Visual Short-term Memory Binding Research Articles

Associations between sex and lifestyle activities with cognitive reserve in mid-life adults with genetic risk for Alzheimer's disease.

Females have a higher age-adjusted incidence of Alzheimer's Disease (AD) than males, even when accounting for longer lifespan and, therefore, stand to benefit the most from dementia prevention efforts. As exposure to many modifiable risk factors for dementia begins in mid-life, interventions must be implemented from middle-age. Building cognitive reserve, particularly through stimulating avocational activities and occupational attainment presents a crucial, underexplored, dementia prevention approach for mid-life. It is currently unknown, however, whether modifiable lifestyle factors can protect against AD processes, from mid-life, differentially for females and males who carry inherited risk for late-life dementia. To address this gap, this study investigated the impact of biological sex and APOE4 carrier status on the relationship between stimulating activities, occupational attainment, and cognition in mid-life. We leveraged the PREVENT-Dementia program, the world's largest study investigating the origins and early diagnosis of dementia in mid-life at-risk individuals (N = 700; 40-59 years). Cognitive performance was measured using the Cognito Battery and the Visual Short Term Memory Binding task. Mid-life specific reserve contributors were assessed via the Lifetime of Experiences Questionnaire. Females had significantly better episodic and relational memory (p < 0.001), and lower occupational attainment than males (p < 0.001). Engagement in stimulating activities was positively associated with episodic and relational memory, regardless of sex and APOE4 status (β = 0.05, CI 0.03-0.07, p < 0.001). APOE4 carriers showed significant sex differences in the association between occupational attainment and episodic and relational memory (β = 0.38, CI 0.12-0.63, p = 0.003). APOE4 carrier females with higher occupational attainment showed better cognition (β = 0.16, CI -0.002-0.32, p = 0.053), whereas APOE4 carrier males showed the opposite effect (β = -0.20, CI -0.40 - -0.001, p = 0.049). Our findings suggest that occupational attainment in mid-life contributes to cognitive reserve against inherited risk of dementia in females, but not males. They highlight the need for high precision approaches that consider biological sex and APOE4 carrier status to inform Alzheimer's disease prevention strategies and clinical trials.

Short-term memory binding is insensitive to the socioeconomic status of older adults with and without mild cognitive impairment

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.

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).

Age‐related hearing loss and neural correlates of visual short‐term memory

AbstractBackgroundAge‐related hearing loss (ARHL) may be a potential modifiable risk factor for neurocognitive decline and dementia. Previous studies have reported HL is associated with decline in visual memory function. Evidence also suggests that following ARHL, there is neural reorganization in regions critical for memory. The aim of this pilot was to explore the association of ARHL with neural correlates of visual short‐term memory binding (VSTMB).MethodParticipants over the age of 65 were recruited and divided into three groups (controls (n = 14), mild HL (n = 21), and moderate or greater HL (n = 23)) based on results from a tablet‐based hearing measure. Volunteers completed the VSTMB task (shapes and binding conditions) while electroencephalography (EEG) data was synchronously recorded using a high‐density EEG array (128 scalp electrodes). Analysis was focused on comparing 5 different components (P1, N1, P2, P3, and late positive potential (LPP)) between both HL groups to controls for the memory encoding and testing phases on both shapes and binding conditions. Statistical analysis of source reconstructions (sLORETA) was also performed to explore neural regions underlying VSTMB.ResultThere was no difference between groups in behavioral performance on the VSTMB task. There were a limited number of differences in electrophysiological activity, primarily in P1, P2, P3 and LPP which increased from mild to moderate or greater HL. Analyses of source reconstructions suggested there were bilateral differences in frontal, central, parietal, temporal, and occipital neural regions between groups.ConclusionThere were no differences in behavioral outcomes in VSTMB with HL. There may be underlying differences in neural activity on this task with greater HL which is in accordance with prior research. Further investigation into differences in neural processes underlying episodic memory with HL would be informative, particularly to examine if such differences are associated with future memory function.

Memory markers in the continuum of the Alzheimer’s clinical syndrome

BackgroundThe 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.MethodsHealthy 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).ResultsOnly 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.DiscussionThe 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.

Abnormal Functional Hierarchies of EEG Networks in Familial and Sporadic Prodromal Alzheimer's Disease During Visual Short-Term Memory Binding.

Alzheimer's Disease (AD) shows both complex alterations of functional dependencies between brain regions and a decreased ability to perform Visual Short-Term Memory Binding (VSTMB) tasks. Recent advances in network neuroscience toward understanding the complexity of hierarchical brain function here enables us to establish a link between these two phenomena. Here, we study data on two types of dementia at Mild Cognitive Impairment (MCI) stage-familial AD patients (E280A mutation of the presenilin-1 gene) and elderly MCI patients at high risk of sporadic AD, both with age-matched controls. We analyzed Electroencephalogram (EEG) signals recorded during the performance of Visual Short-Term Memory (VSTM) tasks by these participants. Functional connectivity was computed using the phase-lag index in Alpha and Beta; and network analysis was employed using network indices of hierarchical spread (degree variance) and complexity. Hierarchical characteristics of EEG functional connectivity networks revealed abnormal patterns in familial MCI VSTMB function and sporadic MCI VSTMB function. The middle-aged familial MCI binding network displayed a larger degree variance in lower Beta compared to healthy controls (p = 0.0051, Cohen's d = 1.0124), while the elderly sporadic MCI binding network displayed greater hierarchical complexity in Alpha (p = 0.0140, Cohen's d = 1.1627). Characteristics in healthy aging were not shown to differ. These results indicate that activity in MCI exhibits cross-frequency network reorganization characterized by increased heterogeneity of node roles in the functional hierarchy. Aging itself is not found to cause VSTM functional hierarchy differences.

Memory-driven eye movements prospectively predict dementia in people at risk of Alzheimer's disease.

Oculomotor behaviors linked to cognitive performance revealed neurocognitive features of Alzheimer's disease (AD) that can enhance the accuracy of its assessment and diagnosis. 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. 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. The analysis of eye movement behavior combined with cognitive markers for AD can effectively predict progression to ADS among patients with MCI.

Variability in Cognitive Performance on Mobile Devices Is Sensitive to Mild Cognitive Impairment: Results From the Einstein Aging Study.

Background and Objective: Within-person variability in cognitive performance has emerged as a promising indicator of cognitive health with potential to distinguish normative and pathological cognitive aging. We use a smartphone-based digital health approach with ecological momentary assessments (EMA) to examine differences in variability in performance among older adults with mild cognitive impairment (MCI) and those who were cognitively unimpaired (CU).Method: A sample of 311 systematically recruited, community-dwelling older adults from the Einstein Aging Study (Mean age = 77.46 years, SD = 4.86, Range = 70–90; 67% Female; 45% Non-Hispanic White, 40% Non-Hispanic Black) completed neuropsychological testing, neurological assessments, and self-reported questionnaires. One hundred individuals met Jak/Bondi criteria for MCI. All participants performed mobile cognitive tests of processing speed, visual short-term memory binding, and spatial working memory on a smartphone device up to six times daily for 16 days, yielding up to 96 assessments per person. We employed heterogeneous variance multilevel models using log-linear prediction of residual variance to simultaneously assess cognitive status differences in mean performance, within-day variability, and day-to-day variability. We further tested whether these differences were robust to the influence of environmental contexts under which assessments were performed.Results: Individuals with MCI exhibited greater within-day variability than those who were CU on ambulatory assessments that measure processing speed (p < 0.001) and visual short-term memory binding (p < 0.001) performance but not spatial working memory. Cognitive status differences in day-to-day variability were present only for the measure of processing speed. Associations between cognitive status and within-day variability in performance were robust to adjustment for sociodemographic and contextual variables.Conclusion: Our smartphone-based digital health approach facilitates the ambulatory assessment of cognitive performance in older adults and the capacity to differentiate individuals with MCI from those who were CU. Results suggest variability in mobile cognitive performance is sensitive to MCI and exhibits dissociative patterns by timescale and cognitive domain. Variability in processing speed and visual short-term memory binding performance may provide specific detection of MCI. The 16-day smartphone-based EMA measurement burst offers novel opportunity to leverage digital technology to measure performance variability across frequent assessments for studying cognitive health and identifying early clinical manifestations of cognitive impairment.

Brain functional connectivity during visual short‐term memory binding after cognitive training in preclinical phases of dementia

AbstractBackgroundNeuroimaging studies have shown changes in functional connectivity after cognitive training in preclinical phases of dementia. What is not yet clear is the neurophysiological aspects of these changes. Our objective was analyze the effect of cognitive training on brain functional connectivity during visual short term memory binding (VSTMB) task in preclinical phases of dementia.MethodThe final sample was composed of 5 older adults with subjective cognitive decline (mean age = 62.08, SD = 6.48) and 4 with mild cognitive impairment (mean age = 62.93, SD = 6.75). All participants underwent assessment with VSTMB test (shape only and shape‐color) while we recorded their EEG with 160‐channel system (Brain Vision ActiChamp), at baseline and 3 months after cognitive training. The program lasted 24 sessions and was focused on attention, executive function and memory domains.ResultWe found a significant improvement of visuospatial memory at behavioral level (p&lt;.05). In shape only test phase, we found a post training activity diminution in fronto‐central right ROIs, in intermediate and late time windows (FDR p &lt; .05), an enhancement in fronto‐central right ROI and early time window (FDR p &lt; .05) and parietal‐posterior left ROI in late time windows (FDR p&lt;.05). In shape‐color binding condition, significant differences were found for encoding phase presenting post training activity enhancement for fronto‐central left ROI in intermediated and late time windows (FDR p &lt; .05).ConclusionCognitive training changed functional connectivity in anterior and posterior regions during shape only test phase. During shape‐color condition there was a connectivity increased in anterior regions during encoding phase. These findings are discussed in the light of cognitive and neurophysiological aging models.

Visual short-term memory impairments in presymptomatic familial Alzheimer's disease: A longitudinal observational study

Visual short-term memory (VSTM) deficits including VSTM binding have been associated with Alzheimer's disease (AD) from preclinical to dementia stages, cross-sectionally. Yet, longitudinal investigations are lacking. The objective of this study was to evaluate VSTM function longitudinally and in relation to expected symptom onset in a cohort of familial Alzheimer's disease. Ninety-nine individuals (23 presymptomatic; 9 symptomatic and 67 controls) were included in an extension cross-sectional study and a sub-sample of 48 (23 presymptomatic carriers, 6 symptomatic and 19 controls), attending two to five visits with a median interval of 1.3 years, included in the longitudinal study. Participants completed the “What was where?” relational binding task (which measures memory for object identification, localisation and object-location binding under different conditions of memory load and delay), neuropsychology assessments and genetic testing. Compared to controls, presymptomatic carriers within 8.5 years of estimated symptom onset showed a faster rate of decline in localisation performance in long-delay conditions (4s) and in traditional neuropsychology measures of verbal episodic memory. This study represents the first longitudinal VSTM investigation and shows that changes in memory resolution may be sensitive to tracking cognitive decline in preclinical AD at least as early as changes in the more traditional verbal episodic memory tasks.

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.

Visual short-term memory relates to tau and amyloid burdens in preclinical autosomal dominant Alzheimer\u2019s disease

BackgroundOver 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.MethodsIn 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.ResultsWe 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.ConclusionsThe 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.

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.

Differential age-related effects on conjunctive and relational visual short-term memory binding

ABSTRACTAn age-related associative deficit has been described in visual short-term binding memory tasks. However, separate studies have suggested that ageing disrupts relational binding (to associate distinct items or item and context) more than conjunctive binding (to integrate features within an object). The current study directly compared relational and conjunctive binding with a short-term memory task for object–colour associations in 30 young and 30 older adults. Participants studied a number of object–colour associations corresponding to their individual object span level in a relational task in which objects were associated to colour patches and a conjunctive task where colour was integrated into the object. Memory for individual items and for associations was tested with a recognition memory test. Evidence for an age-related associative deficit was observed in the relational binding task, but not in the conjunctive binding task. This differential impact of ageing on relational and conjunctive short-term binding is discussed by reference to two underlying age-related cognitive difficulties: diminished hippocampally dependent binding and attentional resources.