Memory Test Performance Research Articles

Evaluation of the behavioral, histopathological, and immunohistochemical effects resulting from ventriculosubcutaneous shunt obstruction in kaolin-induced hydrocephalus in rats.

Hydrocephalus is a brain disease prevalent in the pediatric population that presents complex pathophysiology and multiple etiologies. The best treatmentis still ventricular shunting. Mechanical obstruction is the most frequent complication, but the resulting pathological effects are still unknown. Evaluation and comparison of clinical, histopathological, and immunohistochemical aspects in the acute phase of experimental hydrocephalus induced by kaolin, after treatment with adapted shunt, and after shunt obstruction and posterior disobstruction. Wistar rats aged 7days were used and divided into 4 groups: control group without kaolin injection (n = 6), untreated hydrocephalic group (n = 5), hydrocephalic group treated with ventriculosubcutaneous shunt (DVSC) (n = 7), and hydrocephalic group treated with shunt, posteriorly obstructed and disobstructed (n = 5). The animals were submitted to memory and spatial learning evaluation through the Morris water maze test. The rats were sacrificed at 28days of age and histological analysis of the brains was performed with luxol fast blue, in addition to immunohistochemical analysis in order to evaluate reactive astrocytosis, inflammation, neuronal labeling, and apoptotic activity. The group with shunt obstruction had worse performance in memory tests. Reactive astrocytosis was more evident in this group, as was the inflammatory response. Obstruction of the shunt results in impaired performance of behavioral tests and causes irreversible histopathological changes when compared to findings in the group with treated hydrocephalus, even after unblocking the system. The developed model is feasible and efficient in simulating the clinical context of shunt dysfunction.

Class I histone deacetylases inhibition reverses memory impairment induced by acute stress in mice.

While chronic stress induces learning and memory impairments, acute stress may facilitate or prevent memory consolidation depending on whether it occurs during the learning event or before it, respectively. On the other hand, it has been shown that histone acetylation regulates long-term memory formation. This study aimed to evaluate the effect of two inhibitors of class I histone deacetylases (HDACs), 4-phenylbutyrate (PB) and IN14 (100 mg/kg/day, ip for 2 days), on memory performance in mice exposed to a single 15-min forced swimming stress session. Plasma corticosterone levels were determined 30 minutes after acute swim stress in one group of mice. In another experimental series, independent groups of mice were trained in one of three different memory tasks: Object recognition test, Elevated T maze, and Buried food location test. Subsequently, the hippocampi were removed to perform ELISA assays for histone deacetylase 2 (HDAC2) expression. Acute stress induced an increase in plasma corticosterone levels, as well as hippocampal HDAC2 content, along with an impaired performance in memory tests. Moreover, PB and IN14 treatment prevented memory loss in stressed mice. These findings suggest that HDAC2 is involved in acute stress-induced cognitive impairment. None of the drugs improved memory in non-stressed animals, indicating that HDACs inhibitors are not cognitive boosters, but rather potentially useful drugs for mitigating memory deficits.

An enriched environment promotes cognitive recovery and cerebral blood flow in aged mice under sevoflurane anaesthesia.

Sevoflurane is an inhalation anaesthetic agent widely used in clinical settings. Despite good surgical outcomes using sevoflurane, patients frequently develop postoperative cognitive dysfunction (POCD). An enriched environment (EE), as a rehabilitation technique, could provide objects and tools to facilitate neuromotor and visual stimuli and brain activity, and is reported to improve cognitive functions. We aim to investigate the impairments of sevoflurane inhalation on cognitive function in mice and determine the benefits of EE in ameliorating POCD. Eighteen-month-old mice were exposed to sevoflurane inhalation for 2 h and then placed in standard environment (SE) or EE cages. The mice without sevoflurane exposure in standard or EE cages were used as controls. The behavioural tests include Morris water maze, Y maze and novel object recognition. Magnetic resonance imaging (MRI) was used to determine the blood circulation in the brains. The proangiogenic factors (CD31, angiopoietin-1, vascular endothelial growth factor, and N-cadherin) and neurotrophic (brain-derived neurotrophic factor, post-synaptic density protein 95) expression in hippocampus of aged mice were evaluated by Western blotting and RT-PCR analysis. Sevoflurane-exposed mice demonstrated reduced performance in learning, memory and spatial memory tests. Enriched environment improved the behavioural performance of sevoflurane-exposed animals. Sevoflurane exposure reduced the blood flow in the brains, and these effects were ameliorated by EE habitation. The EE also promoted the expression of angiogenic and neurotropic factors in sevoflurane-exposed animals. In summary, EE is effective in ameliorating the side-effects of sevoflurane exposure in aged mice.

ИССЛЕДОВАНИЕ ПСИХИЧЕСКОЙ РАБОТОСПОСОБНОСТИ И ГРУППОВОЙ ДИНАМИКИ В АВТОНОМНЫХ УСЛОВИЯХ ЗИМОВКИ НА СТАНЦИИ «ВОСТОК»

The paper deals with the investigation of psychic performance and group dynamics during Russian Antarctic expedition RAE66. Eight winterers were tested 7 times with the use of the cognitive Master-Test. Group dynamics was assessed by sociometry and cohesion diagnostics on the basis of common goals and values. Psychophysiological status was assessed weekly using the actigraphy and HR data, and questionnaires. At the end of the polar day and in early autumn, it was the mood that went down first (autumn and winter), then accuracy of sensorimotor reactions degraded (winter) and mistakes in a simple math test became more frequent (winter and spring). On the contrary, performance of short-term memory tests improved in winter and spring. Motor activity reduced during the first half of the expedition and started increasing gradually at the beginning of the polar night. Though the sleeping time was normally from 7 to 8.5 hours, sleep quality subjectively changed during the wintering it correlated with physical activity and consequent changes of heart rate variability (stress) and blood oxygen saturation. The latter remained low throughout the period of life on station Vostok in comparison to measurements made on the ship. Cohesion was high but for some slackening by the third quarter of wintering; at the end of wintering cohesion grew strong again. The sociometric status of winterers varied with intensity of negative emotions.

Pannexin1 Mediates Early-Life Seizure-Induced Social Behavior Deficits.

There is a high co-morbidity between childhood epilepsy and autism spectrum disorder (ASD), with age of seizure onset being a critical determinant of behavioral outcomes. The interplay between these comorbidities has been investigated in animal models with results showing that the induction of seizures at early post-natal ages leads to learning and memory deficits and to autistic-like behavior in adulthood. Modifications of the excitation/inhibition (glutamate/GABA, ATP/adenosine) balance that follows early-life seizures (ELS) are thought to be the physiological events that underlie neuropsychiatric and neurodevelopmental disorders. Although alterations in purinergic/adenosinergic signaling have been implicated in seizures and ASD, it is unknown whether the ATP release channels, Pannexin1 (Panx1), contribute to ELS-induced behavior changes. To tackle this question, we used the ELS-kainic acid model in transgenic mice with global and cell type specific deletion of Panx1 to evaluate whether these channels were involved in behavioral deficits that occur later in life. Our studies show that ELS results in Panx1 dependent social behavior deficits and also in poor performance in a spatial memory test that does not involve Panx1. These findings provide support for a link between ELS and adult behavioral deficits. Moreover, we identify neuronal and not astrocyte Panx1 as a potential target to specifically limit astrogliosis and social behavioral deficits resultant from early-life seizures.

Effects of reading instructions on pre-service teachers’ judgment bias when learning from texts

Learning from texts means acquiring and applying knowledge, which requires students to judge their text comprehension accurately. However, students usually overestimate their comprehension, which can be caused by a misalignment between the cues used to judge one’s comprehension and the cognitive requirements of future test questions. Therefore, reading instructions might help students to use more valid cues and hence to make more accurate judgments. In two randomized experiments, we investigated the effect of application instructions (in contrast to general and memory instructions) on judgment bias regarding memory test performance and application test performance. In Experiment 1, 131 pre-service teacher students read two texts: For the first text (pretest phase), all participants received general reading instructions. For the second text (testing phase), they received one of the three reading instructions. Main results were that the general reading instructions in the pretest phase resulted in underestimation for memory test performance and overestimation for application test performance. Results from the testing phase yielded mixed effects and, overall, no strong evidence that reading instructions, and in particular application instructions, are beneficial for debiasing judgments of comprehension. Experiment 2 (N = 164 pre-service teachers) restudied the effects with the same texts but a different study design. Results replicated the effects found in the testing phase of Experiment 1. Overall, the results indicated that reading instructions without further support are not sufficient to help students to accurately judge their comprehension and suggested that text characteristics might impact the effect of reading instructions on judgment bias.

ASSESSING BIDIRECTIONAL LONGITUDINAL ASSOCIATIONS BETWEEN SOCIAL RESOURCES AND COGNITIVE DECLINE IN LATE LIFE

Abstract Objectives To better understand bidirectional longitudinal relationships between social networks and cognitive decline. Method: We examined nine waves of data from the National Health and Aging Trends Study (2011-2019). Our primary outcome was global cognition, consisting of a summation of scores on episodic memory, orientation, and executive function tests. Social network measures included measures of social participation, number and type of social ties, attributes of network alter, and neighborhood markers of social cohesion and disorder. We applied linear mixed models to study associations between time-invariant measures of social cohesion and disorder with cognitive decline over time. We employed dual-outcomes mixed models to examine the bidirectional linkages between time-varying measures of social network structures and cognitive decline. Result: Eligible participants (N = 7,325) were included at baseline and followed for an average of 4.86±3.22 years/waves. Having more friend-ties and a higher percentage of college graduates within a social network at baseline were associated with slower declines in global cognition and episodic memory. Additionally, higher global cognition at baseline was associated with smaller reductions in social network size. Less disorientation at baseline was associated with a slower decline in social participation. Social cohesion and environmental disorder were not associated with cognitive decline. Conclusion Social networks may improve cognitive health but are also vulnerable to declining orientation. Results suggest that bidirectional longitudinal relationships link social network structure with cognitive decline and inform our understanding of the framework of associations between diverse aspects of social resources and cognitive decline in a longitudinal setting.

Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters)

BackgroundEvidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer’s disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application.MethodsThe study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work.DiscussionSuccessful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD.Trial RegistrationClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

ASSOCIATIVE AND EXECUTIVE INFLUENCES ON MEMORY FOR EVENTS AS REVEALED BY AGING AND DISTRACTION

Abstract Diagnostic tests of memory functioning typically employ verbal material, potentially encouraging mnemonic strategies ranging from rehearsal to visual imagery. Poor performance could thus reflect either impairments in basic associative mechanisms or impairments in executive functions underlying strategy deployment. Kersten et al. (2018) developed a more ecologically valid test of episodic memory, the Person-Action Conjunction (PAC) Test, involving memory for who did what in events. They found that when many different actors performed the actions, memory for who performed each action was related to tests of associative functioning, whereas when only two actors performed all the actions, memory performance was related to executive functioning. The present research tested the ensuing prediction that manipulating the availability of executive resources through distraction should only impact performance when a small number of actors perform the actions. The PAC Test was administered to 207 young adults (M age = 20.39) and 163 healthy older adults (M age = 70.80), either with no distraction or while performing a tone counting distractor task. Young adults performed better than older adults at remembering who did what, consistent with an age-related associative deficit. When two actors performed all the actions, distraction impacted both age groups’ memory for which actor performed each action. When many different actors performed the actions, distraction had no specific impact on memory for who did what. Implications will be discussed for the development of diagnostic tests to differentiate impairments in basic memory mechanisms (e.g., early-stage Alzheimer’s disease) from impairments of executive functioning (e.g., vascular dementia).

A RANDOMIZED CONTROLLED TRIAL OF THE EVERYDAY MEMORY AND METACOGNITIVE INTERVENTION IN OLDER ADULTS

Abstract This study evaluated an intervention to improve remembering in everyday life, the Everyday Memory and Metacognitive Intervention (EMMI). EMMI uses strategies designed to enhance everyday remembering and self-regulatory approaches to monitor goal pursuit, anticipate, and address memory demands. A randomized controlled trial compared a group assigned to EMMI with a traditional memory strategy training control (MSC) group. Expanding on earlier work (Pearman et al., 2020) we created a new event-based ecological momentary assessment (EB-EMA) smartphone application for reporting everyday memory errors when they occurred, synched to a nightly diary for collecting additional information about each event. The pretest-posttest design assessed changes in subjective memory beliefs and episodic memory performance and also measured posttest-only performance measures, including EB-EMA frequency of memory errors and a laboratory contact task assessing everyday prospective memory. The protocol was reduced in scope to accommodate fully remote participation due to the pandemic. The final sample included 30 EMMI and 32 MSC participants. Memory strategy training differentially improved MSC associative memory test performance. There were no group differences in EB-EMA reported memory errors or successful prospective memory contacts. The EMMI group showed more improvement in memory self-efficacy than the MSC group; both groups showed increases in perceived control over everyday memory. Individual differences in EMMI intervention benefits suggest that the program worked well in reducing memory errors for some but not all older adults. The EMMI shows promise but may require more extensive in-person training and behavioral shaping than this study provided to improve everyday memory.

Reading for Meaning: The Influence of Reader Characteristics on Paragraph Understanding in Aphasia.

The study improves our understanding of the reading comprehension difficulties seen in people with aphasia. It investigates the influence of reader characteristics, including personal demographic variables, and linguistic and wider cognitive skills, on text comprehension. Seventy-five people with aphasia and 87 neurologically typical readers completed a test of paragraph comprehension. People with aphasia also completed background tests of language, attention, recognition memory, and executive functions. The influence of demographic variables (age, gender, and level of education) was analyzed separately in the group of people with aphasia and the typical readers using analyses of variance. In the people with aphasia, the relationship between paragraph comprehension and the language and cognitive tests was explored using correlational analyses. In the typical readers, there was a significant effect of gender and level of education and a significant three-way interaction. For the people with aphasia, there were no significant effects of demographic variables. Significant positive correlations were found between performance on paragraph comprehension and each of the language tests and with tests of auditory attention, executive functions, and recognition memory for words. In people with aphasia, the effects of demographic variables were overshadowed by the effect of their language difficulties. The association seen across language measures reflects the shared semantic representations across single-word, sentence, and text levels, across modalities. The study emphasizes the importance of attention, executive functions, and short-term memory in the comprehension of and memory for what we read. The contribution of both language difficulties and wider cognitive skills needs to be considered when planning intervention. https://doi.org/10.23641/asha.24695451.

Efficacy of transcranial direct current stimulation in mild cognitive impairment – a meta‐analysis

AbstractBackgroundMCI or Mild Cognitive Impairment is a state of cognitive decline which is in between that of normal ageing and dementia. People with MCI have a higher chance of progressing to dementia because of which introducing interventions at this stage becomes increasingly important. Transcranial Direct Current Stimulation (tDCS) is one non‐invasive brain stimulation technique that is considered as an effective intervention strategy for people with MCI to prevent their progression to dementia.MethodFrom 221 and 686 results obtained from PubMed and Google Scholar respectively using the search term ‘(“tDCS”) AND (“MCI”) AND (Randomized) AND (sham controlled)’, 8 studies were included for the current meta‐analysis. Among these studies, the most commonly used cognitive tests namely MMSE (Mini Mental State Examination), MoCA (Montreal Cognitive Assessment), TMT (Trail Making Test) A and B, DST (Digit Span Test) forward and backward and Logical Memory Test were considered for the analysis. The standard mean difference between active and sham treatments in different tests were computed.ResultThe standard mean difference and the 95% confidence interval for the test scores are MoCA: 0.37 (‐0.22,0.95), MMSE: 0.26 (‐0.25, 0.77), TMT A: ‐0.01 (‐0.42, 0.40), TMT B: 0.07 (‐0.41, 0.55), DST F: ‐0.09 (‐0.44, 0.25), DST B: ‐0.11 (‐0.54, 0.31) and Logical memory test: 0.80 (‐0.24, 1.83). It is found that there is an improvement in the performance in MoCA, MMSE, TMT A and logical memory test after treatment with active tDCS but the improvement is statistically insignificant.ConclusionAlthough there is an evident clinical effectiveness, the study identified no significant improvement in cognitive performance with active tDCS in comparison with sham tDCS. This might be due to difference in protocols followed among studies, lower duration of stimulation in a few studies and smaller sample size in each.

Relationships between sleep apnea and insomnia with cognition among Latinos in the National Alzheimer’s Coordinating Center (NACC)

AbstractBackgroundSleep difficulties (e.g., sleep apnea, insomnia) have been associated with worse late life cognitive health and increased risk for dementia. However, the role of sleep, a potentially modifiable factor, in cognitive aging is understudied among Hispanics/Latinos/Latinxs (henceforth Latinos)—a group that faces dementia disparities. Therefore, we examined the relationships between sleep difficulties and cognition in this population using data from the National Alzheimer’s Coordinating Center (NACC).MethodParticipants included 1,633 Latinos (64% females) ages 21 to 98 years old from the NACC (funded by NIA/NIH Grant U24 AG072122). This analysis used data collected at 35 ADRCs from 2015‐2022. Exposures included history of self‐reported and/or clinically assessed sleep apnea (n = 261) and hyposomnia/insomnia (n = 384). Outcomes were concurrent cognitive scores from tests of learning, memory, semantic fluency, processing speed, confrontation naming, and executive functioning. Covariates included age, sex, education, heritage (e.g., Cuban), cognitive status, and body mass index. General linear models separately tested the associations between sleep difficulties with cognition in crude and fully‐adjusted models. Additionally, we examined whether sex, age, or heritage modified these associations.ResultsSleep apnea was associated with faster processing speed, and insomnia was associated with worse confrontation naming in crude but not fully‐adjusted models. In fully adjusted models, sex modified the associations of both sleep apnea and insomnia with semantic fluency. Specifically, men without sleep apnea had worse semantic fluency than all other groups; no other group differences emerged. Females in either insomnia group had better semantic fluency than men in either insomnia group, and women without insomnia had marginally better semantic fluency than women with insomnia. Older age (continuous) was associated with worse executive functioning, specifically working memory, among individuals with insomnia to a greater extent than those without insomnia. Heritage did not modify associations between sleep difficulties with cognition.ConclusionConsistent with previous, we found that sleep measures were associated with cognition in this group of Latinos from a wide age‐range. Our findings were specific to semantic fluency and varied based on demographic factors (e.g., sex). Future studies should examine the relationships between sleep with longitudinal change in cognition in this underserved community.

Plasma rejuvenation factor GDF11 associates with amyloid‐related cognitive decline in older adults across the Alzheimer’s Disease spectrum

AbstractBackgroundThrough studies of animal heterochronic parabiosis (fusion of juvenile and older adult animal circulatory systems), growth differentiation factor 11 (GDF11) has been identified as a blood rejuvenation factor that can promote neurogenesis, vascular remodeling, and memory improvement in the presence of age‐related declines. However, it is unknown whether GDF11’s associations with cognitive and neural outcomes translate to humans. We assessed the relationship between plasma GDF11, cerebral amyloid pathology, and cognitive performance in older adults across the Alzheimer’s disease (AD) spectrum.MethodParticipants were 71 older adults from the UCSF Memory and Aging Center who ranged in age from 63 to 93 (Meanage = 79.5; Meanedu = 17.5, 66 cognitively unimpaired, 56% women, 38% amyloid PET positive) and completed blood draws with plasma analyzed on Somascan (version 4.1), neuropsychological evaluations, and amyloid PET scans (18‐AV‐45). Cognition was operationalized as a of validated tests of memory and executive function. Pearson’s correlations examined interrelationships among plasma GDF11, cognition, and amyloid PET centiloids. To determine whether plasma GDF11 moderated the effects of amyloid on cognition, linear regression examined cognition as a function of GDF11, amyloid, and their interaction, controlling for age, sex, and education.ResultHigher amyloid PET centiloids correlated with worse cognition (r = ‐0.20, p = 0.09) and lower levels of GDF11 (r = ‐0.15, p = 0.20), though relationships did not reach statistical significance. GDF11 also did not strongly univariately correlate with cognition (r = ‐0.07, p = 0.59). However, there was a significant interaction between GDF11 and amyloid PET centiloids on cognition (β = 0.55, 95% CI = 0.15, 0.95, p = 0.008) such that the negative relationship between amyloid PET centiloids and cognition was significantly in participants with higher levels of GDF11.ConclusionGDF11 is a blood‐based rejuvenation factor that supports neurogenesis and cognition in animal models and attenuates the association between higher amyloid burden and worse cognition in cognitively unimpaired older adults. These results coupled with prior findings provide translational evidence that GDF11 supports brain resilience and further examination of GDF11 as a therapeutic target for Alzheimer’s disease is warranted.

Cerebrovascular reactivity in amnestic and non‐amnestic mild cognitive impairment

AbstractBackgroundCerebrovascular disease (CVD) is implicated in the pathogenesis and clinical presentation of Alzheimer’s Disease. Cerebrovascular reactivity (CVR) is considered a more direct estimate of cerebrovascular integrity. CVR is a potential promising biomarker for examining pathological cognitive decline in older adults though, to date, findings have been inconclusive, possibly partly due to variability in methodological approaches. In this study, we add to the limited literature on CVR in mild cognitive impairment (MCI). We provide preliminary evidence for CVR differences in MCI phenotypes compared to older adult cognitively normal controls. We hypothesized that they amnestic phenotype (aMCI) will have lower CVR than non‐amnestic (naMCI) and both groups will show lower CVR compared to controls. We also performed exploratory correlational analyses between CVR and neuropsychological test scores.MethodCVR was assessed in 22 controls, 11 aMCI, 9 naMCI cohorts using a breath‐holding task functional magnetic resonance imaging (fMRI). fMRI data were preprocessed and analyzed using AFNI. All participants underwent neuropsychological testing. T‐tests and ANOVA/ANCOVA analyses were conducted to compare controls to MCI groups on CVR metrics and cognitive tests of memory, language, processing speed, and executive functioning. Partial correlation analyses between CVR derived from regions‐of‐interest (Yeo 1‐7 ROIs) and different cognitive functions were conducted.ResultsCVR was found to be significantly lower in MCI compared to controls across all Yeo functional networks, ps < .001, which was mostly driven by the aMCI phenotype. naMCI showed intermediate patterns between aMCI and controls, though results were not significant, ps > .05. Regional CVR values along Yeo networks were positively correlated with cognitive measures of processing speed, executive functioning, and memory.ConclusionThis is the first study to evaluate CVR differences in MCI phenotypes. Consistent with previous research, we found that CVR is lower in MCI compared to controls. While group differences between naMCI and controls (also between naMCI and aMCI) did not reach statistical significance, visual inspection of CVR mean values showed preliminary evidence that naMCI had lower mean values across all ROIs compared to controls and higher mean values compared to aMCI. Future research is needed to examine differences in CVR between MCI phenotypes.

Development of a cognitive composite for preclinical Alzheimer’s disease (CPAD) in Korean older adults

AbstractBackgroundAs tracking subtle cognitive declines in the preclinical stage of Alzheimer’s disease (AD) is difficult with traditional individual outcome measures, need for cognitive composite for preclinical AD is widely recognized. We aimed to develop culturally appropriate cognitive composite that sensitively identifies subtle cognitive decline of preclinical AD in Korean older adults.MethodA total 225 cognitively normal elderly individuals, who completed baseline and 2‐year follow‐up evaluation including clinical assessments and comprehensive neuropsychological tests and baseline amyloid positron emission tomography (PET) in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE), were included. Tests of episodic memory, orientation, and executive function were carefully selected through review of previously established composite scores. Three candidate composites including Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list recall (WLR), logical memory (LM) II, and Mini‐mental status examination (MMSE) in common, and letter fluency test, category fluency test, or Stroop color and word test, were selected.ResultStudent t‐tests demonstrated that only the composite composed of WLR, LM II, MMSE, and LF (Composite 1) showed a significant difference in score decline over two‐year follow‐up period between Aβ positive and negative group (P = 0.03). Linear mixed model analyses also showed that the Aβ x time interaction effect was significant only for Composite 1 (P = 0.026). In contrast, we did not find any significant results for other two candidate composites (Composite 2 and 3). Based on the results, Composite 1 was chosen as the final CPAD.ConclusionCPAD can be used to assess subtle cognitive decline of preclinical AD in clinical research settings, especially in clinical trials with Korean older adults with preclinical AD. It also may be used for monitoring progression or treatment benefits in clinical practices.

The association between microbiome and white matter integrity in the elderly with youthful memory in superaging

AbstractBackgroundAging‐related cognitive decline has been regarded as a normal consequence of aging. However, previous research on ‘SuperAgers’ suggests that such decline is not inevitable. The purpose of this study was to investigate the relationship between the microbiome and white matter integrity in SuperAgers, which may help us understand the mechanism that preserves memory function in these individuals.MethodWe enrolled a total of 115 elderly individuals aged 60 years or older with normal cognitive function, which was defined as scoring one standard deviation or more above the population norm on tests of memory, attention, language, visuospatial ability, and frontal function in the Seoul Neuropsychological Screening Battery. SuperAgers were defined based on their delayed recall scores compared to middle‐aged adults (45 years old) in both the Seoul Verbal Learning Test and the Rey‐Osterrieth Complex Figure Test. Diffusion tensor images were analyzed using tract‐based spatial statistics (TBSS). Parameters related to diffusion tensors were calculated at the voxel level to generate fractional anisotropy (FA) images using the DTIFit. FA values, a diffusion tensor parameter reflecting white matter fiber tract integrity, were measured and compared between SuperAgers and typical agers using the FSL randomise program. For microbiome analysis, EZ biocloud was used to perform alpha diversity, taxonomic hierarchy, and taxonomic composition analysis for each subject analysis. Group analysis was also conducted using the taxonomic composition values, and further group analysis was carried out using ACE, Chao1, and Jacknife, which are indicators of species richness. Statistical analyses were conducted using Statistical Package for Social Science 19.ResultCompared to typical agers, superagers showed a higher number of Firmicutes and Actinobacteria, which have been associated with higher cognitive function. However, there was no significant difference between superagers and typical agers. Additionally, an analysis of the association between p_firmicutes, c_mollicutes, o_lactobacilales and f_erysipelotrichaceae with white matter integrity showed no significant association.ConclusionBased on these results, it can be inferred that superagers may have a correlation with microbiome strains that are closely related to cognitive function, as well as white matter in the brain

The association between cognitive reserve and age‐related neuroimaging features in homozygous APOE ε4 carriers

AbstractBackgroundAlzheimer’s disease (AD) is the most common neurodegenerative dementia syndrome, which is characterized by irreversibly progressive cognitive decline, neuropsychiatric symptoms, and impaired function of independent daily living. The majority of AD occurs in individuals aged over 65 years and is termed late‐onset AD. The apolipoprotein E (APOE) ε4 allele is the highest individual risk factor. Despite lifelong influences of APOE ε4, not all APOE ε4 carriers develop cognitive decline, some APOE ε4 carriers appear to be better than others in maintaining structural and functional properties of their brains while aging. Although previous studies showed that the AD patients with higher levels of cognitive reserve had more advanced Alzheimer’s type pathology in the comparable clinical severity, the underlying mechanism is unclear. Thus, the association between the individual’s cognitive reserve and the aging‐related brain pathologies need further investigation.MethodThis study recruited dementia free homozygous APOE ε4 allele carriers and all participants’ cognitive statuses were evaluated by neuropsychological tests. Cognitive reserve was evaluated by Cognitive Reserve Index questionnaire (CRIq). In neuroimage study, we collected brain MRI images and analyzed the severity of hippocampal atrophy and white matter hyperintensities (WMH). The relationship between different kinds of cognitive reserve and age‐related neuroimaging findings were analyzed.ResultIn total, 39 participants carrying two APOE ε4 alleles were analyzed, with an average age of 61.5 years, an education level of 13.1 years, and an average MMSE of 26.4 points. Correlation analysis showed significant associations between CRI and neuropsychological tests, especially in short‐term memory, visuospatial function, and language function tests. In neuroimaging analysis, CRI‐education was associated with hippocampal atrophy, which suggested more education might help to prevent the hippocampal atrophy. The correlation between WMH severity of brain MRI and the CRI was not statistically significant.ConclusionCognitive reserve is associated with the cognitive function in dementia free homozygous APOE ε4 allele carriers and education might prevent hippocampal atrophy.

2960. A Gut Pathobiont Triggers Neuroinflammation and Neurocognitive Impairment via Breaching the Gut-Brain Axis in a Preclinical Model of Alzheimer’s Disease: From Microbial Pathogenesis to Neuropathogenesis

Abstract Background Klebsiella pneumoniae (Kpn) is notorious for causing nosocomial infections and is commonly found in elderly patients in hospitals with Alzheimer's disease (AD). This bacterium can cause bloodstream infection, which may worsen AD pathophysiology, but there are no studies demonstrating the mechanistic role of this pathogen in AD. Methods We infected APP/PS mice intestinally with Kpn with (Kpn+Ab) and without antibiotics (Kpn) for a week and then fecal and serum samples were collected 1 and 3 weeks afterwards. Neurocognitive function and motor coordination were tested followed by collection of intestinal and brain tissues at 5 weeks. Microbiome profiles were measured using 16S rRNA amplicon sequencing. Study design Results Kpn was found to have explosively increased in the gut of all mice that received antibiotics and negatively correlated with microbial diversity. Conversely, Kpn was barely detected in the mice that did not receive antibiotics. This underscores the role of antibiotic-induced gut dysbiosis in instigating a ‘pathobiome’ signature. Notably, after five weeks post-infection, Kpn was found to be more abundantly colonized in the small intestine than large colon. Importantly, in the Kpn+Ab group, Kpn was detected not only in the blood but also in the brain, indicating the translocation of Kpn from the intestine to the brain via circulation. In mice in which Kpn was found in the brain, a substantial amount of neuroinflammation caused by bacterial infection was observed. Subsequent neurocognitive and behavioral tests revealed that mice infected with Kpn, especially those in the Kpn+Ab group, had impaired memory function and motor coordination. Effects of Klebsiella pneumoniae colonization. A. Changes in microbial composition before and after K. pn colonization, B. Correlation between microbial diversity (Shannon entropy) and abundance of Kpn of Kpn+Ab group C. Assessment of motor coordination (incline screen and hanging wire test) and memory function (T-maze) test. D. Neuroinflammation after K.pn translocation from gut to brain, E. Abundance of K.pn in the three parts of small intestine, colon, blood, and brain. Conclusion These results corroborate the emerging notion of the implicating role of the gut dysbiosis and consequent gut-brain axis impairment in Alzheimer’s neuropathology. Our findings suggest that Alzheimer's patients who are hospitalized and treated with antibiotics are at a higher risk of contracting multi-drug resistant Kpn. Further, these data also hint that gut pathobiome may increase the host’s predisposition to AD by breaching the gut-brain axis thereby triggering neuroinflammation and impairing neurocognitive function. Our ongoing studies are anticipated to reveal underlying mechanisms and will be presented at the conference. Disclosures All Authors: No reported disclosures

Sex differences in the pre and postoperative neuropsychological function of epilepsy surgery candidates

Objective: As programs expand globally, epilepsy surgery is becoming increasingly available as an effective treatment for some people with medically intractable seizures. Prospective candidates require careful neuropsychological evaluation and follow-up. The aim of this study was to examine the sex differences in neuropsychological function in presurgical presentation and postoperative outcomes in people with temporal lobe epilepsy referred for epilepsy surgery. Methods: Three hundred and seventy-two patients (202 Female; 170 Male) with a homogenous underlying pathology (hippocampal sclerosis) underwent a preoperative assessment on tests of intellectual, language, and memory function and were followed up one year after undergoing a unilateral temporal lobe resection; n = 169 Right (RTL), n = 203 Left (LTL). Results: There was no impact of sex or laterality of surgery on seizure outcome; 84% of males and 80% of females were seizure free at follow-up. Before surgery, sex effects were evident on tests of verbal memory with females performing better than males. Declines in verbal memory function following surgery were greater in females than males. Being female had a stronger association with postoperative decline on immediate prose recall (partial eta squared η 2 = 0.029), than side of surgery (η 2 = 0.018) albeit with a small effect size. Conclusions: There are subtle but significant sex differences in the neuropsychological profiles of people with temporal lobe epilepsy, before and following surgery. Whilst females generally perform better than males on tests of verbal memory function before surgery they demonstrate greater post-operative declines on these measures following surgery.