Visual Short-term Memory Binding Task Research Articles

The development and validation of a digital biomarker for remote assessment of Alzheimer's diseases risk.

Digital cognitive assessment is becoming increasingly widespread in ageing research and care, especially since the COVID-19 pandemic. Remote online collection provides opportunities for ageing and dementia professionals to collect larger datasets, increase the diversity of research participants and patients and offer cost-effective screening and monitoring methods for clinical practice and trials. However, the reliability of self-administered at-home tests compared to their lab-based counterparts often goes unexamined, compromising the validity of adopting such measures. Our aim is to validate a self-administered web-based version of the visual short-term memory binding task (VSTMBT), a potential digital biomarker sensitive to Alzheimer's disease processes, suitable for use on personal devices. A final cross-sectional sample of 37 older-adult (51-77 years) participants without dementia completed our novel self-administered version of the VSTMBT, both at home on a personal device and in the lab, under researcher-controlled conditions. ANOVA and Bayesian t-test found no significant differences between the task when it was remotely self-administered by participants at home compared to when it was taken under controlled lab conditions. These results indicate the VSTMBT can provide reliable data when self-administered at-home using an online version of the task and on a personal device. This finding has important implications for remote screening and monitoring practices of older adults, as well as supporting clinical practices serving diverse patient communities. Future work will assess remote administration in older adults with cognitive impairment and diverse socio-economic and ethno-cultural backgrounds as well as a bench-to-bedside application.

The "when" matters: Evidence from memory markers in the clinical continuum of Alzheimer's disease.

Cognitive assessment able to detect impairments in the early neuropathological stages of Alzheimer's disease (AD) is urgently needed. The visual short-term memory binding task (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) have been recommended by the neurodegenerative disease working group as promising tests to aid in the early detection of AD. In this study, we investigated their complementary value across the clinical stages of the AD continuum. One hundred and seventeen older adults with subjective cognitive complaint (SCC), 79 with mild cognitive impairment (MCI), 31 patients with AD dementia (ADD), and 37 cognitively unimpaired (CU) subjects, underwent assessment with the VSTMBT and the picture version of the Spanish FCSRT. After controlling for multiple comparisons, significant differences were found across groups. The VSTMBT was the only test that "marginally" differentiated between CU and SCC (d = 0.47, p = .052). Moreover, whereas the FCSRT showed a gradient (CU = SCC) > MCI > ADD, the VSTMBT gradient was CU > SCC > (MCI = ADD) suggesting that conjunctive binding deficits assessed by the latter may be sensitive to the very early stages of the disease. Our results suggest that the VSTMBT and the FCSRT are sensitive to the clinical continuum of AD. Whereas the former detects changes in the early prodromal stages, the latter is more sensitive to the advanced prodromal stages of AD. These novel tests can aid in the early detection, monitor disease progression and response to treatment, and thus support drug development programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The eye as a biomarker for Alzheimer’s disease: oculomotor behaviours yield a novel digital biomarker for preclinical risk detection

AbstractBackgroundThey eyes seem to hold a key to unveil early manifestations of Alzheimer’s disease (AD) pathology beyond retinal analysis. We have recently confirmed that eye‐tracking (ET) metrics recorded during performance on memory tasks can identify early and subtle changes in individuals at risk of or with AD dementia. There is a need for more robust and automatic classification methods that can provide affordable digital biomarker solutions for the preclinical detection of AD. This was the aim of this study.MethodsA sample of 16 asymptomatic carriers (AC) of the mutation E280A‐PSEN1 from the widely investigated cohort of Antioquia, Colombia, and 55 healthy controls (HC) entered the study. Both groups were assessed with the novel Visual Short‐Term Memory Binding Task (VSTMBT) coupled with an ET device. The VSTMBT assesses the ability to temporarily hold bicoloured objects whose colours had to be remembered either as individual features (baseline) or integrated within unified representations (binding). Oculomotor behaviours (i.e., fixations, saccades, pupillometry) recorded using ET were subjected to Artificial Intelligence technology. This relied on Machine Learning classification using Lasso and Elastic‐Net Regularized Generalized Linear Models ("glmnet").ResultsAC and HC could not be distinguished based on traditional neuropsychological assessment (e.g., MMSE: HC = 29.7(0.4), AC = 29.5(0.8), p= 0.09). ML accuracy for classifying subjects into correct groups (HC and AC) was 98%. For a cut‐off of 0.72, 55 out of 55 HC and 14 out of 16 AC were correctly classified (see Fig 1).ConclusionRelative to behavioural measures (i.e., percentage correct recognition) drawn from the VSTMBT, AI‐powered technology can significantly enhance the detection of at risk individuals. By better characterising abnormal oculomotor behaviours, phenotypic features of the preclinical stages of AD can be unveiled. The facts that such a phenotypic expression characterised the majority of AC warrants further investigation in populations who hold less‐well known risk for AD.

Optimizing Subjective Cognitive Decline to Detect Early Cognitive Dysfunction.

The utility of subjective cognitive decline (SCD) as an indicator of preclinical AD is overshadowed by its inconsistent association with objective cognition. This study examines if manipulations of SCD measurement affect its association with early cognitive dysfunction characteristic of preclinical AD. Cognitively healthy older adults (n = 110) completed SCD questionnaires that elicited complaints in general, compared to 5 years ago (retrospective SCD) and compared to their peers (age-anchored SCD) in binary and Likert scales. Outcome cognitive tasks included an associative memory task (Face-Name Test), a visual short-term memory binding task (STMB test), and a clinical neuropsychological list learning test (Selective Reminder Test). SCD complaints, when compared to age-matched peers (age-anchored SCD) were endorsed less frequently than complaints compared to 5 years ago (retrospective SCD) (p < 0.01). In demographically adjusted regressions, age-anchored ordinal-rated SCD was associated with short term memory binding (β= -0.22, p = 0.040, CI = -0.45, -0.01), associative memory (β= -0.26, p = 0.018, CI = -0.45, -0.06), and list learning (β= -0.31, p = 0.002, CI = -0.51, -0.12). Retrospective and general ordinal-rated SCD was associated with associative memory (β= -0.25, p = 0.012, CI = -0.44, -0.06; β= -0.29, p = 0.003, CI = -0.47, -0.10) and list learning only (β= -0.25, p = 0.014, CI = -0.45, -0.05; β= -0.28, p = 0.004, CI = -0.48, -0.09). Ordinal age-anchored SCD appears better suited than other SCD measurements to detect early cognitive dysfunction characteristic of preclinical AD.

Impact of intrathecal cell therapy with autologous stromal cells on short‐term memory binding in early Alzheimer’s disease: One‐year follow‐up assessment

AbstractBackgroundWe had previously reported that the administration of autologous stromal cells (ASCs) therapy to two patients with mild AD dementia led to a global increase in cerebral glucose metabolism which was accompanied by significant improvement of visual short‐term memory binding (VSTMB), a function known to be a marker of AD. We suggested that intrathecal administration of autologous ASCs could be considered a new therapeutic strategy for AD dementia (Vaquero et al., 2019). We were interested in investigating the post‐intervention durability of such cognitive improvements.MethodsWe studied two AD patients with cerebral beta‐amyloid neuritic plaques detected with 18FFDG‐PET. The patients received every three months 100 million of ASCs by intrathecal route, until a total dose of 300 million. None received any other medication for its disease at the time of receiving cell therapy. Clinical and neuroimaging studies were performed previous and after the therapy, including brain glucose metabolism by 18F‐FDG‐PET and assessment with the visual short‐term memory binding task (VSTMBT). This task has been proposed as a preclinical marker of AD. It requires subjects to detect whether or not two combinations of shape and colour change across two sequential arrays. Here we report on the assessment of these patients one year after the therapy. We compared them with 4 AD patients who did no undergo stem cell therapy.ResultsSingle case statistics revealed that benefits drawn by treated patients from the therapy remained a year after. Using a more taxing version of the VSTMB test (memory load of 3 items) we observed that, after the therapy, the chance that an untreated AD patient would show more impairment was 75.45% (p= 0.24) for Case 1 and 89.23% (p=0.11) for case 2. This chance remained after 1 year post‐treatment for Case 1 (75.45%, p=0.24) and increased for Case 2 (96.89%, p=0.031).ConclusionImprovements of memory functions known to be marker for AD in patients who underwent stem cell therapy remained stable after one year post‐intervention. This offers a new therapeutic strategy for AD.

Translating Visual Short-Term Memory Binding Tasks to Clinical Practice: From Theory to Practice.

Translating Visual Short-Term Memory Binding Tasks to Clinical Practice: From Theory to Practice.

Neurocognitive mechanisms underlying working memory encoding and retrieval in Attention-Deficit/Hyperactivity Disorder

Working memory (WM) impairments in ADHD have been consistently reported along with deficits in attentional control. Yet, it is not clear which specific WM processes are affected in this condition. A deficient coupling between attention and WM has been reported. Nevertheless, most studies focus on the capacity to retain information rather than on the attention-dependent stages of encoding and retrieval. The current study uses a visual short-term memory binding task, measuring both behavioral and electrophysiological responses to characterize WM encoding, binding and retrieval comparing ADHD and non-ADHD matched adolescents. ADHD exhibited poorer accuracy and larger reaction times than non-ADHD on all conditions but especially when a change across encoding and test displays occurred. Binding manipulation affected equally both groups. Encoding P3 was larger in the non-ADHD group. Retrieval P3 discriminated change only in the non-ADHD group. Binding-dependent ERP modulations did not reveal group differences. Encoding and retrieval P3 were significantly correlated only in non-ADHD. These results suggest that while binding processes seem to be intact in ADHD, attention-related encoding and retrieval processes are compromised, resulting in a failure in the prioritization of relevant information. This new evidence can also inform recent theories of binding in visual WM.

Visual short-term memory binding deficit with age-related\xa0hearing loss in cognitively normal older adults

Age-related hearing loss (ARHL) has been posited as a possible modifiable risk factor for neurocognitive impairment and dementia. Measures sensitive to early neurocognitive changes associated with ARHL would help to elucidate the mechanisms underpinning this relationship. We hypothesized that ARHL might be associated with decline in visual short-term memory binding (VSTMB), a potential biomarker for preclinical dementia due to Alzheimer’s disease (AD). We examined differences in accuracy between older adults with hearing loss and a control group on the VSTMB task from a single feature (shapes) condition to a feature binding (shapes-colors) condition. Hearing loss was associated with a weaker capacity to process bound features which appeared to be accounted for by a weaker sensitivity for change detection (A’). Our findings give insight into the neural mechanisms underpinning neurocognitive decline with ARHL and its temporal sequence.

P3‐013: PRELIMINARY EVIDENCE OF THE IMPACT OF INTRATHECAL CELL THERAPY WITH AUTOLOGOUS STROMAL CELLS ON SHORT‐TERM MEMORY BINDING IN EARLY ALZHEIMER'S DISEASE CASES

Background: A decrease in brain glucose metabolism in Alzheimer’s disease (AD) patients is considered a critical driver of cognitive impairment, and medications used in AD target this metabolic dysfunction. Recent evidence has shown a significant increase in glucose metabolism associated with neurocognitive improvement after intrathecal administration of bone marrow mesenchymal stromal cells (MSCs) in patients suffering from severe TBI or haemorrhagic stroke. We hypothesise that this cell therapy could also be useful in AD patients. Methods: We studied two AD patients with cerebral beta-amyloid neuritic plaques detected with 18FFDG-PET. The patients received every three months 100 million of autologous MSCs by intrathecal route, until a total dose of 300 million. None received any other medication for its disease at the time of receiving cell therapy. Clinical and neuroimaging studies were performed previous and after the therapy, including brain glucose metabolism by 18F-FDG-PET and assessment with the visual short-term memory binding task (VSTMBT). This task has been proposed as a preclinical marker of AD. It requires subjects to detect whether or not two combinations of shape and colour change across two sequential arrays. Results: A global increase in cerebral glucose metabolism was observed after each administration of cell therapy. Single case statistics revealed that treated and untreated patients did not differ on their pre-treatment VSTMBT scores and both were significantly impaired relative to controls. The chance that an untreated AD patient would show more impairment than treated patients was 39.25% (p= 0.785) for case 1, and 50.00% (p=1.0) for case 2. This chance increased post-treatment to 97.40% (p=0.05) and 99.74% (p=0.005) respectively. Conclusion: These preliminary findings suggest that intrathecal administration of autologous MSCs should be considered as a new therapeutic strategy for Alzheimer’s dementia and deserves further studies.

Visual Processing during Short-Term Memory Binding in Mild Alzheimer's Disease.

Patients with Alzheimer's disease (AD) typically present with attentional and oculomotor abnormalities that can have an impact on visual processing and associated cognitive functions. Over the last few years, we have witnessed a shift toward the analyses of eye movement behaviors as a means to further our understanding of the pathophysiology of common disorders such as AD. However, little work has been done to unveil the link between eye moment abnormalities and poor performance on cognitive tasks known to be markers for AD patients, such as the short-term memory-binding task. We analyzed eye movement fixation behaviors of thirteen healthy older adults (Controls) and thirteen patients with probable mild AD while they performed the visual short-term memory binding task. The short-term memory binding task asks participants to detect changes across two consecutive arrays of two bicolored object whose features (i.e., colors) have to be remembered separately (i.e., Unbound Colors), or combined within integrated objects (i.e., Bound Colors). Patients with mild AD showed the well-known pattern of selective memory binding impairments. This was accompanied by significant impairments in their eye movements only when they processed Bound Colors. Patients with mild AD remarkably decreased their mean gaze duration during the encoding of color-color bindings. These findings open new windows of research into the pathophysiological mechanisms of memory deficits in AD patients and the link between its phenotypic expressions (i.e., oculomotor and cognitive disorders). We discuss these findings considering current trends regarding clinical assessment, neural correlates, and potential avenues for robust biomarkers.

Locating Temporal Functional Dynamics of Visual Short-Term Memory Binding using Graph Modular Dirichlet Energy

Visual short-term memory binding tasks are a promising early marker for Alzheimer’s disease (AD). To uncover functional deficits of AD in these tasks it is meaningful to first study unimpaired brain function. Electroencephalogram recordings were obtained from encoding and maintenance periods of tasks performed by healthy young volunteers. We probe the task’s transient physiological underpinnings by contrasting shape only (Shape) and shape-colour binding (Bind) conditions, displayed in the left and right sides of the screen, separately. Particularly, we introduce and implement a novel technique named Modular Dirichlet Energy (MDE) which allows robust and flexible analysis of the functional network with unprecedented temporal precision. We find that connectivity in the Bind condition is less integrated with the global network than in the Shape condition in occipital and frontal modules during the encoding period of the right screen condition. Using MDE we are able to discern driving effects in the occipital module between 100–140 ms, coinciding with the P100 visually evoked potential, followed by a driving effect in the frontal module between 140–180 ms, suggesting that the differences found constitute an information processing difference between these modules. This provides temporally precise information over a heterogeneous population in promising tasks for the detection of AD.

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

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.

Visual short-term memory binding in Alzheimer’s disease and depression

The differential diagnosis between Alzheimer's disease (AD) and major depression (MD) in the elderly can be problematic because the cognitive profile of the two conditions overlaps. Associative learning tasks seem to separate AD from MD. However, they are sensitive to the effects of normal ageing. Short-term memory-binding tasks have proved insensitive to the effects of normal ageing and highly sensitive to AD. However, they have not been used to differentiate AD from MD. The present study was aimed at investigating visual short-term memory binding in AD and MD. Fourteen AD patients, 14 patients with MD, and 14 healthy older adults were asked to perform a visual short-term memory binding task that investigated the retention of shapes, colors, or combinations of shapes and colors. Participants were to recognize changes occurring between two consecutive displays either in a single dimension (i.e., shape or color only) or in two dimensions (i.e., shape-color binding). Short-term memory performance for shape or color only was equivalent across groups. The only significant effect found was in short-term memory for shape-color binding and this was due to AD patients performing poorly in this condition only. The results extend previous findings in AD to visual short-term memory and suggest that the specific impairment in binding information in memory differentiates between the performance of AD and patients with MD.