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.

Plasma MCP-1 and changes on cognitive function in community-dwelling older adults

Background Monocyte Chemoattractant Protein-1 (MCP-1), a glial-derived chemokine, mediates neuroinflammation and may regulate memory outcomes among older adults. We aimed to explore the associations of plasma MCP-1 levels (alone and in combination with β-amyloid deposition—Aβ42/40) with overall and domain-specific cognitive evolution among older adults. Methods Secondary analyses including 1097 subjects (mean age = 75.3 years ± 4.4; 63.8% women) from the Multidomain Alzheimer Preventive Trial (MAPT). MCP-1 (higher is worse) and Aβ42/40 (lower is worse) were measured in plasma collected at year 1. MCP-1 in continuous and as a dichotomy (values in the highest quartile (MCP-1+)) were used, as well as a dichotomy of Aβ42/40. Outcomes were measured annually over 4 years and included the following: cognitive composite z-score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive function z-score, composite attention z-score, Free and Cued Selective Reminding Test (FCSRT - memory). Results Plasma MCP-1 as a continuous variable was associated with the worsening of episodic memory over 4 years of follow-up, specifically in measures of free and cued delayed recall. MCP-1+ was associated with worse evolution in the CCS (4-year between-group difference: β = −0.14, 95%CI = −0.26, −0.02) and the CDR sum of boxes (2-year: β = 0.19, 95%CI = 0.06, 0.32). In domain-specific analyses, MCP-1+ was associated with declines in the FCSRT delayed recall sub-domains. In the presence of low Aβ42/40, MCP-1+ was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values Aβ42/40× MCP-1 × time was significant in models with CDR sum of boxes and FCSRT DTR as dependent variables. Conclusions Baseline plasma MCP-1 levels were associated with longitudinal declines in overall cognitive and episodic memory performance in older adults over a 4-year follow-up. How plasma MCP-1 interacts with Aβ42/40 to determine cognitive decline at different stages of cognitive decline/dementia should be clarified by further research. The MCP-1 association on cognitive decline was strongest in those with amyloid plaques, as measured by blood plasma Aβ42/40.

Effectiveness of immediate vs. delayed recall in detecting invalid performance in coached and uncoached simulators: Results of two experimental studies

Objective: Two experimental studies were conducted to compare the ability of immediate and delayed recall indicators to discriminate between performances of simulators and full-effort clinical and nonclinical participants. Methods: Three groups of simulators (uncoached, symptom-coached, and testcoached), one group of community controls, and one group of cognitively impaired patients were assessed with four experimental memory tests, in which the immediate and delayed recall tasks were separated by three other tasks. Results: Across both studies, delayed recall demonstrated higher accuracy than immediate recall in classifying simulated performances as invalid, as compared to performances of bona fide clinical participants. ROC curve results showed sensitivities below 50% for both indicators at specificities of ≥ 90%. Computing performance curves across recall trials revealed descending trends for all three simulator groups indicating a suppressed learning effect as a marker of noncredible performances. Among types of coaching, test-coaching proved to decrease differences between simulators and patients. Discussion: The effectiveness of such indicators in clinical evaluations and their vulnerability to information about test-taking strategies are discussed.

Active maintenance in working memory reinforces bindings for future retrieval from long-term episodic memory

Many theories assume that actively maintaining information in working memory (WM) predicts its retention in episodic memory (EM), as revealed by the beneficial effects of more WM time. Here, we examined whether affording more time for intentional WM maintenance does indeed drive EM. Participants either intentionally or incidentally encoded sequences of four words presented during trials of simple span (short time) and complex and slow span (long time). Long time intervals entailed a pause of equivalent duration between the words that presented an arithmetic problem to read aloud and solve (complex span) or a blank screen (slow span). To ensure similar encoding of the words across the intentional and incidental encoding groups, participants silently decided whether each word was a living or nonliving thing via keypress (i.e., an animacy judgment; Experiment 1) or read the words aloud while pressing the spacebar (Experiment 2). A surprise delayed recall test at the end of the experiment assessed EM. Longer time in WM, particularly during slow span, improved retrieval from EM for both intentional and incidental encoding groups relative to short time, but for different reasons: modeling of the data indicated that longer intentional encoding increased binding memory (i.e., retrieval of the items’ positions in the trial; Experiments 1 and 2), whereas longer elaborative but incidental encoding increased item memory (i.e., memory of items irrespective of their bindings; Experiment 1). This suggests that time spent actively keeping information in WM is special for EM because WM is a system that maintains bindings.

Repetitive transcranial magnetic stimulation in the treatment of mild cognitive impairment due to cerebral small vessel disease

Introduction. Mild cognitive impairment (MCI) negatively affects patients quality of life and is a risk factor for dementia. One of the main causes of MCI is cerebral small vessel disease (CSVD). The previously established link between decreased activity in the supplementary motor area (SMA) and cognitive impairment in patients with CSVD makes it possible to consider repetitive transcranial magnetic stimulation (rTMS) of the SMA with functional magnetic resonance imaging (fMRI)-assisted positioning as a promising method for treating MCI caused by CSVD. The aim of the study was to evaluate the efficacy and tolerability of fMRI-guided rTMS of the SMA in patients with MCI caused by CSVD. Materials and methods. Twenty patients were randomly assigned to the intervention (SMA stimulation; n = 10) and the control (vertex stimulation; n = 10) groups. All patients underwent 10 sessions of high-frequency rTMS. The MoCA scale, trail making test, Tower of London test, and copying and delayed recall in the ReyOsterrieth complex figure test were used to assess treatment effect. Testing was conducted before, immediately after and 3 months post rTMS. Results. The intervention group demonstrated a significant improvement in the MoCA, the Tower of London test and delayed recall in the ReyOsterrieth complex figure test immediately after rTMS. Statistically significant improvement in the MoCA and the Tower of London test results was maintained after 3 months. No statistically significant improvements were found in the control group. Groups were comparable in the incidence of headache during and in the 24-hour period after the stimulation session, and in unpleasant sensations during the session. Conclusion. fMRI-guided rTMS of the SMA is an effective and promising treatment method for MCI caused by CSVD, with effects lasting three or more months, and good tolerability.

Regression-Based Normative Data for Independent and Cognitively Active Spanish Older Adults: Free and Cued Selective Reminding Test, Rey–Osterrieth Complex Figure Test and Judgement of Line Orientation

The aim of this work was to develop normative data for neuropsychological tests for the assessment of independent and cognitively active Spanish older adults over 55 years of age. Methods: regression-based normative data were calculated from a sample of 103 nondepressed independent community-dwelling adults aged 55 or older (66% women). The raw data for the Free and Cued Selective Reminding Test (FCSRT), the Rey–Osterrieth Complex Figure Test (ROCF) and the Judgement of Line Orientation Test (JLO) were regressed on age, sex and education. The model predicting the FCSRT delayed-recall (FCSRT-Del) scores also included the FCSRT immediate-recall (FCSRT-Imm) scores. The model predicting the ROCF immediate-recall (ROCF-Imm) scores included the ROCF copy-trial (ROCF-C) scores, and the model predicting the ROCF delayed-recall (ROCF-Del) scores included both the ROCF-C and the ROCF-Imm scores. In order to identify low scores, z-scores were used to determine the discrepancy between the observed and the predicted scores. The base rates of the low scores for both the SABIEX normative data and the published normative data obtained from the general population were compared. Results: the effects of the different sociodemographic variables (age, sex and education) varied throughout the neuropsychological measures. Despite finding similar proportions of low scores between the normative data sets, the agreement was irrelevant or only fair-to-good. Conclusions: the normative data obtained from the general population might not be sensitive enough to identify low scores in cognitively active older adults, incorrectly classifying them as cognitively normal compared to the less active population.

Working Memory and Language Contribution to Verbal Learning and Memory in Drug-Resistant Unilateral Focal Temporal Lobe Epilepsy

We aimed to investigate the working memory (WM) and language separate contributions to verbal learning and memory in patients with unilateral drug-resistant temporal lobe epilepsy (drTLE); additionally, we explored the mediating role of WM on the relationship between the number of antiepileptic drugs (AEDs) and short-term verbal memory. We retrospectively enrolled 70 patients with left (LTLE; n = 44) and right (RTLE; n = 26) drTLE. About 40 similar (age and education) healthy controls were used to determine impairments of groups at WM, language (naming and verbal fluency), and verbal learning and memory (five trials list-learning, story memory—immediate recall). To disentangle the effect of learning from the short-term memory, we separately analyzed performances at the first trial, last trial, and delayed-recall list-learning measures, in addition to the total learning capacity (the sum of the five trials). Correlation and regression analyses were used to assess the contribution of potential predictors while controlling for main clinical and demographic variables, and ascertain the mediating role of WM. All patients were impaired at WM and story memory, whereas only LTLE showed language and verbal learning deficits. In RTLE, language was the unique predictor for the most verbal learning performances, whereas WM predicted the results at story memory. In LTLE, WM was the sole predictor for short-term verbal learning (list-learning capacity; trial 1) and mediated the interaction between AED number and the performance at these measures, whereas language predicted the delayed-recall. Finally, WM confounded the performance at short-term memory in both groups, although at different measures. WM is impaired in drTLE and contributes to verbal memory and learning deficits in addition to language, mediating the relationship between AED number and short-term verbal memory in LTLE. Clinicians should consider this overlap when interpreting poor performance at verbal learning and memory in drTLE.

The Effectiveness of Computer-Assisted Cognitive Rehabilitation and the Degree of Recovery in Patients with Traumatic Brain Injury and Stroke

Objectives: To determine the effectiveness of computer-assisted cognitive rehabilitation and compare the patterns of cognitive function recovery occurring in both traumatic brain injury (TBI) and stroke. Methods: A total of 62 patients were finally enrolled, consisting of 30 with TBI and 32 with stroke. The patients received 30 sessions of computer-assisted cognitive rehabilitation (Comcog) five times per week. Each session lasted for 30 min. Before and immediately after cognitive rehabilitation, all patients were evaluated by computerized neuropsychological test (CNT), Mini-Mental State Examination (MMSE), and modified Barthel index (MBI). Results: We analyzed the differences between pre- and post-cognitive rehabilitation in each TBI and stroke group. Significant differences were observed in MMSE, MBI, and some CNT contents, including digit span forward, verbal learning, verbal learning delayed recall, visual span forward, visual span backward, visual learning, trail making test A and B, and intelligence quotient (IQ) in the TBI group (p < 0.05). In the stroke group, in addition to significant differences that appeared in the TBI group, additional significant differences in the digit span backward, visual learning delayed recall, auditory continuous performance test (CPT), visual CPT, and card sorting test. We compared the difference values at pre- and post-cognitive rehabilitation for cognitive recovery between the TBI and stroke groups. All contents, except the digital span forward, visual learning, word-color test, and MMSE, had greater mean values in the stroke group; and thus, statistically significant higher values were observed in the visual span forward and card sorting test (p < 0.05). Conclusion: Most evaluation results showed improvement and the evaluation between the TBI and stroke groups also showed significant differences in cognitive functions in addition to more CNT contents, which significantly change in the stroke group. The stroke group showed a high difference value in most CNT contents. Therefore, those with stroke in the focal brain region tend to have better cognitive function recovery after a computer-assisted cognitive rehabilitation than those with TBI, which could cause diffuse brain damage and post-injury inflammation.

Is Retrieval Practice Always Superior to Restudy?

A classic study by Roediger and Karpicke (2006a) investigated the relative benefits of restudy versus retrieval practice, or “test”, on memory retention. Repeated studying was superior to repeated testing when memory was tested immediately (all study &gt; multiple study/single test &gt; single study/multiple tests). Strikingly, the pattern reversed when memory was tested after a days-long delay, with best performance in a single study/multiple tests condition. As each study period was minutes-long and contained repeated reading of a to-be-remembered text passage, we were interested whether the striking benefit for repeated testing at the expense of any restudy replicates when study opportunities are brief, akin to a single mention of a fact in a lecture. Participants encountered academically relevant facts a total of three times, each time either studied (S) or self-tested (T). Final test followed immediately or after a delay (Experiment 1: two days, Experiment 2: seven days). Partially replicating prior work, immediate memory benefited from repeated study (SSS &gt; SST &gt; STT), but the pattern did not reverse after a delay. Instead, memory was superior for facts the were restudied in addition to self-tested (SST &gt; STT = SSS). We further investigated whether restudy after a test (STS) provides additional benefits compared to restudy before test (SST), but found comparably high delayed recall in both conditions. The results show that under some circumstances, balancing repetition and testing can allow for more information to be learned and retained long-term.