Memory Binding Test Research Articles

The memory binding test in a longitudinal study of cognitive aging and preclinical disease.

The Memory Binding Test (MBT) shows promise in detecting early cognitive changes associated with Alzheimer's disease (AD). This study assesses the psychometric properties (i.e., construct and criterion validity, test-retest reliability) of the MBT and its sensitivity to incipient disease and incident cognitive impairment. One hundred forty-nine cognitively unimpaired adults ages 45-85 completed the MBT and neuropsychological tests at baseline; 132 returned for 2-year follow-up. Based on neuroradiological ratings of amyloid positron emission tomography and MRI markers at baseline, they were categorized as healthy (n = 94) or having preclinical disease (n = 55, either on the AD continuum or having non-AD pathologic change). Construct validity was assessed by the associations between MBT scores, demographics, and neuropsychological scores within the healthy group. Criterion validity was assessed by testing how MBT scores correlate with AD biomarkers, differ and discriminate between groups at baseline, and predict incident cognitive impairment. MBT scores decreased with age and were strongly associated with memory and global cognition. MBT scores were largely not associated with amyloid, hippocampal volume, or AD signature cortical volume but related to white matter lesion volume in those with preclinical disease. The preclinical groups performed worse on MBT immediate free recall at baseline than the healthy group, but no scores predicted incident cognitive impairment at follow-up. Most scores demonstrated modest test-retest reliability. This study demonstrates that the MBT has adequate construct validity in cognitively unimpaired adults, moderate sensitivity to preclinical disease cross-sectionally, and limited prognostic utility. Careful consideration of demographic influences on score interpretation remains necessary. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for The Memory Binding Test in a Longitudinal Study of Cognitive Aging and Preclinical Disease

Supplemental Material for The Memory Binding Test in a Longitudinal Study of Cognitive Aging and Preclinical Disease

Awareness of episodic memory and meta-cognitive profiles: associations with cerebrospinal fluid biomarkers at the preclinical stage of the Alzheimer's continuum.

The lack of cognitive awareness, anosognosia, is a clinical deficit in Alzheimer's disease (AD) dementia. However, an increased awareness of cognitive function, hypernosognosia, may serve as a marker in the preclinical stage. Subjective cognitive decline (SCD) might correspond to the initial symptom in the dynamic trajectory of awareness, but SCD might be absent along with low awareness of actual cognitive performance in the preclinical stage. We hypothesized that distinct meta-cognitive profiles, both hypernosognosia and anosognosia, might be identified in preclinical-AD. This research evaluated the association between cerebrospinal fluid (CSF) AD biomarkers and the awareness of episodic memory, further exploring dyadic (participant-partner) SCD reports, in the preclinical Alzheimer's continuum. We analyzed 314 cognitively unimpaired (CU) middle-aged individuals (mean age: 60, SD: 4) from the ALFA+ cohort study. Episodic memory was evaluated with the delayed recall from the Memory Binding Test (MBT). Awareness of episodic memory, meta-memory, was defined as the normalized discrepancy between objective and subjective performance. SCD was defined using self-report, and dyadic SCD profiles incorporated the study partner's report using parallel SCD-Questionnaires. The relationship between CSF Aβ42/40 and CSF p-tau181 with meta-memory was evaluated with multivariable regression models. The role of SCD and the dyadic contingency was explored with the corresponding stratified analysis. CSF Aβ42/40 was non-linearly associated with meta-memory, showing an increased awareness up to Aβ-positivity and a decreased awareness beyond this threshold. In the non-SCD subset, the non-linear association between CSF Aβ42/40 and meta-memory persisted. In the SCD subset, higher Aβ-pathology was linearly associated with increased awareness. Individuals presenting only study partner's SCD, defined as unaware decliners, exhibited higher levels of CSF p-tau181 correlated with lower meta-memory performance. These results suggested that distinct meta-cognitive profiles can be identified in preclinical-AD. While most individuals might experience an increased awareness associated with the entrance in the AD continuum, hypernosognosia, some might be already losing insight and stepping into the anosognosic trajectory. This research reinforced that an early anosognosic profile, although at increased risk of AD-related decline, might be currently overlooked considering actual diagnostic criteria, and therefore its medical attention delayed.

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 Memory Binding Test Detects Early Subtle Episodic Memory Decline in Preclinical Alzheimer's Disease: A Longitudinal Study.

The asymptomatic at-risk phase might be the optimal time-window to establish clinically meaningful endpoints in Alzheimer's disease (AD). We investigated whether, compared with the Free and Cued Selective Reminding Test (FCSRT), the Memory Binding Test (MBT) can anticipate the diagnosis of emergent subtle episodic memory (EM) deficits to an at-risk phase. Five-year longitudinal FCSRT and MBT scores from 45 individuals matched for age, education, and gender, were divided into 3 groups of 15 subjects: Aβ-/controls, Aβ+/stable, and Aβ+/progressors (preclinical-AD). The MBT adds an associative memory component (binding), particularly sensitive to subtle EM decline. In the MBT, EM decline started in the Aβ+/progressors (preclinical-AD) up to 4 years prior to diagnosis in delayed free recall (FR), followed by decline in binding-associated scores 1 year later. Conversely, in the FCSRT, EM-decline began later, up to 3 years prior to diagnosis, in the same group on both immediate and delayed versions of FR, while on total recall (TR) and intrusions decline started only 1 year prior to diagnosis. The MBT seems more sensitive than the FCSRT for early EM-decline detection, regarding the year of diagnosis and the number of scores showing AD-linked EM deficits (associated with the AD-characteristic amnesic hippocampal syndrome). Considering the MBT as a detection tool of early subtle EM-decline in an asymptomatic at-risk phase, and the FCSRT as a classification tool of stages of EM-decline from a preclinical phase, these tests ought to potentially become complementary diagnostic tools that can foster therapies to delay cognitive decline. Clinical trial registration title: Electrophysiological markers of the progression to clinical Alzheimer disease in asymptomatic at-risk individuals: a longitudinal event-related potential study of episodic memory in the INSIGHT pre-AD cohort (acronym: ePARAD).

Specific memory binding indexes and their potential to discriminate between Alzheimer´s disease biomarker‐positive and biomarker‐negative older adults with amnestic mild cognitive impairment

AbstractBackgroundThe Memory Binding Test (MBT) and Face‐Name Associative Memory Exam (FNAME‐12) are challenging tests based on relational memory binding paradigm. Recent studies support their sensitivity to subtle memory changes; however, their specificity to Alzheimer´s disease (AD) related memory deficit has not been studied. This study aimed to explore differences in MBT and FNAME‐12 scores between patients with amnestic mild cognitive impairment (aMCI) due to AD (aMCI‐AD), those with aMCI with non‐Alzheimer´s etiology (aMCI‐nonAD), and cognitively normal older adults (CN) as a control group, and to compare the potential of the challenging tests and the standard Rey Auditory Verbal Learning Test (RAVLT) to discriminate between the aMCI groups.MethodSixty‐seven Czech Brain Aging Study participants (aMCI, n = 37; CN, n = 30) underwent neuropsychological assessment (including the MBT and FNAME‐12), laboratory evaluation, and brain magnetic resonance imaging, and were further classified as aMCI‐AD (n = 18) or aMCI‐nonAD (n = 19) based on the results of amyloid positron emission tomography or AD cerebrospinal fluid biomarkers. The groups were compared using the multivariate analysis of covariance controlling for sex, age, education, and global cognition.ResultIn MBT, aMCI‐AD patients scored the lowest on the paired cued recall scores (CR) (aMCI‐AD<aMCI‐nonAD<CN, ps≤0.003). In FNAME‐12, aMCI‐AD patients scored the lowest on the CR of face‐occupation pairs (aMCI‐AD<aMCI‐nonAD<CN, ps<0.001). On the CR of face‐name pairs, both aMCI groups scored lower than CN (p<0.001); however, they did not differ from each other [p = 0.525; (aMCI‐AD = aMCI‐nonAD)<CN]. In RAVLT, aMCI‐AD patients did not differ from the aMCI‐nonAD patients, except for the delayed free recall (FR) (p<0.001). Adding the RAVLT delayed FR as covariate, the differences in the MBT and FNAME‐12 paired CR scores remained significant. To discriminate aMCI‐AD from aMCI‐nonAD, the MBT paired CR and FNAME‐12 CR of face‐occupation pairs yielded areas under the curve (AUCs) of 88% and 85%, respectively, which was comparable to RAVLT delayed FR (87%). Controlling for RAVLT, the AUCs were 91% for MBT and 88% for FNAME‐12.ConclusionOur findings support excellent discriminative ability of selected MBT and FNAME‐12 scores for AD‐related memory deficit and suggest their potential for differential diagnosis of memory deficit in older adults in addition to the standard RAVLT.

The Memory Binding Test: a new tool to assess emerging episodic memory decline in asymptomatic at‐risk individuals to Alzheimer’s disease

AbstractBackgroundEpisodic memory (EM) deficits are a hallmark of Alzheimer’s disease (AD). The Free and Cued Selective Reminding Test (FCSRT) is the most specific official diagnostic tool detecting AD‐linked EM alterations in advanced preclinical stages (Grober et al., 2021). However, new tools that anticipate diagnosis to the at‐risk phase are needed, to reach more meaningful therapies. Based on existing research, we aim to investigate the Memory Binding Test (MBT) promising capacity to detect the appearance of subtle AD‐linked EM alterations and anticipate AD‐diagnosis to an at‐risk phase (Bushcke ey al., 2017; Mowrey et al., 2018).MethodsFCSRT and MBT scores were collected yearly during 5 years from the INSIGHT‐preAD cohort. We selected 3 groups controlled for age, education level, gender, beta‐amyloid burden (AB+), and neurodegeneration status based on 15 individuals who converted to prodromal‐AD during follow‐up, as follows: converters/AB+; non‐converters/AB+; controls/AB‐. Evaluation of both list‐learning tests is mainly based on free recall (FR) and total (cued) recall (TR) scores. The FCSRT uses 1‐list of words to remember while the MBT uses 2‐lists, introducing a binding component sensitive to subtle EM alterations. Data was analysed using mixed effect models including age, gender, and education as covariates.ResultsWhen compared with the FCSRT, the MBT anticipated the detection of AD‐linked EM alterations in the converters/AB+ versus the other groups. In the MBT decline started up to 5 years prior to diagnosis, in delayed FR (mainly associated to executive dysfunction), followed by decline in 4 binding‐associated scores 1 year later (linked to storage deficits associated with the amnesic hippocampal syndrome characteristic of AD). Therefore, at an at‐risk phase, MBT outperformed FCSRT, both in the year of diagnosis and in the number of scores confirming AD‐linked EM deficits.ConclusionWe show the MBT capacity to detect the initial subtle EM alterations and to anticipate diagnosis to the at‐risk phase, while participants remain cognitively normal. We argue that the MBT (at‐risk phase detection) and the FCSRT (preclinical phase classification) could be complementary rather than concurrent tools, fostering meaningful innovative treatments to prolong quality of life in AD, a disease that remains without a cure.

Comparison between verbal and visual working memory in subjects with frontotemporal dementia and Alzheimer’s participating in the Redlat study

AbstractBackgroundAlterations in working memory have been reported in people with Alzheimer’s disease and frontotemporal degeneration, and have been associated with executive impairment related to the frontal areas of the brain.MethodThe objective of this work is to compare the capacity of verbal and visual working memory in a sample of 70 Colombian people with dementia (32 with Alzheimer’s Dementia and 30 with Frontotemporal Dementia and 22 healthy controls) participating in the RedLat study. For this, the performance in a digit retention task and the Short Term Memory Binding Test (STMB) are studied.ResultIn general, there is a decrease in the performance of the two groups of patients (AD and FTD). Also AD patients shows worst performance at visual working memory tasks. Results shows differences between dementia groups and controls, but not between AD and FTD.ConclusionThis converges with what has been reported about the dissociation between verbal and visual working memory, and could suggest alternative strategies for the recall of immediate information. Additionally, both low performances are explained by differents reasons in each neurodegenerative disorder.

First Steps Toward the French Validation of the Memory Binding Test (fMBT): Adaptation, Convergent Validity and Application to Normal Aging

Le test d’intégration mnésique (TIM) permet de repérer les atteintes débutantes de la mémoire. La nouveauté du test est de cibler l’intégration mnésique, processus précocement altéré dans la forme prodromale de la maladie d’Alzheimer. L’objectif de cette étude est d’adapter et valider en français ce test (fMBT) et d’explorer les effets de l’âge (16 jeunes adultes et 14 personnes âgées). Le fMBT présente une bonne à excellente validité convergente avec le RL/RI-16. La performance des jeunes adultes est supérieure à celle des personnes âgées pour presque tous les indices du fMBT. Le test est aussi sensible et spécifique que le RL/RI-16 pour distinguer les personnes âgées des jeunes adultes, mais le fMBT a l’avantage de ne pas produire d’effet plafond. Ce test pourrait donc servir à évaluer la mémoire d’adultes jeunes. Cette étude offre ainsi les premières étapes de la validation du fMBT. Il reste à déterminer si le fMBT permet bien de détecter des troubles subtiles de la mémoire.

Characteristics and Potential Neural Substrates of Encoding and Retrieval During Memory Binding in Amnestic Mild Cognitive Impairment.

Whether encoding or retrieval failure contributes to memory binding deficit in amnestic mild cognitive impairment (aMCI) has not been elucidated. Also, the potential brain structural substrates of memory binding remained undiscovered. To investigate the characteristics and brain atrophy pattern of encoding and retrieval performance during memory binding in aMCI. Forty-three individuals with aMCI and 37 cognitively normal controls were recruited. The Memory Binding Test (MBT) was used to measure memory binding performance. The immediate and delayed memory binding indices were computed by using the free and cued paired recall scores. Partial correlation analysis was performed to map the relationship between regional gray matter volume and memory binding performance. The memory binding performance in the learning and retrieval phases was worse in the aMCI group than in the control group (F = 22.33 to 52.16, all p < 0.001). The immediate and delayed memory binding index in the aMCI group was lower than that in the control group (p < 0.05). The gray matter volume of the left inferior temporal gyrus was positively correlated with memory binding test scores (r = 0.49 to 0.61, p < 0.05) as well as the immediate (r = 0.39, p < 0.05) and delayed memory binding index (r = 0.42, p < 0.05) in the aMCI group. aMCI may be primarily characterized by a deficit in encoding phase during the controlled learning process. Volumetric losses in the left inferior temporal gyrus may contribute to encoding failure.

Multimodal, scalable and affordable neurocognitive biomarkers

AbstractBackgroundAlzheimer’s disease (AD) biomarkers targeting Aβ, Tau, and Neurodegeneration are creating unprecedented opportunities for its early detection. Adhering to the A/T/N biomarker framework though comes with several challenges, mainly due to high costs. The Joint Program for Neurodegenerative Diseases (JPND) suggested that efforts should also be directed to harmonise promising cognitive tests. The group recommended the Short‐Term Memory Binding (STMB) and Selective Reminding Tests (SRT). To that aim, we need to explore if such memory markers hold differential sensitivity to the AD continuum (Aim1). Whether such deficits are observable in preclinical and prodromal stages of AD regardless of the disease variants (sporadic and familial) is also unclear (Aim2). Moreover, whether combining these cognitive makers with EEG and Eye‐Tracking (ET) would yield neurocognitive biomarkers for AD (Aim3) needs further research.MethodsMemory tests recommended by the JPND and standard neuropsychological assessments entered harmonised research protocols supporting three large international collaborations. Aim1: Project 1 (UK based) involved 150 participants (HC=70, MCI=80) and Project 2, ran in collaboration with GERO, Chile, involved 264 participants (HC=37, SCC=117, MCI=79, ADD=31). Aim2: Project 3: ran in collaboration with the Neuroscience Group, University of Antioquia, Colombia involved 334 participants (HC=210, AC=124). Aim3: The STMBT combined with EEG was recorded from 20 participants and combined with Eye‐tracking from 71 participants all from Project 3.ResultsAim1: STMB deficits are detectable from the very early stages of AD (HC&gt;SCC&gt;(MCI=ADD)) before associative memory deficits (SRT) become apparent ((HC=SCC)&gt;MCI&gt;ADD). Aim2: Such deficits are also prominent in AC when their associative memory abilities remain intact. Aim3: When combined with EEG, STMB differentiated AC from HC with 89% accuracy while with ET classification accuracy reached 98%.ConclusionThe collaborative efforts here presented suggest that AD can be detected with appropriate, affordable, culture‐free and scalable neurocognitive biomarkers recently recommended by the JPND before clinical manifestations of the disease become apparent.GlossaryAC = Asymptomatic Carriers of the mutation E280A‐PSEN1; ADD = Alzheimer’s disease Dementia; GERO = The Geroscience Center for Brain Health and Metabolism; HC = Healthy Controls; MCI = Mild Cognitive Impairment; SCC = Subjective Cognitive Complaint; STMBT: Short‐Term Memory Binding Test.

Overestimation of performance after a memory task in cognitively unimpaired individuals is related to lower cortical thickness in Alzheimer’s disease vulnerable regions and to executive decline, particularly in men.

AbstractBackgroundLow awareness of cognitive decline is a common feature in Alzheimer’s disease (AD) dementia, and it relates to higher risk of progression in individuals with Mild Cognitive Impairment. Previous research suggests that, in cognitively unimpaired individuals, it has prognostic value and is related to AD biomarkers. We aimed at exploring the associations between the ability to judge performance after a memory task and demographic, clinical (cognitive complaints), structural neuroimaging, cognitive and amyloid status variables in cognitively unimpaired individuals.MethodsWe analyzed data from 225 ALFA+ study participants (mean[SD] age = 68.9[4.9], 63.6% female). We defined a discrepancy score between objective and subjective memory measures by subtracting the self‐ratings of performance in the delayed recall of the Memory Binding Test (range 0–100) from the percentage of words actually recalled. Structural MRI (AD signature cortical thickness), amyloid (PET visual read), and Subjective Cognitive Decline (SCD) status measures were available. We classified individuals as decliners vs non decliners (change &gt;‐0.5 z‐score after 3 years) using executive and memory composites. Linear models with the discrepancy score as dependent variable and age, sex, education, AD signature, amyloid and SCD status as predictors, and with decline/non decline in executive and memory composites as predictors, were constructed.ResultsMales overestimate their memory performance more than females (p = 0.003, Figure 1). Lower cortical thickness in the AD signature was also related to overestimation (p = 0.035, Table 1). Age, education, amyloid and SCD were not significant predictors and did not interact with sex or AD signature. Decline in the executive composite was related to overestimation of performance (p = 0.048), being this association driven by men (men p = 0.032, women p = 0.403, Figure 2). We did not find associations with decline in memory performance.ConclusionsOur results suggest that, in cognitively unimpaired individuals, the overestimation of objective memory performance relates to lower cortical thickness in AD vulnerable regions and to a subtle decline in executive abilities. Men seem to overestimate their ability more than women, particularly those that have decline in executive scores. Future research to define the value of altered self‐judgment of cognitive ability in presymptomatic stages of AD and its relationship with SCD is granted.

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.

Characterization of memory profile in idiopathic REM sleep behavior disorder

ABSTRACT Objective The present study aims to examine whether declarative memory dysfunction relates to impaired core memory mechanisms or attentional and executive dysfunction in idiopathic REM Sleep Behavior Disorder (iRBD). Method In this observational, cross-sectional study, were enrolled 82 individuals with the diagnosis of iRBD according to the International Classification of Sleep Disorders and 49-matched healthy controls fulfilling inclusion criteria. All participants underwent two memory tasks, namely the Rey Auditory Verbal Learning Test (RAVLT) and Memory Binding Test (MBT), which include conditions of varying degrees of dependence on executive functioning, as well as different indicators of core memory processes (e.g., learning, retention, relational binding). Results We used Bayesian multivariate generalized linear model analysis to evaluate the effect of iRBD on memory performance controlled for effects of age and sex. Individuals with iRBD displayed worse memory performance in the delayed free recall task (b = −0.37, 95% PPI [−0.69, −0.05]), but not on delayed recognition of the same material. Their performance in cued recall tasks both in immediate and delayed conditions was in comparison to controls relatively spared. Moreover, the deficit in delayed free recall was mediated by attention/processing speed. Conclusions In iRBD, we replicated findings of reduced free recall based on inefficient retrieval (retrieval deficit), which was small in terms of effect size. Importantly, the memory profile across measures does not support the presence of core memory dysfunction, such as poor learning, retention or associative binding.

Subjective Cognitive Decline Is More Accurate When Metamemory Is Better.

ObjectiveSubjective cognitive decline (SCD) has emerged as one of the first manifestations of Alzheimer’s disease (AD). However, discrepancies in its relationship with tests of memory and other cognitive abilities have hindered SCD’s diagnostic utility. Inter-individual heterogeneity in metamemory, or memory awareness, and the use of clinical measures of cognition lacking sensitivity to early cognitive dysfunction, may contribute to these discrepancies. We aimed to assess if the relationship between SCD and markers of early cognitive dysfunction is moderated by metamemory abilities.MethodsThe sample included 79 cognitively healthy older adults (77% female, 68% White, and 32% Black participants) with a mean age of 74.4 (SD = 6.1) and 15.9 (SD = 2.7) years of education. Metamemory was assessed using an episodic Feeling of Knowing test with four 5-item trials. Outcome measures included a resolution metric defined as a gamma correlation reflecting the accuracy of item-level predictions (“Will you know the correct answer?”). Early cognitive dysfunction was measured through the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L) and the Short-Term Memory Binding Test (STMB), measures sensitive to preclinical AD. SCD was assessed with a 20-item questionnaire that asked participants to compare themselves to others their age on a 7-point Likert scale. Regression analyses examined whether a potential relation between SCD and early cognitive dysfunction was moderated by metamemory.ResultsSubjective cognitive decline was associated with susceptibility to semantic proactive interference such that greater complaints were associated with increased susceptibility to semantic proactive interference (b = −0.30, p = 0.003) only. Metamemory moderated the association between SCD and susceptibility to and recovery of semantic proactive interference such that those with more accurate metamemory showed a stronger association between increased complaints and susceptibility to semantic proactive interference (b = −0.71, p = 0.005; b = −0.62, p = 0.034). Metamemory, however, did not moderate the association of SCD with retroactive semantic interference nor short term memory binding.DiscussionThe accuracy of an individual’s metamemory, specifically their ability to adjust moment to moment predictions in line with their performance, can influence the extent to which SCD maps onto objective cognition. Such self-referential assessment should be considered when interpreting SCD.

Memory Binding Test and Its Associations With Hippocampal Volume Across the Cognitive Continuum Preceding Dementia.

Innovative memory paradigms have been introduced to capture subtle memory changes in early Alzheimer's disease (AD). We aimed to examine the associations between different indexes of the challenging Memory Binding Test (MBT) and hippocampal volume (HV) in a sample of individuals with subjective cognitive decline (SCD; n = 50), amnestic mild cognitive impairment (aMCI) due to AD (n = 31), and cognitively normal (CN) older adults (n = 29) recruited from the Czech Brain Aging Study, in contrast to traditional verbal memory tests. Both MBT free and cued recall scores in immediate and delayed recall conditions were associated with lower HV in both SCD and aMCI due to AD, whereas in traditional verbal memory tests only delayed recall scores were associated with lower HV. In SCD, the associations with lower HV in the immediate recall covered specific cued recall indexes only. In conclusion, the MBT is a promising test for detecting subtle hippocampal-associated memory decline during the predementia continuum.

Older Adults Performed Worse on Cognitive Assessment at Lonelier Moments: Using Ambulatory Assessment Approach

This study focused on investigating the short-term effect of loneliness on older adults’ cognitive performances in daily life. Loneliness is suggested as a risk factor for cognitive health, but results in previous studies are inconsistent due to the lack of valid measures and limited research design. The attention-depletion hypothesis highlights that acute stress could immediately compromise cognitive ability by consuming attentional resources. Accordingly, this study examined whether loneliness, as one of the stressors related to one’s social relationship, was immediately associated with worse daily cognitive performances in older adults. Using an ecological momentary assessment approach, 311 community-dwelling older adults (Mage=77.5 (range=70-90), 67% female, 45% white) reported their level of loneliness as well as performed cognitive assessment five times a day for 16 days. Multilevel modeling showed that on occasion when participants reported a higher level of loneliness than normal, they performed worse in the processing speed test (p<.01) and the short-term memory binding test (p<.01) during those moments, controlling for age, gender, education, ethnicity, IADL, and retest-practice effect. Moreover, those momentary associations between loneliness and cognitive performances remained significant after controlling for the momentary level of feeling depressed. Unlike the concurrent effect, there was no lagged effect of loneliness on daily cognitive performances. These results suggest that transient but intense feelings of loneliness can function as acute stress and thus, compromise daily cognitive functioning short-term. Results will be discussed in terms of the potential benefit of momentary real-time interventions to lessen feelings of loneliness to maintain older adults’ cognitive functioning.

Memory assessment and dementia risk in the PREVENT Study

AbstractBackgroundPromising memory markers for Alzheimer´s dementia (AD) tap into either relational (face‐name) or conjunctive (object‐colour) functions (Rentz et al., 2013). Whereas relational functions appear affected in the early symptomatic stages of AD, conjunctive functions have been found impaired in the pre‐symptomatic stages. Relational but not conjunctive functions are age sensitive. This can delay the detection of AD‐related impairments. No study to date has traced the progression or memory decline in people at risk of AD using these markers. This is an aim of the PREVENT study.MethodsA cohort of 183 healthy adults with age ranging from 40‐60 years (M: 52) underwent assessment at baseline and two‐year follow up (T1). The assessment consisted of the neuropsychological test battery COGNITO (Ritchie et al., 2017), a demographic questionnaire, and four memory tests (relational: Virtual Reality Supermarket Trolley Task (VRST), Name‐Face Association Test (NFAT), and 4 Mountain Test (4MT), and conjunctive: Visual Short‐Term Memory Binding Test (VSTMBT)). Participants also underwent genetic testing to identify APOE genotypes. Risk profiles were defined by the present of Family History and APOE4, with High Risk subjects being positive to both, Middle Risk to either, and Low Risk to neither. Cross‐sectional and longitudinal comparisons were carried out within and across risk groups.ResultsNeither cross‐sectional nor longitudinal comparisons revealed differences across risk groups on the memory markers. Only the NFAT significantly correlated with age (p&lt;0.01). The VRST and VSTMBT were not associated to the level of education while the NFAT and 4MT were (p&lt;0.05). Correlations between baseline and T1 were large for all the tests. Performance on the VSTMBT did not correlate with that on any relational memory tasks. The VSRT and 4MT did reveal significant correlations (p&lt;0.001).ConclusionWe have identified an early time window in the ageing continuum where people at risk of dementia show intact cognitive functions known to be markers of AD. We have replicated the previously reported patterns of sensitivity to demographic variables (age and education) and confirmed their potential to dissociate trajectories of memory decline across constructs and risk profiles.

Memory markers can help trace the Alzheimer’s disease continuum: Evidence from the GERO Cohort

AbstractBackgroundCognitive assessments able to detect impairments as early as neuropathological changes that occur in neurodegenerative diseases initiate are urgently needed. The Visual Short‐Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCRST) have been recently recommended by the Neurodegenerative Diseases Working Group (Costa et al., 2017) as promising preclinical markers of AD. They have never been used before to assess elderlies with cognitive complain recruited from the community.MethodA total of 271 subjects (37 healthy controls (HC), 112 subjective cognitive complain (SCC), 96 mild cognitive impairment (MCI) and 26 Alzheimer’s disease dementia (ADD)), recruited from Geroscience Center for Brain Health and Metabolism (GERO) Cohort and the Memory and Neuropsychiatric Clinic (CMYN), underwent assessment with the VSTMBT and the Visual Version of the FCRST (FCRST‐Visual). Two memory loads were used for the VSTMBT (low and high). The ability of these tests to discriminate between groups.ResultSignificant differences were found between HC, MCI and ADD using the VSTMBT and the FCRST‐Visual version. Notably, the STMB was the only test that “marginally” differentiated between HC from SCC (p = 0.055). Moreover, whereas the FCRST‐Visual showed a gradient (HC = SCC) &gt; MCI &gt; AD, the VSTMBT’s gradient was HC &gt; (SCC = MCI = ADD) suggesting that the function assessed by the latter test may be sensitive to the very early stages of the disease dropping to levels that cannot decline further.ConclusionOur results suggest that the VSTMBT and FCSRT are sensitive to the early stages of dementia. Whereas the former detects changes in the early subjective stages, the latter is more sensitive to later objective stages of cognitive decline. The latter but not the former could help monitor disease progression. These results raise important questions about the usefulness of cognitive screening tools to detect and monitor disease progression and to separate normal and abnormal ageing trajectories. We propose the need of cognitive assessments that detect subtle differences as early as neuropathological changes occur in the brain, which will lead to the development of new “cognitive biomarkers” for dementia.

Oculomotor Behaviors and Integrative Memory Functions in the Alzheimer's Clinical Syndrome.

Biological information drawn from eye-tracking metrics is providing evidence regarding drivers of cognitive decline in Alzheimer's disease. In particular, pupil size has proved useful to investigate cognitive performance during online activities. To investigate the oculomotor correlates of impaired performance of patients with mild Alzheimer's Clinical Syndrome (ACS) on a recently developed memory paradigm, namely the Short-Term Memory Binding Test (STMBT). We assessed a sample of eighteen healthy controls (HC) and eighteen patients with a diagnosis of mild ACS with the STMBT while we recorded their oculomotor behaviors using pupillometry and eye-tracking. As expected, a group (healthy controls versus ACS) by condition (Unbound Colours versus Bound Colours) interaction was found whereby behavioral group differences were paramount in the Bound Colours condition. Healthy controls' pupils dilated significantly more in the Bound Colours than in the Unbound Colours condition, a discrepancy not observed in ACS patients. Furthermore, ROC analysis revealed the abnormal pupil behaviors distinguished ACS patients from healthy controls with values of sensitivity and specify of 100%, thus outperforming both recognition scores and gaze duration. The biological correlates of Short-Term Memory Binding impairments appear to involve a network much wider than we have thought to date, which expands across cortical and subcortical structures. We discuss these findings focusing on their implications for our understanding of neurocognitive phenotypes in the preclinical stages of Alzheimer's disease and potential development of cognitive biomarkers that can support ongoing initiatives to prevent dementia.