Behavioral and Electrophysiological Correlates of Memory Binding Deficits in Patients at Different Risk Levels for Alzheimer’s Disease

Abstract

Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimer's disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving prodromal stages with different risk levels of conversion to AD. We assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance and neural correlates of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test) while event related potentials (ERPs) were recorded. Changes always occurred in the test array and consisted of new features replacing studied features (shape-only) or features swapping across items (shape-color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Early electrophysiological activity (100-250 ms) was significantly reduced in both clinical groups, particularly over fronto-central and parieto-occipital regions. However, shape-color binding performance and their reduced neural correlates were similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion. The combined analysis of behavioral and ERP data gleaned with the VSTM binding task can offer a valuable memory biomarker for AD.

Precuneus Failures in Subjects of the PSEN1 E280A Family at Risk of Developing Alzheimer’s Disease Detected Using Quantitative Electroencephalography

“…Different to the approach using ERP tasks in PSEN1 mutation carriers [16][17][18]20,64], the resting paradigm diminishes the confounding error due to the performance in symptomatic subjects and it is suitable for clinical trials in AD [73]. Different works using resting EEG have reported differences in E280A mutation carriers when compared against non-carriers.…”

“…Using a connectivity approach, the encoding of information has been also studied, finding an increase of connectivity in asymptomatic carriers in relation to controls [18,19]. The visual short-term memory, which has been proposed as an early marker for AD, is related to reduction in electrical activity in fronto-central and parieto-occipital regions, in carriers at symptomatic stage [20]. The quantitative EEG analysis has also shown modification of spectral parameters in fronto-temporal regions [21].…”

Enhanced Working Memory Binding by Direct Electrical Stimulation of the Parietal Cortex

“…As in previous studies (Parra et al, 2010, 2015; Pietto et al, 2016), recognition during the visual working memory task was calculated by subtracting the proportion of false alarms from the hits. The subject’s indexes were compared to those of a control sample through a modified two-tailed t test (Crawford and Garthwaite, 2002; Crawford et al, 2009, 2011).…”

“…We used the visual working memory task developed by Parra and colleagues (Parra et al, 2010, 2015; Pietto et al, 2016). This task involves two sets of stimuli, one with black shapes, used to evaluate memory for shapes; and a second one with colored shapes, assessing shape-color binding in working memory (see Figure 1).…”

Dementia in Latin America: An Emergent Silent Tsunami

“…Some research groups in Latin America are already addressing relevant clinical issues regarding Alzheimer's disease (Parra et al, 2009, 2010, 2015; Pietto et al, 2016) and other dementias (Cardona et al, 2013; Ibáñez et al, 2013; Baez et al, 2014a,b, 2015, 2016a,b,c; Kargieman et al, 2014; Garcia-Cordero et al, 2015, 2016; Melloni et al, 2015, 2016; Santamaria-Garcia et al, 2016; Sedeno et al, 2016). The urgent need now is to develop and implement health-care strategies and national plans that meet the needs of individuals with dementia and their families.…”