Abstract
Cortical sources of resting state electroencephalographic (EEG) rhythms are abnormal in subjects with Alzheimer's disease (AD). Here we tested the hypothesis that these sources are also sensitive to the progression of early stage AD over the course of one year. The resting state eyes-closed EEG data were recorded in 88 mild AD patients at baseline (Mini Mental State Evaluation, MMSE I = 21.7 ± 0.2 standard error, SE) and at approximately one-year follow up (13.3 months ± 0.5 SE; MMSE II = 20 ± 0.4 SE). All patients received standard therapy with acetylcholinesterase inhibitors. EEG recordings were also performed in 35 normal elderly (Nold) subjects as controls. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). Cortical EEG sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Compared to the Nold subjects, the mild AD patients were characterized by a power increase of widespread delta sources and by a power decrease of posterior alpha sources. In the mild AD patients, the follow-up EEG recordings showed increased power of widespread delta sources as well as decreased power of widespread alpha and posterior beta 1 sources. These results suggest that the resting state EEG sources were sensitive, at least at group level, to the cognitive decline occurring in the mild AD group over a one-year period, and might represent cost-effective and non-invasive markers with which to enrich cohorts of AD patients that decline faster for clinical studies.
Highlights
Alzheimer’s disease (AD) is an irreversible disorder characterized by a progressive neuronal deterioration resulting in a loss of cognitive functions [1]
A statistically significant difference was found for Mini Mental State Examination (MMSE) (p < 0.00001; higher MMSE for normal elderly (Nold) than mild AD subjects)
These results extend previous EEG data generated from our group showing remarkable abnormalities of the posterior cortical sources of the resting state delta and alpha rhythms in AD patients compared to Nold subjects [38,39,40,41, 55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71, 73, 107]
Summary
Alzheimer’s disease (AD) is an irreversible disorder characterized by a progressive neuronal deterioration resulting in a loss of cognitive functions [1]. Several instrumental markers are available for the assessment of AD patients [2,3,4,5,6] They include the analysis of cerebrospinal fluid (CSF) sampled by lumbar puncture measuring amyloid- (A) and tau metabolites as key indicators of pathology [7]. PET-amyloid Pittsburg Compound B (PIB) is used for the visualization in vivo of A deposition in the brain of AD patients [15,16,17]. All of these instrumental markers are relatively expensive and invasive, and cannot be systematically applied to all AD patients. With the need to perform drug studies in the pre-clinical or at-risk population, there is a major requirement for the AD scientific community to develop novel non-invasive and relatively cheap markers that accurately reflect the progression of AD pathology
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