motor areas may reflect a compensatory strategy in an attempt to facilitate rehearsal speed.