Episodic Memory Tests Research Articles

Validity of a remote supervised preclinical Alzheimer’s disease cognitive composite (PACC) score in preclinical and prodromal Alzheimer’s disease.

AbstractBackgroundNeuropsychological tests administered to individuals in locations different from the assessor (i.e., remote assessment) can provide substantial reductions in patient burden, study cost and barriers to access. However, such tests must be optimized and validated for use in remote settings. The preclinical cognitive composite score (PACC) is derived from neuropsychological tests of episodic memory, complex attention, and general mental status. This study determined whether a set of neuropsychological tests of these domains, which can provide a PACC score, can be given in a remote supervised setting and remain sensitive to AD related cognitive impairment.MethodOlder adults classified as cognitively unimpaired (CU, n = 30), preclinical AD (n = 30) or prodromal AD (n = 25), with conventional PACC scores known, completed three computerized tests; the International Shopping list Test (ISLT), Continuous Paired Associate Learning Test (CPAL) and the International Digit Symbol Substitution Test, while supervised by a neuropsychologist in in‐clinic and remote settings. All individuals then completed the remote assessments two more times 7days (+/‐4 days) apartResultMain performance measure from each test on each assessment was standardized using the mean and SD of the CU group, assessed under supervision, at baseline. Standardized scores for each assessment were then averaged to yield a PACC score. There was no difference in rates of missing data or group mean score on individual test scores or PACC score, between in‐clinic and remote settings. Compared to the CU group, impairment in performance on the digital PACC in the prodromal AD was substantial (z = ‐1.56) but equivalent between in clinic (9z = 1.57) and remote (z = ‐1.56) settings. Performance on the digital PACC was slightly worse in the preclinical AD group (z = –0.42) but did not differ for settings. The reliability of the digital PACC score was very high (r = 0.87).ConclusionThe digital PACC derived from neuropsychological tests given in remote supervised contexts is acceptable, valid, reliable and sensitive to AD related cognitive impairment when given in‐clinic or remotely.

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 = <.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.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.

Comparability and usability of Paired Associates Learning task (PAL) delivered on a smartphone

AbstractBackgroundDelivering episodic memory tests on a mobile device can support increased accessibility across diverse health settings. This is particularly important for increasing access to memory screening tools for participants at risk of memory impairment including Alzheimer’s and dementia.CANTAB PAL task is a short (8‐12 minutes) task of memory performance that is currently validated for delivery on a tablet, laptop or desktop device. Cambridge Cognition developed a prototype version of PAL that can be delivered on a smartphone (iPhone or Android). A key component of making the task available on smartphone is to understand the comparability to the original version of the task. For tasks delivered direct to patient, usability becomes even more important. This study was designed to evaluate the comparability and usability of PAL on smartphone device.MethodParticipants (N = 98, mean age 55 ± 5.59 years, gender balanced (50% (49)) were recruited through the Prolific platform to remotely complete both smartphone and desktop versions of CANTAB PAL on two consecutive days followed by a usability questionnaire. A cross‐over design was used with 50:50 participants smartphone first: desktop first to counterbalance for exposure to the task. Participants used their own devices for assessment and the device operating system was captured.ResultMost participants used Android smartphones (74.1% (69)) and Windows desktops (90% (81)). Smartphone and desktop versions of PAL were shown to be highly correlated (r = 0.61, p &lt; 0.05). Average performance was better on the desktop device; an upwards bias estimated as 3.52 (±1.96 SD 27 to ‐20) adjusted errors. The usability questionnaire found that 76.6% (59) participants strongly agreed they found the instructions clear and easy to follow and 42.9% (33) strongly agreed that they could see the symbols easily on their mobile phone. Most participants preferred using PAL on a desktop device in terms of ease of use (70.1% (54)) and enjoyment 66.2% (51).ConclusionWe have shown good correlation between iPhone and computer versions of the test, but with some important caveats. The usability data collected here will inform improvements to ensure suitability of PAL on a smartphone device for near patient assessments.

Multi‐modal inadvertent signals enabling the capture of the learning process in real‐time. A new opportunity for preclinical intervention?

AbstractBackgroundGold standard episodic memory tests used to detect AD‐related cognitive decline are insensitive to subjective cognitive decline evident in preclinical AD. We believe a breakdown in the healthy learning process may be a cornerstone in preclinical AD cognitive impairment. We demonstrate the ability to capture the learning process in real‐time using strategic test design, inadvertent eye‐movements and digital ink behavior. We show early evidence of previously unseen learning strategies using data from three participants.MethodWe used the Digital Symbol Digit Learning Test (dSDLT) that we designed to explore learning. One condition presents a key that pairs elementary geometric symbols with numbers and a section of symbols alone, and is administered twice. The participant writes the appropriate digit beneath each symbol using a digitizing pen (providing time‐stamped digital ink coordinates) while wearing a lightweight PupilLabs eye‐tracker (permitting unconstrained head movement, reporting gaze position 240 times/sec to ±2 mm). Time‐synchronized signals measure gaze time in the key. Heat maps show fixation points in the key and response boxes.ResultFigure 1 shows gaze time in the key for each administration (by item, in sequence for one subject), revealing no time in key for some items and less total time in the key for the second administration. We interpret no time in key as paired‐learning. Fixation heat maps showed an expected gaze pattern of looking from the stimulus symbol up to and scanning the key. Unexpected gaze patterns also emerged: Targeted gazes from the stimulus symbol directly to the corresponding symbol in the key, Figure 2, (suggesting spatial placement learning); Within‐key symbol comparisons, indicated by looking back‐and‐forth between items, suggesting figure discrimination learning (Figure3); and Referring back to a recently completed response box containing the same symbol, suggesting working memory (Figure 4).ConclusionMultimodal behavior capture combining inadvertent eye‐tracking signals with digital ink enables the capture of real‐time learning and provides insights into what participants are thinking in addition to what they are doing. The identification of unexpectedly rich, previously unseen learning behaviors provides a glimpse of the complex healthy learning process, provides opportunity to identify strategies heralding preclinical AD and potential preclinical intervention targets.

Normative data for the story recall subtest of the BEM-144 in the Quebec-French population aged 50 years and over

Objective The story recall subtest of the Batterie d’Efficience Mnésique (BEM-144) is a verbal episodic memory test that assesses immediate and episodic memory. Variables such as age, sex, and education level can impact performance on this type of memory test, as can cultural differences. Therefore, the purpose of this study was to establish normative data for the story recall subtest of the BEM-144 in the elderly French-Quebec population. Method The normative sample consisted of 260 healthy individuals aged 50–90 years, all from the province of Quebec, Canada. Analyses were performed to estimate the association between age, sex, and education level on one hand, and immediate and delayed recall performance, on the other hand. Results The results show that all sociodemographic variables are significantly associated with story recall performance. Normative data are proposed in the form of regression equations. Conclusions Overall, these norms will be beneficial for the evaluation and detection of episodic memory impairment in middle-aged and older adults.

The Use of Episodic Memory Tests for Screening in Clinical Trials for Early Alzheimer’s Disease: A Comparison of the Free and Cued Selective Reminding Test (FCSRT) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

BackgroundScreening procedures for early Alzheimer’s disease (AD) trials seek to efficiently identify participants who fulfill clinical and biomarker criteria for AD and enrich for those most likely to experience significant clinical progression during the study. Episodic memory performance is often assessed in screening, but the utility of different memory tests for optimizing screening efficiency and/or rates of clinical progression remains uncertain.ObjectivesCross-study comparisons of the effects of inclusion criteria based on performance on the Free and Cued Selective Reminding Test (FCSRT) or the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) on screen-failure rates for episodic memory and β-amyloid (Aβ) positivity (by CSF or PET) and on subsequent rates of clinical disease progression in randomized participants across three clinical trials in early (prodromal-to-mild) AD.DesignSecondary analyses of cross-sectional and longitudinal clinical trial data.SettingMulti-center international clinical trials.ParticipantsIndividuals with prodromal-to-mild AD screened and/or randomized in clinical trials for crenezumab (CREAD, CREAD2) or semorinemab (Tauriel). Cross-sectional analyses of screening data for episodic memory impairment included participants from CREAD2 (n=2897) and Tauriel (n=887) and for Aβ positivity included participants from CREAD (n=1138), CREAD2 (n=1119), and Tauriel (n=483). Longitudinal analyses of rates of clinical progression included participants from CREAD (n=779), CREAD2 (n=773), and Tauriel (n=331).MeasurementsCross-sectional analyses examined eligibility rates per cutoffs defined for the FCSRT (CREAD, CREAD2) or RBANS (Tauriel) and per Aβ positivity using CSF and/or PET biomarkers. Longitudinal analyses examined rates of clinical progression on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the 13-item version of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), and Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL).ResultsLower rates of study eligibility per episodic memory criteria were seen with the FCSRT (CREAD2) relative to the RBANS (Tauriel), but similar rates of eligibility per Aβ positivity criteria were seen amongst participants with episodic memory impairment per the cutoffs used on either assessment. Similar rates of clinical decline over 18 months on the CDR-SB, ADAS-Cog13, and ADCS-ADL were observed in study populations enriched using the FCSRT (CREAD, CREAD2) or the RBANS (Tauriel).ConclusionsCutoffs for episodic memory impairment on the FCSRT used in the CREAD and CREAD2 studies are more stringent than those on the RBANS used in the Tauriel study, resulting in lower rates of eligibility. However, given that study enrichment with either test yields similar rates of Aβ positivity and clinical progression, considerations beyond these factors may drive the decision of which assessment to use for screening in early AD clinical trials.

Discordant Amyloid Status Diagnosis in Alzheimer's Disease.

Early and accurate Alzheimer's disease (AD) diagnosis has evolved in recent years by the use of specific methods for detecting its histopathological features in concrete cases. Currently, biomarkers in cerebrospinal fluid (CSF) and imaging techniques (amyloid PET) are the most used specific methods. However, some results between both methods are discrepant. Therefore, an evaluation of these discrepant cases is required. The aim of this work is to analyze the characteristics of cases showing discrepancies between methods for detecting amyloid pathology. Patients from the Neurology Department of La Fe Hospital (n = 82) were diagnosed using both methods (CSF biomarkers and amyloid-PET). Statistical analyses were performed using logistic regression, and sex and age were included as covariables. Additionally, results of standard neuropsychological evaluations were taken into account in our analyses. The comparison between CSF biomarker (Aβ42) and amyloid PET results showed that around 18% of cases were discrepant-mainly CFS-negative and PET-positive cases had CSF levels close to the cut-off point. In addition, a correlation between the episodic memory test and CSF biomarkers levels was observed. However, the same results were not obtained for other neuropsychological domains. In general, CSF- and PET-discrepant cases showed altered episodic memory in around 66% of cases, while 33% showed normal performance. In common clinical practice at tertiary memory centers, result discrepancies between tests of amyloid status are far more common than expected. However, episodic memory tests remain an important support method for AD diagnosis, especially in cases with discrepant results between amyloid PET and CSF biomarkers.

Structural and Functional MRI Data Differentially Predict Chronological Age and Behavioral Memory Performance.

Human cognitive abilities decline with increasing chronological age, with decreased explicit memory performance being most strongly affected. However, some older adults show "successful aging," that is, relatively preserved cognitive ability in old age. One explanation for this could be higher brain-structural integrity in these individuals. Alternatively, the brain might recruit existing resources more efficiently or employ compensatory cognitive strategies. Here, we approached this question by testing multiple candidate variables from structural and functional neuroimaging for their ability to predict chronological age and memory performance, respectively. Prediction was performed using support vector machine (SVM) classification and regression across and within two samples of young (N = 106) and older (N = 153) adults. The candidate variables were (1) behavioral response frequencies in an episodic memory test; (2) recently described functional magnetic resonance imaging (fMRI) scores reflecting preservation of functional memory networks; (3) whole-brain fMRI contrasts for novelty processing and subsequent memory; (4) resting-state fMRI maps quantifying voxel-wise signal fluctuation; and (5) gray matter volume estimated from structural MRIs. While age group could be reliably decoded from all variables, chronological age within young and older subjects was best predicted from gray matter volume. In contrast, memory performance was best predicted from task-based fMRI contrasts and particularly single-value fMRI scores, whereas gray matter volume has no predictive power with respect to memory performance in healthy adults. Our results suggest that superior memory performance in healthy older adults is better explained by efficient recruitment of memory networks rather than by preserved brain structure.

The Retrograde Memory for News Events Test (RM-NET) and the relationship between news event memory and performance on standard neuropsychological tests.

Novel tests of semantic memory (SM)-for example, memory for news events (NE; news facts) or famous personalities-are useful for estimating the severity of retrograde amnesia. Individuals with mild cognitive impairment exhibit relatively intact SM/language on traditional neuropsychological tests but exhibit consistent impairment on novel tests of SM, suggesting novel SM tests are dissimilar from traditional SM tests. To identify the relationship between NE memory and traditional cognitive measures, older adults (N = 51) completed a traditional neuropsychological battery and the Retrograde Memory News Events Test (RM-NET; a new test that robustly measures NE memory across the adult life span with high temporal resolution), and the relationship between performance on these tests was examined. Total RM-NET scores were more closely aligned with episodic memory scores than SM scores. The strength of the association between NE scores and episodic memory scores decreased as the age of NE memory increased. Tests of news events appear to reflect performance on traditional tests of episodic memory rather than SM, especially when recent news events are tested.

Effects of saccadic eye movements on episodic & semantic memory fluency in older and younger participants

ABSTRACT Research has demonstrated that performing a sequence of saccadic horizontal eye movements prior to retrieval facilitates performance on tests of episodic memory. This has been observed in both laboratory tasks of retention and autobiographical memory. To date, the work has centred on performance in younger individuals. This paper extends previous investigations by examining the effects of saccadic eye movements in older persons. Autobiographical episodic and semantic memory fluency was assessed in younger (age range 18–35, mean = 22.50), and older (age range 55–87, mean = 70.35) participants following saccadic (vs. fixation control) manipulations. The main effects of eye movements and age were found for episodic autobiographical memory (greater fluency after eye movements and in younger participants). Semantic autobiographical memory showed a main effect of age (greater fluency in younger participants), whereas general semantic memory showed no effect of age or eye movement. These findings indicate that saccadic horizontal eye movements can enhance episodic personal memory in older individuals. This has implications as a technique to improve autobiographical recollection in the elderly and as an adjunct in reminiscence therapy.

The transdiagnostic relationship of cumulative lifetime stress with memory, the hippocampus, and personality psychopathology

Stress has a detrimental impact on memory, the hippocampus, and psychological health. Psychopathology research on stress has centered mainly on psychiatric diagnoses rather than symptom dimensions, and less attention has been given to the neurobiological factors through which stress might be translated into psychopathology. The present work investigates the transdiagnostic relationship of cumulative stress with episodic memory and the hippocampus (both structure and function) and explores the extent to which stress mediates the relationship between personality psychopathology and hippocampal size and activation. Cumulative lifetime stress was assessed in a sample of females recruited to vary in stress exposure and severity of personality psychopathology. Fifty-six participants completed subjective and objective tests of episodic memory, a T2-weighted high-resolution magnetic resonance imaging (MRI) scan of the medial-temporal lobe, and functional MRI (fMRI) scanning during a learning and recognition memory task. Higher cumulative stress was significantly related to memory complaints (but not episodic memory performance), lower bilateral hippocampal volume, and greater encoding-related hippocampal activation during the presentation of novel stimuli. Furthermore, cumulative stress significantly mediated the relationship between personality psychopathology and both hippocampal volume and activation, whereas alternative mediation models were not supported. The findings suggest that structural and functional activation differences in the hippocampus observed in case-control studies of psychiatric diagnoses may share cumulative stress as a common factor, which may mediate broadly reported relationships between psychopathology and hippocampal structure and function.

Distinct neuroanatomical correlates of interference-related verbal episodic memory test in healthy older adults

ABSTRACT Verbal learning test can include a trial of interference process that intrude initial learning and impose additional cognitive stress. However, it has been unclear whether the multiple memory processes underly different brain structural bases. We measured performances of word retrieval that represents distinct memory processes (initial learning, interference, and retention) and regional gray matter morphology from 230 cognitively unimpaired older adults. We identified three distinct multivariate pattern modes using canonical correlation analysis that map correspondence between memory and brain morphometry. The first mode comprised weights highly loaded on temporal lobe and overall performances. The second mode reflected subcortical volumes and initial learning performances. The third mode comprised thickness in the lateral prefrontal and parietal cortex and captured an ability to resist retroactive interference effect. While overall test performance reflected the temporal lobe and whole-gray matter volume, the interim trial of interference signifies neural correlates extending to subcortical and frontoparietal regions.

Perception of Fragmented Letters by Patients With Pathologically Confirmed Dementia With Lewy Bodies or Alzheimer Disease.

Patients with dementia with Lewy bodies perform worse than those with Alzheimer disease (AD) on tests of visual perception, but the clinical utility of these tests remains unknown because studies often had clinically diagnosed groups that may inadvertently cross-contaminate Lewy body disease (LBD) with pure AD pathology, used experimental tests not easily adaptable for clinical use, and had no way to examine relationships between the severity of LBD pathology and degree of cognitive impairment. Therefore, we sought to determine whether performance on a widely used clinical test of visuoperceptual ability effectively differentiates between patients with autopsy-confirmed LBD or AD and correlates with the severity of LBD pathology. Patients with mild to moderate dementia (n = 42) and cognitively healthy controls (n = 22) performed a Fragmented Letters Test in which they identified letters of the alphabet that were randomly visually degraded by 70% and additional visuospatial and episodic memory tests. At autopsy, dementia cases were confirmed to have LBD (n = 19), all with concomitant AD, or only AD (n = 23). Severity of α-synuclein pathology in the hippocampus and neocortex was rated on an ordinal scale. Patients with LBD performed worse than those with AD (B = -2.80 ± 0.91, p = 0.009) and healthy controls (B = -3.34 ± 1.09, p = 0.01) on the Fragmented Letters Test after adjustment for age, sex, education, Mini-Mental State Examination score, and ability to name intact letters. Patients with AD did not differ from controls (B = -0.55 ± 1.08, p = 0.87). The test effectively distinguished between patients with LBD or AD with 73% sensitivity and 87% specificity, and the area under the curve in receiver operating characteristic analyses was 0.85 (95% CI 0.72-0.95), higher than for standard tests of visuospatial ability (Block Design; 0.72; CI 0.35-0.75) or memory (California Verbal Learning Test, trials 1-5; 0.55; CI 0.57-0.88). Fragmented Letters Test scores were negatively correlated with LBD pathology density ratings in hippocampus and neocortical regions (Spearman rs = -0.53 to -0.69). Fragmented Letters Test performance can effectively differentiate patients with LBD pathology from those with only AD pathology at a mild to moderate stage of dementia, even when LBD occurs with significant concomitant AD pathology, and may also be useful for gauging the severity of cortical α-synuclein pathology in those with LBD.

Remote self-administration of digital cognitive tests using the Brief Assessment of Cognition: Feasibility, reliability, and sensitivity to subjective cognitive decline.

Cognitive impairment is a common and pervasive feature of etiologically diverse disorders of the central nervous system, and a target indication for a growing number of symptomatic and disease modifying drugs. Remotely acquired digital endpoints have been recognized for their potential in providing frequent, real-time monitoring of cognition, but their ultimate value will be determined by the reliability and sensitivity of measurement in the populations of interest. To this end, we describe initial validation of remote self-administration of cognitive tests within a regulatorily compliant tablet-based platform. Participants were 61 older adults (age 55+), including 20 individuals with subjective cognitive decline (SCD). To allow comparison between remote (in-home) and site-based testing, participants completed 2 testing sessions 1 week apart. Results for three of four cognitive domains assessed demonstrated equivalence between remote and site-based tests, with high cross-modality ICCs (absolute agreement) for Symbol Coding (ICC = 0.75), Visuospatial Working Memory (ICC = 0.70) and Verbal Fluency (ICC > 0.73). Group differences in these domains were significant and reflected sensitivity to objective cognitive impairment in the SCD group for both remote and site-based testing (p < 0.05). In contrast, performance on tests of verbal episodic memory suggested inflated performance during unmonitored testing and indicate reliable use of remote cognitive assessments may depend on the construct, as well as the population being tested.

Psychological well-being and cognitive aging in Black, Native American, and White Alzheimer's Disease Research Center participants.

Psychological well-being is associated with cognition in later life but has not been examined across diverse populations—including minoritized communities at disproportionately high risk of dementia. Further, most previous work has not been able to examine links between specific facets of psychological well-being and performance within distinct cognitive domains that can capture subclinical impairment. Using a well-characterized sample followed through enrollment in an NIH-funded Alzheimer’s Disease Center, we sought to test these associations within three racial groups at baseline. Participants were N = 529 cognitively unimpaired Black, American Indian/Alaska Native (AI/AN), and white middle-aged and older adults (mean age = 63.6, SD = 8.1, range = 45–88 years) enrolled in the Wisconsin Alzheimer’s Disease Research Center’s Clinical Core. Predictors included validated NIH Toolbox Emotion Battery scales assessing positive affect, general life satisfaction, and meaning and purpose. Outcomes included performance on widely used tests of executive functioning and episodic memory. We conducted race-stratified regression models to assess within-group relationships. Black and AI/AN participants reported lower life satisfaction than white participants. Racial disparities were not observed for positive affect or meaning and purpose scores. Across groups, life satisfaction predicted better executive functioning. Similar associations were observed for positive affect in Black and AI/AN samples but not among whites. In general, well-being measures were not related to performance on tests of episodic memory. Our results highlight well-being as a potentially important determinant of late-life cognitive health, particularly executive functioning, that is modifiable if older adults are connected with appropriate resources and supports. Further, psychological well-being may represent a potent target for brain health interventions tailored for Black and Native communities.

The Western Australia Olfactory Memory Test: Reliability and Validity in a Sample of Older Adults.

The Western Australia Olfactory Memory Test (WAOMT) is a newly developed test designed to meet a need for a comprehensive measure of olfactory episodic memory (OEM) for clinical and research applications. This study aimed to establish the psychometric properties of the WAOMT in a sample of 209 community-dwelling older adults. An independent sample of 27 test-naïve participants were recruited to assess test retest reliability (between 7 and 28days). Scale psychometric properties were examined using item response theory methods, combined samples (final N = 241). Convergent validity was assessed by comparing performance on the WAOMT with a comprehensive neuropsychological battery of domains (verbal and visual episodic memory, and odor identification), as well as other neuropsychological skills. Based on previous literature, it was predicted that the WAOMT would be positively correlated with conceptually similar cognitive domains. The WAOMT is a psychometrically sound test with adequate reliability properties and demonstrated convergent validity with tests of verbal and episodic memory and smell identification. Patterns of performance highlight learning and memory characteristics unique to OEM (e.g., learning curves, cued and free recall). Clinical and research implications include streamlining future versions of the WAOMT to ease patient and administrative burden, and the potential to reliably detect early neuropathological changes in healthy older adults with nonimpaired OEM abilities.

The structural brain network topology of episodic memory.

Episodic memory is supported by a distributed network of brain regions, and this complex network of regions does not operate in isolation. To date, neuroscience research in this area has typically focused on the activation levels in specific regions or pairwise connectivity between such regions. However, research has yet to investigate how the complex interactions of structural brain networks influence episodic memory abilities. We applied graph theory methods to diffusion-based anatomical networks in order to examine the structural architecture of the medial temporal lobe needed to support effective episodic memory functioning. We examined the relationship between performance on tests of verbal and non-verbal episodic memory with node strength, which indexes how well connected a brain region is in the network. Findings mapped onto the Posterior Medial memory system, subserved by the parahippocampal cortex and overlapped with findings of previous studies of episodic memory employing different methodologies. This expands our current understanding by providing independent evidence for the importance of identified regions and suggesting the particular manner in which these regions support episodic memory.

Deficits in spontaneous and stimulus-dependent retrieval as an early sign of abnormal aging

Research on early cognitive markers of Alzheimer’s disease is primarily focused on episodic memory tests that involve deliberate retrieval. Our purpose was to provide clear evidence to support a novel Spontaneous Retrieval Deficit hypothesis, which predicts that people at pre-clinical stages of dementia, including those with amnestic Mild Cognitive Impairment (aMCI), are particularly impaired on tasks based on spontaneous retrieval. We compared 27 aMCI individuals and 27 healthy controls on mind-wandering while performing a task during which there were exposed to either highly meaningful or unmeaningful pictures. The substantial reduction in mind-wandering among individuals with aMCI was found with exposure to highly meaningful stimuli, but not to unmeaningful pictures, and it was most pronounced for past-oriented thoughts, i.e., involuntary autobiographical memories. Those findings provide strong support for this novel hypothesis, and show that it is the spontaneous, but bottom-up and cue-driven processes, for which meaningful environmental stimuli are crucial, that are very promising early markers of the disease.

Lesion-symptom mapping corroborates lateralization of verbal and nonverbal memory processes and identifies distributed brain networks responsible for memory dysfunction

Memory disorders are a common consequence of cerebrovascular accident (CVA). However, uncertainties remain about the exact anatomical correlates of memory impairment and the material-specific lateralization of memory function in the brain.We used lesion-symptom mapping (LSM) in patients with first-time CVA to identify which brain structures are pivotal for verbal and nonverbal memory and to re-examine whether verbal and nonverbal memory functions are lateralized processes in the brain.The cognitive performance of a relatively large cohort of 114 patients in five classic episodic memory tests was analysed with factor analysis. Two factors were extracted that distinguished the verbal and nonverbal components of these memory tests, and their scores were subsequently tested for anatomical correlates by combining univariate and multivariate LSM.LSM analysis revealed for the verbal factor exclusively left-hemispheric insular, subcortical and adjacent white matter regions and for the nonverbal factor exclusively right-hemispheric temporal, occipital, insular, subcortical and adjacent white matter structures.These results corroborate the long-standing hypothesis of a material-specific lateralization of memory function in the brain and confirm a robust association between right temporal lobe lesions and nonverbal memory dysfunction. The right-hemispheric correlates for the nonverbal aspects of episodic memory include not only classic memory structures in the medial temporal lobe but also a more distributed network that includes cortical and subcortical structures also known for implicit memory processes.