[Show abstract][Hide abstract] ABSTRACT: Here we presented a single electroencephalographic (EEG) marker for a neurophysiological assessment of Alzheimer's disease (AD) patients already diagnosed by current guidelines. The ability of the EEG marker to classify 127 AD individuals and 121 matched cognitively intact normal elderly (Nold) individuals was tested. Furthermore, its relationship to AD patients' cognitive status and structural brain integrity was examined. Low-resolution brain electromagnetic tomography (LORETA) freeware estimated cortical sources of resting state eyes-closed EEG rhythms. The EEG marker was defined as the ratio between the activity of parieto-occipital cortical sources of delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms. Results showed 77.2% of sensitivity in the recognition of the AD individuals; 65% of specificity in the recognition of the Nold individuals; and 0.75 of area under the receiver-operating characteristic curve. Compared to the AD subgroup with the EEG maker within one standard deviation of the Nold mean (EEG-), the AD subgroup with EEG+ showed lower global cognitive status, as revealed by Mini-Mental State Evaluation score, and more abnormal values of white-matter and cerebrospinal fluid normalized volumes, as revealed by structural magnetic resonance imaging. We posit that cognitive and functional status being equal, AD patients with EEG+ should receive special clinical attention due to a neurophysiological "frailty". EEG+ label can be also used in clinical trials (i) to form homogeneous groups of AD patients diagnosed by current guidelines and (ii) as end-point to evaluate intervention effects.
Full-text · Article · Oct 2015 · Journal of Alzheimer's disease: JAD
[Show abstract][Hide abstract] ABSTRACT: Background: The ItalianDIAfN project aims at laying the foundations for an Italian network of centres of excellence with the capabilities to recruit and assess families carrying mutations linked to familial Alzheimer's disease (fAD) or frontotemporal lobar degeneration (fFTLD). The first phase of the project aimed to define standard protocols for the recruitment and data collection of families with fAD and fFTLD.
Methods: A survey of local protocols for patients recruitment (including genetic counselling) and data collection (including clinical, neuropsychological, neuroimaging, molecular imaging, biological and neurophysiological assessment) was conducted. The major international protocols for the biomarkers assessment of fAD and fFTLD were also surveyed. Differences and commonalities among protocols were identified and discussed among ItalianDIAfN partners to reach consensus.
Results: The ItalianDIAfN network converged on a standard protocol for genetic counselling of patients with clinically diagnosed AD/FTLD and/or their at-risk-relatives. Genetic counselling will be provided by a multidisciplinary team, including a geneticist, a psychologist/psychiatrist, and a neurologist/geriatrician, according to the following schedule (Figure, left panel): (i) supportive and informational consultations; (ii) clinical, cognitive and personality assessment; (iii) genetic testing if appropriate; (iv) genetic status disclosure (for those who wish to know); (v) follow-up supportive consultations. A decision tree was developed to assist in the search of the mutation: for cases with abnormal CSF Aβ levels, AD mutations will be searched first; for cases with normal CSF values or data not available, the search for the mutation will be guided by the clinical phenotype first and the age at onset secondly (Figure, central panel). For the data collection, the ItalianDIAfN network converged on disease-specific, internationally compliant protocols as detailed in the Table.
Conclusions: A standard protocol for the assessment and the genetic counselling of fAD and fFTLD cases was defined. These protocols will now be validated on subjects from 12 families with a known pathogenic mutation for fAD or fFTLD (Figure, right panel). The procedures will be disseminated to reach academia, medical societies, and the public at large. The project will contribute to the most innovative initiatives under way in this field by increasing the pool of subjects for disease modifiers trials.
[Show abstract][Hide abstract] ABSTRACT: Cortical sources of resting state electroencephalographic (EEG) rhythms are abnormal in subjects with mild cognitive impairment (MCI). Here, we tested the hypothesis that these sources in amnesic MCI subjects further deteriorate over 1 year. To this aim, the resting state eyes-closed EEG data were recorded in 54 MCI subjects at baseline (Mini Mental State Examination I = 26.9; standard error [SE], 0.2) and at approximately 1-year follow-up (13.8 months; SE, 0.5; Mini Mental State Examination II = 25.8; SE, 0.2). As a control, EEG recordings were also performed in 45 normal elderly and in 50 mild Alzheimer's disease subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10.5 Hz), alpha2 (10.5-13 Hz), beta1 (13-20 Hz), and beta2 (20-30 Hz). Cortical EEG sources were estimated using low-resolution brain electromagnetic tomography. Compared with the normal elderly and mild Alzheimer's disease subjects, the MCI subjects were characterized by an intermediate power of posterior alpha1 sources. In the MCI subjects, the follow-up EEG recordings showed a decreased power of posterior alpha1 and alpha2 sources. These results suggest that the resting state EEG alpha sources were sensitive-at least at the group level-to the cognitive decline occurring in the amnesic MCI group over 1 year, and might represent cost-effective, noninvasive and widely available markers to follow amnesic MCI populations in large clinical trials.
Full-text · Article · Jul 2013 · Neurobiology of aging