Cued Recall Research Articles

Associative memory in alcohol-related contexts: An fMRI study with young binge drinkers.

Alcohol-related cues are known to influence craving levels, a hallmark of alcohol misuse. Binge drinking (BD), a pattern of heavy alcohol use, has been associated with cognitive and neurofunctional alterations, including alcohol attentional bias, memory impairments, as well as disrupted activity in prefrontal- and reward-related regions. However, literature is yet to explore how memories associated with alcohol-related cues are processed by BDs, and how the recall of this information may influence their reward processing. The present functional magnetic resonance imaging (fMRI) study aimed to investigate the neurofunctional signatures of BD during an associative memory task. In all, 36 university students, 20 BDs and 16 alcohol abstainers, were asked to memorize neutral objects paired with either alcohol or non-alcohol-related contexts. Subsequently, neutral stimuli were presented, and participants were asked to classify them as being previously paired with alcohol- or non-alcohol-related contexts. While behavioral performance was similar in both groups, during the recall of alcohol-related cues, BDs showed increased brain activation in two clusters including the thalamus, globus pallidus and dorsal striatum, and cerebellum and occipital fusiform gyrus, respectively. These findings suggest that BDs display augmented brain activity in areas responsible for mental imagery and reward processing when trying to recall alcohol-related cues, which might ultimately contribute to alcohol craving, even without being directly exposed to an alcohol-related context. These results highlight the importance of considering how alcohol-related contexts may influence alcohol-seeking behavior and, consequently, the maintenance or increase in alcohol use.

Associations of Microbleeds and Their Topography With Imaging and CSF Biomarkers of Alzheimer Pathology in Individuals With Down Syndrome.

Cerebral hemorrhages are an exclusion criterion and potential adverse effect of antiamyloid agents. It is, therefore, critical to characterize the natural history of cerebral microbleeds in populations genetically predisposed to Alzheimer disease (AD), such as Down syndrome (DS). We aimed to assess microbleed emergence in adults with DS across the AD spectrum, defining their topography and associations with clinical variables, cognitive outcomes, and fluid and neuroimaging biomarkers. This cross-sectional study included participants aged 18 years or older from the Down-Alzheimer Barcelona Neuroimaging Initiative and Sant Pau Initiative on Neurodegeneration with T1-weighted and susceptibility-weighted images. Participants underwent comprehensive assessments, including apolipoprotein E (APOE) genotyping; fluid and plasma determinations of beta-amyloid, tau, and neurofilament light; cognitive outcomes (Cambridge Cognitive Examination and modified Cued Recall Test); and vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia). We manually segmented microbleeds and characterized their topography. Associations between microbleed severity and AD biomarkers were explored using between-group comparisons (none vs 1 vs 2+) and multivariate linear models. We included 276 individuals with DS and 158 healthy euploid controls (mean age = 47.8 years, 50.92% female). Individuals with DS were more likely to have microbleeds than controls (20% vs 8.9%, p < 0.001), with more severe presentation (12% with 2+ vs 1.9%). Microbleeds increased with age (12% 20-30 years vs 60% > 60 years) and AD clinical stage (12.42% asymptomatic, 27.9% prodromal, 35.09% dementia) were more common in APOEε4 carriers (26% vs 18.3% noncarriers, p = 0.008), but not associated with vascular risk factors (p > 0.05). Microbleeds were predominantly posterior (cerebellum 33.66%; occipital 14.85%; temporal 21.29%) in participants with DS. Associations with microbleed severity were found for neuroimaging and fluid AD biomarkers, but only hippocampal volumes (standardized β = -0.18 [-0.31, -0.06], p < 0.005) and CSF p-tau-181 concentrations (β = 0.26 [0.12, 0.41], p < 0.005) survived regression controlling for age and disease stage, respectively. Microbleeds had limited effect on cognitive outcomes. In participants with DS, microbleeds present with a posterior, lobar predominance, are associated with disease severity, but do not affect cognitive performance. These results suggest an interplay between AD pathology and vascular lesions, implicating microbleeds as a risk factor limiting the use of antiamyloid agents in this population.

Amyloid age and tau PET timeline to symptomatic Alzheimer's disease in Down syndrome.

Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD). Recent natural history cohort studies have characterized AD biomarkers, with a focus on PET amyloid-beta (Aβ) and PET tau. Leveraging these well-characterized biomarkers, the present study examined the timeline to symptomatic AD based on estimated years since reaching Aβ+, referred to as "amyloid age", and in relation to tau in a large cohort of individuals with DS. In this multicenter cohort study, 25 - 57-year-old adults with DS (n = 167) were assessed twice from 2017 to 2022, with approximately 32 months between visits as part of the Alzheimer Biomarker Consortium - Down Syndrome. Adults with DS completed amyloid and tau PET scans, and were administered the modified Cued Recall Test and the Down Syndrome Mental Status Examination. Study partners completed the National Task Group-Early Detection Screen for Dementia. Mixed linear regressions showed significant quadratic associations between amyloid age and cognitive performance and cubic associations between amyloid age and tau, both at baseline and across 32 months. Using broken stick regression models, differences in mCRT scores were detected beginning 2.7 years following Aβ+ in cross-sectional models, with an estimated decline of 1.3 points per year. Increases in tau began, on average, 2.7 - 6.1 years following Aβ+. On average, participants with mild cognitive impairment were 7.4 years post Aβ+ and those with dementia were 12.7 years post Aβ+. There is a short timeline to initial cognitive decline and dementia from Aβ+ (Centiloid = 18) and tau deposition in DS relative to late onset AD. The established timeline based on amyloid age (or equivalent Centiloid values) is important for clinical practice and informing AD clinical trials, and avoids limitations of timelines based on chronological age. Funding. National Institute on Aging and the National Institute for Child Health and Human Development. Evidence before this study: We searched PubMed for articles published involving the progression of Aβ and tau deposition in adults with Down syndrome from database inception to March 1, 2024. Terms included "amyloid", "Down syndrome", "tau", "Alzheimer's disease", "cognitive decline", and "amyloid chronicity," with no language restrictions. One previous study outlined the progression of tau in adults with Down syndrome without consideration of cognitive decline or clinical status. Other studies reported cognitive decline associated with Aβ burden and estimated years to AD symptom onset in Down syndrome. Amyloid age estimates have also been created for older neurotypical adults and compared to cognitive performance, but this has not been investigated in Down syndrome.Added value of this study: The timeline to symptomatic Alzheimer's disease in relation to amyloid, expressed as duration of Aβ+, and tau has yet to be described in adults with Down syndrome. Our longitudinal study is the first to provide a timeline of cognitive decline and transition to mild cognitive impairment and dementia in relation to Aβ+.Implications of all the available evidence: In a cohort study of 167 adults with Down syndrome, cognitive decline began 2.7 - 5.4 years and tau deposition began 2.7 - 6.1 years following Aβ+ (Centiloid = 18). Adults with Down syndrome converted to MCI after ~7 years and dementia after ~12-13 years of Aβ+. This shortened timeline to AD symptomology from Aβ+ and tau deposition in DS based on amyloid age (or corresponding Centiloid values) can inform clinical AD intervention trials and is of use in clinical settings.

Assessing amyloid PET positivity and cognitive function in Down syndrome to guide clinical trials targeting amyloid.

Trisomy 21, or Down syndrome (DS), predisposes individuals to early-onset Alzheimer's disease (AD). While monoclonal antibodies (mAbs) targeting amyloid are approved for older AD patients, their efficacy in DS remains unexplored. This study examines amyloid positron emission tomography (PET) positivity (A+), memory function, and clinical status across ages in DS to guide mAb trial designs. Cross-sectional data from the Alzheimer Biomarker Consortium-Down Syndrome (ABC-DS) was analyzed. PET amyloid beta in Centiloids classified amyloid status using various cutoffs. Episodic memory was assessed using the modified Cued Recall Test, and clinical status was determined through consensus processes. Four hundred nine DS adults (mean age=44.83 years) were evaluated. A+ rates increased with age, with mean amyloid load rising significantly. Memory decline and cognitive impairment are also correlated with age. These findings emphasize the necessity of tailoring mAb trials for DS, considering age-related AD characteristics. There is rapid increase in prevalence of amyloid beta (Aβ) positron emission tomography (PET) positivity in Down syndrome (DS) after the age of 40 years. Aβ PET positivity thresholds have significant impact on prevalence rates in DS. There is a significant lag between Aβ PET positivity and clinical symptom onset in DS.

Recall and recognition of similarities items in neuropsychological assessment: Memory, validity, and meaning

The current study examined whether the Memory Similarities Extended Test (M-SET), a memory test based on the Similarities subtest of the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II), has value in neuropsychological testing. The relationship of M-SET measures of cued recall (CR) and recognition memory (REC) to brain injury severity and memory scores from the Wechsler Memory Scale, Fourth Edition (WMS-IV) was analyzed in examinees with traumatic brain injuries ranging from mild to severe. Examinees who passed standard validity tests were divided into groups with intracranial injury (CT + ve, n = 18) and without intracranial injury (CT-ve, n = 50). In CT + ve only, CR was significantly correlated with Logical Memory I (LMI: rs = .62) and Logical Memory II (LMII: rs = .65). In both groups, there were smaller correlations with delayed visual memory (VRII: rs = .38; rs = .44) and psychomotor speed (Coding: rs = .29; rs = .29). The REC score was neither an indicator of memory ability nor an internal indicator of performance validity. There were no differences in M-SET or WMS-IV scores for CT-ve and CT + ve, and reasons for this are discussed. It is concluded that M-SET has utility as an incidental cued recall measure.

Amnesia after Repeated Head Impact Is Caused by Impaired Synaptic Plasticity in the Memory Engram.

Subconcussive head impacts are associated with the development of acute and chronic cognitive deficits. We recently reported that high-frequency head impact (HFHI) causes chronic cognitive deficits in mice through synaptic changes. To better understand the mechanisms underlying HFHI-induced memory decline, we used TRAP2/Ai32 transgenic mice to enable visualization and manipulation of memory engrams. We labeled the fear memory engram in male and female mice exposed to an aversive experience and subjected them to sham or HFHI. Upon subsequent exposure to natural memory recall cues, sham, but not HFHI, mice successfully retrieved fearful memories. In sham mice the hippocampal engram neurons exhibited synaptic plasticity, evident in amplified AMPA:NMDA ratio, enhanced AMPA-weighted tau, and increased dendritic spine volume compared with nonengram neurons. In contrast, although HFHI mice retained a comparable number of hippocampal engram neurons, these neurons did not undergo synaptic plasticity. This lack of plasticity coincided with impaired activation of the engram network, leading to retrograde amnesia in HFHI mice. We validated that the memory deficits induced by HFHI stem from synaptic plasticity impairments by artificially activating the engram using optogenetics and found that stimulated memory recall was identical in both sham and HFHI mice. Our work shows that chronic cognitive impairment after HFHI is a result of deficiencies in synaptic plasticity instead of a loss in neuronal infrastructure, and we can reinstate a forgotten memory in the amnestic brain by stimulating the memory engram. Targeting synaptic plasticity may have therapeutic potential for treating memory impairments caused by repeated head impacts.

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.

Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

1. Validity and reliability of CAMCOG‐DS2 and other cognitive outcomes measures for clinical trials of AD in DS

AbstractBackgroundDown syndrome (DS) is an important population to include in clinical trials aiming to prevent or delay Alzheimer’s disease (AD). This talk will summarise previous work in trajectory modelling to identify the earliest ages of change in cognition and the optimal sample sizes needed for clinical trials in DS. It will present validate data on the new version of the Cambridge Cognitive Examination–Down syndrome version II (CAMCOG‐DS‐II) alongside established cognitive tests. The CAMCOG‐DS‐II has been developed to assess cognitive impairments associated with dementia in people with DS.MethodThis was an observational, multicentre, longitudinal study (n = 174) across seven existing cohorts in six different European languages to validate cognitive tests in adults with DS aged 25 years and older. It assessed the relationships between tests of cognition, behaviour, function, and health. Cognitive assessments included the CAMCOG‐DS‐II, the CANTAB Paired Associates Learning (PAL) Task, the modified Cued Recall Test (mCRT) and the Purdue Pegboard Test. We examined correlations between tests, group differences between those with and without dementia and explored test‐retest reliability of the CAMCOG‐DS‐II.ResultOur results showed that completion rates for the CAMCOG‐DS‐II were high, and floor and ceiling effects were low. The CAMCOG‐DS‐II memory sub‐score correlated significantly with the mCRT total recall score (Spearman’s ∼0.5), and the praxis sub‐score significantly correlated with the Purdue Pegboard total score (Spearman’s &gt;0.7).ConclusionThere is currently a critical lack of suitable diagnostic and outcome measures that can be used in clinical trials. These results show that the CAMCOG‐DS‐II is a feasible test of cognition and will help to provide sensitive cognitive endpoints for clinical trials which are seeking to find suitable treatments for AD in adults with DS. Future analysis will include trajectories of change from baseline to one year of follow up for each primary outcome measure.

Memory impairment in Alzheimer’s disease is associated with Dentate Gyrus atrophy: A pilot study using the Uniform Data Set Neuropsychological Battery and 7 Tesla MRI

AbstractBackgroundThe neuropsychological battery of the Uniform Data Set (UDSNB3.0) (Weintraub et al., 2009) assesses cognition. The neuroanatomical correlates of the UDSNB3.0 have not yet been investigated. 7T MRI was used to investigate correlations between hippocampal subfield volumes and the UDSNB3.0 for Alzheimer’s disease (AD) and age‐matched healthy control (HC).Method28 (15 AD, 13 HC) participants (61% female; aged 42‐79) were recruited. A Phillips Achieva 7T scanner used a Nova Medical (Wilmington MA, USA) single‐channel transmit, 32 channel receive (1Tx32Rx) head‐coil. PSIR images (TE/TR = 119/59001ms, FA = 90o, 0.38×0.39×1.50 mm3 resolution) were segmented into Cornu Ammonis (CA = CA1+CA2+CA3), Subiculum (SUB), Dentate Gyrus (DG), and Entorhinal Cortex (ERC) (Figure 1). The UDSNB3.0, administered by trained Assistant Psychologists, included the MoCA and a variety of cognitive tests assessing memory (immediate/delayed recall, un‐cued/cued recall, and recognition), attention, language and visuospatial abilities.ResultIn the whole analysed sample (n = 28), there were strong positive correlations between UDS3.0 memory test scores and hippocampal subfield volumes (Figure 2). There were significant reductions in the volume of each hippocampal subfield in AD, compared with controls (p&lt;0.05). No significant decrease in the whole brain volume was noted between the two groups (p&gt;0.05), indicating that hippocampal volume loss was not part of whole brain atrophy. One‐way ANOVA’s demonstrated significant differences between HC and AD test scores (p&lt;0.05), thus HC and AD participants were analysed separately. In AD participants, whole hippocampal volume correlated with MoCA memory category cue scores (R2 = 0.54, p&lt;0.05) but only significantly in the DG of the hippocampal subfields (R2 = 0.52, p&lt;0.05) (Figure 3), supporting Novellino et al.’s (2018) previous finding of associations between the DG volume and cued recall. No such significant correlations were observed in HC participants.ConclusionThe results of this study confirm that hippocampal atrophy in AD is associated with cognitive decline. Additionally, our results suggest that 7T MRI may be able to detect subtle in vivo DG atrophy in AD that is related to cued memory. The 7T scans appear to reveal DG changes in AD that to date have been confirmed in neuropathological studies only.Funding: The Medical Research Council, UK has funded AAH (MR/T005580/1).

Association Between Neuroimaging Biomarkers, Plasma NfL, and Memory Performance in Adults With Down Syndrome With and Without Dementia

AbstractBackgroundDown syndrome (DS) is associated with early development of Alzheimer’s disease pathology. Both the severity of tau pathology and the increase of neurofilament light chain (NfL) protein are correlated with cognitive decline in the neurotypical populations. Here, we assessed whether tau accumulation in the hippocampus and entorhinal cortex and plasma NfL concentrations were associated with memory performance in adults with DS.MethodWe used 18F‐AV‐1451 (FTP) positron emission tomography (PET) to assess tau accumulation in 44 participants enrolled in the multi‐site Alzheimer’s Disease in Down syndrome (ADDS) study (age 50.72 + 6.21). FTP‐PET scans were partial volume‐corrected, and weighted standardized uptake value ratio (SUVR) were calculated for each of the following regions of interests (ROIs): entorhinal cortex, hippocampus, and the precentral gyrus (control). Participants' plasma NfL concentration (in pg/mL) was measured on a single plex plate using the ultra‐sensitive single molecule array (Simoa) technology platform HD‐X. Memory performance was measured with the modified Cued Recall Test. We evaluated the relationship between FTP SUVRs, NfL, and memory performance using linear regression analysis. Sex and site were used as covariates.ResultIncreased FTP SUVR in the hippocampus and entorhinal cortex were associated with lower scores on free recall (hippocampus: r2 = 0.53, p &lt;0.001; entorhinal: r2 = 0.35, p &lt;0.001) and total recall (hippocampus: r2 = 0.46, p &lt;0.001; entorhinal: r2 = 0.29, p &lt;0.01). As expected, no association between FTP SUVRs and memory performance was found in the precentral gyrus. Additionally, higher plasma NfL concentrations were associated with lower free recall (r2 = 0.35, p &lt;0.001) and total recall (r2 = 0.29, p &lt;0.01). Further, increased levels of plasma NfL were associated with increased FTP SUVRs in the hippocampus (r2 = 0.38, p &lt;0.001), entorhinal cortex (r2 = 0.28, p&lt;0.01), and precentral gyrus (r2 = 0.19, p&lt;0.05).ConclusionIncreased levels of both in‐vivo tau in medial temporal ROIs and NfL in plasma were associated with worse memory performance, consistent with observations in the neurotypical population. Future work will investigate the impact of tau accumulation and NfL concentration on longitudinal cognitive decline in older adults with DS.

Nucleus accumbens local circuit for cue-dependent aversive learning

Response to threatening environmental stimuli requires detection and encoding of important environmental features that dictate threat. Aversive events are highly salient, which promotes associative learning about stimuli that signal this threat. The nucleus accumbens is uniquely positioned to process this salient, aversive information and promote motivated output, through plasticity on the major projection neurons in the brain area. We describe a nucleus accumbens core local circuit whereby excitatory plasticity facilitates learning and recall of discrete aversive cues. We demonstrate that putative nucleus accumbens substance P release and long-term excitatory plasticity on dopamine 2 receptor-expressing projection neurons are required for cue-dependent fear learning. Additionally, we find that fear learning and recall is dependent on distinct projection neuron subtypes. Our work demonstrates a critical role for nucleus accumbens substance P in cue-dependent aversive learning.

52 Memory Learning Curve and in vivo Brain Pathology in Non-Demented Individuals with Autosomal Dominant Alzheimer’s Disease: Findings from the Colombia-Boston Biomarker Study

Objective:Associative memory is impacted early in Alzheimer’s disease (AD). Poorer performance on associative memory tests has been related to greater amyloid and regional tau burden in preclinical AD. Our group previously examined the association of brain pathology and performance on the Free and Cued Selective Reminding Test (FCSRT) in Autosomal Dominant Alzheimer’s Disease (ADAD), finding that associative memory summary scores distinguished non-demented mutation carriers from non-carriers several years before clinical onset of cognitive impairment. In the current study, we examined whether FCSRT learning slopes were associated with brain pathology in a sample of ADAD carriers and non-carriers.Participants and Methods:There were 119 participants including 57 non-demented carriers of the Colombian kindred with the Presenilin1 E280A mutation and 62 non-carrier family members (mean age= 36.3, 60% female). Participants were administered the Mini-Mental State Examination (MMSE), a measure of global cognitive status, and the FCSRT, which consists of three trials in which participants are asked to freely recall the same list of 16 items. It is a well-established measure known to be sensitive to early changes in AD. A subsample of 69 participants (32 carriers and 37 non-carriers) underwent positron emission tomography (PET) to measure in vivo cortical amyloid-beta (Pittsburgh compound B, PiB), and regional tau (Flortaucipir, FTP) burden in entorhinal and precuneus regions, which are among the earliest sites of tau accumulation in this ADAD population. Mann Whitney U tests, Spearman correlations, and chi-square tests were used to examine group differences and relations among variables of interest. Learning slope was calculated by subtracting the number of items freely recalled in FCSRT Trial 1 from the number of items freely recalled in Trial 3.Results:Compared to non-carriers, carriers had greater cortical amyloid-ß and regional tau burden, lower MMSE scores (mean [SD]: carriers= 27.5 [2.7]; non-carriers= 28.8 [1.0]), and lower scores on total immediate/ delayed free/ cued recall scores on the FCSRT (all p&lt;.01). The groups did not differ on age, sex, or education level (all p&gt; 0.05). In the whole sample and in carriers only, we found that higher MMSE scores were associated with higher learning slope, meaning faster learning (whole group p= 0.25, p= 0.006; carriers p= 0.30, p=0.029). In the whole sample, we found that lower learning slope was associated with higher levels of amyloid (p=-.34, p=.006) and tau in the left, right, and bilateral precuneus region (p=-.43, p&lt;.001; p=-.46, p&lt;.001; p=-.45, p&lt;.001). In carriers only, lower learning slope was associated with higher tau burden in the left, right, and bilateral precuneus specifically (p=-.43, p=.017; p=-.48, p=.008; p=-.46, p=.010, respectively). No significant associations were found in non-carriers.Conclusions:These findings suggest that learning curves on an associative memory test may be sensitive to preclinical pathological changes in AD, specifically within the precuneus, a brain region known to be involved in cue reactivity, episodic memory retrieval, and mental imagery strategies. Future studies with larger samples are warranted to further examine associations between the FCSRT learning curves and regional tau accumulation in individuals with ADAD.

13 Verbal Memory and Learning Strategies in an Autistic Sample Using the CVLT

Objective:The present study aims to better understand learning strategies and difficulties in autistic youth. Previous studies have found that autistic youth have difficulties with executive function skills and poorer performance in memory and learning tasks, especially those that require spontaneous retrieval of information compared to memory tasks that provide external retrieval cues. Additionally, it has been theorized that autistic youth employ a serial approach rather than a semantic approach to learning. The current study hypothesized that the autistic sample will have (a) significant difficulties in learning and memory, (b) employ a serial approach more frequently and a semantic approach less frequently than the CVLT normative sample, and (c) will benefit significantly when provided with external retrieval cues.Participants and Methods:Archival data from a mixed clinical and research database were examined for this study. Participants include 740 autistic individuals between the ages of 5.50 and 24.3 (M = 10.90, SD = 2.98). The sample consisted of 22.2% girls and 34.0% Black, Indigenous, and people of color (BIPOC). All individuals had a FSIQ &gt; 70 (M = 99.91, SD = 16.09) and were clinically diagnosed with autism using DSM-IV-TR or DSM-V criteria by a clinician at an autism diagnostic center. Participants completed the age-appropriate California Verbal Learning Test (CVLT, Delis et al. 1987) which is a neuropsychological measure that examines verbal memory and learning. One-sample t-tests were used to examine the sample's verbal memory abilities and their learning strategies. A paired sample t-test was used to evaluate the sample's performance before and after an external retrieval cue was given.Results:Results from the one-sample t-tests indicate that the autistic sample performed worse than the CVLT normative data with a large effect size (t(739)= -9.440, p &lt;.001, Cohen's d = 1.292). Secondly, the autistic sample was less likely to use a semantic learning approach (t(739) = -1.841, p = .033, Cohen's d = 1.234), but not more likely to use a serial approach (t(739)=-.040, p=.484) compared to the normative sample. Lastly, the paired sample t-test results show that the sample performed significantly better after receiving the external retrieval cue (t(739)=-2.570, p=.005, Cohen's d = .770).Conclusions:The data supported the first hypothesis; autistic individuals have increased difficulties with learning and verbal memory. However, the data only partially support the second hypothesis. The sample was less likely to use a semantic approach to learning but was not more likely to use serial learning. This finding is opposed to the Weak Central Coherence (WCC) theory, which suggests that autistic individuals are more likely to have detail-oriented, bottom-up cognitive thinking styles, consistent with a serial learning strategy. Lastly, data showed improvement when autistic individuals received a retrieval cue. This result supports the Task Support Hypothesis (TSH) and indicates that autistic individuals benefit from cues for memory recall, particularly those that capitalize on their areas of strength. This study did not use a control group and is limited in ethno-racial diversity; therefore, these are preliminarily findings that require further replication.

AT(N) biomarker profiles and Alzheimer's disease symptomology in Down syndrome.

Down syndrome (DS) is a genetic cause of early-onset Alzheimer's disease (AD). The National Institute on Aging-Alzheimer's Association AT(N) Research Framework is a staging model for AD biomarkers but has not been assessed in DS. Data are from the Alzheimer's Biomarker Consortium-Down Syndrome. Positron emission tomography (PET) amyloid beta (Aβ; 15 mCi of [11 C]Pittsburgh compound B) and tau (10 mCi of [18 F]AV-1451) were used to classify amyloid (A) -/+ and tau (T) +/-. Hippocampal volume classified neurodegeneration (N) -/+. The modified Cued Recall Test assessed episodic memory. Analyses included 162 adults with DS (aged M=38.84 years, standard deviation=8.41). Overall, 69.8% of participants were classified as A-/T-/(N)-, 11.1% were A+/T-/(N)-, 5.6% were A+/T+/(N)-, and 9.3% were A+/T+/(N)+. Participants deemed cognitively stable were most likely to be A-T-(N)- and A+T-(N)-. Tau PET (T+) most closely aligning with memory impairment and AD clinical status. Findings add to understanding of AT(N) biomarker profiles in DS. Overall, 69.8% of adults with Down syndrome (DS) aged 25 to 61 years were classified as amyloid (A)-/tau (T)-/neurodegeneration (N)-, 11.1% were A+/T-/(N)-, 5.6% were A+/T+/(N)-, and 9.3% were A+/T+/(N)+. The AT(N) profiles were associated with clinical Alzheimer's disease (AD) status and with memory performance, with the presence of T+ aligned with AD clinical symptomology. Findings inform models for predicting the transition to the prodromal stage of AD in DS.

Variability across subjects in free recall versus cued recall.

Memory scientists usually compare mean performance on some measure(s) (accuracy, confidence, latency) as a function of experimental condition. Some researchers have made within-subject variability in task performance a focal outcome measure (e.g., Yao et al., Journal of Clinical and Experimental Neuropsychology, 38, 227-237, 2016). Here, we explored between-subject variability in accuracy as a function of experimental conditions. This work was inspired by an incidental finding in a previous study, in which we observed greater variability in accuracy of memory performance on cued recall (CR) versus free recall (FR) of English animal/object nouns (Mah et al., Frontiers in Psychology, 14, 1146200, 2023). Here we report experiments designed to assess the reliability of that pattern and to explore its causes (e.g., differential interpretation of instructions, [un]relatedness of CR word pairs, encoding time). In Experiment 1 (N = 120 undergraduates), we replicated the CR:FR variability difference with a more representative set of English nouns. In Experiments 2A (N = 117 Prolific participants) and 2B (N = 127 undergraduates), we found that the CR:FR variability difference persisted in a forced-recall procedure. In Experiment 3 (N = 260 Prolific participants), we used meaningfully related word pairs and still found greater variability in CR than in FR performance. In Experiment 4 (N = 360 Prolific participants), we equated CR and FR study phases by having all participants study pairs and, again, observed greater variability in CR than FR. The same was true in Experiment 5 (N = 120 undergraduates), in which study time was self-paced. Comparisons of variability across subjects can yield insights into the mechanisms underlying task performance.

Physical activity engagement, memory function, and hippocampal volume in adults with down syndrome

AbstractBackgroundHigher engagement in moderate‐to‐vigorous physical activity (PA) is related to better cognitive functioning in neurotypical adults; however, little is known about the impact of PA on cognitive aging in adults with Down syndrome (DS). Individuals with DS have three copies of the chromosome 21, which includes the gene for the amyloid precursor protein, resulting in an increased risk for/earlier onset of Alzheimer’s disease. The goal of this study was to understand the relationship between moderate PA engagement and memory functioning in non‐demented adults with DS.MethodAdults with DS participated in an ancillary Lifestyle study linked to the Alzheimer’s Biomarkers Consortium for Down Syndrome (N = 54). Participants completed the Cued Recall Test (CRT) to measure episodic memory. The total free + cued CRT score was used in analyses. Participants wore a wrist‐worn accelerometer (GT9X) for 7 days to measure PA. Moderate PA was classified using the Freedson cutpoints in ActiLife software and was defined as the daily average minutes. Structural MRI data were acquired within 18 months of actigraphy/cognitive data collection. Hippocampal volume was extracted using Freesurfer v5.3. Associations between moderate PA engagement, memory, and hippocampal volume were evaluated with hierarchical linear regressions controlling for relevant covariates (age, body mass index (BMI), intracranial volume (ICV)).ResultParticipants were 37.81 years old (SD = 8.15 years) and 55.6% female. They spent ∼10.67% of their time engaged in moderate PA (SD = 7.48%). Participants recalled an average of 32.09 items on the CRT (SD = 6.09, range = 7‐36). After controlling for age and BMI, greater moderate PA engagement was associated with higher total recall score (b = 0.279, p = 0.044). After controlling for age and ICV, moderate PA engagement was not significantly associated with hippocampal volume (p = 0.48). Greater hippocampal volume was associated with higher total recall score after controlling for age and ICV (b = 0.496, p = 0.004).ConclusionA higher proportion of time spent engaging in moderate PA was related to better memory function in adults with DS. While greater hippocampal volume was related to better memory performance, it was not associated with moderate PA engagement. Greater moderate PA engagement may be a promising lifestyle behavior to preserve memory in aging adults with DS.

Free recall versus combined cued recall and recognition to detect true memory impairment on the Montreal Cognitive Assessment

AbstractBackgroundThe Montreal Cognitive Assessment (MoCA) is widely used as a brief screening measure to characterize overall cognitive status. Although only delayed free recall of the brief 5‐item memory list contributes to widely used MoCA total scores, the optional cued recall and multiple‐choice recognition subtests may provide better diagnostic accuracy than free recall alone.MethodData on 719 individuals with Mild Cognitive Impairment and 601 cognitively unimpaired controls were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The Rey Auditory Verbal Learning Test (AVLT) delayed free recall condition was used to characterize level of memory performance. Participants with demographically adjusted T‐scores of ≤ 2 SDs below the mean were classified as ‘impaired.’ Binary logistic regressions assessed if combined MoCA cued/recognition performance was a significant predictor of impaired delayed recall on the AVLT beyond the contribution of free recall and while covarying for age, education, and gender. Sensitivity, specificity, and likelihood ratio values were also examined for the MoCA free recall and combined cued/recognition scores.ResultFree recall on the MoCA was a significant predictor of delayed recall on the AVLT (b = ‐1.207, Wald χ2 (1) = 128.044, p &lt; 0.001, OR = 0.299, 95%CI = [0.243, 0.369]. The addition of the combined MoCA cued recall/recognition conditions improved the overall model fit (χ2(1) = 30.616, p&lt;.001) and predicted impaired AVLT recall such that for every additional word on combined MoCA cued recall/recognition, the likelihood of being in the AVLT memory impaired group decreased by 33% (b = ‐0.400, Wald χ2 (1) = 29.834, p &lt; 0.001, OR = 0.670, 95%CI = [0. 581, 0.774]). Combined MoCA cued recall/recognition had both higher specificity and likelihood ratios in detecting AVLT memory impairment than MoCA free recall, while higher sensitivity values were present for MoCA free recall (see Table 1).ConclusionUse of combined cued/recognition memory conditions provides clinicians with improved diagnostic accuracy in detecting memory impairment. In settings where specificity in detecting memory impairment is important, administration of the MoCA free recall as well as cued recall and recognition conditions is recommended.

Amyloid and tau deposition influences cognitive and functional decline in Down Syndrome

AbstractBackgroundDown Syndrome (DS) is the most common neurodevelopmental disorder caused by the presence of trisomy 21 (1:800 to 1:1000 live births worldwide). The extra copy of chromosome 21 is associated with a 4‐5 fold overexpression of the amyloid precursor protein (APP) gene, increased accumulation of cerebral beta‐amyloid (Aβ) in the brain, subsequent neurofibrillary tangle (NFT) formation and neurodegeneration. This study investigates whether tau has (i) an independent effect from amyloid on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid in the exacerbation of decline in aging DS.Method105 participants with DS underwent baseline PET AV‐1451 and PET PiB scans to quantify tau deposition in Braak regions II‐VI and Striatum and amyloid‐β status respectively. A longitudinal cognitive testing battery was performed consistent with previous research in the same study cohort, with all participants completing at least two timepoints, and 26 completing three timepoints, with an average of 17 months between study visits. Linear Mixed Effects models were implemented to assess how tau and amyloid deposition are related to change over three time points.ResultThree cognitive outcome measures showed a significant effect of time: the Free + Cued Recall (t = ‐6.09, p &lt; 0.01), Cued Intrusions (t = 3.19, p &lt; 0.01) and NTG (z = 5.33, p = 0) variables. Tau SUVR was a significant independent predictor of cognitive and functional change. The three‐way interaction between time, PiB status and tau was significant in the models of episodic memory and visuospatial cognition (Figures 1‐3).ConclusionOur results contribute to an emerging framework in which the elevated risk of developing dementia involves mechanisms associated with both amyloid‐β and tau aggregation. This is supported by our finding that when including the two‐way interactions between amyloid status and time and regional tau and time in the same model, tau seems to be a more significant predictor of cognitive change over time than amyloid status. Our results suggest a synergistic relationship between PiB status and tau as predictors of change in memory and visuospatial cognition.

AT(N) Biomarker profiles and Alzheimer’s Disease clinical status and memory in adults with down syndrome

AbstractBackgroundDown syndrome (DS) is seen as a genetic form of Alzheimer’s disease (AD). The National Institute on Aging and the Alzheimer’s Association proposed the AT(N) model for classifying AD biomarkers of amyloid (A), tau (T), and neurodegeneration or neuronal injury ([N]) in non‐DS populations. It is not yet known how the AT(N) classification system maps onto AD pathology and symptomology in DS. The goals of the present study were to: 1) examine AT(N) profiles in DS based on PET amyloid‐beta (Aβ) (A), tau PET (T), and hippocampal volume ([N]); and 2) evaluate potential differences in clinical AD status and memory performance by AT(N) profile in DS.MethodAnalyses included 138 adults with DS (age: M = 39.1, SD = 8.0) enrolled in the Alzheimer’s Biomarker Consortium‐ Down Syndrome study. PET Aβ and tau were assessed using [11C]PiB and [18F]AV‐1451. Structural MRI data was used to index hippocampal volume and adjusted for intracranial volume. Thresholds for elevated (+ vs. ‐) A (Aβ CL &gt;19), T (tau composite SUVr &gt;1.21) and (N) (hippocampal volume &lt; 1 SD from sample mean) were based on prior studies. Clinical AD status (cognitively stable, mild cognitive impairment [MCI‐DS], dementia, and unable to determine) were based on direct measures and caregiver‐report but blind to imaging and biofluid data. The Cued Recall Test was used to assess episodic memory.ResultOverall, 66% of participants were A‐/T‐/(N)‐, 14% were A+/T‐/(N)‐, 9% were A+/T+/(N)‐, and 5% were A+/T+/(N)+. The remaining 6% had an alternative profile (e.g. A‐/T‐/(N)+). One‐way analyses of variance indicated a significant difference in age and clinical AD status by A/T/N profile. General linear models controlling for age and premorbid intellectual disability level indicated differences in memory by A/T/(N) profile.ConclusionThis study adds to the understanding of AT(N) biomarker profiles in DS and their association with AD symptomology. Clinical AD status of MCI‐DS and dementia and worse memory performance were associated with elevated T and (N), in line with non‐DS populations. The unable to determine status paralleled the MCI and dementia status groups. Findings inform models that predict the transition to AD in DS.aging after age 90.

A direct replication and extension of Popp and Serra (2016, experiment 1): better free recall and worse cued recall of animal names than object names, accounting for semantic similarity.

Free recall tends to be better for names of animate concepts such as animals than for names of inanimate objects. In Popp and Serra's 2016 article, the authors replicated this "animacy effect" in free recall but when participants studied words in pairs (animate-animate pairs intermixed with inanimate-inanimate pairs) and were tested with cued recall, performance was better for inanimate-inanimate pairs than for animate-animate pairs ("reverse animacy"). We tested the replicability of this surprising effect and one possible explanation for the effect (semantic similarity). Our Experiment 1 was a preregistered direct replication (N = 101) of Popp and Serra's Experiment 1 (mixed-lists condition). In a second preregistered experiment conducted in four different samples (undergraduate N = 153, undergraduate N = 143, online Prolific N = 101, online Prolific/English-as-a-first-language N = 150), we manipulated the within-category semantic similarity of animal and object wordlists. AIn Experiment 1, just as in Popp and Serra, we observed an animacy effect for free recall and a reverse animacy effect for cued recall. Unlike Popp and Serra, we found that controlling for interference effects rendered the reverse animacy effect non-significant. We took this as evidence that characteristics of the stimulus sets (e.g., category structure, within-category similarity) may play a role in animacy and reverse animacy effects. In Experiment 2, in three out of our four samples, we observed reverse animacy effects when within-category similarity was higher for animals and when within-category similarity was equated for animals and objects. Our results suggest that the reverse animacy effect observed in Popp and Serra's 2016 article is a robust and replicable effect, but that semantic similarity alone cannot explain the effect.