Assessment Of Episodic Memory Research Articles

Episodic memory assessment: effects of sex and age on performance and response time during a continuous recognition task.

Continuous recognition tasks (CRTs) assess episodic memory (EM), the central functional disturbance in Alzheimer's disease and several related disorders. The online MemTrax computerized CRT provides a platform for screening and assessment that is engaging and can be repeated frequently. MemTrax presents complex visual stimuli, which require complex involvement of the lateral and medial temporal lobes and can be completed in less than 2 min. Results include number of correct recognitions (HITs), recognition failures (MISSes = 1-HITs), correct rejections (CRs), false alarms (FAs = 1-CRs), total correct (TC = HITs + CRs), and response times (RTs) for each HIT and FA. Prior analyses of MemTrax CRT data show no effects of sex but an effect of age on performance. The number of HITs corresponds to faster RT-HITs more closely than TC, and CRs do not relate to RT-HITs. RT-HITs show a typical skewed distribution, and cumulative RT-HITs fit a negative survival curve (RevEx). Thus, this study aimed to define precisely the effects of sex and age on HITS, CRs, RT-HITs, and the dynamics of RTs in an engaged population. MemTrax CRT online data on 18,255 individuals was analyzed for sex, age, and distributions of HITs, CRs, MISSes, FAs, TC, and relationships to both RT-HITs and RT-FAs. HITs corresponded more closely to RT-HITs than did TC because CRs did not relate to RT-HITs. RT-FAs had a broader distribution than RT-HITs and were faster than RT-HITs in about half of the sample, slower in the other half. Performance metrics for men and women were the same. HITs declined with age as RT-HITs increased. CRs also decreased with age and RT-FAs increased, but with no correlation. The group over aged 50 years had RT-HITs distributions slower than under 50 years. For both age ranges, the RevEx model explained more than 99% of the variance in RT-HITs. The dichotomy of HITs and CRs suggests opposing cognitive strategies: (1) less certainty about recognitions, in association with slower RT-HITs and lower HIT percentages suggests recognition difficulty, leading to more MISSes, and (2) decreased CRs (more FAs) but faster RTs to HITs and FAs, suggesting overly quick decisions leading to errors. MemTrax CRT performance provides an indication of EM (HITs and RT-HITs may relate to function of the temporal lobe), executive function (FAs may relate to function of the frontal lobe), processing speed (RTs), cognitive ability, and age-related changes. This CRT provides potential clinical screening utility for early Alzheimer's disease and other conditions affecting EM, other cognitive functions, and more accurate impairment assessment to track changes over time.

A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices

Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer’s disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls (n = 97), individuals with subjective cognitive decline (n = 59), or patients with mild cognitive impairment (n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.

A proof of concept phase II study with the PDE-4 inhibitor roflumilast in patients with mild cognitive impairment or mild Alzheimer’s disease dementia (ROMEMA): study protocol of a double-blind, randomized, placebo-controlled, between-subjects trial

BackgroundResearch into the neurobiological underpinnings of learning and memory has demonstrated the cognitive-enhancing effects associated with diverse classes of phosphodiesterase (PDE) inhibitors. Specific PDE inhibitors have been identified to improve neuronal communication through selective inhibition of PDE activity. Roflumilast, a PDE4 inhibitor, has demonstrated efficacy in enhancing episodic memory in healthy adults and elderly participants with pronounced memory impairment, indicative of amnestic mild cognitive impairment (aMCI). In alignment with these findings, the present protocol aims to provide a proof of concept phase II of the potential of roflumilast to aid patients diagnosed with (a)MCI or mild Alzheimer’s disease (AD) dementia.MethodsThe study will be conducted according to a double-blind, randomized placebo-controlled, between-subjects design. Participants with (a)MCI and mild AD dementia will be recruited through the Memory Clinic at the Maastricht University Medical Centre + (MUMC +) in Maastricht, the Netherlands, alongside outreach through regional hospitals, and social media. The study will have three arms: placebo, 50 μg roflumilast, and 100 μg roflumilast, with a treatment duration of 24 weeks. The primary outcome measure will focus on the assessment of episodic memory, as evaluated through participants’ performance on the 15-word Verbal Learning Task (VLT). Our secondary objectives are multifaceted, including an exploration of various cognitive domains. In addition, insights into the well-being and daily functioning of participants will be investigated through interviews with both the participants and their (informal) caregivers, we are interested in the well-being and daily functioning of the participants.DiscussionThe outcomes of the present study aim to elucidate the significance of the PDE4 inhibition mechanism as a prospective therapeutic target for enhancing cognitive function in individuals with (a)MCI and mild AD dementia. Identifying positive effects within these patient cohorts could extend the relevance of this treatment to encompass a broader spectrum of neurological disorders.Trial registrationThe Medical Ethics Committee of MUMC + granted ethics approval for the 4th version of the protocol on September 10th, 2020. The trial was registered at the European Drug Regulatory Affairs Clinical Trials (EudraCT) registered on the 19th of December 2019 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004959-36/NL) and ClinicalTrial.gov (NCT04658654, https://clinicaltrials.gov/study/NCT04658654?intr=roflumilast&cond=mci&rank=1) on the 8th of December 2020. The Central Committee on Research Involving Human Subjects (CCMO) granted approval on the 30th of September 2020.

A 10‐minute Digitally Administered and Scored Neuropsychological Protocol Assessing Executive Control and Episodic Memory

AbstractBackgroundDigital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assessing these neurocognitive constructs.Method229 community dwelling participants were assessed (age = 68.32+9.85; education = 15.01+2.58, MMSE = 26.84+2.78; 144 females). Executive abilities were assessed with three trials of 5‐digits backward digit span test (BDST) and the ‘animal’ fluency test. Episodic memory was assessed with a 6‐word Philadelphia (repeatable) Verbal Learning Test (PrVLT) consisting of 2 immediate free recall (IFR) trials, delayed free recall (DFR), and delayed recognition. Traditional pencil and paper testing was not used. Data were obtained with an iPad processed using automatic speech recognition.ResultA K‐means cluster analysis (k = 3) classified participants with possible dementia (pDem = 31), MCI (n = 96), and cognitively normal (CN, n = 100; Table 1). Groups differed from each other on all three P(r)VLT parameters (p = 0.001). CN participants outperformed other groups on executive measures (p = 0.001). All between‐group analyses yielded large effect sizes (η2 = 0.277–0.642). Logistic regression analysis using P(r)VLT‐DFR, P(r)VLT‐recognition, BDST, and ‘animal’ fluency parameters classify MCI and pDem participants into their respective groups compared to CN participants (p = 0.003). For the pDem group, within‐group t‐tests found rapid forgetting (PrVLT‐DFT<PrVLT‐IFR trial 2, p = 0.013; PrVLT‐recognition<PrVLT‐DFR (p = 0.013). Additional, within‐group pDem group comparisons found no differences between P(r)VLT‐recognition and either executive tests. Within group comparisons for the MCI group found P(r)VLT delayed recognition improved compared to P(r)VLT delayed free recall (p<0.001), and worse performance on both executive measures compared to P(r)VLT‐ recognition (p = .001). All of these comparisons are consistent with a mild dysexecutive syndrome.ConclusionThe protocol described above is efficient, reliable, removes any inter‐rater reliability issues, and is able to operationally‐define dysexecutive and amnestic cognitive impairment ‐ key neurocognitive constructs related to ADRD and MCI. This 10‐minute digitally administered and automatically scored neuropsychological protocol assessing executive abilities and episodic memory could easily be deployed in clinical trials and in primary‐ and specialty‐care settings to screen for emergent cases of MCI and ADRD by efficient assessment of episodic memory and executive abilities.

A 10‐minute Digitally Administered and Scored Neuropsychological Protocol Assessing Executive Control and Episodic Memory

AbstractBackgroundDigital assessment technology provides rapid and reliable assessment of neurocognitive abilities associated with Alzheimer’s Disease and Related Dementia (ADRD) and Mild Cognitive Impairment (MCI). Dysexecutive and amnestic impairment typify many ADRD and MCI disorders. Here, we evaluate a 10‐minute digitally administered protocol assessing these neurocognitive constructs.Method229 community dwelling participants were assessed (age = 68.32+9.85; education = 15.01+2.58, MMSE = 26.84+2.78; 144 females). Executive abilities were assessed with three trials of 5‐digits backward digit span test (BDST) and the ‘animal’ fluency test. Episodic memory was assessed with a 6‐word Philadelphia (repeatable) Verbal Learning Test (PrVLT) consisting of 2 immediate free recall (IFR) trials, delayed free recall (DFR), and delayed recognition. Traditional pencil and paper testing was not used. Data were obtained with an iPad processed using automatic speech recognition.ResultA K‐means cluster analysis (k = 3) classified participants with possible dementia (pDem = 31), MCI (n = 96), and cognitively normal (CN, n = 100; Table 1). Groups differed from each other on all three P(r)VLT parameters (p = 0.001). CN participants outperformed other groups on executive measures (p = 0.001). All between‐group analyses yielded large effect sizes (η2 = 0.277–0.642). Logistic regression analysis using P(r)VLT‐DFR, P(r)VLT‐recognition, BDST, and ‘animal’ fluency parameters classify MCI and pDem participants into their respective groups compared to CN participants (p = 0.003). For the pDem group, within‐group t‐tests found rapid forgetting (PrVLT‐DFT<PrVLT‐IFR trial 2, p = 0.013; PrVLT‐recognition<PrVLT‐DFR (p = 0.013). Additional, within‐group pDem group comparisons found no differences between P(r)VLT‐recognition and either executive tests. Within group comparisons for the MCI group found P(r)VLT delayed recognition improved compared to P(r)VLT delayed free recall (p<0.001), and worse performance on both executive measures compared to P(r)VLT‐ recognition (p = .001). All of these comparisons are consistent with a mild dysexecutive syndrome.ConclusionThe protocol described above is efficient, reliable, removes any inter‐rater reliability issues, and is able to operationally‐define dysexecutive and amnestic cognitive impairment ‐ key neurocognitive constructs related to ADRD and MCI. This 10‐minute digitally administered and automatically scored neuropsychological protocol assessing executive abilities and episodic memory could easily be deployed in clinical trials and in primary‐ and specialty‐care settings to screen for emergent cases of MCI and ADRD by efficient assessment of episodic memory and executive abilities.

The reliability and validity of the snellen memory test for point‐of‐care detection of Alzheimer’s risk in cognitively unimpaired older adults

AbstractBackgroundEpisodic memory decline is one of the earliest cognitive indicators in Alzheimer’s disease (AD) with impairment in memory in older adults an important indicator of incipient AD. Optometry has potential for population based, point‐of‐care screening as retinal biomarkers can detect both symptomatic and preclinical AD. Here, we aimed to develop and optimize a test of episodic memory for use in clinical optometry/ophthalmology settings alongside retinal imaging methods to detect both preclinical and early symptomatic AD.Method30 cognitively normal (CN) older adults (55‐81 years; 68.5±7) from the Atlas of Retinal Imaging in Alzheimer’s Study (ARIAS) completed the Snellen Memory Test (SMT). Participants completed a a Snellen Eye Chart for three learning trials of 10 seconds exposures, followed by immediate free recall. After a 20‐minute delay, participants completed delayed free recall in which they were asked to recall as many of the letters as they had been shown. This was followed by a recognition test in which participants viewed a mock chart identifying the correct letters and if they were in the correct location as the original chart.ResultAn intraclass correlation coefficient was calculated to determine the inter‐rater reliability among three raters for 10 randomly selected administrations. Overall results indicated good reliability with a mean coefficient of 0.87 (95% CI: 0.71‐1.03). Convergent and divergent validity for the 30 participants was assessed by comparing SMT performance to RBANS indices and the Free and Cued Selective Reminding Test (FCSRT). The SMT significantly correlated with the RBANS Immediate Memory Index (r = 0.38‐0.52), Language Index (r = 0.39‐0.51), and Attention Index (r = 0.39‐0.46) as well as with selective reminding trial 1 and 2 (r = 0.45‐0.78), and free and cued recall for trial 3 (r = 0.45‐0.47).ConclusionThe SMT has potential as an episodic memory test that could be used for point of care detection of preclinical AD. Future work will continue to validate the SMT against reference standard neuropsychological assessments of episodic memory and against AD retinal imaging biomarkers.

Associations Between Ambient Air Pollution and Cognitive Abilities from Midlife to Early Old Age: Modification by APOE Genotype.

Fine particulate matter (PM2.5) and nitrogen dioxide (NO2) measures of ambient air pollution are associated with accelerated age-related cognitive impairment, and Alzheimer's disease and related dementias (ADRD). We examined associations between air pollution, four cognitive factors, and the moderating role of apolipoprotein E (APOE) genotype in the understudied period of midlife. Participants were ∼1,100 men in the Vietnam Era Twin Study of Aging. Baseline cognitive assessments were from 2003 to 2007. Measures included past (1993-1999) and recent (3 years prior to baseline assessment) PM2.5 and NO2 exposure, in-person assessment of episodic memory, executive function, verbal fluency, and processing speed, and APOE genotype. Average baseline age was 56 years with a 12-year follow-up. Analyses adjusted for health and lifestyle covariates. Performance in all cognitive domains declined from age 56 to 68. Higher PM2.5 exposures were associated with worse general verbal fluency. We found significant exposure-by-APOE genotype interactions for specific cognitive domains: PM2.5 with executive function and NO2 with episodic memory. Higher PM2.5 exposure was related to worse executive function in APOE ɛ4 carriers, but not in non-carriers. There were no associations with processing speed. These results indicate negative effects of ambient air pollution exposure on fluency alongside intriguing differential modifications of cognitive performance by APOE genotype. APOE ɛ4 carriers appeared more sensitive to environmental differences. The process by which air pollution and its interaction with genetic risk for ADRD affects risk for later life cognitive decline or progression to dementia may begin in midlife.

A Pilot Study of Free and Cued Selective Reminding Test in a Lebanese Sample: A study on Normal, MCI and AD patients (P6-6.009)

<h3>Objective:</h3> Our aim was to assess the suitability of the use of a culturally adapted version of the FCSRT in the Lebanese population diagnosed with MCI and AD through comparing between three groups of subjects – normal, MCI and AD. <h3>Background:</h3> The Free and Cued Selective Reminding Test (FCSRT) is a memory test that assesses learning and acquisition, by providing category cues in the learning process. It is a reliable tool for the assessment of episodic memory, used to differentiate between Alzheimer Disease (AD) patients and patients with Mild Cognitive Impairment (MCI). <h3>Design/Methods:</h3> Subjects were recruited based on their visit, for a regular memory consultation in a memory clinic in Beirut. All of them completed the test conducted by a clinician. <h3>Results: Results:</h3> The sample included 3 populations divided as follows: 29 normal, 22 MCI and 24 AD subjects. Our results showed that the adapted Arabic version of the FCSRT is discriminating between the 3 populations with a major significant difference between the healthy and AD population. The overall profile on the FCSRT revealed that normal subjects had the highest scores followed by MCI and then AD subjects. The learning curve of normal controls and MCI patients is ascendant while AD subjects exhibit a depressed learning curve. <h3>Conclusions:</h3> This study represents a novel contribution regarding the adequacy of the Arabic version of the FCSRT in terms of distinguishing between AD and non-AD subjects. Besides, it gives new possibilities concerning the use of the FCSRT in the evaluation of the spectrum of memory disorders. <b>Disclosure:</b> Dr. Abou-Mrad has nothing to disclose.

Evidence for the role of affective theory of mind in face-name associative memory

ABSTRACT Poor face-name recall has been associated with age-related impairments in cognitive functioning, namely declines in episodic memory and executive control. However, the role of social cognitive function – the ability to remember, process, and store information about others – has been largely overlooked in this work. Extensive work has shown that social and nonsocial cognitive processes rely on unique, albeit overlapping, mechanisms. In the current study, we explored whether social cognitive functioning – specifically the ability to infer other people’s mental states (i.e., theory of mind) – facilitates better face-name learning. To do this, a sample of 289 older and young adults completed a face-name learning paradigm along with standard assessments of episodic memory and executive control alongside two theory of mind measures, one static and one dynamic. In addition to expected age differences, several key effects emerged. Age-related differences in recognition were explained by episodic memory, not social cognition. However, age effects in recall were explained by both episodic memory and social cognition, specifically affective theory of mind in the dynamic task. Altogether, we contend that face-name recall can be supported by social cognitive functioning, namely understanding emotions. While acknowledging the influence of task characteristics (i.e., lures, target ages), we interpret these findings in light of existing accounts of age differences in face-name associative memory.

Encoding of everyday objects in older adults: Episodic memory assessment in virtual reality.

Age-related decline in episodic memory performance in otherwise healthy older adults is indisputably evident. Yet, it has been shown that under certain conditions episodic memory performance in healthy older adults' barely deviates from those seen in young adults. Here we report on the quality of object encoding in an ecologically valid, virtual-reality based memory assessment in a sample of healthy older and younger adults with comparable memory performance. We analyzed encoding by establishing both a serial and semantic clustering index and an object memory association network. As expected, semantic clustering was superior in older adults without need for additional allocation of executive resources whereas young adults tended more to rely on serial strategies. The association networks suggested a plethora of obvious but also less obvious memory organization principles, some of which indicated converging approaches between the groups as suggested by a subgraph analysis and some of which indicated diverging approaches as suggested by the respective network interconnectivity. A higher interconnectivity was observed in the older adults' association networks. We interpreted this as a consequence of superior semantic memory organization (extent to which effective semantic strategies diverged within the group). In conclusion, these results might indicate a diminished need for compensatory cognitive effort in healthy older adults when encoding and recalling everyday objects under ecologically valid conditions. Due to an enhanced and multimodal encoding model, superior crystallized abilities might be sufficient to counteract an age-related decline in various other and specific cognitive domains. This approach might potentially elucidate age-related changes in memory performance in both healthy and pathological aging.

A novel episodic memory test optimized for smart phone high‐frequency assessments

AbstractBackgroundDecline in episodic memory is a strong marker of neurodegenerative diseases, making it an important target for cognitive assessment. We present a new remote, repeatable, and brief assessment of episodic memory and visual short‐term memory (VSTM) for smart phone deployment. We evaluated this task for sensitivity to age and established cognitive measures of memory and attention.MethodThe task consists of a learning phase where participants see a sequence of items, then are asked to replicate the item order and location by dragging and dropping these items on‐screen. A recall phase follows a minimum 12‐hour delay, with replication of the earlier response. Each session takes less than 2 minutes. The first phase supplies metrics of spatial and order precision VSTM, with the second phase characterising long‐term episodic memory.Experiment 1 (n = 133) compares the task with CANTAB assessments of visuospatial memory. In Experiment 2 (n = 80) the novel task was repeated twice daily for a week, alongside momentary mood ratings, and a more comprehensive battery of CANTAB tasks at baseline.In Experiment 1, multiple regression and dominance analyses explore the independent and shared variance of measures in explaining age. In Experiment 2, clustering and multivariate autoregressive models outline differences in timeseries relationships between mood and memory, and age.ResultExperiment 1 revealed that CANTAB measures and novel spatial and order metrics were correlated with age (r = .20 to r = .37, adjusted P = &lt;.05). Multiple regression showed models with CANTAB Paired Associate Learning (PAL) score, and delayed novel spatial metrics were significantly predictive of age (t = ‐4.08, 3.17, p &lt;.005). The dominance analysis revealed novel immediate precision overlapped with existing measures in predicting Age, while delayed precision had more unique variance (4.6% vs 0.62% unique sample variance explained in Age, accounting for PAL).Experiment 2 characterised variance in individual learning curves over time and differing autoregressive processes associated with age and CANTAB measures.ConclusionWe present a brief novel episodic memory task that can be deployed remotely, with delayed spatial precision significantly predictive of healthy Ageing. Additionally, we show this test’s suitability as a repeated assessment, compatible with high‐frequency study designs in older populations.

A novel episodic memory test optimized for smart phone high-frequency assessments.

Decline in episodic memory is a strong marker of neurodegenerative diseases, making it an important target for cognitive assessment. We present a new remote, repeatable, and brief assessment of episodic memory and visual short-term memory (VSTM) for smart phone deployment. We evaluated this task for sensitivity to age and established cognitive measures of memory and attention. The task consists of a learning phase where participants see a sequence of items, then are asked to replicate the item order and location by dragging and dropping these items on-screen. A recall phase follows a minimum 12-hour delay, with replication of the earlier response. Each session takes less than 2 minutes. The first phase supplies metrics of spatial and order precision VSTM, with the second phase characterising long-term episodic memory. Experiment 1 (n=133) compares the task with CANTAB assessments of visuospatial memory. In Experiment 2 (n=80) the novel task was repeated twice daily for a week, alongside momentary mood ratings, and a more comprehensive battery of CANTAB tasks at baseline. In Experiment 1, multiple regression and dominance analyses explore the independent and shared variance of measures in explaining age. In Experiment 2, clustering and multivariate autoregressive models outline differences in timeseries relationships between mood and memory, and age. Experiment 1 revealed that CANTAB measures and novel spatial and order metrics were correlated with age (r=.20 to r=.37, adjusted P= <.05). Multiple regression showed models with CANTAB Paired Associate Learning (PAL) score, and delayed novel spatial metrics were significantly predictive of age (t= -4.08, 3.17, p <.005). The dominance analysis revealed novel immediate precision overlapped with existing measures in predicting Age, while delayed precision had more unique variance (4.6% vs 0.62% unique sample variance explained in Age, accounting for PAL). Experiment 2 characterised variance in individual learning curves over time and differing autoregressive processes associated with age and CANTAB measures. We present a brief novel episodic memory task that can be deployed remotely, with delayed spatial precision significantly predictive of healthy Ageing. Additionally, we show this test's suitability as a repeated assessment, compatible with high-frequency study designs in older populations.

How is semantic memory affected in Mild Cognitive Impairment?

AbstractBackgroundMild cognitive impairment (MCI) is a condition considered by many as a transitional stage between healthy aging and Alzheimer’s disease. Although its diagnosis is typically based on the assessment of episodic memory, evidences show that impairment in semantic memory would be one of the first manifestations of cognitive impairment. This study aims to investigate how semantic memory is affected in MCI. Precisely, we will explore if core memory of common knowledge is impaired in MCI, and if the performance in semantic memory task vary with the modality of presentation of the stimuli (verbal vs visual).MethodA group of healthy people aged between 60 and 90 years old (mean: 77.4 N = 43), and a age‐matched group meeting the criteria for MCI (N = 32), who have lived in Quebec (Canada) for at least 30 years, completed two neuropsychological tests evaluating the semantic memory of famous people, which have been proven to be the most sensible way to detect even subtle variation in semantic memory.ResultResults indicate that performance in both tests is impaired in the MCI group, compared to the healthy elderly group. This means that the MCI group have more difficulty to name famous people (t (69) = 5,173, p &lt; 0.01), as well as answer basic questions on them (ex: their profession, nationality, etc.), when presented from their picture (t (69) = 4.849, p &lt; 0.01) or their name (t (65) = 3.488, p &lt; 0.01), compared to healthy people of the same age. There was no difference between their performances when the stimuli was presented in the visual or verbal modality (t (30) = 0.928, p &gt; 0.05).ConclusionThis study demonstrates that semantic memory of famous people is impaired in MCI, and that impairment affects the capacity to name famous people as well as remembering facts about them. In addition, there are no difference if the stimuli are presented visually or verbally. This suggests that the impairment in semantic memory in MCI is due to a degradation of the memory, and is not modulated by other cognitive functions or modality.

Novel remote episodic memory assessment: An Agile development pipeline methodology for task selection

AbstractBackgroundThere is a growing need to remotely monitor episodic memory decline. Recent advances in available device technology offer an opportunity to deploy novel smart phone‐based cognitive assessments. However, candidate task design options are numerous and selecting the most clinically sensitive and usable by the target population is not a trivial task. Inspired by Agile software development, we present a case‐study of a rapid iterative process for developing and selecting candidates.MethodDesign requirements: 1) Potential for early sensitivity to episodic memory changes, defined by satisfactory performance distributions; 2) Optimized for high frequency Smart Phone deployment; 3) Acceptable user feedback.Three tasks were created: Exp 1 “Serial positioning task”, sequences of objects were memorized and recalled using a drag‐drop response (n=55). Exp 2 “Biographical association task”, AI generated faces were paired with information in a social media profile and later recalled either with questions or by clicking on probe faces (n=73). Exp 3 “Self‐generated pairing task”, where participants generated pairs of identities and later had to recall them (n=65). Each task implemented a minimum learning‐recall delay of 12 hours. Exp 4 ‐ Final versions were compared within participants and against validated CANTAB tasks using Exploratory Factor Analysis (n=155).ResultExp 1 “Serial positioning task”, identified a cognitive load of between 3‐4 items giving good performance‐based variability. Engaging stimuli using emoji and map‐backgrounds increased user ratings without negatively impacting variability. Exp 2 “Biographical association task”, demonstrated good distributions for recall, but only in a forced‐choice format. This was rated the least enjoyable. Exp 3 “Self‐generated pairing task”, showed ceiling effects. This task was rated equally enjoyable as Experiment 1. After comparing the Exp 4 results, the “Serial positioning task” was most predictive of age (tau‐b .256, Bf=113.7), as well as unique according to the factor analysis, and rated as most enjoyable.ConclusionOur agile development pipeline titrated the suitability of three candidate episodic memory tasks for future remote deployment in target clinical populations. By implementing this methodology, it was determined that the "Serial positioning task” was the best candidate for further development and testing for monitoring symptoms of memory decline.

Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease.

ObjectiveThis study aimed to assess whether non‐invasive brain stimulation with transcranial alternating current stimulation at gamma‐frequency (γ‐tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer's disease (AD).MethodsIn this randomized, double‐blind, sham controlled, crossover study, 60 AD patients underwent a clinical and neurophysiological evaluation including assessment of episodic memory and cholinergic transmission pre and post 60 minutes treatment with γ‐tACS targeting the precuneus or sham tACS. In a subset of 10 patients, EEG analysis and individualized modelling of electric field distribution were carried out. Predictors to γ‐tACS efficacy were evaluated.ResultsWe observed a significant improvement in the Rey Auditory Verbal Learning (RAVL) test immediate recall (p < 0.001) and delayed recall scores (p < 0.001) after γ‐tACS but not after sham tACS. Face‐name associations scores improved with γ‐tACS (p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after γ‐tACS (p < 0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to γ‐tACS. Clinical improvement correlated with the increase in gamma frequencies in posterior regions and with the amount of predicted electric field distribution in the precuneus.InterpretationPrecuneus γ‐tACS, able to increase γ‐power activity on the posterior brain regions, showed a significant improvement of episodic memory performances, along with restoration of intracortical excitability measures of cholinergic transmission. Response to γ‐tACS was dependent on genetic factors and disease stage. ANN NEUROL 2022;92:322–334

Episodic Memory in Older Adults Without Dementia: A Meta-Analysis of Aerobic Exercise Interventions

The effect of aerobic exercise interventions on episodic memory performance among older adults without dementia remains a matter of intense debate. Prior meta-analyses examining this association have reported minimal improvements in episodic memory performance following exercise training but have also been plagued by several limitations, including restrictive inclusion criteria, combined sample populations, and infrequent examination of the effect of exercise parameters (e.g., volume). To address these gaps, we conducted a meta-analysis of randomized controlled trials (RCTs) to determine if aerobic exercise interventions influence episodic memory performance in older adults without dementia and to examine potential moderators of these effects (e.g., sample and intervention characteristics). Included studies met the following criteria: (1)Studies of adults (M≥55 years) with normal cognition, subjective cognitive decline, or mild cognitive impairment; (2)Aerobic exercise RCTs; and (3)Assessment of episodic memory. Intervention effects were represented by Hedges’ g and combined into pooled effect sizes using random- and mixed-effects models. Thirty-three studies met inclusion criteria, representing data from 2,488 participants. The primary analysis yielded a significant positive effect of aerobic exercise on episodic memory (Hedges’ g[CI]=0.28[0.10-0.47]; p=0.003). Mixed-effects analyses demonstrated a positive effect on episodic memory among studies with a high percentage of females (>66%), participants with normal cognition, studies reporting intensity, studies with a no-contact or nonaerobic physical activity control group, and studies prescribing 2,100–3,900 total minutes of activity (range 540–8,190 minutes). These results suggest that aerobic exercise may act as an accessible, non-pharmaceutical intervention to improve episodic memory in late adulthood before changes in cognition are detected.

Increases in Cognitive Activity Reduce Aging-Related Declines in Executive Functioning.

Declines in cognitive functioning are commonly experienced with aging, yet there is wide variation in the nature and extent of these changes. Previous research has shown associations between the frequency of engaging in stimulating cognitive activities and performance on cognitive tests. However, it is not known whether it is important to increase the amount of cognitive activity as one gets older in order to curtail cognitive declines. We examined cognitive activities and cognition in a national sample of 2,130 community-dwelling middle-aged and older adults from the Midlife in the United States longitudinal study. Participants completed cognitive assessments of episodic memory (EM) and executive functioning (EF) on two occasions, ~9 years apart. At the first assessment, participants ranged in age between 33 and 83 years (M = 55.76, SD = 11.09), with 56.1% women. Multilevel models were tested to examine educational level and change in cognitive activity as predictors of change in EM and EF, controlling for initial level of cognitive activity and key correlates of cognitive decline. Results indicated that increases in cognitive activity were important over and above earlier levels of cognitive activity for reducing declines in EF. Further analysis also showed differential results by educational level. Increased cognitive activity was not associated with changes in EF among individuals with a college degree. In contrast, individuals without a college degree who increased their cognitive activity showed significantly less decline in EF compared to those without a college degree who decreased or maintained their cognitive activity across the 9 years. Thus, the results suggest that increased engagement in cognitive activity makes more of a difference for EF declines among those without a college degree. The results have particular relevance given that aging-related changes in domains such as work status, health, or social relationships can lead to reductions in stimulating cognitive activities. The findings emphasize the importance of increasing cognitive activities especially among those with lower educational attainment.

Longitudinal Cognitive Decline in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer\u2019s Disease

Sensitive cognitive assessments accurately detect and track cognitive decline in Alzheimer’s disease. The Cogstate battery was used to measure cognitive change in cognitively normal participants and in individuals with mild cognitive impairment and mild Alzheimer’s disease enrolled in the Australian Imaging, Biomarker and Lifestyle Rate of Change Substudy. Over 18 months, verbal episodic memory performance declined for mild cognitive impairment and mild Alzeheimer’s disease groups when compared to cognitively normal participants. Frequent assessments of episodic memory may facilitate early detection of cognitive decline due to Alzheimer’s disease.

Episodic Memory–Related Imaging Features as Valuable Biomarkers for the Diagnosis of Alzheimer’s Disease: A Multicenter Study Based on Machine Learning

BackgroundIndividualized and reliable biomarkers are crucial for diagnosing Alzheimer’s disease (AD). However, lack of accessibility and neurobiological correlation are the main obstacles to their clinical application. Machine learning algorithms can effectively identify personalized biomarkers based on the prominent symptoms of AD. MethodsEpisodic memory–related magnetic resonance imaging (MRI) features of 143 patients with amnesic mild cognitive impairment (MCI) were identified using a multivariate relevance vector regression algorithm. The support vector machine classification model was constructed using these MRI features and verified in 2 independent datasets (N = 994). The neurobiological basis was also investigated based on cognitive assessments, neuropathologic biomarkers of cerebrospinal fluid, and positron emission tomography images of amyloid-β plaques. ResultsThe combination of gray matter volume and amplitude of low-frequency fluctuation MRI features accurately predicted episodic memory impairment in individual patients with amnesic MCI (r = 0.638) when measured using an episodic memory assessment panel. The MRI features that contributed to episodic memory prediction were primarily distributed across the default mode network and limbic network. The classification model based on these features distinguished patients with AD from normal control subjects with more than 86% accuracy. Furthermore, most identified episodic memory–related regions showed significantly different amyloid-β positron emission tomography measurements among the AD, MCI, and normal control groups. Moreover, the classification outputs significantly correlated with cognitive assessment scores and cerebrospinal fluid pathological biomarkers' levels in the MCI and AD groups. ConclusionsNeuroimaging features can reflect individual episodic memory function and serve as potential diagnostic biomarkers of AD.

Development of the Snellen Memory Test (SMT): An episodic memory test to screen for AD risk in a clinical optometry/ophthalmology setting

AbstractBackgroundAlthough we have been working to discover and validate retinal imaging biomarkers for preclinical AD risk, the cognitive assessment of episodic memory function remains the most commonly relied on screening approach. Here, we sought to develop a brief screening test for episodic memory, to augment retinal biomarkers in the early detection of AD. By relying on the standard Snellen Eye Chart as the stimulus field, we aim to create an instrument that can be seamlessly incorporated into standard clinical optometry/ophthalmology practices. This pilot study sought to identify episodic memory questions of equivalent difficulty, based on the Snellen Eye Chart, that can eventually be scored using a mobile application.Method12 cognitively normal (CN) older adults (24‐56 years) completed the SMT, consisting of 2 x 11 question forms, with both free‐ and cued‐recall components: one form immediately after encoding and one form after a 20‐minute delay. Item analysis was performed for each test question at immediate and delayed recall, and the mean difficulty index (DI) of all questions was computed along with a 95% confidence interval (CI).ResultThe mean DI for all questions at immediate recall was 0.66 (95% CI: 0.53‐0.79) with two questions falling below the 95% CI lower bound (0.53). The mean DI at delayed recall was 0.70, (95% CI: 0.57, 0.82) with one question falling below and one falling above the 95% CI upper bound. We eliminated 4 questions, leaving a pool of 18 questions of equivalent difficulty at immediate and delayed recall.ConclusionMany of the items for the SMT were moderately difficult for CN individuals. These questions may be further developed to screen for AD risk in CN older adults in a clinical setting. We are currently collecting data in a cohort (N=100) of CN older adults (55‐80) at both low‐ and high‐risk for preclinical AD, which will be used to further refine this novel memory test. Our next step is to validate the SMT against gold standard neuropsychological assessments of episodic memory, and to examine the added prognostic value of this test in conjunction with our panel of retinal imaging AD risk biomarkers.