Memory Test Research Articles

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116).

To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time. Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results. BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.

Algorithmic Spaced Retrieval Enhances Long-Term Memory in Alzheimer Disease: Case-Control Pilot Study.

Spaced retrieval is a learning technique that involves engaging in repeated memory testing after increasingly lengthy intervals of time. Spaced retrieval has been shown to improve long-term memory in Alzheimer disease (AD), but it has historically been difficult to implement in the everyday lives of individuals with AD. This research aims to determine, in people with mild cognitive impairment (MCI) due to AD, the efficacy and feasibility of a mobile app that combines spaced retrieval with a machine learning algorithm to enhance memory retention. Specifically, the app prompts users to answer questions during brief daily sessions, and a machine learning algorithm tracks each user's rate of forgetting to determine the optimal spacing schedule to prevent anticipated forgetting. In this pilot study, 61 participants (young adults: n=21, 34%; healthy older adults: n=20, 33%; people with MCI due to AD: n=20, 33%) used the app for 4 weeks to learn new facts and relearn forgotten name-face associations. Participation during the 4-week period was characterized by using the app once per day to answer 15 questions about the facts and names. After the 4-week learning phase, participants completed 2 recognition memory tests approximately 1 week apart, which tested memory for information they had studied using the app as well as information they had not studied. After using the mobile app for 1 month, every person with MCI due to AD demonstrated improvements in memory for new facts that they had studied via the app compared to baseline (P<.001). All but one person with MCI due to AD (19/20, 95%) showed improvements of more than 10 percentage points, comparable to the improvements shown by young adults and healthy older adults. Memory for name-face associations was similarly improved for all participant groups after using the app but to a lesser degree. Furthermore, for both new facts and name-face associations, we found no memory decay for any participant group after they took a break of approximately 1 week from using the app at the end of the study. Regarding usability, of the 20 people with MCI due to AD, 16 (80%) self-adhered to the app's automated practice schedule, and half of them (n=10, 50%) expressed an interest in continuing to use it. These results demonstrate early evidence that spaced retrieval mobile apps are both feasible for people with early-stage AD to use in their everyday lives and effective for supporting memory retention of recently learned facts and name-face associations.

Objective and subjective cognitive outcomes one year after COVID-19.

This study aimed to evaluate subjective cognitive, physical, and mental health symptoms as well as objective cognitive deficits in COVID-19 patients 1 year after infection. This was a cross-sectional study. Seventy-four patients, who contracted a SARS-CoV-2 infection in 2020, underwent an in-person neuropsychological assessment in 2021. This included standardized tests of memory, attention, and executive functions. In addition, participants also responded to scales on subjective attention deficits, mental health symptoms, and fatigue. Patients' scores were compared to published norms. Patients (N = 74) had a median age of 56 years (42% female). According to the initial disease severity, they were classified as mild (outpatients, 32%), moderate (hospitalized, non-ICU-admitted, 45%), or severe (ICU-admitted, 23%). Hospitalized patients were more often affected than outpatients. In general, deficits were most common in attention (23%), followed by memory (15%) and executive functions (3%). Patients reported increased levels of fatigue (51%), anxiety (30%), distractibility in everyday situations (20%), and depression (15%). An additional analysis suggested an association between lower scores in an attention task and hyperferritinemia. As indicated by a hierarchical regression analysis, subjective distractibility was significantly predicted by current anxiety and fatigue symptoms but not by objective attention performance (final model, adj-R2 = 0.588, P < 0.001). One year after infection, COVID-19 patients can have frequent attention deficits and can complain about symptoms such as fatigue, anxiety, and distractibility. Anxiety and fatigue, more than objective cognitive deficits, have an impact on the patients' experienced impairments in everyday life.

Recovery of Learning and Memory Deficits Despite Persistent Pyknosis of the Hippocampal Pyramidal Neurons of Adult Hydrocephalic Mice

Abstract Background: The hippocampal alterations resulting from hydrocephalus are associated with various cognitive dysfunctions. Reduced learning and memory are early functional deficits that recover with time in experimental hydrocephalus. This study investigated the recovery processes of learning and memory loss in relation to the morphology of hippocampal pyramidal neurons and the degree of expansion of the ventricles. Materials and Methods: Hydrocephalus was induced in adult mice by intracisternal injection of sterile kaolin while controls received sham operation. Neurobehavioral tests for memory and learning were conducted, after which the animals were sacrificed in batches: 7 (acute) and 28 (subacute) days postinduction. After sacrifice, mice were categorized into mild and moderate hydrocephalus, and their fixed brain samples were processed for hematoxylin, eosin, and Nissl stains. Results: In moderate acute hydrocephalus, the indices of learning and memory were reduced escape latency (67.20 ± 12.83 s), number of platform crossing (4.000 ± 1.658), duration in platform quadrant (4.000 ± 1.658), and percent of total investigation (44.857% ± 3.981%) but not in the subacute stage. Pyknotic indices (PI) were significantly higher in the cornu ammonis (CA)1 and 3 regions in all hydrocephalic groups than in controls. However, within groups, PI was significantly higher only in the CA1 of moderate acute (28.149% ± 1.875%) compared to moderate subacute hydrocephalic group (12.903% ± 3.23%). Conclusion: Hydrocephalus caused cellular injury to the hippocampus associated with spatial learning and memory deficits. However, these functional deficits were partially reversed in moderate subacute hydrocephalus despite the persistence of the structural alterations in the CA1 and CA3 subregions.

The Penn Electrophysiology of Encoding and Retrieval Study.

The Penn Electrophysiology of Encoding and Retrieval Study (PEERS) aimed to characterize the behavioral and electrophysiological (EEG) correlates of memory encoding and retrieval in highly practiced individuals. Across five PEERS experiments, 300+ subjects contributed more than 7,000 memory testing sessions with recorded EEG data. Here we tell the story of PEERS: its genesis, evolution, major findings, and the lessons it taught us about taking a big scientific approach in studying memory and the human brain. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Toward better understanding and management of chemobrain: the potential utilities of the MemTrax memory test

ObjectiveTo study the effects of chemotherapy on cognitive function in breast cancer patients, and to investigate the relationship of MemTrax test of memory and related functions to the FACT-Cog functional self-assessment for the evaluation and management of chemobrain.MethodsIn this prospective cohort study, clinical information of pathologically confirmed female breast cancer patients who decided to receive chemotherapy were collected in a questionnaire which was developed for this study and provided as a supplementary file. The FACT-Cog self-assessment and MemTrax test were administered before and after the chemotherapy treatments. Patients with chemobrain were identified using published criteria based on FACT-Cog scores, and MemTrax scores from chemobrain patients were analyzed.ResultsFifty-six patients participated in this study, of which 41 participants completed 4 or more cycles of chemotherapy and were included in the final analyses here. Using the reported high end of minimal clinical differences (10.6 points) of FACT-Cog before and after chemotherapy, 18 patients suffered from chemobrain in this study. In these 18 chemobrain patients, no cognitive impairments were detected by MemTrax, which paradoxically demonstrated an improvement in the normal cognitive range.ConclusionThe cognitive impairment induced by chemotherapy in breast cancer patients is detectable by the FACT-Cog in a Chinese cohort but is not detected by the MemTrax memory test. The fact that the more objective MemTrax could not detect the impairment could alleviate patients’ concerns which in turn would be beneficial for patients’ mental health.

Effects of background music on numerical and spatial location working memory: differences between extraverts and introverts

This experimental research explored background music’s influence on the performance of numerical and spatial location working memory of extraverts and introverts. Sixty participants (30 extraverts and 30 introverts) were asked to complete numerical and spatial location working memory tests, under the conditions of background music and silence. Results showed a main negative effect of background music on the participants’ performance of spatial location working memory. A significant interaction effect between music and personality (extroversion and introversion) on this performance was also observed. It revealed that a more negative effect of music in introverts as compared with extroverts. In contrast, no main or interaction effect was observed for the performance of numerical working memory. According to the influence of music on working memory, introversion-extraversion personality factors of workers such as cashiers or drivers require consideration.

Poly(ethylene terephthalate) glycol/carbon black composites for 4D printing

This research introduces PETG-CB (poly(ethylene terephthalate) glycol modified with carbon black) composites, a new class of shape memory polymers 4D printed using the Fused Deposition Modeling (FDM) method. Nanocomposites with varying concentrations of CB (0.5 %, 1 %, and 3 % by weight) are developed to enhance the functional performance of PETG in 4D printing applications. Comprehensive characterization at the micro- and macro-scale, including dynamic thermal mechanical analysis (DMTA), scanning electron microscopy (SEM), and mechanical testing, is employed to assess the viscoelastic behavior, microstructural integrity, and mechanical strength under thermal stimulation. Experimental results reveal that CB addition significantly alters the glass transition temperature and improves mechanical properties, with the 1 % CB composite demonstrating optimal tensile strength and enhanced shape memory effects. SEM analysis confirms a uniform distribution of CB particles, contributing to the improved mechanical properties and printability of the nanocomposites. The shape memory tests show excellent recovery rates above 97 %, with faster recovery observed in composites with higher CB content. These findings highlight the potential of PETG-CB composites in applications requiring rapid response and high mechanical performance, making them promising materials for future advancements in the 4D printing technology.

Sleep apnea in schizophrenia: Estimating prevalence and impact on cognition

Undertreated medical illnesses can compound the disabling cognitive deficits of schizophrenia. Obstructive sleep apnea (OSA) impairs cognitive domains also affected by schizophrenia, is common, and is treatable. The effects of sleep apnea on cognition in schizophrenia, however, are not well understood. We estimated the prevalence of OSA in a previously characterized sample of 3942 Veterans with schizophrenia by self-report and with a predictive model to identify individuals at high risk for OSA. We then compared neuropsychological and functional capacity assessment results between those who reported OSA versus those who did not, and between those predicted to have OSA versus predicted to not have OSA. We expected that many Veterans not reporting sleep apnea would be predicted to have it, and that both reported and predicted sleep apnea would be associated with lower cognitive and functional performance. The reported prevalence of OSA in the sample was 14%, whereas 72% were predicted to be at high risk of OSA. Interestingly, participants who reported having OSA had better cognitive and functional capacity performance (p's < 0.001) compared to those who did not report OSA, particularly on speed of processing assessments (p < 0.001). Predicted OSA, by contrast, was associated with lower speed of processing, verbal learning and working memory test scores (p's < 0.001). One possible interpretation of these results is that people with higher cognitive capacity may be more likely to seek medical care, while those with cognitive impairments are at greater risk for having untreated co-occurring medical conditions that further compromise cognition.

Persistent activity during working memory maintenance predicts long-term memory formation in the human hippocampus.

Working Memory (WM) and Long-Term Memory (LTM) are often viewed as separate cognitive systems. Little is known about how these systems interact when forming memories. We recorded single neurons in the human medial temporal lobe while patients maintained novel items in WM and a subsequent recognition memory test for the same items. In the hippocampus but not the amygdala, the level of WM content-selective persist activity during WM maintenance was predictive of whether the item was later recognized with high confidence or forgotten. In contrast, visually evoked activity in the same cells was not predictive of LTM formation. During LTM retrieval, memory-selective neurons responded more strongly to familiar stimuli for which persistent activity was high while they were maintained in WM. Our study suggests that hippocampal persistent activity of the same cell supports both WM maintenance and LTM encoding, thereby revealing a common single-neuron component of these two memory systems.

Exploring transfer effects on memory and its neural mechanisms through a computerized cognitive training in mild cognitive impairment: randomized controlled trial.

Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non-memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial. Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning-based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non-cognitive scales, and resting-state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within- and between-group comparisons, group × time interactions, and seed-to-voxel analyses in memory-involving brain networks were performed. The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η2 = 0.31), which was related with the increased connectivity in the hippocampal-frontal and fusiform-occipital network. No other cognitive and non-cognitive symptoms differed between groups after adjusting for covariates. Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis.

Effect of serial night shifts on the cognitive, psychomotor, and moral performance of residents in the department of Emergency Medicine.

The objective was to study the effect of serial night shifts on the cognitive, psychomotor, and moral performance of emergency medicine residents of an academic Emergency Medicine Department. This prospective case-crossover study compared emergency medicine residents' sleep time, subjective sleepiness, cognitive function, moral judgment, and psychomotor skills after 5 consecutive days versus night shifts using sleep diaries, activity monitors, and multiple performance tests. Paired t-tests and Wilcoxon signed-rank tests were used to analyze data based on normality. Correlation analysis was done using Spearman's correlation test. Subgroup analysis was also performed to find any difference based on gender and year of residency. Twenty-seven emergency medicine residents participated (13 males, 48.1%). The distribution across residency years was as follows: 44.4% in their first year, 25.9% in their second year, and 29.6% in their third year. Following five consecutive night shifts, total sleep duration decreased significantly from 338.1 ± 67.8 to 307.4 ± 71.0 min (p < 0.001), while subjective sleepiness scores increased from 9.6 ± 3.3 to 13.6 ± 4.6. Psychomotor performance and reaction times did not significantly differ between night and day shifts. However, working memory declined, assessed by self-paced three-back test scores (median [IQR] 517.1 [471.9-546.7] vs. 457.6 [334.4-508.8]; p = 0.034) and interference test scores (445.5 ± 59.9 vs. 407.2 ± 56.8; p < 0.001), along with moral judgment (median [IQR] 19 [18-28] vs. 15 [11-21]; p = 0.010) after serial night shifts. No correlations existed between performance measures nor differences based on gender or residency year. Residents sleep less following night versus day shifts, reporting the highest sleepiness levels after 5 consecutive nights. Despite this, psychomotor performance and reaction times did not significantly differ. However, considerable reductions occurred in moral judgment, working memory, and interference test performance after serial night shifts.

Monitoring the Breath-Hold Training Load during an Ecological Session: A Pilot Study.

This study aimed to create a training load index to measure physiological stress during breath-hold (BH) training and examine its relationship with memory performance. Eighteen well-trained BH divers (Age: 35.8±6.6 years, BH training practice: 5.3±4.5 years) participated in this study. During a standard 1.5-hour BH training in the pool, perceived exertion, heart rate, distance, and duration were measured. The training load index was modelled on the basis of a TRIMP (TRaining IMPulse) with four different equations and was used to measure the stress induced by this BH training. A reference value, based on the ratio between the average heart rate during all BHs and the lowest heart rate during BH training, was used for comparing training load index. Memory assessment was conducted both before and after this training. Of the four equations proposed, equation no. 4, named aTRIMP for "apnoea," showed the strongest correlation with our reference value (r=0.652, p<0.01). No difference was found between any of the memory tests before and after the BH training. The aTRIMP was a new representative index for monitoring habitual training of well-trained BH divers. Furthermore, this training had no negative impact on memory performance.

Long-term cognitive and affective consequences of mild traumatic brain injury: comparison with older adults

ABSTRACT Objective Memory and affective processing were compared in young adults with a remote mild traumatic brain injury (mTBI), to healthy younger and older adults. We evaluated memory performance when encoding was done under multi-tasking (divided attention) conditions, likely to exacerbate cognitive and psychological symptoms in mTBI. Methods Participants studied pairs of unrelated words under either full or divided attention conditions. Memory for single words (item memory) and for pairs of words (associative memory) was then assessed in sequential independent recognition tests, under full attention. Results Associative memory was poorer than item memory, and worse when encoding was done under divided than full attention. The decline in recognition accuracy from full to divided attention conditions on the associative memory test was significantly greater in mTBI compared to young adults and was similar in magnitude to that observed in older adults under full attention. Self-reported mental and total fatigue increased significantly as performance on the memory tests, following the divided attention condition, decreased, but only in the mTBI group. Conclusions Results show lingering memory deficits, and suggest that cognitive tasks may be experienced as psychologically more demanding in those with a mTBI, even months or years after injury.

White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

Acute effects of cannabigerol on anxiety, stress, and mood: a double-blind, placebo-controlled, crossover, field trial

Cannabigerol (CBG) is a phytocannabinoid increasing in popularity, with preclinical research indicating it has anxiolytic and antidepressant effects. However, there are no published clinical trials to corroborate these findings in humans. The primary objective of this study was to examine acute effects of CBG on anxiety, stress, and mood. Secondary objectives were to examine whether CBG produces subjective drug effects or motor and cognitive impairments. A double-blind, placebo-controlled cross-over field trial was conducted with 34 healthy adult participants. Participants completed two sessions (with a one-week washout period) via Zoom. In each, they provided ratings of anxiety, stress, mood, and subjective drug effects prior to double-blind administration of 20 mg hemp-derived CBG or placebo tincture (T0). These ratings were collected again after participants ingested the product and completed an online survey (T1), the Trier Social Stress Test (T2), a verbal memory test and the DRUID impairment app (T3). Relative to placebo, there was a significant main effect of CBG on overall reductions in anxiety as well as reductions in stress at T1. CBG also enhanced verbal memory relative to placebo. There was no evidence of subjective drug effects or impairment. CBG may represent a novel option to reduce stress and anxiety in healthy adults.

Skills and cautiousness predict performance in difficult search.

People differ in how well they search. What are the factors that might contribute to this variability? We tested the contribution of two cognitive abilities: visual working memory (VWM) capacity and object recognition ability. Participants completed three tasks: a difficult inefficient visual search task, where they searched for a target letter T among skewed L distractors; a VWM task, where they memorized a color array and then identified whether a probed color belonged to the previous array; and the Novel Object Memory Test (NOMT), where they learnt complex novel objects and then identified them amongst objects that closely resembled them. Exploratory and confirmatory factor analyses revealed that there are two latent factors that explain the shared variance among these three tasks: a factor indicative of the level of caution participants exercised during the challenging visual search task, and a factor representing their visual cognitive abilities. People who score high on the search cautiousness tend to perform a more accurate but slower search. People who score high on the visual cognitive ability factor tend to have a higher VWM capacity, a better object recognition ability, and a faster search speed. The results reflect two points: (1) Visual search tasks share components with visual working memory and object recognition tasks. (2) Search performance is influenced not only by the search display's properties but also by individual predispositions such as caution and general visual abilities. This study introduces new factors for consideration when interpreting variations in visual search behaviors.

The disconnect between metamemory and memory for emotional images

ABSTRACT Emotional information is reliably predicted to be remembered better than neutral information, and this has been found for words, images, and facial expressions. However, many studies find that these judgments of learning (JOLs) are not predictive of memory performance (e.g. [Hourihan, K. L. (2020). Misleading emotions: Judgments of learning overestimate recognition of negative and positive emotional images. Cognition and Emotion, 34(4), 771–782. https://doi.org/10.1080/02699931.2019.1682972]). The present study investigates and rules out numerous potential causes for this discrepancy between memory predictions and performance, including (1) reactivity to making JOLs, (2) idiosyncrasies of specific images used, (3), type of memory test, and (4) effects of fluency. Three additional experiments investigate whether JOLs can become more predictive of memory performance, either by experience with the task or by manipulating prior beliefs about memory for emotional images. In all experiments, we found the same effect: Emotional images are inaccurately predicted to be remembered better than neutral images. The results suggest that emotion is used as a heuristic for learning, resulting in low metamnemonic accuracy for emotional stimuli.

Effectiveness of Schema-Based Instruction Strategy in Improving Mathematical Word Problem Solving and Working Memory of Students with Learning Disabilities in The Sultanate of Oman

This study aimed to examine the effectiveness of a schema-based instruction strategy in improving mathematics word problem solving and working memory performance of third grade students with learning disabilities in schools in Oman. Students received a diagnosis of specific learning disability (SLD) based on the aptitude discrepancy model in which an achievement test and an aptitude test (Raven’s Coloured Successive Matrices) were used to determine the existence of a discrepancy. Students were then divided into two matched groups, a control group and an experimental group; each group included (20) students. Study instruments included a mathematics word problem solving test, a working memory test, and the schema-based intervention program. Results of the study showed that participants in the experimental group differed from controls in word problem solving and working memory performance following exposure to the intervention program. More specifically, performance of experimental group participants in the word problem solving varied across the pre, during the implementation, and post intervention phases in favor of the post intervention phases and in favor of the type of Assembly problems. Implications of using schema-based instruction strategy with students with SLD are discussed in the light of the study findings.

Dissecting the contribution of human chromosome 21 syntenic regions to recognition memory processes in adult and aged mouse models of Down syndrome.

Trisomy of human chromosome 21 (Hsa21) results in a constellation of features known as Down syndrome (DS), the most common genetic form of intellectual disability. Hsa21 is orthologous to three regions in the mouse genome on mouse chromosome 16 (Mmu16), Mmu17 and Mmu10. We investigated genotype-phenotype relationships by assessing the contribution of these three regions to memory function and age-dependent cognitive decline, using three mouse models of DS, Dp1Tyb, Dp(17)3Yey, Dp(10)2Yey, that carry an extra copy of the Hsa21-orthologues on Mmu16, Mmu17 and Mmu10, respectively. Prior research on cognitive function in DS mouse models has largely focused on models with an extra copy of the Mmu16 region and relatively little is known about the effects of increased copy number on Mmu17 and Mmu10 on cognition and how this interacts with the effects of aging. As aging is is a critical contributor to cognitive and psychiatric changes in DS, we hypothesised that ageing would differentially impact memory function in Dp1Tyb, Dp(17)3Yey, and Dp(10)2Yey, models of DS. Young (12-13 months and old (18-20 months mice Dp1Tyb, Dp(17)3Yey and Dp(10)2Yey mice were tested on a battery of object recognition memory test that assessed object novelty detection, novel location detection and associative object-in place memory. Following behavioral testing, hippocampal and frontal cortical tissue was analysed for expression of glutamatergic receptor proteins using standard immunoblot techniques. Young (12-13 months and old (18-20 months mice Dp1Tyb, Dp(17)3Yey and Dp(10)2Yey mice were tested on a battery of object recognition memory test that assessed object novelty detection, novel location detection and associative object-in place memory. Following behavioral testing, hippocampal and frontal cortical tissue was analysed for expression of glutamatergic receptor proteins using standard immunoblot techniques. Our results show that distinct Hsa21-orthologous regions contribute differentially to cognitive dysfunction in DS mouse models and that aging interacts with triplication of Hsa21-orthologous genes on Mmu10.