Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

The Mediterranean diet is not associated with neuroimaging or cognition in middle-aged adults: a cross-sectional analysis of the PREVENT dementia programme.

BACKGROUND AND PURPOSE: The Mediterranean diet (MedDiet) has been associated with reduced dementia incidence in several studies. It is important to understand if diet is associated with brain health in midlife, when Alzheimer's disease and related dementias are known to begin. METHODS: This study used data from the PREVENT dementia programme. Three MedDiet scores were created (the Pyramid, Mediterranean Diet Adherence Screener [MEDAS] and MEDAS continuous) from a self-reported food frequency questionnaire. Primary outcomes were hippocampal volume and cube-transformed white matter hyperintensity volume. Secondary outcomes included cornu ammonis 1 and subiculum hippocampal subfield volumes, cortical thickness and measures of cognition. Sex-stratified analyses were run to explore differential associations between diet and brain health by sex. An exploratory path analysis was conducted to study if any associations between diet and brain health were mediated by cardiovascular risk factors for dementia. RESULTS: In all, 504 participants were included in this analysis, with a mean Pyramid score of 8.10 (SD 1.56). There were no significant associations between any MedDiet scoring method and any of the primary or secondary outcomes. There were no differences by sex in any analyses and no significant mediation between the Pyramid score and global cognition by cardiovascular risk factors. CONCLUSIONS: Overall, this study did not find evidence for an association between the MedDiet and either neuroimaging or cognition in a midlife population study. Future work should investigate associations between the MedDiet and Alzheimer's disease and related dementias biomarkers as well as functional neuroimaging in a midlife population.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Biomarkers for dementia in Latin American countries: Gaps and opportunities.

Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.

Deficits in short-term memory binding are detectable in individuals with brain amyloid deposition in the absence of overt neurodegeneration in the Alzheimer's disease continuum.

The short-term memory binding (STMB) test involves the ability to hold in memory the integration between surface features, such as shapes and colours. The STMB test has been used to detect Alzheimer's disease (AD) at different stages, from preclinical to dementia, showing promising results. The objective of the present study was to verify whether the STMB test could differentiate patients with distinct biomarker profiles in the AD continuum. The sample comprised 18 cognitively unimpaired (CU) participants, 30 mild cognitive impairment (MCI) and 23 AD patients. All participants underwent positron emission tomography (PET) with Pittsburgh compound-B labelled with carbon-11 ([11C]PIB) assessing amyloid beta (Aß) aggregation (A) and 18fluorine-fluorodeoxyglucose ([18F]FDG)-PET assessing neurodegeneration (N) (A-N- [n = 35]); A+N- [n = 11]; A+ N+ [n = 19]). Participants who were negative and positive for amyloid deposition were compared in the absence (A-N- vs. A+N-) of neurodegeneration. When compared with the RAVLT and SKT memory tests, the STMB was the only cognitive task that differentiated these groups, predicting the group outcome in logistic regression analyses. The STMB test showed to be sensitive to the signs of AD pathology and may represent a cognitive marker within the AD continuum.

Challenges to recruitment of participants with MCI in a multicentric neuropsychological study.

BACKGROUND: Data on recruitment of Mild Cognitive Impairment (MCI) samples are seldom reported and this issue can be an important source of research waste. AIM: To describe the recruitment challenges and reasons for non-eligibility faced during a bi-centre clinical study assessing the predictive value of a neuropsychological battery of the progression to dementia. METHODS: Potential MCI participants were identified from databases of the two memory clinics based in Milan (Italy) and invited to the screening assessment. RESULTS: About 50% of the cases initially identified were ineligible according to inclusion/exclusion criteria and the two sites took 22 months to recruit the planned 150 people. The main reasons for non-eligibility were the MMSE score (41%), age (14%), presence of cerebrovascular disorders (9%), perceptual deficits (6%), neurological (6%) or psychiatric (4%) comorbidities and low education (5%). CONCLUSION: Awareness of the reasons for exclusion and of the time needed to recruit the planned sample would provide hints for the planning of future studies on MCI.

Addressing dementia challenges through international networks: Evidence from the Latin American and Caribbean Consortium on Dementia (LAC-CD).

BACKGROUND: LAC-CD has recently reported that challenges faced by LAC countries are very similar to those experienced by HIC, and that regional networks will be needed to bridge gaps. ReDLat is a US-LAC multi-partner consortium aimed at expanding dementia research in LAC. The UK-Latin America Brain Connectivity Research Network (UL-BCRN) focuses on developing new affordable EEG-based biomarkers for dementia. The Language and Brain Health Network (LBHN) integrate international multidisciplinary efforts to reveal linguistic markers of neurodegenerative diseases. METHODS: ReDLat is collecting genomic, neuroimaging, clinical, cognitive, and socioeconomic data from a first-in-class cohort anchored in six LAC (Argentina, Chile, Colombia, Brazil, Mexico, and Peru) and will compare these to US data (> 4200 participants, including 2100 controls, 1050 AD patients, and 1050 FTD patients). The 5-year project will develop innovative, harmonized, and cross-nation approaches on two of the most prevalent neurodegenerative diseases, Alzheimer's disease (AD) and Frontotemporal Dementia (FTD). The UL-BCRN currently links seven EEG labs from Colombia, Argentina, Chile, Brazil and the UK. The network's vision is to forge strong relationships between labs through which new methodologies, EEG plus multidimensional datasets, and experience will be developed and shared. The LBHN will analyze speech samples from massive AD, FTD, and control cohorts across LAC, Spain, and the US. This effort aims to identify low-cost disease-specific markers in diverse Latino and English-speaking patients. RESULTS: ReDLat will aims to reveal unique risk factors for AD and FTD in LAC compared to US populations. Data collection strategies have been adapted to face the challenges brought by the COVID-19 pandemic. The UL-BCRN has now standardised recording protocols across LAC and UK labs and is collecting data from longitudinal cohorts of patients at risk of dementia relying on novel culture-free cognitive paradigms. Preliminary LBHN data shows that, automated speech analyses can identify Latinos with AD and FTD, with good generalization across socio-biological profiles, dialects, and languages. CONCLUSION: By broadening our understanding of dementia phenotypes, risk factors, and affordable diagnostic approaches in LAC, adding new evidence on variability across HIC and LMIC, the above networks will contribute unique knowledge that will help enhance future global dementia strategies.

Profiles of cognitive impairment in the continuum from normal cognition to Alzheimer's clinical syndrome: Contributions of the short-term memory binding tests.

BACKGROUND: Short-term memory binding (STMB) tests assess conjunctive binding, in which participants should remember the integration of features, such as shapes (or objects) and colors, forming a unique representation in memory. In this study, we investigated two STMB paradigms: change detection (CD) and free recall (FR). OBJECTIVE: To investigate the cognitive profile in the CD and FR tasks of three diagnostic groups: cognitively unimpaired (CU), mild cognitive impairment (MCI), and Alzheimer's clinical syndrome (ACS). In addition, we aimed to calculate and compare the accuracy of the CD and FR tasks to identify MCI and ACS. METHODS: Participants were 24 CU, 24 MCI, and 37 ACS. The cognitive scores of the clinical groups were compared using analysis of variance (ANOVA) and receiver-operating characteristic (ROC) analyses were carried out to verify the accuracy of the STMB tasks. RESULTS: In the CD task, CU was different from MCI and ACS (CU > MCI = ACS), while in the FR task all groups were different (CU > MCI > ACS). The ROC analyses showed an area under the curve (AUC) of 0.855 comparing CU with MCI for the CD task and 0.975 for the FR. The AUC comparing CU and ACS was 0.924 for the CD and 0.973 for the FR task. The FR task showed better accuracy to identify MCI patients, and the same accuracy to detect ACS. CONCLUSION: The present findings indicate that impairments in CD and FR of bound representations are features of the cognitive profiles of MCI and ACS patients.

GERO Cohort Protocol, Chile, 2017-2022: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint elderly.

BACKGROUND: With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in the elderly and the most rapidly growing cause of death in the last 20 years. Cognitive complaint is considered a predictor for cognitive and functional decline, incident mild cognitive impairment, and incident dementia. The GERO cohort is the Chilean core clinical project of the Geroscience Center for Brain Health and Metabolism (GERO). The objective of the GERO cohort is to analyze the rate of functional decline and progression to clinical dementia and their associated risk factors in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. We also aim to undertake clinical research on brain ageing and dementia disorders, to create data and biobanks with the appropriate infrastructure to conduct other studies and facilitate to the national and international scientific community access to the data and samples for research. METHODS: The GERO cohort aims the recruitment of 300 elderly subjects (> 70 years) from Santiago (Chile), following them up for at least 3 years. Eligible people are adults not diagnosed with dementia with subjective cognitive complaint, which are reported either by the participant, a proxy or both. Participants are identified through a household census. The protocol for evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool samples are also obtained. This multidimensional evaluation is carried out in a baseline and 2 follow-ups assessments, at 18 and 36 months. In addition, in months 6, 12, 24, and 30, a telephone interview is performed in order to keep contact with the participants and to assess general well-being. DISCUSSION: Our work will allow us to determine multidimensional risks factors associated with functional decline and conversion to dementia in elderly with subjective cognitive complain. The aim of our GERO group is to establish the capacity to foster cutting edge and multidisciplinary research on aging in Chile including basic and clinical research. TRIAL REGISTRATION: NCT04265482 in ClinicalTrials.gov. Registration Date: February 11, 2020. Retrospectively Registered.

Predictors of Performance in Real and Virtual Scenarios across Age.

BACKGROUND: Virtual reality applications to assist older adult with cognitive and functional decline are fast growing. However, such technological developments face limitations such as due to limited constructs and ecological validity. This study was aimed at investigating age-related changes in functional abilities and their associated cognitive underpinnings during task performance in virtual and real environments. METHOD: Twenty-two younger adults (university students) and 22 older adults (aged 58-74) performed a multiple errands task twice, once in the "Discoveries" section of the National Museum of Scotland and once in the same room as a virtual environment. Accuracy and distance traveled were measured in both groups. Cognitive and daily living abilities were recorded in older adults using standard and novel questionnaires. RESULTS: The testing environment had a significant effect on how efficient individuals performed the task. Older and younger adults' performance was alike but older adults relied on more cognitive resources. Older adults struggled in the virtual but not in the real environment. Younger but not older adults could transfer knowledge between environments. CONCLUSION: The use of technology to assist frail older adults and those affected by dementia is growing rapidly. For these novel tools to be theoretically valid, they need to incorporate knowledge of the challenges they pose to these vulnerable groups. Here we present evidence of such challenges and their cognitive underpinnings. This theory may be considered by future applications aimed at enhancing functional abilities in these populations.

Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

Interaction effects on common measures of sensitivity: choice of measure, type I error, and power.

Here we use simulation to assess previously unaddressed problems in the assessment of statistical interactions in detection and recognition tasks. The proportion of hits and false-alarms made by an observer on such tasks is affected by both their sensitivity and bias, and numerous measures have been developed to separate out these two factors. Each of these measures makes different assumptions regarding the underlying process and different predictions as to how false-alarm and hit rates should covary. Previous simulations have shown that choice of an inappropriate measure can lead to inflated type I error rates, or reduced power, for main effects, provided there are differences in response bias between the conditions being compared. Interaction effects pose a particular problem in this context. We show that spurious interaction effects in analysis of variance can be produced, or true interactions missed, even in the absence of variation in bias. Additional simulations show that variation in bias complicates patterns of type I error and power further. This under-appreciated fact has the potential to greatly distort the assessment of interactions in detection and recognition experiments. We discuss steps researchers can take to mitigate their chances of making an error.

A transcultural cognitive marker of Alzheimer's Disease.

OBJECTIVE: Temporary binding (TB) is sensitive and specific to Alzheimer's Disease (AD), is not affected by age, repeated testing or level of education. Hence, TB is useful to assess patients with very different socio-cultural backgrounds. However, the current computerised version of the test is not suitable for use in clinical settings. The aim of this study was to investigate whether a clinically friendly version of the TB task results in overlapping outcomes compared to the computerised version. METHODS: A newly devised Flash-card version of the TB assesses temporary visual binding for arrays of stimuli such as shapes (polygons), colours, or combinations of shapes and colours. In Experiment 1, this version was compared with the laboratory computerised version. In Experiment 2, 33 AD patients and 33 matched controls, recruited from various geriatric centres in Romania, were assessed with the new TB test and with Free and Cued Selective Reminding test. RESULTS: The results with the Flash-card version of the TB test were comparable to those obtained with the computerised version. TB was not affected by age, but it was impaired by AD. The sensitivity and specificity of the new TB test were found to be greater than those achieved by a Selective Reminding test. CONCLUSIONS: TB deficits may be conceived as a fundamental marker of AD. The Flash-card version is suitable for clinical use also in primary care facilities and in intervention trials, requires minimal training for administration and scoring, is quick to administer, non-invasive, inexpensive, and facilitates cross-cultural studies. Copyright © 2016 John Wiley & Sons, Ltd.

The effect of age on the FCSRT-IR and temporary visual memory binding.

ABSTRACTBackground:Cognitive markers of early Alzheimer's disease (AD) should be sensitive and specific to memory impairments that are not associated with healthy cognitive aging. In the present study, we investigated the effect of healthy cognitive aging on two proposed cognitive markers of AD: the Free and Cued Selective Reminding Task with Immediate Recall (FCSRT-IR) and a temporary visual memory binding (TMB) task. METHOD: Free recall and the cost of holding bound information in visual memory were compared between 24 younger and 24 older participants in a mixed, fully counterbalanced experiment. RESULTS: A significant effect of age was observed on free recall in the FCSRT-IR only and not on the cost of binding in the TMB task. CONCLUSIONS: Of these two cognitive markers, the TMB task is more likely to be specific to memory impairments that are independent of age.

Attentional bias during emotional processing: evidence from an emotional flanker task using IAPS.

Attention is biased towards threat-related stimuli. In three experiments, we investigated the mechanisms, processes, and time course of this processing bias. An emotional flanker task simultaneously presented affective or neutral pictures from the international affective picture system database either as central response-relevant stimuli or surrounding response-uninformative flankers. Participants' response times to central stimuli was measured. The attentional bias was observed when stimuli were presented either for 1500 ms (Experiment 1) or 500 ms (Experiment 2). The threat-related attentional bias held regardless of the stimuli competing for attention even when presentation time was further reduced to 200 ms (Experiment 3). The results indicate that automatic and controlled mechanisms may interact to modulate the orientation of attention to threat. The data presented here shed new light on the mechanisms, processes, and time course of this long investigated by still largely unknown processing bias.

Memory binding and white matter integrity in familial Alzheimer's disease.

Binding information in short-term and long-term memory are functions sensitive to Alzheimer's disease. They have been found to be affected in patients who meet criteria for familial Alzheimer's disease due to the mutation E280A of the PSEN1 gene. However, only short-term memory binding has been found to be affected in asymptomatic carriers of this mutation. The neural correlates of this dissociation are poorly understood. The present study used diffusion tensor magnetic resonance imaging to investigate whether the integrity of white matter structures could offer an account. A sample of 19 patients with familial Alzheimer's disease, 18 asymptomatic carriers and 21 non-carrier controls underwent diffusion tensor magnetic resonance imaging, neuropsychological and memory binding assessment. The short-term memory binding task required participants to detect changes across two consecutive screens displaying arrays of shapes, colours, or shape-colour bindings. The long-term memory binding task was a Paired Associates Learning Test. Performance on these tasks were entered into regression models. Relative to controls, patients with familial Alzheimer's disease performed poorly on both memory binding tasks. Asymptomatic carriers differed from controls only in the short-term memory binding task. White matter integrity explained poor memory binding performance only in patients with familial Alzheimer's disease. White matter water diffusion metrics from the frontal lobe accounted for poor performance on both memory binding tasks. Dissociations were found in the genu of corpus callosum which accounted for short-term memory binding impairments and in the hippocampal part of cingulum bundle which accounted for long-term memory binding deficits. The results indicate that white matter structures in the frontal and temporal lobes are vulnerable to the early stages of familial Alzheimer's disease and their damage is associated with impairments in two memory binding functions known to be markers for Alzheimer's disease.

Prediction of general hospital admission in people with dementia: cohort study.

BACKGROUND: People with dementia are extremely vulnerable in hospital and unscheduled admissions should be avoided if possible. AIMS: To identify any predictors of general hospital admission in people with dementia in a well-characterised national prospective cohort study. METHOD: A cohort of 730 persons with dementia was drawn from the Scottish Dementia Research Interest Register (47.8% female; mean age 76.3 years, s.d. = 8.2, range 50-94), with a mean follow-up period of 1.2 years. RESULTS: In the age- and gender-adjusted multivariable model (n = 681; 251 admitted), Neuropsychiatric Inventory score (hazard ratio per s.d. disadvantage 1.21, 95% CI 1.08-1.36) was identified as an independent predictor of admission to hospital. CONCLUSIONS: Neuropsychiatric symptoms in dementia, measured using the Neuropsychiatric Inventory, predict non-psychiatric hospital admission of people with dementia. Further studies are merited to test whether interventions to reduce such symptoms might reduce unscheduled admissions to acute hospitals.

Relational and conjunctive binding functions dissociate in short-term memory.

Remembering complex events requires binding features within unified objects (conjunctions) and holding associations between objects (relations). Recent studies suggest that the two functions dissociate in long-term memory (LTM). Less is known about their functional organization in short-term memory (STM). The present study investigated this issue in patient AE affected by a stroke which caused damage to brain regions known to be relevant for relational functions both in LTM and in STM (i.e., the hippocampus). The assessment involved a battery of standard neuropsychological tasks and STM binding tasks. One STM binding task (Experiment 1) presented common objects and common colors forming either pairs (relations) or integrated objects (conjunctions). Free recall of relations or conjunctions was assessed. A second STM binding task used random polygons and non-primary colors instead (Experiment 2). Memory was assessed by selecting the features that made up the relations or the conjunctions from a set of single polygons and a set of single colors. The neuropsychological assessment revealed impaired delayed memory in AE. AE's pronounced relational STM binding deficits contrasted with his completely preserved conjunctive binding functions in both Experiments 1 and 2. Only 2.35% and 1.14% of the population were expected to have a discrepancy more extreme than that presented by AE in Experiments 1 and 2, respectively. Processing relations and conjunctions of very elementary nonspatial features in STM led to dissociating performances in AE. These findings may inform current theories of memory decline such as those linked to cognitive aging.

Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age.

The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding.

FAST functional connectivity implicates P300 connectivity in working memory deficits in Alzheimer's disease.

Measuring transient functional connectivity is an important challenge in Electroencephalogram (EEG) research. Here, the rich potential for insightful, discriminative information of brain activity offered by high temporal resolution is confounded by the inherent noise of the medium and the spurious nature of correlations computed over short temporal windows. We propose a novel methodology to overcome these problems called Filter Average Short-Term (FAST) functional connectivity. First, long-term, stable, functional connectivity is averaged across an entire study cohort for a given pair of Visual Short Term Memory (VSTM) tasks. The resulting average connectivity matrix, containing information on the strongest general connections for the tasks, is used as a filter to analyse the transient high temporal resolution functional connectivity of individual subjects. In simulations, we show that this method accurately discriminates differences in noisy Event-Related Potentials (ERPs) between two conditions where standard connectivity and other comparable methods fail. We then apply this to analyse activity related to visual short-term memory binding deficits in two cohorts of familial and sporadic Alzheimer's disease. Reproducible significant differences were found in the binding task with no significant difference in the shape task in the P300 ERP range. This allows new sensitive measurements of transient functional connectivity, which can be implemented to obtain results of clinical significance.