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Objective: The Visual Short-Term Memory Binding (VSTMB) Test is a useful tool in the assessment of Alzheimer's disease (AD). Research has suggested that short-term memory binding is insensitive to the sociocultural characteristics of the assessed individuals. Such earlier studies addressed this influence by considering years of education. The current study aims to determine the influence of sociocultural factors via a measure of Socioeconomic Status (SES) which provides a more holistic approach to these common confounders. Methods: A sample of 126 older adults, both with (n = 59) and without (n = 67) amnestic mild cognitive impairment (aMCI), underwent assessment using a neuropsychological protocol including VSTMB test. All participants were classified as either high SES or low SES, employing the Standard Demographic Classification from the European Society for Opinion and Marketing Research. Results: ANOVA/ANCOVA models confirmed that performance of healthy and aMCI participants on traditional neuropsychological tests were sensitive to SES whereas the VSTMB Test was not. The results add to the growing array of evidence suggesting that there are cognitive abilities which are unaffected by socioeconomic factors, regardless of clinical condition. Conclusions: The lack of sensitivity to sociocultural factors previously reported for the VSTMB test is accompanied by a lack of sensitivity to socioeconomic factors thus broadening the scope of this test to aid in the detection of dementia across populations with different backgrounds. Future studies should take these findings forward and explore the potential influences of AD biomarkers (A/T/N) on the association between cognitive functions and demographic variables. [ABSTRACT FROM AUTHOR]

Dementia is a syndrome characterized by cognitive and neuropsychiatric symptoms associated with progressive functional decline (FD). FD is a core diagnostic criterion for dementia, setting the threshold between its prodromal stages and the full-blown disease. The operationalization of FD continues to generate a great deal of controversy. For instance, the threshold of FD for the diagnosis of dementia varies across diagnostic criteria, supporting the need for standardization of this construct. Moreover, there is a need to reconsider how we are measuring FD to set boundaries between normal aging, mild cognitive impairment, and dementia. In this paper, we propose a multidimensional framework that addresses outstanding issues in the assessment of FD: i) What activities of daily living (ADLs) are necessary to sustain an independent living in aging? ii) How to assess FD in individuals with suspected neurocognitive disorders? iii) To whom is the assessment directed? and iv) How much does FD differentiate healthy aging from mild and major neurocognitive disorders? Importantly, the To Whom Question introduces a person-centered approach that regards patients and caregivers as active agents in the assessment process of FD. Thus, once impaired ADLs have been identified, patients can indicate how significant such impairments are for them in daily life. We envisage that this new framework will guide future strategies to enhance functional assessment and treatment of patients with dementia and their caregivers. [ABSTRACT FROM AUTHOR]

Background: The individual and complementary value of the Visual Short-Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) as markers to trace the AD continuum was investigated. It was hypothesised that the VSTMBT would be an early indicator while the FCSRT would inform on imminent progression. Methods: Healthy older adults (n=70) and patients with mild cognitive impairment (MCI) (n=80) were recruited and followed up between 2012 and 2017. Participants with at least two assessment points entered the study. Using baseline and follow-up assessments four groups were defined: Older adults who were healthy (HOA), with very mild cognitive but not functional impairment (eMCI), and with MCI who did and did not convert to dementia (MCI converters and non-converters). Results: Only the VSTMBT predicted group membership in the very early stages (HOA vs eMCI). As the disease progressed, the FCSRT became a strong predictor excluding the VSTMB from the models. Their complementary value was high during the mid-prodromal stages and decreased in stages closer to dementia. Discussion: The study supports the notion that neuropsychological assessment for AD needs to abandon the notion of one-size-fits-all. A memory toolkit for AD needs to consider tools that are early indicators and tools that suggest imminent progression. The VSTMBT and the FSCRT are such tools. [ABSTRACT FROM AUTHOR]

Introduction: Oculomotor behaviors linked to cognitive performance revealed neurocognitive features of Alzheimer's disease (AD) that can enhance the accuracy of its assessment and diagnosis. Methods: A sample of 107 participants (i.e., 65 mild cognitive impairment [MCI] and 42 controls) were recruited and followed up for 40 months. At baseline, they underwent assessment with the ViewMind digital biomarker, which draws cognitive‐related patterns of eye movement while people perform the visual short‐term memory binding task. Results: Baseline data predicted that 36 patients with MCI would progress to the AD clinical syndrome (ADS Progressing). The remaining 29 MCI patients were predicted to remain as MCI or progress to other forms of dementia. After 40 months of follow‐up, 94% of ADS Progressing patients had received a diagnosis of dementia, whereas none of the non‐ADS Progressing had. Discussion: The analysis of eye movement behavior combined with cognitive markers for AD can effectively predict progression to ADS among patients with MCI. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Recent research pointed to executive dysfunction as a potential early predictor of the progression of mild cognitive impairment (MCI) to dementia in Alzheimer's clinical syndrome (ACS). Such cognitive impairments account for functional impairments in instrumental activities of daily living (IADL).Objective: The present study analyzes the contributions of executive functions to predict MCI-dementia progression in ACS.Methods: We assessed 145 participants, 51 cognitively unimpaired and 94 MCI. The latter were divided using the traditional, memory-based MCI classification (single domain amnestic, multidomain amnestic, and non-amnestic). Eight tests assessing executive functions were administered at baseline and at 1-year follow-up, together with cognitive screening tools and IADL measures. MCI patients were reclassified based on the outcomes from a K-mean cluster analysis which identified three groups. A simple lineal regression model was used to examine whether the classification based on executive functioning could more accurately predict progression to dementia a year later.Results: Clusters based on executive function deficits explained a significant proportion of the variance linked to MCI-dementia conversion, even after controlling for the severity of MCI at baseline (F(1, 68) = 116.25, p = 0.000, R2 = 0.63). Classical memory-based MCI classification failed to predict such a conversion (F(1, 68) = 5.09, p = 0.955, R2 = 0.07). Switching, categories generation, and planning were the executive functions that best distinguished between MCI converters and stable.Conclusion: MCI with a dysexecutive phenotype significantly predicts conversion to dementia in ACS a year later. Switching abilities and verbal fluency (categories) must be evaluated in MCI patients to assess risk of future dementia. [ABSTRACT FROM AUTHOR]

• Short-term memory binding (STMB) can inform about the predementia stages of AD. • Tailoring the test difficulty to the disease severity helps trace the AD continuum. • STMB and hippocampal volume identify MCI patients who may be on the AD trajectory. Alzheimer's disease (AD) affects temporary memory for bound features more remarkably than for individual features. Such selective impairments manifest from presymptomatic through dementia stages via titration procedures. A recent study suggested that without titration and with high memory load the binding selectivity may disappear in people at risk of AD such as those with Mild Cognitive Impairment (MCI). We compared data from two studies on temporary binding which assessed people with MCI and controls using different memory loads (2 or 3 items). Selective binding impairments were found in MCI, but relative to controls, such selectivity was contingent upon memory load (i.e., present with 2 items). Further analysis with MCI people who tested positive to neuroimaging biomarkers (i.e., hippocampal atrophy) confirmed that this specific binding impairments are a feature of prodromal AD. The temporary binding task has been recently suggested by consensus papers as a potential screening tool for AD. The results presented here inform on task properties that can maximize the reliability of this new assessment tool for the detection of memory impairments in prodromal cases of AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Feature binding is a sensitive and specific cognitive marker for Alzheimer's disease (AD). Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are clinical categories associated with an increased risk for AD.Objective: To investigate whether the SCD and MCI group are impaired with regard to feature binding.Methods: The feature binding test was administered to memory clinic patients with either SCD (n = 19, mean MMSE: 29.2) or with MCI (n = 23, mean MMSE: 26.5), and to a group of healthy controls (HC, n = 23, mean MMSE: 29.0). Participants were assessed with the CERAD Plus neuropsychological test battery. Cognitive performance of the three groups was compared by ANCOVA with age, gender and education as covariates and planned contrasts.Results: Groups differed in the binding condition. Planned contrasts showed significant differences in adjusted means between HC and SCD (p = 0.003), as well as between HC and MCI (p <  0.0001).Discussion: The feature binding task detects subtle cognitive impairments in participants with SCD, who are unimpaired in traditional neuropsychological testing. This corroborates the use of feature binding tests in preclinical AD studies and suggests that specific cognitive deficits can be found in SCD. Future studies incorporating AD biomarkers and longitudinal follow-up are needed to further establish the clinical utility of feature binding. [ABSTRACT FROM AUTHOR]

Background: Relative to intentional memory encoding, which quickly declines in Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), incidental memory for emotional stimuli appears to deteriorate more slowly. We hypothesised that tests of incidental emotional memory may inform on different aspects of cognitive decline in MCI and AD. Methods: Patients with MCI, AD and Healthy Controls (HC) were asked to attend to emotional pictures (i.e., positive and neutral) sequentially presented during an fMRI session. Attention was monitored behaviourally. A surprise post-scan recognition test was then administered. Results: The groups remained attentive within the scanner. The post-scan recognition pattern was in the form of (HC = MCI) > AD, with only the former group showing a clear benefit from emotional pictures. fMRI analysis of incidental encoding demonstrated clusters of activation in para-hippocampal regions and in the hippocampus in HC and MCI patients but not in AD patients. The pattern of activation observed in MCI patients tended to be greater than that found in HC. Conclusions: The results suggest that incidental emotional memory might offer a suitable platform to investigate, using behavioural and fMRI measures, subtle changes in the process of developing AD. These changes seem to differ from those found using standard episodic memory tests. The underpinnings of such differences and the potential clinical use of this methodology are discussed in depth. [ABSTRACT FROM AUTHOR]

Only a small proportion of individuals with Mild Cognitive Impairment (MCI) will convert to dementia. Methods currently available to identify risk for conversion do not combine enough sensitivity and specificity, which is even more problematic in loweducated populations. Current guidelines suggest the use of combined markers for dementia to enhance the prediction accuracy of assessment methods. The present study adhered to this proposal and investigated the sensitivity and specificity of the electrophysiological component P300 and standard neuropsychological tests to assess patients with Alzheimer's disease (AD) and MCI recruited from a low-income country. The neuropsychological battery comprised tests of memory, attention, language, praxis and executive functions. The P300 was recorded using a classical visual odd-ball paradigm. Three variables were found to achieve sensitivity and specificity values above 80% (Immediate and Delayed recall of word list - CERAD - and the latency of P300) for both MCI and AD. When they entered the model together (i.e., combined approach) the sensitivity for MCI increased to 96% and the specificity remained high (80%). Our preliminary findings suggest that the combined use of sensitive neuropsychological tasks and the analysis of the P300 may offer a very useful method for the preclinical assessment of AD, particularly in populations with low socioeconomic and educational levels. Our results provide a platform and justification to employ more resources to convert P300 and related parameters into a biological marker for AD. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, visual short-term memory (VSTM) binding tests have been shown to be one of the most sensitive behavioral indicators of Alzheimer's disease (AD), especially when they require the binding of multiple features (e.g., color and shape). Recently, it has become possible to directly measure amyloid and tau levels in vivo via positron emission tomography (PET). To this point, these behavioral and neurochemical markers have not been compared in humans with AD or at risk for it. Methods: In a cross-sectional study, we compared VSTM performance to tau and amyloid concentrations, measured by PET, in individuals certain to develop AD by virtue of their inheritance of the presenilin-1 E280A mutation. These included 21 clinically unimpaired subjects and 7 subjects with early mild cognitive impairment (MCI), as well as 30 family members who were not carriers of the mutation. Results: We found that VSTM performance correlated strongly with tau in entorhinal cortex and inferior temporal lobe, and also with amyloid when examining asymptomatic carriers only. The condition requiring binding was not preferentially linked to tau—in fact, the non-binding "shape only" condition showed a stronger relationship. Conclusions: The results confirm VSTM's status as an early marker of AD pathology and raise interesting questions as to the course of binding-specific versus non-binding aspects of VSTM in early AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease dementia (ADD) is the most diffuse neurodegenerative disorder belonging to mild cognitive impairment (MCI) and dementia in old persons. This disease is provoked by an abnormal accumulation of amyloid-beta and tauopathy proteins in the brain. Very recently, the first disease-modifying drug has been licensed with reserve (i.e., Aducanumab). Therefore, there is a need to identify and use biomarkers probing the neurophysiological underpinnings of human cognitive functions to test the clinical efficacy of that drug. In this regard, event-related electroencephalographic potentials (ERPs) and oscillations (EROs) are promising candidates. Here, an Expert Panel from the Electrophysiology Professional Interest Area of the Alzheimer's Association and Global Brain Consortium reviewed the field literature on the effects of the most used symptomatic drug against ADD (i.e., Acetylcholinesterase inhibitors) on ERPs and EROs in ADD patients with MCI and dementia at the group level. The most convincing results were found in ADD patients. In those patients, Acetylcholinesterase inhibitors partially normalized ERP P300 peak latency and amplitude in oddball paradigms using visual stimuli. In these same paradigms, those drugs partially normalize ERO phase-locking at the theta band (4–7 Hz) and spectral coherence between electrode pairs at the gamma (around 40 Hz) band. These results are of great interest and may motivate multicentric, double-blind, randomized, and placebo-controlled clinical trials in MCI and ADD patients for final cross-validation. • The multidisciplinary expert panel aimed to review the effects of medications on ERO/ERP EEG oscillations in ADD. • Treatment effects were mostly pronounced in the ERP P300 component along with theta and gamma ERO measures. • Electrophysiological markers may probe thalamocortical and subcortical neural de/synchronization regarding treatment effects. [ABSTRACT FROM AUTHOR]

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 (Aβ) 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. [ABSTRACT FROM AUTHOR]