Event-related potential markers of brain changes in preclinical familial Alzheimer disease

Abstract

Objectives: Event-related potentials (ERPs) can reflect differences in brain electrophysiology underlying cognitive functions in brain disorders such as dementia and mild cognitive impairment. To identify individuals at risk for Alzheimer disease (AD) we used high-density ERPs to examine brain physiology in young presymptomatic individuals (average age 34.2 years) who carry the E280A mutation in the presenilin-1 (PSEN1) gene and will go on to develop AD around the age of 45.Methods: Twenty-one subjects from a Colombian population with familial AD participated: 10 presymptomatic subjects positive for the PSEN1 mutation (carriers) and 11 siblings without the mutation (controls). Subjects performed a visual recognition memory test while 128-channel ERPs were recorded.Results: Despite identical behavioral performance, PSEN1 mutation carriers showed less positivity in frontal regions and more positivity in occipital regions, compared to controls. These differences were more pronounced during the 200-300 msec period. Discriminant analysis at this time interval showed promising sensitivity (72.7%) and specificity (81.8%) of the ERP measures to predict the presence of AD pathology. Conclusions:Presymptomatic PSEN1 mutation carriers show changes in brain physiology that can be detected by high-density ERPs. The relative differences observed showing greater frontal positivity in controls and greater occipital positivity in carriers indicates that control subjects may use frontally mediated processes to distinguish between studied and unstudied visual items, whereas carriers appear to rely more upon perceptual details of the items to distinguish between them. These findings also demonstrate the potential usefulness of ERP brain correlates as preclinical markers of AD. Neurology Recognition memory impairments in Alzheimer disease (AD) have been linked to neocortical association areas including temporal and parietal lobes.1 Event-related potentials (ERPs) are less expensive, more widely available, and more comfortable than many other imaging modalities (e.g., MRI, PET, SPECT). ERPs, along with other EEG measures, have proven to be a useful marker in neurodegenerative conditions. 2-5 ERP components of recognition memory are sensitive to decline in old age 6 and amnestic mild cognitive impairment (aMCI). 7 Studies have proposed ERPs as a sensitive method for early detection of AD, separating EEG activity related to AD pathology from normal aging. [8][9][10][11][12] Preclinical markers and early detection are increasingly

Biomarkers identification in Alzheimer’s disease using effective connectivity analysis from electroencephalography recordings

“…These differences were more pronounced during the (200-300) ms period. Discriminant analysis at this time interval showed promising sensitivity (72,7 %) and specificity (81,8 %) for predicting the presence of AD (Y T Quiroz et al, 2011).…”

“…Recordings were obtained while subjects performed a memory encoding task using color pictures of concrete and nameable objects ( Figure 1). This task is based on a paradigm previously used in the same population (Y T Quiroz et al, 2011). 50 stimuli were presented.…”

“…Changes have also been shown in regional brain activity using positron emission tomography (Fleisher et al, 2015), functional magnetic resonance imaging (Yakeel T Quiroz et al, 2010), spectral energy alterations in EEG, and potential modulation in event related potentials studies (Bobes et al, 2010;Duque-Grajales et al, 2014;Y T Quiroz et al, 2011;Rodriguez et al, 2014;Tobon et al, 2015). These findings show the disease to be a dynamical phenomenon (Y T Quiroz et al, 2011). To our knowledge, there are no studies on how the effective connectivity in the PSEN1 E280A mutation can help to differentiate pre-symptomatic and symptomatic AD PSEN1 E280A mutation carriers from non-carriers using EEG signals.…”

Dynamic Causal Modeling of Preclinical Autosomal-Dominant Alzheimer’s Disease

“…For example, in individuals with mild cognitive impairment (MCI), reductions in sensor-space N400 (see below) or P600 word repetition effects are associated with greater likelihood of subsequent transition to AD dementia [6]. Using EEG data from the Colombian kindred, Quiroz et al [7] found differences in sensor-space event-related potentials (ERPs) between a Presymptomatic Carrier (PreC) group (carrying the PSEN1 mutation) and a Non-Carrier (NonC) group. The PreC group showed less positivity in frontal regions and more positivity in occipital regions compared to NonCs.…”

Genistein downregulates presenilin 1 and ubiquilin 1 expression

“…Neurotoxic amyloid-β is a peptide generated via cleavage of amyloid-β precursor protein (APP) by the γ-secretase complex. Presenilins are catalytic members of the complex, and mutations in the presenilin gene are the major cause of familial AD (2). Presenilin is involved in several biological functions, but is well known for its role in the generation of the amyloid-β peptide in AD.…”