Auditory Verbal Learning Test Research Articles

Decreased neutrophil-to-lymphocyte ratio predicted cognitive improvement in late-life depression treated with vortioxetine: Findings from an eight-week randomized controlled trial.

Elevated neutrophil-to-lymphocyte ratio, a marker of inflammation, has been reported in adult and late-life depression. Vortioxetine has shown efficacy in treatment of late-life depression, yet little is known regarding its immunomodulatory role in clinical trials. This is a post-hoc analysis of an eight-week randomized controlled trial. Depressed patients aged 65 or above were treated by vortioxetine, duloxetine or placebo. 321 patients that have taken blood tests at baseline and endpoint were included in the analysis. Neutrophil-to-lymphocyte ratio (NLR) was calculated using the absolute counts of each cell type. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery-Åsberg Depression Rating Scale (MADRS) and Geriatric Depression Scale (GDS). NLR levels decreased significantly in the entire analysis set (t(320) = 2.64, p = 0.008) and in the vortioxetine group (M = -0.186, t(105) = 2.070, p = 0.041, Cohen's d = 0.20), but not in the two other groups. This decrease was not significantly different compared to placebo (F(1, 213) = 0.420, p = 0.517). Furthermore, larger NLR changes in vortioxetine arm predicted significant cognitive improvement (β = -4.03, p = 0.03), specifically regarding the DSST correct symbols (β = -1.97, p = 0.04) and RAVLT delayed recall (β = -1.87, p = 0.02) tasks. Additionally, decreased NLR significantly predicted reduced GDS score (β = 1.82, p = 0.02), yet not MADRS score. Vortioxetine treatment was associated with decreased NLR levels in late-life depression, and reductions in NLR predicted improvements in cognitive function and depressive symptoms, suggesting a potential link between inflammation and clinical outcomes.

BDNF expression mediates verbal learning and memory in women in a cohort enriched with risk for Alzheimer's disease.

This study examined whether sex differences in verbal learning and memory (VLM) are mediated by plasma brain-derived neurotrophic factor (BDNF) expression. In a sample of n=201 participants (63.81±6.04 years, 66.2% female, 65.7% family history of Alzheimer's disease [AD], 38% apolipoprotein E [APOE] ε4+) from the Wisconsin Registry for Alzheimer's Prevention, VLM was measured using trials 3 through 5 and delayed recall from the Rey Auditory Verbal Learning Test. Plasma BDNF was measured using a Human BDNF Quantikine Immunoassay. Mediation analysis used bootstrapping, and stratified mediation models tested the conditional dependence of APOE ε4 carriage. BDNF partially mediated the sex-VLM relationship (β=-0.07; 95% confidence interval [CI]: -0.18, -0.01). Female APOE ε4 carriers had higher VLM scores (β=-0.53; p=0.03), while female non-carriers had both higher BDNF levels (β=-0.68; p<0.01) and VLM scores (β=-1.06; p<0.01); BDNF was again a significant mediator (β=-0.18; 95% CI: -0.37, -0.05). This study found that circulating BDNF mediates higher verbal memory scores in females-particularly in APOE ε4 non-carriers. Sex differences in verbal learning and memory (VLM) were mediated by plasma brain-derived neurotrophic factor (BDNF) levels.Women exhibited higher VLM scores and plasma BDNF levels compared to men.The protective effect of BDNF in women was attenuated by apolipoprotein E ε4 carriage.Findings suggest sex-specific mechanisms against verbal memory decline in aging.

High definition transcranial direct current stimulation as an intervention for cognitive deficits in Alzheimer's dementia: A randomized controlled trial.

Recent disease-modifying treatments for Alzheimer's disease show promise to slow cognitive decline, but show no efficacy towards reducing symptoms already manifested. To investigate the efficacy of a novel noninvasive brain stimulation technique in modulating cognitive functioning in Alzheimer's dementia (AD). Pilot, randomized, double-blind, parallel, sham-controlled study SETTING: Clinical research site at UT Southwestern Medical Center PARTICIPANTS: Twenty-five participants with clinical diagnoses of AD were enrolled from cognition specialty clinics. Treatment consisted of high definition transcranial direct current stimulation (HD-tDCS) delivered for 20 min over the medial prefrontal cortex. Ten sessions of sham, 1 mA, or 2 mA stimulation were received. Cognitive outcomes were measured at baseline, after the last HD-tDCS session, and 8-weeks post-treatment. The primary outcome was change in total learning and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) immediately post-treatment and at 8-weeks. Secondary outcomes included measures of language, processing speed, and executive functioning. A multi-stage approach was used to examine cognitive outcomes, which included evaluation of effect sizes, statistical effects, and rate of clinically meaningful responses. In this pilot trial, no statistically significant differences on cognitive outcomes were found between sham and active HD-tDCS immediately post-treatment (p's > 0.05). However, moderate-to-large effect sizes were identified for enhanced RAVLT total learning (Cohen's d = 0.69-0.93) and phonemic fluency (d = 1.08-1.49) for both active HD-tDCS conditions compared to sham, with rates of clinically relevant improvement between 25 and 33%. Meaningful enhancement persisted to 8 weeks only for the 1 mA condition. Multiple sessions of HD-tDCS over the medial prefrontal cortex appears to have potential to produce meaningful cognitive enhancements in a proportion of patients having AD with improvements maintained for at least 8 weeks in some. ClinicalTrials.gov (NCT05270408). Registered December 30, 2021.

Multidimensional Classification and Prediction of Outcome Following Traumatic Brain Injury.

This study aimed to identify outcome clusters among individuals with traumatic brain injury (TBI), 6months to 10years post-injury, in an Australian rehabilitation sample, and determine whether scores on 12 dimensions, combined with demographic and injury severity variables, could predict outcome cluster membership 1 to 3years post-injury. Rehabilitation hospital. A total of 467 individuals with TBI, aged 17 to 87 (M =44.2years), 70% male, with mean post-traumatic amnesia 24days (range 0.5-455days), were assessed a mean of 3.4years post-injury (range 0.5-10years). A subgroup of 138 participants was also evaluated as rehabilitation inpatients and followed up 1 year post-injury. Prospective observational study. TBI Quality of Life subscales (Upper Extremity, Pain Interference, Headache Pain, Anxiety, Resilience, Emotional and Behavioral Dyscontrol, General Cognitive Concerns, Independence, and Economic Quality of Life Scale), Neurobehavioral Symptom Inventory, Family Assessment Device General Functioning Scale, Wechsler Adult Intelligence Scale-IV Letter-Number-Sequencing and Coding, Rey Auditory Verbal Learning Test, Trail Making Test Part A, Verbal Fluency Test, Word Memory Test, Participation Assessment with Recombined Tools-Objective, and Glasgow Outcome Scale-Extended. K-means cluster analysis revealed 5 clusters across 12 dimensions: Good Outcome, High Cognition, Poor Cognition, Poor Outcome, and Poor Adjustment, aligning with Sherer and colleagues' clusters. Inpatient assessments (n=138) identified profiles predictive of outcome group membership. Participants with Good Outcomes exhibited lower anxiety and higher independence, self-esteem, and resilience, despite some cognitive deficits. High Cognition correlated with robust Economic and Family Support. Poor Cognition aligned with impaired cognitive function but positive psychosocial ratings suggest limited self-awareness. Poor Outcome featured low initial cognitive scores and poor psychosocial adjustment. Poor Adjustment participants, without inpatient cognitive impairments, reported persistent pain, physical symptoms, and emotional distress. Findings support the evaluation of cognitive and psychosocial factors during rehabilitation to predict outcomes with potential to inform rehabilitative interventions to optimize outcomes.

Electroacupuncture combined with cognitive rehabilitation outperforms cognitive rehabilitation alone in treating post-stroke cognitive impairment: a randomized controlled trial

This study aimed to evaluate the effects of a 12-week intervention combining electroacupuncture (EA) with conventional cognitive rehabilitation (CR) on cognitive recovery and brain network topological properties in stroke patients. Thirty-four post-stroke cognitive impairment (PSCI) patients were randomly assigned to either an EA + CR group or a CR-only group, with both undergoing five weekly interventions for 12 weeks. Cognitive assessments and Diffusion Tensor Imaging tests were performed pre- and post-intervention. Primary outcomes included the Montreal Cognitive Assessment (MoCA), Digit Span Test (DST), Auditory Verbal Learning Test (AVLT-H), and Aphasia Screening Scale. Secondary outcomes measured brain network global and nodal properties. The EA + CR group showed significant improvements in MoCA (p &amp;lt; 0.001), AVLT-H (p = 0.004), and in areas like naming (p = 0.022), attention (p &amp;lt; 0.001), and delayed recall (p &amp;lt; 0.001). Local brain network metrics, such as clustering coefficients (Cp) and local efficiency (Eloc), were significantly higher (p &amp;lt; 0.05) in the EA + CR group, though global efficiency (Eglob) was unchanged. Improvements in Eloc were positively correlated with MoCA scores (r = 0.0716, p = 0.018). Specific brain regions, including the medial and paracentral cingulate gyrus, inferior temporal gyrus, and left supramarginal gyrus, exhibited significant nodal property differences, suggesting that EA may enhance cognitive recovery by targeting cognitively relevant regions. These findings indicate that EA, combined with CR, is a safe and effective treatment for cognitive impairment following stroke, potentially via structural brain network improvements.Clinical trial registrationhttps://clinicaltrials.gov/, ChiCTR2200066160.

Sociodemographic factors, cognitive performance and cognitive reserve in brazilian High Performance Older Adults (HPOAs)

Given the increasing aging population, investigating the cognitive functioning of older adults is crucial. Various factors are associated with both cognitive decline and preservation. High Performance Older Adults (HPOAs) are a subset of older individuals demonstrating exceptional cognitive abilities, often exhibiting phenotypic characteristics such as superior cognitive skills. This study aims to investigate the relationship between sociodemographic factors, cognitive reserve and cognitive performance in a sample of brazilian older adults identified as having high cognitive abilities. To examine this phenomenon, data were collected via a sociodemographic questionnaire and cognitive assessments. Of an initial sample of 62 participants, 54 completed the study (38.8% men, 61.1% women). Analysis revealed 12 participants (22.2%) met HPOA criteria, while 42 (77.7%) were classified as Standard Performance Older Adults (SPOAs). HPOAs demonstrated significantly better performance on the Rey Auditory Verbal Learning Test (RAVLT) in trials A1-A5, A6, A7, and Recognition Memory (p &lt; 0.001); on the Rey Complex Figure in Immediate and Delayed Recall (p = 0.006), and on the Trail Making Test A (TMT A) (p = 0.003). Significant differences were also found in the analysis items of the Cognitive Reserve Scale (CRS) (p &lt; 0.001; p = 0.008; p = 0.002). The findings reveal that HPOAs exhibit superior performance in episodic memory, attention and processing speed tasks. The model coefficients in logistic regression revealed a statistically significant association between Total Points in CRS and HPOA (β = 0.0508, standard error = 0.0147, z = 3.45, p &lt; 0.001). These results emphasize the importance of cognitive reserve for preserving cognitive performance in the elderly. New research should aim to elucidate the complex interplay of markers associated with HPOAs, employing rigorous research protocols sensitive to sociocultural context.

Sex and APOE genotype modulate neuropsychological profile and depression in temporal lobe epilepsy.

Temporal lobe epilepsy is the most common form of focal epilepsy, often associated with cognitive impairments, particularly in memory functions, and depression. Sex and APOE ε4 genotype play a crucial role in modulating cognitive outcomes and depression in various neurological conditions like Alzheimer's disease. However, the combined effects of APOE genotype and sex on cognitive performance and depression in temporal lobe epilepsy have not been previously investigated. This study aims to (i) identify impaired cognitive performance and clinically relevant depression; (ii) explore the interaction between sex and APOE ε4 genotype on cognitive performance and depression in individuals with temporal lobe epilepsy. We used a comprehensive battery of neuropsychological tests to assess domains such as learning and memory, attention, executive functions, language, and visuo-spatial constructional skills and the Hamilton Depression Rating Scale. We also performed APOE genotyping to assess its role in the study. The final sample was composed by fifty-four patients (53.7% female). Cognitive performance and depression were analyzed using normative cut-off scores. To examine the main effects and interactions of sex and APOE ε4 carrier status on neuropsychological test scores and the Hamilton Depression Rating Scale, we also conducted a two-way Analysis of Variance (ANOVA). Female APOE ε4 carriers compared to normative cut-offs, exhibited poor performance on multiple test scores, including the MMSE, The Rey Auditory Verbal Learning Test (immediate and delayed recall), The Corsi Block-Tapping Task, The Verbal Fluency Test, The Raven's Standard Progressive Matrices and The Pentagon-copying Test. Males showed impairment only in visuo-spatial short-term memory. ANOVA analysis revealed significant main effects of APOE ε4 status and sex on the MMSE, The Rey Auditory Verbal Learning Test, The Verbal Fluency, The Raven's Standard Progressive Matrices and The Pentagon-copying Test scores. Specifically, female APOE ε4 carriers performed consistently worse than other groups on many tasks. For depression, only an effect of sex emerged. Females scored higher besides APOE genotype. These findings underscore the importance of considering both sex and APOE genotype when assessing cognitive performance in patients with temporal lobe epilepsy. The significant cognitive deficits we observed among females carrying the APOE ε4 allele highlight previously unexplored genetic and sex-related influences on cognition. This has potential implications for personalized therapeutic strategies, emphasizing the need for targeted assessment and intervention.

Alterations of gray matter volume and functional connectivity in patients with cognitive impairment induced by occupational aluminum exposure: a case-control study.

Cognitive impairment (CI) is a condition in which an individual experiences noticeable impairment in thinking abilities. Long-term exposure to aluminum (Al) can cause CI. This study aimed to determine the relationship between CI and MRI-related changes in postroom workers exposed to Al. Thirty patients with CI and 25 healthy controls were recruited. Plasma aluminum levels were measured using inductively coupled plasma-mass spectrometry. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and an auditory-verbal learning test (AVLT). All participants underwent magnetic resonance imaging scans. 3D T1-weighted anatomical images and resting-state functional magnetic resonance imaging data were acquired, and voxel-based morphometry and ROI-based FC were used for analysis. A mediation analysis was also conducted. Plasma aluminum levels were significantly higher in the CI group than in the normal control group. The gray matter (GM) volume in the left caudate and bilateral hippocampus was lower in the CI group and was positively correlated with cognitive scale scores. There was no significant difference in functional connectivity (FC) between the left caudate and the whole brain between the two groups. Significant alterations in hippocampal FC were observed in certain brain areas, mainly in the left cerebellar vermis, left middle frontal gyrus (BA9), and right superior frontal gyrus relative to the supplementary motor area (BA6). The FC coefficients were also associated with cognitive scale scores. Furthermore, plasma Al concentration was negatively correlated with the Montreal Cognitive Assessment score, bilateral hippocampal GM volume, and FC coefficient between the left hippocampus and left cerebellar vermis. Mediation analysis showed GM alteration of left caudate and bilateral hippocampus and FC alteration of left hippocampus to left cerebellar vermis could explained 19.80-32.07% of the effect of MoCA scores change related to Al exposure, besides the GM alteration of right hippocampus acted as indirect mediator (68.75%) of the association between Al and AVLT delayed recall scores. Our data indicates that alterations in the structure and function of special brain domain, especially the hippocampus, are associated with Al-induced CI. These brain regions can partly explain the effect of Al on cognitive impairment.

Verbal Memory is Higher After Aerobic Exercise When Compared to Muscle Stretching.

Acute exercise is linked to memory improvement. Several mediators may influence the effect of exercise such as the type of exercise (aerobic exercise, muscle stretching). Purpose: The primary aim was to analyze memory outcomes after a 20-min bout of aerobic exercise or muscle stretching. Methods: 42 healthy participants ages 18-35 were randomized to perform 20min of either moderate-intensity aerobic exercise (AE) on a treadmill or muscle stretching exercise (SE). After exercise, memory was assessed using the Rey Auditory Verbal Learning Test (RAVLT). The relationship between exercise heart rate and memory outcomes were evaluated within each group. Results: Immediate learning as well as delayed recall was higher after AE compared to SE. Heart rate during exercise correlated with immediate learning in the AE group only. Conclusion: Acute exercise that elicits a heart rate response may be important for improving memory.

Insulin resistance, cognition, and functional brain network topology in older adults with obesity.

Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral and neuronal insulin resistance (IR) relate to executive function and functional brain network topology. Older adults (n=71) with obesity but without type 2 diabetes were included. Peripheral IR was quantified by HOMA2-IR. Neuronal IR was quantified according to a proposed neuron-derived exosome-based method (NDE-IR). An executive function composite score, summed scores to the Auditory Verbal Learning Test (AVLT) trials 1-5, and functional brain networks generated from resting-state functional magnetic resonance imaging were outcomes in analyses. We used general linear models and a novel regression framework for brain network analysis to identify relationships between IR measures and brain-related outcomes. HOMA2-IR, but not NDE-IR, was negatively associated with executive function. Neither IR measure was associated with AVLT score. Peripheral IR was also related to hippocampal network topology in participants who had undergone functional neuroimaging. Neither peripheral nor neuronal IR were significantly related to network topology of the central executive network. Cognitive and functional imaging effects were observed from HOMA2-IR, but not NDE-IR. The hippocampus may be particularly vulnerable to effects of peripheral IR.

Development of a digital memory and learning test for elderly individuals

BackgroundPopulation aging and the increase in memory-related diseases have motivated the search for accessible cognitive screening instruments. To develop a digital memory and learning test (DMLT) based on Rey’s Auditory Verbal Learning Test (RAVLT) principles to assess cognition in the elderly and identify early cognitive decline.MethodsThe research was divided into two phases: developing the digital test and the experimental phase of comparison with a reference test. The test was designed to assess episodic declarative memory through auditory-verbal learning. The experimental procedure involved 18 elderly participants and aimed to compare the performance on the digital test with the traditional RAVLT, followed by an evaluation of participant satisfaction.ResultsPerformance on the digital test and the RAVLT was comparable, with no significant statistical differences, indicating convergent validity between the instruments. Electroencephalographic activity analyses revealed correlations between wave patterns and test performance, suggesting that the digital test may provide additional insights into the neurophysiological processes underlying cognitive performance. Satisfaction assessment revealed high participant acceptance.ConclusionThe DMLT is a promising tool for cognitive assessment in the elderly, offering an accessible alternative. The high acceptance among elderly participants suggests that the test has potential for clinical and research use, although further studies are needed to validate its effectiveness in broader clinical settings.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Alzheimer's disease (AD) can be diagnosed by invivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions. This study of cognitively unimpaired older individuals examined whether serial position scores in word-list recall cross-sectionally predicted tau PET load in the MTL, and were able to discriminate between biomarker profiles, based on AT classification. Data from 490 participants (mean age=68.8±7.2) were extracted from two cohorts, which were merged into one sample. Linear regression analyses were carried out with regional volume-controlled tau (18F-MK-6240) PET SUVR of the entorhinal cortex (EC), parahippocampal cortex (PHC) and hippocampus (H) as outcomes, cross-sectional memory scores from the Rey Auditory Verbal Learning Test as predictors (total and delayed recall, along with serial position scores) and control variables, in separate analyses for each outcome and predictor. The sample was then stratified by biomarker profile and ANCOVAs were conducted with the strongest scores from the regression analyses, AT groups as fixed factor and the covariates. Higher delayed primacy significantly predicted lower tau PET in EC, PHC, and H, cross-sectionally. Higher total recall scores predicted lower EC tau, but delayed primacy showed the best model fit, as indicated by AICs. ANCOVAs showed that AVLT metrics did not significantly discriminate between A-T- and A+T+, after correcting for multiple comparisons. Serial position analysis of word-list recall, particularly delayed primacy, may be a valuable tool for identifying invivo tau pathology in cognitively unimpaired individuals.

Cumulative blood pressure load and cognitive decline in older adults: An observational analysis of two large cohorts.

Cumulative blood pressure metrics may provide greater precision for measuring temporal risk exposure, especially in later life where data are mixed regarding associations of high blood pressure (BP) on cognitive function. We examined the relationship between greater cumulative exposure to high BP in later life and several domains of cognitive function. Individual cognitive assessment scores and BP measurements in older adults (age ≥70 years) at baseline and over approximately 8 years of follow-up were available in the population-based Canadian Victoria Longitudinal Study (VLS) and Swedish Gothenburg H70 Birth Cohort Studies (H70). Linear mixed models were used to quantify associations between cumulative systolic and diastolic BP and change in cognitive scores. Each additional 100mmHg increase in cumulative BP was related to greater decline in the Rey Auditory Verbal Learning Test (RAVLT) List A, trials 1-5 total score over follow-up: -0.23 (95% confidence interval [CI] -0.32, -0.13) for systolic BP and -0.41 (95%CI -0.58, -0.23) for diastolic BP. Similarly increases cumulative systolic and diastolic BP were related to greater declines Digit Symbol Substitution Task (DSS) scores: -0.59 (95%CI -0.80, -0.38) and -1.04 (95% CI -1.40, -0.67), respectively. There were no associations of cumulative BP and temporal changes in general cognition, other measures of verbal episodic memory, or semantic fluency. Higher cumulative BP is associated with greater declines in RAVLT measured immediate memory span and complex attention, information processing speed and visuospatial scanning in older adults, but the scale of change is small. Additional research is required to further define these relationships and identify opportunities for prevention.

Explainable machine learning on clinical features to predict and differentiate Alzheimer's progression by sex: Toward a clinician-tailored web interface.

Alzheimer's disease (AD), the most common neurodegenerative disorder world-wide, presents sex-specific differences in its manifestation and progression, necessitating personalized diagnostic approaches. Current procedures are often costly and invasive, lacking consideration of sex-based differences. This study introduces an explainable machine learning (ML) system to predict and differentiate the progression of AD based on sex, using non-invasive, easily collectible predictors such as neuropsychological test scores and sociodemographic data, enabling its application in every day clinical settings. The ML model uses SHapley Additive explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) to provide clear insights into its decision-making, making complex outcomes easier to interpret. The system includes a user-friendly graphical interface designed in collaboration with clinicians, supporting its integration into medical practice. The study extends the cohort to include healthy and Mild Cognitive Impairment subjects, aiming to support early diagnosis in AD pre-clinical stages. The ML system was trained on a large dataset of 2407 subjects from the ADNI open dataset, enhancing its robustness and applicability. By focusing on sex-specific features and utilizing longitudinal data, the system aims to improve prediction accuracy and early detection of AD, ultimately advancing personalized diagnostic and therapeutic approaches. Key findings highlight the significance of the Mini-Mental State Examination, Rey Auditory Verbal Learning Test, Logical Memory - Delayed Recall, and educational attainment in AD diagnosis and progression, with sex-based disparities. Despite performance metrics based on precision, recall, and weighted F1-score demonstrating model efficacy, future research should address the limitations of relying on a single dataset.

ASSOCIATION BETWEEN GUT MICROBIOTA, DIET, AND COGNITION IN ELDERLY PATIENTS WITH MILD COGNITIVE IMPAIRMENT

Abstract Objectives To compare the gut microbiota in individuals with mild cognitive impairment (MCI) and normal controls (NCs) and explore the association between dietary intake and various cognitive domains across identified enterotypes, providing a basis for dietary interventions based on the Microbiota-Gut-Brain Axis. Methods We analyzed fecal samples and 16S ribosomal RNA sequences for microbiota among 100 participants (NCs: 50, MCI: 50). Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Auditory Verbal Learning Test (AVLT). A semi-quantitative food frequency questionnaire was used to assess participants’ dietary intake, and differences in dietary habits and cognitive function among distinct enterotypes were analyzed. Results Participants with MCI exhibited lower bacterial richness. Linear Discriminant Analysis of Effect Sizes (LEfSe-LDA) revealed different major microbial genera between the groups, and a random forest model based on dominant bacterial genera could distinguish between MCI and NCs (AUC=0.743, 95%CI:0.646-0.840). Cluster analysis identified two enterotypes: Escherichia-Shigella (enterotype E) and Bacteroides (enterotype B). When grouped by enterotypes, similar dietary intake was associated with different cognitive domains: notably, egg intake positively correlated with MOCA and AVLT scores for enterotype E, but not for enterotype B. Conclusions: Significant differences exist in the gut microbiota of individuals with MCI compared to those with normal cognition, with dominant genera showing good predictive performance. The impact of different enterotypes on the relationship between dietary intake and cognitive function should be considered when making dietary recommendations in clinical practice.

ASSOCIATION BETWEEN GUT MICROBIOTA, DIET, AND COGNITION IN ELDERLY PATIENTS WITH MILD COGNITIVE IMPAIRMENT

Abstract Objectives To compare the gut microbiota in individuals with mild cognitive impairment (MCI) and normal controls (NCs) and explore the association between dietary intake and various cognitive domains across identified enterotypes, providing a basis for dietary interventions based on the Microbiota-Gut-Brain Axis. Methods We analyzed fecal samples and 16S ribosomal RNA sequences for microbiota among 100 participants (NCs: 50, MCI: 50). Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Auditory Verbal Learning Test (AVLT). A semi-quantitative food frequency questionnaire was used to assess participants’ dietary intake, and differences in dietary habits and cognitive function among distinct enterotypes were analyzed. Results Participants with MCI exhibited lower bacterial richness. Linear Discriminant Analysis of Effect Sizes (LEfSe-LDA) revealed different major microbial genera between the groups, and a random forest model based on dominant bacterial genera could distinguish between MCI and NCs (AUC=0.743, 95%CI:0.646-0.840). Cluster analysis identified two enterotypes: Escherichia-Shigella (enterotype E) and Bacteroides (enterotype B). When grouped by enterotypes, similar dietary intake was associated with different cognitive domains: notably, egg intake positively correlated with MOCA and AVLT scores for enterotype E, but not for enterotype B. Conclusions: Significant differences exist in the gut microbiota of individuals with MCI compared to those with normal cognition, with dominant genera showing good predictive performance. The impact of different enterotypes on the relationship between dietary intake and cognitive function should be considered when making dietary recommendations in clinical practice.

GENETIC RISK, MODIFIABLE FACTORS, AND COGNITIVE PERFORMANCE IN MIDDLE- AND OLDER-AGED CANADIANS

Abstract Whether the apolipoprotein E (APOE) e4 allele interacts with modifiable factors to predict cognitive performance is unclear. This study examined 26,448 participants (45 to 86 years of age at baseline) in the Canadian Longitudinal Study on Aging who had their blood genotyped for the APOE e4 allele, of whom 6,305 (24%) were e4 carriers. Cognitive outcomes were Rey Auditory Verbal Learning Test 5-minute delayed recall, Mental Alterations Test, and Animal Fluency Test, which were collected at baseline (December 2011 to July 2015), follow-up 1 (median 2.9 years after baseline), and follow-up 2 (median 5.8 years after baseline). We examined interactions between time from baseline, APOE e4 status and the following exposures: self-reported physical activity and a composite risk score comprised of sedentary behavior, smoking, depressive symptoms, social isolation, whole blood hemoglobin A1c fraction, and percent body fat. Models were adjusted for age, sex, ethnicity, study language (French/English), residential setting (urban/rural), and educational attainment. Across cognitive outcomes, an age by APOE e4 interaction was observed (p values ranging from &amp;lt;.001 to.01), such that the difference in cognitive performance between carriers and non-carriers increased as participant age increased. Although physical activity and composite risk were associated with cognitive performance (all p values &amp;lt;.01), there was not convincing evidence that these associations varied by e4 carrier status after correcting for multiple comparisons. Together, these findings confirm that APOE e4 carriers show greater reductions in cognitive performance but do not suggest that e4 status alters associations between modifiable risk and cognitive decline.

THE PREDICTORS OF SEDENTARY BEHAVIOR AMONG OLDER ADULTS WITH POOR MOBILITY

Abstract Older adults with poor mobility are typically more sedentary, which poses increased risk for disability. Identifying the predictors of objectively measured sedentary behavior may affect targeted treatment strategies. This study aimed to identify the predictors of sedentary behavior in older adults with poor mobility. We recruited 18 older adults with self-reported poor mobility (78.3±8.6 years, 44.4% female) from the community and residential care facilities. Participants reported demographic information (years of education, age, sex, fall history) and completed a battery of assessments, including cognition (Rey Auditory Verbal Learning Test), depression (Geriatric Depression Scale), and gait (gait speed). Participants wore an activity monitor on their non-dominant ankle for 7 days (ActiGraph, Pensacola, FL). We used a minimum wear time of ≥4 days, including 2 weekend days in the analysis. We conducted a linear regression with sedentary behavior percentage as the dependent variable, with moderate-to-vigorous physical activity (MVPA), fall history, depression, memory, and gait speed as variables of interest, and we controlled for age, sex, and education,. All variables were correlated at r≤±0.3. The overall model was significant (R2=0.93, p=0.004). The predictors of high sedentary behavior were: greater depression [β=0.59, CI=0.04,1.14], lower MVPA [β=-0.16, CI=-0.2,-0.13], male sex [β=2.71, CI=0.03,5.39], and better memory [β=1.02, 0.29,1.74]. Our results suggest that older adults with poor mobility who are male, more depressed, less physically active, and have better memory are more at risk for being sedentary. Targeted interventions to reduce sedentary behavior and increase exercise, especially those most at-risk for a sedentary lifestyle, may improve health outcomes.

FEASIBILITY AND EFFECTS OF HIGH-INTENSITY INTERVAL TRAINING ON COGNITIVE FUNCTION AND BRAIN HEALTH IN PERIMENOPAUSE

Abstract Neuroendocrine changes during perimenopause negatively impact cognitive function and brain health (e.g., reduced verbal episodic memory and myelin catabolism in the brain). Exercise promotes cognitive performance and mitigates vascular risk factors for cognitive impairment. High-intensity interval training (HIIT) involves short bursts of high-intensity exercise interspersed with active recovery; it improves cardiovascular fitness and vascular risk profile. HIIT addresses the “lack of time” barrier to exercise that perimenopausal females report. This pre-post pilot study assessed the feasibility and potential effects of 12-weeks of HIIT on cardiovascular fitness, verbal episodic memory, hippocampal volume, and myelin content. Feasibility metrics included recruitment rate (i.e., 1/month), withdrawal rate (i.e., &amp;lt; 15%), adherence (i.e., &amp;gt;60%). Training fidelity was assessed by cardiovascular fitness (VO2max.) Verbal episodic memory was assessed by Rey Auditory Verbal Learning Test delayed recall. Hippocampal volume was measured by T1-weighted magnetic resonance imaging. Myelin content was measured by myelin water fraction. Cohen’s d and one-tailed paired t-tests assessed effect sizes and potential changes. Recruitment rate was 0.35 participants/month (six participants in 17 months). Withdrawal rate was 16.67% and adherence was 88.2%. The intervention had a negligible effect on VO2max (Cohen’s d=0.06, p=0.35), large and significant effect on delayed recall (Cohen’s d=0.94, p=0.04), negligible effect on hippocampal volume (Cohen’s d=0.06, p=0.18), and medium to large effect on sagittal stratum myelin content (Cohen’s d=0.68, p=0.06). Future studies should consider home-based exercise and tailored recruitment methods (e.g. social media) to meet recruitment targets. HIIT may be beneficial for cognitive function and myelin content.

CONSCIENTIOUSNESS MODERATES THE RELATIONSHIP BETWEEN INTERLEUKIN-6 AND MEMORY DECLINE

Abstract Evidence supports the role of the pro-inflammatory cytokine interleukin-6 in accelerating cognitive decline and increasing ADRD risk. Personality may influence this relationship in a pathoplastic way, by protecting against or exacerbating the cognitive consequences of inflammation. Conscientious (i.e., controlled, planful, organized) people are characterized by healthier behaviors, which may play a protective role. Among 182 older adults (Mage=74 years, 41% female), Rey Auditory Verbal Learning Test (RAVLT) performance was measured annually for up to 16.6 years (M=6.5 years). Total learning and delayed recall were regressed on expected performance (norms based on age, gender, and IQ), time, IL-6, conscientiousness, and their interactions with each other and with gender. There was a significant interaction among time, IL-6, and conscientiousness (F(1,167.51)=5.36, p=.021) such that people with high conscientiousness and low IL-6 maintained total learning and thus increased their performance relative to norms over time; people with low conscientiousness and/or high IL-6 maintained performance relative to norms. The same interaction was observed for delayed recall (F(1,165.22)=5.20, p=.024). The recall effect decreased after adjusting for learning, but in a gender-specific way (interaction with gender, F(1,164.74)=4.97, p=.027). Adjusting for total learning eliminated the interaction for men but not for women. Rather than a pathoplastic relationship, IL-6 and conscientiousness had a synergistic effect on memory decline over time. Neither low IL-6 nor high conscientiousness alone were sufficient to preserve memory. The healthy habits of conscientious older people may need an advantageous physical environment in order to affect memory and possibly other cognitive functions.