Wang et al. analyze Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment accuracy as screening tests for detecting dementia associated with Alzheimer's disease (AD). Such tests are at the center of controversy regarding recognition and treatment of AD. The continued widespread use of tools such as MMSE (1975) underscores the failure of advancing cognitive screening and assessment, which has hampered the development and evaluation of AD treatments. It is time to employ readily available, efficient computerized measures for population/mass screening, clinical assessment of dementia progression, and accurate determination of approaches for prevention and treatment of AD and related conditions.

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.

The Memory Binding Test (MBT) Version 1 demonstrated good discriminative validity for distinguishing persons with dementia and amnestic mild cognitive impairment (aMCI) from cognitively normal elder controls (CN). Version 2 of the MBT test was developed to improve brevity, which is essential for screening. We aimed to compare these two versions in terms of cross‐sectional discriminative validity to distinguish A. aMCI vs. CN, B. aMCI and dementia vs. CN, and C. dementia vs. CN and aMCI.

AbstractBackgroundThe Memory Binding Test (MBT) Version 1 demonstrated significant predictive validity for incident amnestic MCI (aMCI) and incident dementia. Version 2 of the MBT was developed to be briefer because brevity is essential for screening. Herein we aimed to compare the two versions in terms of predictive validity for aMCI and dementia, separately.MethodAs sub‐studies of the Einstein Aging Study (EAS), the two MBT versions were administered to two independent study samples between May 2003 and December 2007 at baseline, and these participants were followed up to Jan 2017 (For differences in versions see Table 1). The EAS enrolls a systematically recruited community sample of adults age over 70. The two versions were evaluated in parallel using the same methodologies. We evaluated a range of cut‐scores on the MBT score of choice, the Total Items in the Paired condition (TIP), including the empirical optimal cut‐score which maximized the sum of sensitivity and specificity from the cross‐sectional discriminative analyses. The predictive validity was assessed by Kaplan‐Meier curves, log‐rank tests and Cox regressions.ResultPredicting incident aMCI: Both versions were strong predictors of incident aMCI (Table 2): For the empirical optimal scores for TIP, hazard ratio (HR)=2.33, 95% CI: (1.26, 4.29), p=.007 for Version 1, HR=3.38, 95% CI: (1.09, 10.5), p=0.04 for Version 2; for a range of TIP scores (17−22): HR range: 2.27−6.07, p ≤ .01, for Version 1, and 2.67−5.91, p≤.04 for Version 2. Predicting incident dementia: Both versions were strong predictors of incident dementia (Table 3): For the empirical optimal scores for TIP, HR=8.32, 95% CI: (3.51, 19.7), p<.0001 for Version 1, HR=9.30, 95% CI: (3.43, 25.2), p<.0001 for Version 2; for a range of TIP scores (17−23): HR range: 3.09−8.32, p ≤ .003, for Version 1, and 6.40−9.30, p<.0001 for Version 2.ConclusionThe predictive validity for incident aMCI and incident dementia was strong and similar for the two versions of the MBT based on the overlapping confidence intervals. These results strongly support the hypothesis that poor performance on memory binding is an important marker for the early detection of aMCI and dementia.

Objective: Our study explored the retrieval deficit and the associative deficit hypotheses of memory impairments in Parkinson's disease (PD). The former supports a memory deficit mediated by attention/executive dysfunctions, whereas the latter hypothesizes a hippocampal memory impairment in PD. Method: We studied 31 controls and 34 PD patients classified as PD with normal cognition (PD-NC; n = 18) and PD with mild cognitive impairment (PD-MCI; n = 16). To test the retrieval deficit hypothesis, we measured the performance in encoding, retention, and recognition in verbal and visual domains; to test the associative deficit hypothesis, we used a specific associative binding measure. Using resting-state functional-MRI, we compared the functional connectivity of different hippocampal subfields between PD patients and controls, and we related it to memory performance. Results: Consistently with the retrieval deficit hypothesis, PD-MCI, and PD-NC, were impaired in free recall encoding and retention in comparison to controls, especially in the visual domain. However, as predicted by the associative deficit hypothesis, PD-MCI and, to a lesser extent, PD-NC, showed also significant associative and binding deficits in cued recall. Notably, PD patients compared to controls did not show structural differences, although they had lower connectivity between the anterior hippocampi and the precuneus/superior parietal cortex. Worse performance in memory was associated with a more severe disruption of the hippocampal connectivity. Conclusions: The pervasive pattern of memory impairment in PD supports both hypotheses. The interplay between the hippocampus, related to associative memory deficits, and the precuneus, related to attentional control, provides a neural signature that reconciles them.

BACKGROUND:The Memory Binding Test (MBT) demonstrated good cross-sectional discriminative validity and predicted incident aMCI.OBJECTIVE:To assess whether the MBT predicts incident dementia better than a conventional list learning test in a longitudinal community-based study.METHODS:As a sub-study in the Einstein Aging Study, 309 participants age≥70 initially free of dementia were administered the MBT and followed annually for incident dementia for up to 13 years. Based on previous work, poor memory binding was defined using an optimal empirical cut-score of≤17 on the binding measure of the MBT, Total Items in the Paired condition (TIP). Cox proportional hazards models were used to assess predictive validity adjusting for covariates. We compared the predictive validity of MBT TIP to that of the free and cued selective reminding test free recall score (FCSRT-FR; cut-score:≤24) and the single list recall measure of the MBT, Cued Recalled from List 1 (CR-L1; cut-score:≤12).RESULTS:Thirty-five of 309 participants developed incident dementia. When assessing each test alone, the hazard ratio (HR) for dementia was significant for MBT TIP (HR = 8.58, 95% CI: (3.58, 20.58), p < 0.0001), FCSRT-FR (HR = 4.19, 95% CI: (1.94, 9.04), p = 0.0003) and MBT CR-L1 (HR = 2.91, 95% CI: (1.37, 6.18), p = 0.006). MBT TIP remained a significant predictor of dementia (p = 0.0002) when adjusting for FCSRT-FR or CR-L1.CONCLUSIONS:Older adults with poor memory binding as measured by the MBT TIP were at increased risk for incident dementia. This measure outperforms conventional episodic memory measures of free and cued recall, supporting the memory binding hypothesis.

Cognitive change associated with Alzheimer's disease begins many years before a clinical diagnosis. Utilizing methods that can detect subtle cognitive change, as yet undetected by traditional methods, may aid in discriminating those who later develop mild cognitive impairment (MCI). The Cued-Recall Retrieval Speed Task (CRRST) is a novel computerized list-learning task that measures retrieval speed in response to category cues and has been used to differentiate between cognitively impaired and non-impaired older adults. Our goal was to investigate the CRRST for its prognostic ability to detect MCI in a group of cognitively healthy older adults. At baseline, 499 cognitively healthy participants of the longitudinal community-based Einstein Aging Study of individuals aged 70 and older were administered a comprehensive neuropsychological battery and the CRRST separately. Our variable of interest was the CRRST retrieval speed measured in milliseconds (ms). MCI status was evaluated at baseline and at yearly follow-up assessments. Diagnosis of MCI followed the revised Petersen criteria. Cox proportional hazards models were used to evaluate the effect of CRRST on risk of MCI. Time-dependent receiver operating characteristics(ROC) analysis was used to assess the accuracy of diagnosis of MCI incidence of the CRRST. At follow-up, 155 participants developed MCI. For every 300ms increase in the mean retrieval speed and 60ms increase in the variation (standard error), the risk of MCI incidence increased by 40% and 23%, respectively. Areas under the ROC curves (AUC) using CRRST retrieval speed for diagnosing MCI at 2, 3 and 4 years of follow-up were 0.687 (CI=0.614, 0.760), 0.718 (CI=0.654, 0.783) and 0.772 (CI=0.717, 0.827), respectively. Retrieval speed may be a useful indicator of future MCI. At baseline, CRRST retrieval speed is sensitive to subtle cognitive changes that are present years prior to a clinical diagnosis of MCI. Retrieval speed, as measured by the CRRST, may be able to identify individuals at high-risk for future MCI and should be explored further to understand what underlying neural processes may be responsible for these alterations in speed of performance.

Predicting the onset of cognitive impairment is an important approach to improving the early detection of Alzheimer's disease. Research has shown that reduced speed of performance may be a sensitive early indicator of cognitive impairment. Most memory tests, like the Free and Cued Selective Reminding Test (FCSRT), examine level of performance but not speed. The Cued-Recall Retrieval Speed Task (CRRST) is a novel computerized list-learning task that measures retrieval speed in response to category cues and level of performance. Our goal was to assess the separate and joint effects of level of performance and retrieval speed in predicting incident cognitive impairment. At baseline, 393 cognitively healthy participants of the longitudinal community-based Einstein Aging Study of individuals aged 70 and older, were administered the FCSRT and the CRRST as part of a comprehensive neuropsychological battery. Our variables of interest were the FCSRT level of performance and the CRRST retrieval speed and level of performance. Cognitive status was determined using the Clinical Dementia Rating (CDR) scale, where 0 indicated cognitively healthy and greater than 0 indicated cognitive impairment. Cognitive status was evaluated at baseline and at yearly follow-up assessments. At follow-up, 170 participants developed cognitive impairment. Time-dependent receiver operating characteristics (ROC) analysis assessed the prognostic ability of the FCSRT and CRRST separately and jointly for cognitive impairment. Areas under the ROC curves (AUC) were calculated at 3, 4 and 5 year time points. Comparisons of the AUC of the ROC curves revealed FCSRT alone did not differ from CRRST alone (p>0.05) at any time point. FCSRT and CRRST examined jointly significantly differed from FCSRT alone at 3 (p=0.04), 4 (p=0.05) and 5 years (p=0.02); but not from CRRST alone (p>0.05). Examining CRRST retrieval speed and level of performance jointly with FCSRT level of performance improved prediction of future cognitive impairment over FCSRT level of performance alone. The addition of speed of performance may account for the additional variance explained in the prediction models and may be a symptom of underlying brain function leading to early cognitive impairment.

The availability and increasing popularity of direct-to-consumer genetic testing for the presence of an APOE4 allelle led the Alzheimer's Foundation of America Medical, Scientific and Memory Screening Advisory Board to identify three critical areas for attention: 1) ensure consumer understanding of test results; 2) address and limit potential negative consequences of acquiring this information; and 3) support linking results with positive health behaviors, including potential clinical trial participation. Improving access to appropriate sources of genetic counseling as part of the testing process is critical and requires action from clinicians and the genetic testing industry. Standardizing information and resources across the industry should start now, with the input of consumers and experts in genetic risk and health information disclosure. Direct-to-consumer testing companies and clinicians should assist consumers by facilitating consultation with genetic counselors and facilitating pursuit of accurate information about testing.

Objective We aimed to assess reliability and cross-sectional discriminative validity of the Memory Binding Test (MBT) to distinguish persons with amnestic cognitive impairment (aMCI) and dementia from cognitively normal elderly controls. Method The MBT was administered to 20 participants with dementia, 31 with aMCI and 246 controls, who received the first administration of the MBT from May 2003 to December 2007, as a substudy of the community-based Einstein Aging Study (age range: 70+). The optimal index resulted from comparing the partial area under the receiver operating characteristic curves (ROC AUC) of four major MBT indices for specificities ≥0.70. Optimal cut-score of the optimal index was selected by maximizing the sum of sensitivity and specificity. Age and education effects were assessed using stratified cut-scores and adjusted logistic regression. Reliability was computed as intraclass correlation between scores at baseline and 1-year follow-up for participants who remained cognitively normal. Results Total number of Items recalled in the Paired condition (TIP) was elected the optimal index. TIP cut-score was ⩽22 for differentiating aMCI alone (sensitivity = 0.74, specificity = 0.73) and aMCI and dementia combined (sensitivity = 0.84, specificity = 0.73) from controls. It was ⩽17 for differentiating dementia from aMCI and controls (sensitivity = 0.95, specificity = 0.87). Age and education adjustments did not materially improve discriminative validity. The reliability of TIP was 0.77. Conclusions MBT achieved moderate to good reliability. TIP had superior cross-sectional discriminative validity than the other MBT indices. We recommend using the empirical cut-score of TIP ⩽22 for discriminating aMCI and dementia and ⩽17 for discriminating dementia alone.

In spite of advances in neuroimaging and other brain biomarkers to assess preclinical Alzheimer's disease (AD), cognitive assessment has relied on traditional memory paradigms developed well over six decades ago. This has led to a growing concern about their effectiveness in the early diagnosis of AD which is essential to develop preventive and early targeted interventions before the occurrence of multisystem brain degeneration. We describe the development of novel tests that are more cognitively challenging, minimize variability in learning strategies, enhance initial acquisition and retrieval using cues, and exploit vulnerabilities in persons with incipient AD such as the susceptibility to proactive semantic interference, and failure to recover from proactive semantic interference. The advantages of various novel memory assessment paradigms are examined as well as how they compare with traditional neuropsychological assessments of memory. Finally, future directions for the development of more effective assessment paradigms are suggested.

BACKGROUND:The Memory Binding Test (MBT), previously known as Memory Capacity Test, has demonstrated discriminative validity for distinguishing persons with amnestic mild cognitive impairment (aMCI) and dementia from cognitively normal elderly.OBJECTIVE:We aimed to assess the predictive validity of the MBT for incident aMCI.METHODS:In a longitudinal, community-based study of adults aged 70+, we administered the MBT to 246 cognitively normal elderly adults at baseline and followed them annually. Based on previous work, a subtle reduction in memory binding at baseline was defined by a Total Items in the Paired (TIP) condition score of ≤22 on the MBT. Cox proportional hazards models were used to assess the predictive validity of the MBT for incident aMCI accounting for the effects of covariates. The hazard ratio of incident aMCI was also assessed for different prediction time windows ranging from 4 to 7 years of follow-up, separately.RESULTS:Among 246 controls who were cognitively normal at baseline, 48 developed incident aMCI during follow-up. A baseline MBT reduction was associated with an increased risk for developing incident aMCI (hazard ratio (HR) = 2.44, 95% confidence interval: 1.30-4.56, p = 0.005). When varying the prediction window from 4-7 years, the MBT reduction remained significant for predicting incident aMCI (HR range: 2.33-3.12, p: 0.0007-0.04).CONCLUSION:Persons with poor performance on the MBT are at significantly greater risk for developing incident aMCI. High hazard ratios up to seven years of follow-up suggest that the MBT is sensitive to early disease.

ABSTRACT Background: "Forgetfulness" is frequent in normal aging and characteristic of the early stages of dementia syndromes. The episodic memory test is central for detecting amnestic mild cognitive impairment (MCI). The Memory Binding Test (MBT) is a simple, easy and brief memory test to detect the early stage of episodic memory impairment. Objective: To validate the Argentine version of the MBT in a Latin American population and to estimate the diagnostic accuracy as a tool for early detection of MCI. Methods: 88 subjects (46 healthy controls and 42 patients with amnestic MCI) matched for age and educational level were evaluated by an extensive neuropsychological battery and the memory binding test. Results: A significantly better performance was detected in the control group; all MBT scales were predictive of MCI diagnosis (p<.01). The MBT showed high sensitivity (69%) and high specificity (88%), with a PPV of 93% and a NPV of 55% for associative paired recall. A statistically significant difference (c2=14,164, p<.001) was obtained when comparing the area under the curve (AUC) of the MBT (0.88) and the MMSE (0.70). Conclusion: The Argentine version of the MBT correlated significantly with the MMSE and the memory battery and is a useful tool in the detection of MCI. The operating characteristics of the MBT are well suited, surpassing other tests commonly used for detecting MCI.

Background:Episodic memory testing is fundamental for the diagnosis of Alzheimer's disease (AD). Although the Free and Cued Selective Reminding Test (FCSRT) is widely used for this purpose, it may not be sensitive enough for early detection of subtle decline in preclinical AD. The Memory Binding Te st (MBT) intends to overcome this limitation. Objectives:To analyze the test-retest reliability of the MBT and its convergent validity with the FCRST. Methods:36 cognitively healthy participants of the ALFA Study, aged 45 to 65, were included for the test-retest study and 69 for the convergent analysis. They were visited twice in a period of 6 ± 2 weeks. Test-retest reliability was determined by the calculation of the intra-class correlation coefficient (ICC). Score differences were studied by computing the mean percentage of score variation between visits and visualized by Bland-Altman plots. Convergent validity was determined by Pearson's correlations. Results:ICC values in the test-retest reliability analysis of the MBT direct scores ranged from 0.64 to 0.76. Subjects showed consistent practice effects, with mean amounts of score increasing between 10% and 26%. Pearson correlation between MBT and FCSRT direct scores showed r values between 0.40 and 0.53. The FCSRT displayed ceiling effects not observed in the MBT. Conclusions:The MBT shows adequate test-retest reliability and overall moderate convergent validity with the FCSRT. Unlike the FCSRT, the MBT does not have ceiling effects and it may therefore be especially useful in longitudinal studies, facilitating the measurement of subtle memory performance decline and the detection of very early AD.

Background: The Memory Binding Test (MBT) is emerging as a promising tool for the detection of subtle memory impairment suggestive of Alzheimer’s disease (AD). For such a test to be widely accessed and used, the availability of both alternate forms and language adaptations is required. Objectives: To develop a thorough methodology for obtaining alternate forms (A and B) of the MBT in Spanish and Catalan and to assess their equivalence. Method: According to the original development of the test, frequency was taken as the lexical variable of reference for the Spanish and Catalan adaptations. A crossed design protocol by form and language was used to compare the MBT results in a sample of 290 cognitively normal middle-aged participants. Pairwise Intraclass Correlation Coefficients (ICCs) were calculated among the six possible combinations. Results: The Spanish and Catalan lists of words for the MBT A and B resulting from the adaptation process as well as the original lists in English are presented. ICC indices for the comparisons between forms and languages ranged from 0.56 to 0.82. Conclusion: The MBT A and B in Spanish and Catalan showed similar outcomes and can be considered equivalent. Moreover, the thorough methodology presented here for the transcultural adaptation and equivalence study, could serve as a model for future adaptations of the MBT and other verbal tests.

ObjectivesTo report experience with a large, nation-wide public memory screening program.DesignDescriptive study of community-dwelling elderly adults.SettingLocal community sites (48 sites agreed to provide data) throughout the United States participating in National Memory Screening Day in November 2010.ParticipantsOf 4,369 reported participants, 3,064 had complete data records and are included in this report.MeasurementsParticipants completed a questionnaire that included basic demographic information and a question about subjective memory concerns. Each site selected one of seven validated cognitive screening tests: Mini-Cog, General Practitioner assessment of Cognition, Memory Impairment Screen, Kokmen Short Test of Mental Status, Mini-Mental State Examination, Montreal Cognitive Assessment, Saint Louis University Mental Status Examination.ResultsOverall, 11.7% failed one of the seven screening tests. As expected, failure rates were higher in older and less-educated participants (P's<.05). Subjective memory concerns were associated with a 40% greater failure rate for persons of similar age and education but no memory concerns (odds ratio=1.4, 95% confidence interval=1.07-1.78), although only 11.9% of those who reported memory concerns (75% of all participants) had detectible memory problems.ConclusionScreening for cognitive impairment in community settings yielded results consistent with expected effects of age and education. The event attracted a large proportion of individuals with memory concerns; 88.1% were told that they did not have memory problems detectible with the tests used. Further studies are needed to assess how participants respond to and use screening information, whether this information ultimately influences decision-making or outcomes, and whether memory screening programs outside healthcare settings have public health value.

Deficits in memory binding may be an early cognitive marker of Alzheimer's disease (AD). The Memory Binding Test (MBT) was developed to improve early detection of AD by measuring memory binding. Herein, we assess the test-retest reliability and the discriminative validity of indices of memory binding for amnestic mild cognitive impairment (aMCI) and dementia in a community based sample. The MBT test was administered to 333 older adults (21 dementia cases, 31 aMCI cases, 33 non-amnestic MCI (naMCI) cases and 248 control subjects) and four key measures were collected (N1: The number of cued recalled items from first list, range 0−16; N2: The number of cued recalled items from second list, range 0−16; Npairs: The number of pairs correctly recalled, range 0−16; Nitem@pair: The number of items recalled in paired condition, range 0−32). These measures were compared in terms of sensitivity and specificity for identifying aMCI and dementia. McNemar's test was used to compare specificities when the sensitivities were comparable. Reliability was computed as Pearson's correlation between baseline and Year-1 scores for those subjects whose global cognitive function remained stable measured by the Blessed Information Memory Concentration test (BIMC). The optimal cut-score of Nitem@pair≤22 achieves sensitivity 0.74 and specificity 0.72 to differentiate aMCI from controls and naMCI, and sensitivity 0.84 and specificity 0.72 to differentiate aMCI or dementia from controls and naMCI. The optimal cut-score of Nitem@pair≤;19 achieves sensitivity 1.00 and specificity 0.79 to differentiate dementia cases from the rest. At the sensitivities achieved by these optimal cut-scores, Nitem@pair achieves significantly better specificities than N1, N2, and Npairs (McNemar's p<0.05). Among 203 subjects with an absolute change in BIMC of ≤ 3 the correlation between baseline and Year-1 Nitem@pair was 0.82. The measure Nitem@pair achieves better diagnostic validity than the other key MBT measures in identifying aMCI and dementia, which supports the hypothesis that measure of memory binding may be sensitive to early AD. We recommend using the empirical cut-score of 22 for detecting aMCI or dementia and 19 for detecting dementia alone. The MBT test also shows excellent test-retest reliability.

Background: The Memory Binding Test (MBT) is a novel test based on the learning of two lists of words, developed to detect early memory impairment suggestive of Alzheimer's disease (AD). Objective: To present and provide reference data of the Spanish MBT in a midlife population of mainly first-de gree descendants of AD patients. Methods: 472 cognitively unimpaired subjects, aged 45 to 65 and participants of the ALFA STUDY, were included. Raw scores were transformed to scaled scores on which multivariate regression analysis was applied adjusting by age, gender, and education level. A standard linear regression was employed to derive the scaled score adjusted. Sociodemographic corrections were applied and an adjustment table was constructed. Results: Performance was heterogeneously influenced by sociodemographic factors. Age negatively influenced free recall. Education tends to have an influence in the results showing lower performance with lower education level. Women tend to outperform men in the learning of the first list and total recall. Only a few variables were unaffected by sociodemographic factors such as those related to semantic proactive interference (SPI) and to the retention of learned material. Our results point out that some vulnerability to SPI is expectable in cognitively healthy subjects. Close to 100% of the learned material was maintained across the delay interval. Conclusion: This study contributes with reference data for the MBT providing the necessary adjustments for sociodemographic characteristics. Our data may prove to be useful for detecting asymptomatic at-risk candidates for secondary prevention studies of AD.