Verbal Memory Scores Research Articles

The effect of age on baseline neurocognitive performance

ABSTRACT Objective Evaluate the independent effect of age on baseline neurocognitive performance. Study Design Baseline ImPACT scores from tests taken by 7454 athletes aged 12–22 from 2009 to 2019 were split into three age cohorts: 12–14 years (3244), 15–17 years (3732), and 18–22 years (477). Linear regression analyses were used to evaluate the effect of age on ImPACT composite scores while controlling for demographic differences, medication-use, and symptom burden. Significance values have been set at p < 0.05. Results Linear regression analyses demonstrated that increased age does not significantly affect symptom score (β = 0.06, p = 0.54) but does improve impulse control (β = −0.45, p < 0.0001), verbal memory (β = 0.23, p = 0.03), visualmotor (β = 0.77, p < 0.0001), and reaction time (β = −0.008, p < 0.0001) scores. However, age did not have an effect on visual memory scores (β = −0.25, p = 0.07). Conclusions Age was shown to be an independent modifier of impulse control, verbal memory, visual motor, and reaction time scores but not visual memory or symptom scores. This underscores the previous literature showing developmental differences as age increases among the adolescent athlete population. This data also indicates the need for repeat neurocognitive baseline testing every other year as baseline scoring is likely to change as athletes become older.

Differentiating MCI from depression through verbal memory scores.

The present study aims to assess the differences between major depressive disorder (MDD) and mild cognitive impairment (MCI) in terms of verbal learning profile together with structural changes in the brain on magnetic resonance imaging (MRI) and to reveal predictive factors for MCI. Fifty-six patients with MDD and 31 MCI subjects were assessed using the Turkish Verbal Memory Processes Test (VMPT). Brain MRI was used to evaluate sulcal atrophy (SA), ventricular atrophy, periventricular white matter hyperintensity (WMH), subcortical WMH, basal ganglia infarct, medial temporal lobe atrophy, and infratentorial infarct scores based on the Modified Visual MRI Rating Scale (MVMRS). The symptoms of depression were evaluated with the Beck Depression Inventory in both groups. Demographic factors, VMPT scores, and MVMRS scores between MDD and MCI groups were compared. Also, potential predictors of MCI were analyzed by binary logistic regression analyses. The total scores of VMPT and the scores of VMPT subgroups, including immediate memory, highest learning, total learning, and delayed recall, were significantly higher in the MDD groups compared to MCI patients (Mann-Whitney U, Student's t-test, p < 0.05), indicating that higher scores were associated with better memory. The total MVMRS score and a subgroup of MVMRS, the SA score, were significantly higher in MCI patients compared to the MDD group, suggesting more atrophic changes and a higher burden of infarction in MCI patients. In our statistical analyses, impaired immediate memory (p < 0.001; OR = 6.002; 95% CI: 1.996-18.042), increased SA (p = 0.008; OR = 1.522; 95% CI: 1.118-2.073), and education (p = 0.028; OR = 0.84; 95% CI: 0.719-0.981) were significant predictive values obtained through backward Wald elimination in the binary logistic regression model for detecting MCI. Our findings suggest that VMPT may potentially represent a novel neuropsychiatric test that might be combined with MRI-based morphometric evaluation methods, such as MVMRS.

Elevated lipopolysaccharide binding protein in Alzheimer's disease patients with APOE3/E3 but not APOE3/E4 genotype.

The role of lipopolysaccharide binding protein (LBP), an inflammation marker of bacterial translocation from the gastrointestinal tract, in Alzheimer's disease (AD) is not clearly understood. In this study the concentrations of LBP were measured in n = 79 individuals: 20 apolipoprotein E (APOE)3/E3 carriers with and 20 without AD dementia, and 19 APOE3/E4 carriers with and 20 without AD dementia. LBP was found to be enriched in the 1.21-1.25 g/mL density fraction of plasma, which has previously been shown to be enriched in intestinally derived high-density lipoproteins (HDL). LBP concentrations were measured by ELISA. LBP was significantly increased within the 1.21-1.25 g/mL density fraction of plasma in APOE3/E3 AD patients compared to controls, but not APOE3/E4 patients. LBP was positively correlated with Clinical Dementia Rating (CDR) and exhibited an inverse relationship with Verbal Memory Score (VMS). These results underscore the potential contribution of gut permeability to bacterial toxins, measured as LBP, as an inflammatory mediator in the development of AD, particularly in individuals with the APOE3/E3 genotype, who are genetically at 4-12-fold lower risk of AD than individuals who express APOE4.

Recovery Is Similar Between Black and White College Athletes Following Sport-Related Concussion.

Racial identity may associate with clinical outcomes following sport-related concussion (SRC). This study compared clinical outcome scores before and after recovery from a SRC between Black or White college athletes. Prospective cohort. Participants were self-reported White (n = 61, 18.5 [1.1]y of age) and Black (n = 24, 18.3 [1.1]y of age) NCAA Division 1 college athletes. The revised Head Injury Scale (HIS-r), the Immediate Postconcussion and Cognitive Test (ImPACT) battery, and the Sensory Organization Test (SOT) at baseline (T1), upon symptom resolution (T2) following a diagnosed SRC, and upon establishing a new baseline assessment (T3). Race was collected from paper and electronic medical records. The revised Head Injury Scale total symptom severity, ImPACT's Verbal Memory, Visual Memory, Visual Motor Speed (VMS), and Reaction Time, and the SOT Equilibrium Score, were compared between groups at each time point. Multivariate analyses of variance (2 [group] × 3 [time]) were used to compare revised Head Injury Scale, ImPACT, and SOT outcome scores. Post hoc analyses consisted of independent and paired sample t tests. A significant main effect for time (λ = 0.66, F2,82 = 21.55, P < .001, ηp2=.34) was observed for the SOT. White athletes significantly improved on the Equilibrium Score between all time points (all P < .006). Similarly, Black athletes significantly improved on the Equilibrium Score between T1-T2 and T1-T3 (all P < .001). A significant main effect of time was observed for ImPACT's Verbal Memory, Visual Memory, and VMS outcome scores (all P < .001). VMS improved for White athletes between T1-T2 (P = .02) and T3 (P = .006). Black athletes had improved VMS scores between T1-T3 (P = .015) and T2-T3 (P = .005). A between-group difference was observed for VMS at T2 (P = .004). There was 1 small and not clinically significant difference between groups for the VMS score at T2. Overall, groups performed consistently or improved upon their baseline balance, cognition, and symptom outcome scores at clinically relevant time points following a SRC.

Neuroanatomical profiles of cognitive phenotypes in patients with primary brain tumors.

Patients with brain tumors demonstrate heterogeneous patterns of cognitive impairment, likely related to multifactorial etiologies and variable tumor-specific factors. Cognitive phenotyping offers a patient-centered approach to parsing heterogeneity by classifying individuals based on patterns of impairment. The aim of this study was to investigate the neuroanatomical patterns associated with each phenotype to gain a better understanding of the mechanisms underlying impairments. Patients with primary brain tumors were recruited for a prospective, observational study. Patients were cognitively phenotyped using latent profile analysis in a prior study, revealing 3 distinct groups: generalized, isolated verbal memory, and minimal impairment. Whole brain cortical thickness (CT), fractional anisotropy, and mean diffusivity (MD) were compared across phenotypes, and associations between imaging metrics and cognitive scores were explored. Neurocognitive, structural MRI, and diffusion MRI data were available for 82 participants at baseline. Compared to the minimal impairment group, the generalized impairment group showed a widespread, bi-hemispheric pattern of decreased CT (P-value range: .004-.049), while the verbal memory impairment group showed decreased CT (P-value range: .006-.049) and increased MD (P-value range: .015-.045) bilaterally in the temporal lobes. In the verbal memory impairment group only, increased parahippocampal MD was associated with lower verbal memory scores (P-values < .01). Cognitive phenotypes in patients with brain tumors showed unique patterns of brain pathology, suggesting different underlying mechanisms of their impairment profiles. These distinct patterns highlight the biological relevance of our phenotyping approach and help to identify areas of structural and microstructural vulnerability that could inform treatment decisions.

Investigating the effect of hippocampal sclerosis on parietal memory network.

We aimed to investigate differences in episodic memory networks between patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis and healthy controls, especially with regards to the parietal memory network (PMN), as well as their relation to neuropsychological memory performance after mesial temporal resection. 28 healthy subjects as well as 21 patients with TLE (12 left, 9 right) were investigated using a spatial memory fMRI paradigm, which has been shown to activate the PMN. Regions of interest (ROI) were defined based on the results of the second-level analyses and activations within the predefined ROIs were compared across groups and correlated with postoperative verbal and nonverbal memory scores. Healthy subjects showed activations within regions belonging to the dorsal visual stream and the PMN as well as the bilateral parahippocampal place area, the bilateral frontal eye field, and the bilateral middle frontal gyrus. Comparison between groups revealed that TLE patients activated significantly less in the left middle occipital gyrus and the right precuneus. The activation pattern in left TLE patients showed further reductions, mainly in areas belonging to the dorsal visual stream and the PMN within the left hemisphere. Activations within the left superior parietal lobulus, bilateral inferior parietal lobulus, bilateral middle temporal gyrus, left precuneus, left frontal eye field, and left middle frontal gyrus correlated significantly with postoperative verbal memory scores, and activations within the left superior parietal lobulus, left inferior parietal lobulus, left middle temporal gyrus, and left precuneus correlated significantly with higher performance in postoperative nonverbal memory scores. The PMN is involved in episodic memory encoding. Higher activations in areas belonging to the PMN and the dorsal visual stream, especially within the left hemisphere, before amygdalohippocampectomy may result in higher postoperative memory scores. This study aims to investigate the effects of epilepsy due to hippocampal sclerosis, i.e. scarring in the temporal lobe, on memory networks in the brain. We discovered that especially patients with left-sided hippocampal sclerosis show reduced brain activations in visual areas and memory networks within the left hemisphere of the brain during orientation in space. Importantly, higher activations within these areas may result in better memory after epilepsy surgery.

EFFECTS OF HIGH-INTENSITY AQUATIC EXERCISE ON INFLAMMATION AND COGNITION IN OLDER ADULTS WITH MCI

Abstract Exercise shows immune benefits in older adults and can reduce the risk of late-life cognitive impairment and dementia. This study sought to explore the effects of high-intensity aquatic-based exercise on older adults with mild cognitive impairment (MCI), specifically by examining changes in inflammatory plasma protein concentrations and cognitive performance. A secondary data analysis was conducted on 20 healthy volunteers (mean age 68.2 ±7.75 years) who participated in 6 months of supervised aquatic exercise training. Participants completed a battery of neuropsychological assessments and whole blood draws at pre- and post-intervention. Plasma protein concentration levels were attained using the Olink Target96 Inflammation panel [Uppsala, Sweden]. Mixed effects models assessed the effects of protein concentration change scores on selected cognitive outcomes, while controlling for age. Results indicated that following the exercise intervention, significant changes in two inflammatory-related proteins (Extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]; Interleukin-20 receptor subunit alpha [IL-20RA]) were associated with improved verbal memory and processing speed endpoints. Specifically, decreased EN-RAGE concentrations resulted in significantly improved delayed verbal memory scores (parameter estimate= -0.893, p= .023), while increased IL-20RA concentrations led to better task completion (parameter estimate= 2.145, p= .030). These findings demonstrate the cognitive benefits of aquatic-based exercise for older adults and those with MCI, and suggest these effects are mediated by alterations in pro- and anti-inflammatory protein markers such as EN-RAGE and IL-20RA. Larger studies are warranted to replicate these findings, and to further explore the role of activity-induced inflammatory changes on late-life brain health.

Cognitive decline in thrombotic thrombocytopenic purpura survivors: The role of white matter health as assessed by MRI.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare condition caused by severe ADAMTS13 deficiency, leading to platelet aggregation and thrombosis. Despite treatment, patients are prone to cognitive impairment and depression. We investigated brain changes in iTTP patients during remission using advanced magnetic resonance imaging (MRI) techniques, correlating these changes with mood and neurocognitive tests. Twenty iTTP patients in remission (30 days post-haematological remission) were compared with six healthy controls. MRI scans, including standard and specialized sequences, were conducted to assess white matter health. Increased T1 relaxation times were found in the cingulate cortex (p < 0.05), and elevated T2 relaxation times were observed in the cingulate cortex, frontal, parietal and temporal lobes (p < 0.05). Pathological changes in these areas are correlated with impaired cognitive and depressive scores in concentration, short-term memory and verbal memory. This study highlights persistent white matter damage in iTTP patients, potentially contributing to depression and cognitive impairment. Key regions affected include the frontal lobe and cingulate cortex. These findings have significant implications for the acute and long-term management of iTTP, suggesting a need for re-evaluation of treatment approaches during both active phases and remission. Further research is warranted to enhance our understanding of these complexities.

Personality traits related to cognitive functioning in patients with functional neurological disorder

ABSTRACT Cognitive symptoms are prevalent in patients with functional neurological disorder (FND). Several studies have suggested that personality traits such as neuroticism may play a pivotal role in the development of FND. FND has also been associated with alexithymia: patients with FND report difficulties in identifying, analyzing, and verbalizing emotions. Whether or not alexithymia and other personality traits are associated with cognitive symptomatology in patients with FND is unknown. In the current study, we explored whether the Big Five personality model factors (neuroticism, extraversion, openness, agreeableness, and conscientiousness) and alexithymia were associated with cognitive functioning in FND. Twenty-three patients with FND were assessed using a neuropsychological assessment and questionnaire assessment to explore personality traits (Neuroticism-Extraversion-Openness Five-Factor Inventory) and alexithymia (Bermond-Vorst Alexithymia Questionnaire). The results indicated that high conscientiousness was associated with lower planning scores (ρ = −0.52, p = .012) and high scores on alexithymia were associated with lower scores on verbal memory scores (ρ = −0.46, p = .032) and lower sustained attention scores (ρ = −0.45, p = .046). The results did not remain significant after controlling for multiple testing. The preliminary results of our study suggest that personality and cognitive symptomatology in patients with FND are topics that should be further explored in future studies, as cognitive symptomology can affect treatment results.

High‐density lipoprotein particle size distribution among patients with Alzheimer’s disease, mild cognitive impairment, and age‐matched controls

AbstractBackgroundHigh‐density lipoproteins (HDL) are protective against several chronic diseases, including Alzheimer’s disease (AD). The size distribution of HDL particles is one of the determining factors of HDL function since HDL of various sizes subgroups play unique roles. Yet not much is known about HDL particle size distribution in the context of AD.MethodIn this study negative‐stained transmission electron microscopy (NS‐TEM) was used to explore the particle size distribution of isolated HDL samples from 194 subjects with AD (n = 71), mild cognitive impairment (MCI, n = 40), or no cognitive impairment (n = 83). HDL particles were isolated using density‐adjusted ultracentrifugation followed by size exclusion chromatography and analyzed by NS‐TEM followed by image analysis using the software ImageJ. Individual particle diameter data were obtained, grouped into different size‐based categories and the relative abundances of each subgroup were compared among diagnostic groups and across clinical parameters.ResultPatients with AD and MCI had a significantly higher percentage of 7‐8 nm HDL particles and a lower percentage of 9‐10 nm, 12‐13 nm, and 13‐14 nm particles. Body mass index, clinical dementia rating score, and white matter hyperintensity volume were positively correlated with the percentage of 7‐8 nm particles and negatively correlated with the percentage of 9‐10 nm particles, whereas executive score, semantic memory score, and verbal memory score were negatively correlated with the percentage of 7‐8 nm particles, and positively correlated with the percentage of 9‐10 nm particles.ConclusionThese findings show that specific alterations in HDL particle size distribution in patients with AD and MCI are linked with measures of cognitive function and may be a promising direction for the discovery of new biomarkers and therapeutic targets in AD.

T1 MRI reveals differential hippocampal atrophy in Lewy Body Disorders with and without Alzheimer’s copathology

AbstractBackgroundLewy body disorders (LBD) include Parkinson disease (PD), Parkinson disease dementia (PDD), and dementia with Lewy bodies (DLB). LBD are the second leading cause of neurodegenerative dementia after Alzheimer’s disease (AD). An estimated 50% of LBD patients have coexisting AD pathology (LBD+AD), which correlates with shorter time to dementia and death. Autopsy evidence suggests that verbal memory impairment correlates with the severity of hippocampal tau pathology in LBD. However, it is unknown whether greater hippocampal tau burden in LBD+AD causes neurodegeneration detectable by in vivo structural MRI, and whether hippocampal atrophy explains verbal memory impairment.MethodUsing a case‐control design, we studied 87 patients with clinical diagnoses of LBD (PD, n = 52; PDD, n = 12; DLB, n = 23) with available T1 MRI and AD biomarkers or, and cognitively‐normal controls (n = 131). AD copathology was defined hierarchically by: a) AD “intermediate” or “high” by ABC neuropathologic criteria; 2) positive amyloid PET; and 3) CSF total tau:β‐amyloid1‐42 ratio &gt; 0.3 (autopsy‐validated cutpoint). The Automated Segmentation of Hippocampal Subfields (ASHS) pipeline was applied to subjects’ T1 MRIs. Hippocampal volume (HV) was compared between controls, LBD‐AD, and LBD+AD, and correlated with verbal memory scores. Linear regression was used to test the association of AD copathology (independent variable) and HV (dependent variable), covarying for age, sex, education, and clinical diagnosis.ResultStatistically significant differences (ANOVA p = 0.002) in bilateral HV (expressed as percentage of intracranial volume) were seen between groups (mean 0.456for controls, 0.444±0.045 for LBD‐AD, and 0.416±0.063 for LBD+AD). Tukey’s test showed significant differences between LBD+AD vs controls (p = 0.001) and LBD+AD vs. LBD‐AD (p = 0.047). Linear regression showed statistically significant association of LBD+AD with bilateral HV (p = 0.034). Among all LBD patients, hippocampal volume positively correlated with verbal memory (immediate recall: r2 = 0.24, p = 0.033, delayed recall: r2 = 0.22, p = 0.042, recognition discrimination r2 = 0.58, p&lt;0.001).ConclusionIn patients with LBD, AD copathology is associated with increased hippocampal atrophy as measured by in vivo T1 MRI, which correlates with greater verbal memory deficits. This work supports the that AD copathology impairs cognition in LBD via hippocampal neurodegeneration.

The role of transcranial direct current stimulation in improving learning and memory performances of patients with mild cognitive impairment and mild Alzheimer’s disease: a functional magnetic resonance imaging study

AbstractBackgroundTranscranial direct current stimulation (tDCS) is a safe non‐invasive brain stimulation (NIBS) procedure which helps to stimulate a particular region of interest by modulating the neuronal firing rate, thereby modulating the cognitive functioning. The tDCS intervention is known to show improvement on memory recall and recognition in patients with mild cognitive impairment (MCI) and mild Alzheimer’s Disease (mild AD)MethodWe investigated the effect of anodal stimulation at the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation at the right supra‐orbital area in patients with MCI (n = 18) and mild AD (n = 20) (Refer Table 1), after due approval from Institute Ethics Committee NIMHANS. Both baseline and post‐intervention assessments for a single patient were administered by the different assessors allocated randomly using NIMHANS neuropsychological battery for elderly (NNB‐E). Two resting state functional magnetic resonance imaging (rsfMRI) acquisitions, before and after the ten sessions of tDCS, each session lasting 20 minutes. A spherical mask of 5 mm diameter was chosen a priori on the left middle frontal gyrus (LMFG) as a seed for performing seed based functional connectivity (sbFC) analysis using default preprocessing pipeline and pre‐post analysis setup in CONN 18b toolbox.ResultThe combined sample of patients with MCI and mild AD showed significant improvement in word list learning trial 3 (pre tDCS 5.85 (1.59); post tDCS 6.63 (1.67); Z = 3.586, p&lt;0.0001) and delayed recall (pre tDCS 1.50 (1.88); post tDCS 2.45 (2.33); Z = 3.656, p&lt;0.0001) scores using NNB‐E. The sbFC analysis showed significantly reduced functional connectivity between left MFG (the region of anodal stimulation) and posterior cingulate cortex (PCC) as well as precuneus cortex (cluster‐level extent threshold p‐FDR &lt;0.05) after tDCS. Post‐hoc tests showed that these reductions after tDCS intervention were also found to be significantly associated with attention and auditory verbal learning memory scores (Refer Figure 1 and Table 2).ConclusionThe tDCS intervention helped reducing the functional connectivity at rest, which was responsible for compensatory neuronal processes found in early AD. These findings unravel the therapeutic role of tDCS by enhancing auditory verbal memory performance and altering the functional connectivity at PCC and precuneus cortex in earlier stages of AD.

The effect of light exposure on cognitive outcomes at long term follow up in an at‐risk dementia population

AbstractBackgroundCircadian disturbances are a common occurrence in older adult population but are more prevalent in people with dementia. For some individuals, these occurrences begin many years prior to the onset of clinical symptoms and have been suggested as a potential risk factor. As light is the primary synchroniser of the circadian system, the current study aimed to examine if 14‐day light exposure could predict cognitive outcomes of older adults with varying risks of dementia at 2‐year follow‐up.MethodThe study was a retrospective analysis of 195 participants (age = 67, 60.7% female) who attended the Healthy Brain Ageing Clinic in Sydney. At baseline, participants were neurocognitively assessed and wore an actigraph for 14 days and then completed another neurocognitive test battery at their follow‐up. Binary logistic regression was used to determine if participants converted to either Mild Cognitive Impairment (MCI) or dementia was predicted from light exposure (average and maximum) and average time spent in &gt;1000 lux (OR = 1.00), adjusting for age, sex and years of education. Linear regression was used to investigate the relationship between light variables and differences in verbal memory, processing speed and executive function composite scores from baseline to 2 years.ResultLight exposure at 2 years prior did not appear to predict cognitive performance. There was a trend towards moderate to bright light increasing risk of cognitive decline.ConclusionFurther research is needed to understand light exposure and the relationship to circadian rhythms and cognition. As previous light therapy research has been inconclusive, future research will inform treatment approaches.

Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method.

Cancer patients should be concerned about depression, which can negatively impact their mental health. To develop efficient therapies, it is essential to comprehend the connection between cancer and depression. This study used neuroimaging to investigate the use of mediator-deuterium acupuncture (MDA) for people with cancer-induced depression and its effects on brain regions associated with depression. Resting-state functional magnetic resonance imaging and neurocognitive testing were conducted on the participants, and statistical package for the social sciences was utilized to analyze the behavioral data. Clinical and theoretical data were analyzed to evaluate acupuncture's effectiveness against gynecological cancer. In the research, there were 40 participants, 20 in each group. Except for psychomotor speed, there was no discernible difference in pre-chemotherapy cognitive test results between patients and healthy controls (HCs). However, there were substantial differences in post-treatment cognition test results, showing that the patient group had progressed. According to longitudinal graph analysis, the patient group's local and global brain efficiency significantly declined, and lower local efficiency was associated with lower raw Trail Making Test-A results. Furthermore, poorer verbal memory scores were associated with lower overall performance in the sick group but not in the HC group. According to the research, MDA has potential as a supplemental therapy since it may improve brain function and address depression-related neurological abnormalities in cancer patients. More research is required to fully comprehend the variations between cancer and depression-related brain areas during patient therapy, maybe incorporating MDA.

43 Laterality of Hippocampal Volume Differentially Predicts Verbal Versus Nonverbal Memory Performance

Objective:Epilepsy is a chronic neurological disease, and surgery is a common treatment option for persons who do not respond to medication. Neuropsychology plays an important role in the epilepsy presurgical workup, characterizing the cognitive functioning of patients with epilepsy as well as assisting in the determination of which hemisphere seizures originate in the brain through testing of different cognitive functions. NeuroQuant is a relatively newer software that analyzes clinical neuroimaging to quantify brain volume. The objective of this study was to determine if changes in left versus right total hippocampal volume predicted changes in verbal versus nonverbal memory performance.Participants and Methods:Cognitive performance and NeuroQuant bilateral hippocampal volume were examined in a cross-sectional sample of 37 patients with epilepsy. All patients had undergone a comprehensive presurgical neuropsychological evaluation as well as magnetic resonance imaging (MRI) and these results were analyzed using a series of linear regression analyses.Results:Total left hippocampal volume was a significant predictor of delayed verbal free recall (RAVLT F(1, 31) = 4.79, p&lt; .036, RA2 = 0.13, and ß=.37, p&lt;.036). Even when controlling for the effects of biological sex, education, and depression, left hippocampal volume remained a significant predictor (ß=.42, p&lt;.025). Total left hippocampal volume did not predict other verbal memory scores. Total right hippocampal volume was a significant predictor of delayed nonverbal figure recall (RCFT F(1, 31)= 6.46, p&lt;.016), RA2 = .17 and ß=.42) p&lt;.016). When controlling for the effects of biological sex, education, and depression, right hippocampal volume remained a significant predictor (ß=.404, p&lt;.026). Total right hippocampal volume did not predict other nonverbal memory scores.Conclusions:These findings validate prior research demonstrating the importance of the left hippocampus in verbal memory and right hippocampus in nonverbal memory. Findings also demonstrate the clinical utility of neuropsychological evaluation in determining laterality in the epilepsy presurgical workup process, as well as support NeuroQuants’ inclusion as an additional consideration in that process.

5 Combining Neurophysiology and Behavioral Measures to Identify Biomarkers of Clinical and Preclinical Hippocampus-Dependent Memory Dysfunction

Objective:Memory is a critical piece of the human experience and impairments in neural memory networks can have devastating consequences for the affected person. A subtype of memory, episodic memory generates context for the present based on past experience and allows us to make predictions about the future. Episodic memories become stable fixtures through long-term memory consolidation. It is believed that consolidation of episodic memory requires a dynamic interplay between connected hippocampal-cortical networks, mainly during sleep. Sleep oscillations, slow oscillations and thalamocortical spindles, coupled with hippocampal sharp wave ripples (SWR) is proposed to be mechanistically involved in establishing the crucial cortical-subcortical dialog. The current study aimed to determine alterations in typical sleep oscillations and oscillation coupling in patients with and without structural hippocampal damage and correlate them with neuropsychological measures believed to be sensitive to hippocampal dysfunction, i.e., Rey Auditory Verbal Learning Task (RAVLT) and Verbal Paired Associates (VPA-II).Participants and Methods:We used intracranial electroencephalography (iEEG) in 14 patients with epilepsy to directly record hippocampal and neocortical oscillations and neuropsychological measures obtained prior to implantation. Half of the participants were diagnosed with mesial temporal sclerosis (MTS) in the left hippocampus and healthy tissue in the right hippocampus. The other half did not have MTS and had either mesial temporal epilepsy without MTS or extra-temporal seizures. We analyzed hippocampal SWR output from both hippocampi and characterized neocortical slow oscillations and spindles and their coupling for each participant. We correlated electrophysiological data with behavioral results of neuropsychological testing in order to characterize the clinical relevance.Results:SWR analysis revealed significant differences in the frequency, t(7639) = 15.52, p&gt;.001, p &gt; .001), amplitude, t(7664) = -23.93, p &gt; .001, and waveforms (p &gt; .001) of SWR in the sclerotic versus healthy hippocampi. Patients with a sclerotic hippocampus but relatively preserved verbal memory scores (RAVLT, VPA-II) showed increased SWR amplitudes in the contralateral hippocampus compared to patients with low verbal memory scores. Additionally, we found differences between hemispheres in phase amplitude coupling of SWRs to spindles and SOs (p &gt; 0.001). Results of our correlational analysis were variable and dependent upon additional factors, such as age of onset and diagnosis duration.Conclusions:Results from this work will aid in establishing a criterion for characterizing a relationship between subcortical and cortical oscillations as they relate to memory performance. Besides aiding our understanding of the neural mechanisms underpinning memory consolidation this will ideally help with developing neurophysiological biomarkers that may predict possible memory decline in resective or ablative neurosurgery absent of structural lesion. In addition, this work may potentially provide first evidence of a neurophysiological biomarker directly recorded from the human hippocampus to support possible reorganization of memory functioning in the non-sclerotic hippocampus.

70 Childhood SES and Midlife CVD on Late-life Cognition

Objective:Cardiovascular disease (CVD) is a well-known risk factor for cognitive impairment and dementia, particularly among minoritized groups that have experienced a history of low childhood socioeconomic status (SES). Although previous literature has linked all levels of SES to varying degrees of stress exposure, children raised in higher SES households have more access to resources and services that encourage optimal growth and development than children who grow up in lower SES households. Given the disproportionate burden of dementia and cognitive deficits within minoritized groups, the present study examined whether childhood SES is associated with later life cognition among Black and White older adults and if this association persists after accounting for hypertension, a possible mediator of the relationship between childhood SES.Participants and Methods:1,184 participants were from the first wave of the STAR (n = 397 Black [Mage= 75.0 ±6.8 years]) and KHANDLE (386 Black [Mage= 76.2 ±7.2 years] and 401 White [Mage= 78.4 ±7.5 years]) cohorts. We used general linear models to examine the relationship between childhood SES and later-life executive function, semantic memory, and verbal memory scores, and midlife hypertension. Childhood SES was measured by self-reported perceived financial status (with participants given the following options: ‘pretty well off financially’, ‘about average’, ‘poor’, or ‘it varied’). These models were assessed in the full sample and also stratified by race.Results:In the full sample, childhood financial status was not associated with semantic memory, verbal episodic memory, or executive function. Financial status was associated with semantic memory in Black adults (β = -.124, t(771) = -2.52, p = .01) and this association persisted after accounting for hypertension (β = -.124, t(770) = -2.53, p = .01). There was no association between childhood financial status and later life semantic memory among White adults. There was no association between childhood financial status and later life verbal episodic memory or executive function in either Black or White adults in models with or without adjustment for hypertension.Conclusions:Our findings showed no relationship between childhood SES and cognition, except for semantic memory in Black participants; this relationship persisted after accounting for midlife CVD. Future analyses will assess both direct and indirect effects of more predictive measures of childhood SES on late-life cognition with midlife CVD as a mediator.

28 Challenges to Lateralizing Visual Memory Dysfunction in TLE Patients

Objective:Neuropsychological assessment is an essential part of presurgical evaluation for epilepsy patients with refractory temporal lobe epilepsy. Evaluations assist in localizing and lateralizing epileptogenic focal points and identifying possible risks for cognitive decline following surgery. Researchers and clinicians consistently find that verbal memory dysfunction is an accurate indicator of left temporal lobe epilepsy (TLE) through verbal measures such as the CVLT-II. Although visual memory structures are assumed to be in the right (nondominant) hemisphere, visual memory assessments have not been reliable in identifying right TLE. It is hypothesized that assessments to test visual memory are confounded by verbal cueing to assist in visual learning. To account for this, researchers have identified that comparing verbal and visual score asymmetries does accurately differentiate left and right TLE patients. This study aimed to determine if verbalvisual asymmetry using the CVLT-II and BVMT-R accurately identifies left and right TLE relative weaknesses potentially associated with epileptogenic regions.Participants and Methods:As part of a pre-surgical neuropsychological evaluation, 37 well-characterized medically refractory TLE patients (18 right TLE; 19 left TLE) were administered the Brief Visuospatial Memory Test-Revised to evaluate visuospatial memory and the CVLT-II to evaluate verbal memory. A multivariate analysis of variance was used to compare RTLE and LTLE group performances on BVMT-R delay recall subscales, using T-scores. Then memory asymmetry scores were calculated by converting CVLT-II verbal delay memory scores to T-scores and subtracting BVMT-R delayed recall T-score from the verbal memory T-score. An independent samples t-test was used to compare asymmetry scores between the groups.Results:There were no significant differences between patients with RTLE and LTLE for BVMT-R Delay [F(2,34) = 0.11, p = .895]. There was not a significant difference when accounting for verbal-visual asymmetry (t (35) = 0.422, p = 0.675, d = 12.566) between left (M = -2.42, SD = 13.82) and right side (M = -4.17, SD = 11.09).Conclusions:The BVMT-R did not identify nondominant hemisphere dysfunction in this sample of 18 right TLE patients. Because visual memory performance did not inform lateralization, we investigated the usefulness of memory asymmetry. Inconsistent with our hypothesis, verbal-visual memory asymmetry scores did not differentiate RTLE from LTLE in this sample. These findings add to existing findings that the BVMT-R may not be able to identify visuospatial memory dysfunction in epilepsy. Additionally, these data indicate the inability to assess for visuospatial memory even when accounting for verbal abilities in epilepsy patients. Future research should consider alternate visuospatial measures for the evaluation of epilepsy patients.

4 Neurophenotypes and recovery trajectories following laboratory-confirmed SARS-CoV-2 infection

Objective:Cognitive sequelae are reported in 20-25% of patients following SARS-CoV-2 infection. It remains unclear whether post-infection sequelae cluster into a uniform cognitive syndrome. In this cohort study, we characterized post-COVID neuropsychological outcome clusters, identified factors associated with cluster membership, and examined 6-month recovery trajectories by cluster.Participants and Methods:The Mayo Clinic Institutional Review Board approved study protocols. Informed consent was obtained from all participants. Participants (&gt; 18 years old) were recruited from a hospital-wide registry of Mayo Clinic Florida patients who tested positive for SARS-CoV-2 infection from July 2020 to Feb 2022. We abstracted participant health history and COVID-19 disease severity (NIAID score) from the electronic health record and retrieved Area Deprivation Index (ADI) scores as a measure of neighborhood socioeconomic disadvantage. We assessed objective cognitive performance with the CNS Vital-Signs (CNSVS) and subjective neuropsychological symptoms with the Neuropsych Questionnaire-45 (NPQ-45). Results were used as input features in a K-means clustering analysis to derive neurophenotypes. Chi-square and analysis of variance (AnOvA) tests were used to identify clinical and sociodemographic factors associated with cluster membership. Participants repeated the CNS Vital Signs, NPQ-45, as well as the Medical Outcomes Survey (MOS SF-36) and a posttraumatic stress disorder (PTSD) checklist (PCL-C 17) 6 months following initial testing. Repeated-measures ANOVA was used to assess change in neurocognitive performance over time by cluster. Significance was set at P &lt; 0.05.Results:Our cohort consisted of 205 participants (171 ambulatory, 34 hospitalized) who completed post-acute outcome assessment a mean of 5.7 (± 3.8) weeks following testing positive for SARS-CoV-2. K-means clustering with elbow method fitting identified three subgroups (see figure). The first cluster (N = 31) is characterized by executive dysfunction, greater socioeconomic disadvantage, and higher rates of obesity. The second cluster (N = 32) is characterized by memory and speed impairment, higher COVID severity, prevalent anosmia (70%), and greater severity of memory complaints, depression, anxiety, and fatigue. The third and largest cluster (N = 142) is absent cognitive impairment. Approximately 39% of participants completed the 6-month outcome assessment (N=79). Regardless of cluster membership, verbal memory, psychomotor speed, and reaction time scores improved over time. Regardless of timepoint, cluster 1 (dysexecutive) showed lower scores on cognitive flexibility and complex attention and cluster 2 (memory-speed impaired) showed lower scores on verbal memory, psychomotor speed, and reaction time. Modeling of cluster by timepoint interactions showed a steeper slope of improvement in complex attention and cognitive flexibility in cluster 1 (dysexecutive). Cluster 3 (normal) showed significant improvement in fatigue while cluster 2 (memory-speed impaired) continued to report moderate-severe fatigue, worse medical outcomes, and higher PTSD symptom severity scores at six months.Conclusions:Most participants were cognitively normal or experienced cognitive recovery following SARS-CoV-2 infection. The 25-30% of participants who showed cognitive impairment cluster into two different neurophenotypes. The dysexecutive phenotype was associated with socioeconomic factors and medical comorbidities that are non-specific to COVID-19, while the amnestic phenotype was associated with COVID-19 severity and anosmia. These results suggest that cognitive sequelae following SARS-CoV-2 infection are not uniform. Deficits may be influenced by distinct patient- and disease-specific factors, necessitating differentiated treatment approaches.

12 Measuring effort on a continuum provides improved insight into concussion baseline cognitive assessments

Objective:Baseline assessment of cognitive performance is common practice under many concussion management protocols and is required for collegiate athletes by the NCAA. The purpose of baseline cognitive assessment is to understand an athlete’s individual uninjured cognitive performance, as opposed to using population normative data. This baseline can then serve as a reference point for recovery after concussion and can inform return-to-play decisions. However, multiple factors, including lack of effort, can contribute to misrepresentation of baseline results which raises concern for reliability during return-to-play decision-making. Measuring effort across a continuum, rather than as a dichotomous variable (good versus poor effort) may provide informative insight related to cognitive performance at baseline.Participants and Methods:Collegiate athletes (n = 231) completed the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) as part of their baseline pre-participation concussion evaluation. ImPACT creates composite scores of Verbal Memory, Visual Memory, Visual-Motor Speed, and Reaction Time. Baseline self-reported symptoms and total hours of sleep the night prior to testing are also collected through ImPACT. ImPACT has one embedded indicator within the program to assess effort, and research has identified an additional three embedded indicators. Athletes were also administered one stand-alone performance validity test, either the Medical Symptom Validity Test (n = 130) or the Rey Dot Counting Test (n = 101), to independently measure effort. Effort was estimated across a continuum (zero, one, two, or three or more failed effort indicators) with both stand-alone and embedded effort indicators. We evaluated the relationship between effort, symptoms, self-reported sleep, Reaction Time composite score and Visual-Motor Speed composite score using a linear regression model.Results:We found that 121 athletes passed all effort indicators, while 39 athletes failed only one effort indicator, 40 athletes failed two effort indicators, and 31 athletes failed three or four (three+) effort indicators. Self-reported symptoms and total hours of sleep were not related to effort, but Reaction Time and VisualMotor Speed composites were. Specifically, performance on the Visual-Motor Speed composite was significantly worse for athletes who failed two or three+ effort indicators compared to athletes who did not fail any, and performance on the Reaction Time composite was significantly worse only for athletes who failed three+ effort indicators. Additionally, athletes who failed one or more effort indicators and reported less sleep performed worse on both the Visual-Motor Speed and Reaction Time composites, compared to those who reported less sleep and did not fail any effort indicators.Conclusions:Athletes who failed one effort indicator did not perform significantly worse on Reaction Time and Visual-Motor Speed composites compared to those who passed all effort indicators. However, 31% of athletes failed two or more effort indicators and these athletes performed worse on cognitive tests, likely due to factors impacting their ability to put forth good effort. These results suggest that effort is more complex than a previously used dichotomous variable and highlights the importance of using several indicators of effort throughout baseline assessments. In addition, the importance of sleep should be emphasized during baseline assessments, especially when effort is questionable.