Abstract
In the present exploratory and retrospective study, we hypothesized that cortical sources of resting state eyes-closed electroencephalographic (rsEEG) rhythms might be more abnormal in patients with epileptiform EEG activity (spike-sharp wave discharges, giant spikes) and amnesic mild cognitive impairment not due to Alzheimer's disease (noADMCI-EEA) than matched noADMCI patients without EEA (noADMCI-noEEA). Clinical, neuroimaging, neuropsychological, and rsEEG data in 32 noADMCI and 30 normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were carefully matched among them. No subject had received a clinical diagnosis of epilepsy. Individual alpha frequency peak (IAF) was used to determine the delta, theta, and alpha frequency bands of rsEEG rhythms. Fixed beta and gamma bands were also considered. Regional rsEEG cortical sources were estimated by eLORETA freeware. Area under receiver operating characteristic (AUROC) curves indexed the accuracy of eLORETA solutions in the classification between noADMCI-EEA and noADMCI-noEEA individuals. As novel findings, EEA was observed in 41% of noADMCI patients. Furthermore, these noADMCI-EEA patients showed higher temporal delta source activities as compared to noADMCI-no EEA patients and Nold subjects. Those activities discriminated individuals of the two NoADMCI groups with an accuracy of about 70%. The significant percentage of noADMCI-EEA patients showing EEA and marked abnormalities in temporal rsEEG rhythms at delta frequencies suggest a substantial role of underlying neural hypersynchronization mechanisms in their brain dysfunctions.
Highlights
In most patients with sporadic late-onset Alzheimer’s disease with dementia (ADD), episodic memory disorders are prominent
The inclusion criteria of the noADMCI patients were as follows: [1] age of 55–90 years; [2] reported memory complaints confirmed by a relative; [3] mini mental state evaluation exam (MMSE) score ≥24; [4] Clinical Dementia Rating score of 0.5 [Clinical dementia rating (CDR); [8]]; [5] logical memory test [9] score of 1.5 standard deviation (SD) lower than the mean adjusted as age; [6] cognitive deficits not so strong to interfere significantly with the functional independence in the activities of the daily living; [7] Geriatric Depression Scale [15-item Geriatric depression scale (GDS); [10]] score of ≤5; [8] modified Hachinski ischemia [11] score of ≤4; [9] education of ≥5 years; [10] single amnesic or multi-domain MCI status; and [11] amyloid beta 1-42 (i.e., Aβ 42) level in the cerebrospinal fluid (CSF) higher than 550 pg/mL [12]
In recent unpublished data of our research group, we showed that 25% of ADMCI patients with no clinical diagnosis of epilepsy or previous report of seizures/epileptiform EEG patterns were associated with epileptiform EEG activity and related abnormalities in widespread delta and temporal theta resting state eyes-closed electroencephalographic (rsEEG) source activities compared with normal elderly subjects (Nold) subjects and control ADMCI patients without epileptiform EEG activity
Summary
In most patients with sporadic late-onset Alzheimer’s disease with dementia (ADD), episodic memory disorders are prominent. They are associated with both brain amyloidosis and neurodegenerative neuropathology mainly affecting basal forebrain, hippocampus, and posterior cerebral cortex [1]. ADD patients exhibit a much higher incidence of convulsive epileptic seizures than the age-matched general population do [2, 3]. Electroencephalographic (EEG) recordings have unveiled that ADD patients may present signs of subclinical, non-convulsive, and epileptiform EEG activity (EEA) including spike-sharp wave discharges, giant spikes, etc. About 50% of ADD patients exhibited EEA by high-resolution resting state magnetoencephalographic recordings lasting 1 h [>100 sensors; [7]]
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