Hopkins Verbal Learning Test-Revised Research Articles

The impact of incident stroke on cognitive trajectories in later life

BackgroundCognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals.Methods19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke.ResultsDuring a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants.ConclusionsThese findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention.

Cognition and Functional Capacity: An Initial Comparison of Veteran and Non-Veteran Older Adults.

The U.S. Military Veterans aged 65 and older comprise an estimated 43% of the 22 million living Veterans in the United States. Veterans have high rates of physical, psychiatric, and social challenges, but it is not known whether Veteran status confers additional risk for cognitive or functional impairments in later life. Thus, this investigation specifically compared older Veterans with their non-Veteran peers in cognitive functioning and performance-based functional capacity. Participants (N = 110; 29 Veterans and 81 non-Veterans) were part of a larger longitudinal study on biopsychosocial functioning in independently living older adult residents of a Continuing Care Senior Housing Community. The University of California San Diego Institutional Review Board approved the study and all participants provided written informed consent. Participants provided demographic and mental health information and were administered a comprehensive neuropsychological battery. Functional capacity was assessed using the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), which uses financial and communication role-plays to assess everyday functioning skills. Neuropsychological scores were appropriately normed prior to analysis. Multivariate Analyses of Variances with post hoc t-tests and an Analysis of Covariance were used to examine neuropsychological and functional capacity differences, respectively, between Veterans and non-Veterans. Veterans did not differ from non-Veterans in educational attainment (16.4 years versus 15.5 years, P = 0.110), but they were significantly older (mean age 86.9 years ± 5.7, versus 81.74 years ± 6.53; P < 0.001) and were more likely to be male (X2 [1, N = 110] = 62.39, P < 0.001). Thus, though neuropsychological norms already accounted for demographic differences in our participants, age and sex were controlled in the Analysis of Covariance predicting UPSA-B score from Veteran status. Results suggested that, compared to non-Veterans, Veterans had significantly worse performance in the list learning portion of a test of verbal memory (Hopkins Verbal Learning Test-Revised, Total Recall; t = 2.56, P = 0.012, d = 0.56). Veterans and non-Veterans did not significantly differ in performance on the delayed recall portion of the verbal learning test and did not differ on a cognitive screening test (Montreal Cognitive Assessment) or on measures of premorbid intellectual functioning (Wide Range Achievement Test-4 Reading), language (Boston Naming Test, Verbal Fluency), visual memory (Brief Visuospatial Memory Test-Revised), attention/working memory (WAIS-IV Digit Span), processing speed (WAIS-IV Digit Symbol Coding), executive function (Delis-Kaplan Executive Function System Trails and Color-Word Test), or functional capacity (UPSA-B). Because our examination of multiple outcomes might have inflated Type I error, we performed a post hoc adjustment of P values using Benjamini-Hochberg procedures and the group difference in verbal learning remained significant. Despite largely similar function in most domains, Veterans performed significantly more poorly in verbal list learning than their non-Veteran peers. Additional attention should be given to the understanding, assessment, and possible treatment of learning and memory differences in older Veterans, as this may be an area in which Veteran status confers additional risk or vulnerability to decline. This is the first study to compare objective neuropsychological and functional performance between older (age 65+) US Veterans and non-Veterans.

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

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

Predicting the risk of neurocognitive decline after brain irradiation in adult patients with a primary brain tumor.

Deterioration of neurocognitive function in adult patients with a primary brain tumor is the most concerning side effect of radiotherapy. This study was aimed to develop and evaluate Normal-Tissue Complication Probability (NTCP) models using clinical and dose-volume measures for 6-month, 1-year and 2-year Neurocognitive Decline (ND) post-radiotherapy. A total of 219 patients with a primary brain tumor treated with radical photon and/or proton radiotherapy (RT) between 2019 and 2022 were included. Controlled Oral Word Association (COWA) test, Hopkins Verbal Learning Test-Revised (HVLTR) and Trail Making Test (TMT) were used to objectively measure ND. A comprehensive set of potential clinical and dose-volume measures on several brain structures were considered for statistical modelling. Clinical, dose-volume and combined models were constructed and internally tested in terms of discrimination (Area Under the Curve, AUC), calibration (Mean Absolute Error, MAE) and net benefit. 50%, 44.5% and 42.7% of the patients developed ND at 6-month, 1-year and 2-year timepoints, respectively. Following predictors were included in the combined model for 6-month ND: age at radiotherapy>56 years (OR=5.71), overweight (OR=0.49), obesity (OR=0.35), chemotherapy (OR=2.23), brain V20Gy≥20% (OR=3.53), brainstem volume≥26cc (OR=0.39) and hypothalamus volume≥0.5cc (OR=0.4). Decision curve analysis showed that the combined models had the highest net benefits at 6-month (AUC=0.79, MAE=0.021), 1-year (AUC=0.72, MAE=0.027) and 2-year (AUC=0.69, MAE=0.038) timepoints. The proposed NTCP models use easy-to-obtain predictors to identify patients at high-risk of ND after brain RT. These models can potentially provide a base for RT-related decisions and post-therapy neurocognitive rehabilitation interventions.

Learning ratio performance on a brief visual learning and memory test moderates cognitive training gains in Double Decision task in healthy older adults.

Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there was variability in the achievement of cognitive gains after cognitive training across studies, suggesting moderating factors. Learning trials of visual and verbal learning tasks recruit similar cognitive abilities and have overlapping neural correlates with speed-of-processing/working memory tasks and therefore could serve as potential moderators of cognitive training gains. This study explored the association between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) learning with a commercial UFOV task called Double Decision. Through a secondary analysis of a clinical trial, we assessed the moderation of HVLT-R and BVMT-R learning on Double Decision improvement after a 3-month speed-of-processing/attention and working memory cognitive training intervention in a sample of 75 cognitively healthy older adults. Multiple linear regressions showed that better baseline Double Decision performance was significantly associated with better BVMT-R learning (β = - .303). This association was not significant for HVLT-R learning (β = - .142). Moderation analysis showed that those with poorer BVMT-R learning improved the most on the Double Decision task after cognitive training. This suggests that healthy older adults who perform below expectations on cognitive tasks related to the training task may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes and efficacy of the intervention.

3-Year test-retest reliability in Parkinson’s disease and healthy older adults: The Parkinson’s progression markers initiative study

Repeated neuropsychological assessments are often conducted in clinical and research settings to track cognitive changes over single or multiple intervals in patients with Parkinson’s disease (PD). Yet few studies have documented test-retest reliability in PD. To address this gap, we used data from the Parkinson’s Progression Markers Initiative (PPMI) to investigate the reliability of five well-known neuropsychological tests over a 3-year follow-up assessment in early-stage PD with either normal (PD-NC; N = 158) or abnormal (PD-AC; N = 39) cognitive screening, categorized based on recommended cutoffs for the Montreal Cognitive Assessment (MoCA), and healthy older adults (HOA; N = 102). All participants analyzed maintained the same cognitive status category across the assessment points. Intraclass correlation coefficients (ICCs) estimated reliability. The overall ICCs calculated across time points were as follows: Judgment of Line Orientation (PD-NC = .47, PD-AC = .50, HOA = .59); Letter-Number Sequencing (PD-NC = .64, PD-AC = .64, HOA = .65); Semantic Fluency (PD-NC = .69, PD-AC = .89, HOA = .77); Symbol Digit Modalities Test (PD-NC = .67, PD-AC = .83, HOA = .71). For the two primary components of the Hopkins Verbal Learning Test-Revised, we found the following ICCs: immediate recall (PD-NC = .46, PD-AC = .57, HOA = .58); delayed recall (PD-NC = .42, PD-AC = .57, HOA = .54). Findings from this study provide useful information for clinicians and researchers toward selecting suitable neuropsychological tests to monitor cognition at two or more time points among newly diagnosed individuals with PD and HOA.

A comparative study of cognitive function in young patients with bipolar disorder with and without non-suicidal self-injury

ObjectiveBipolar disorder (BD) is a chronic mental disorder characterized by alternating or mixed episodes of mania or hypomania and depression. Cognitive function impairment is a frequent associated feature of the disease. While many BD patients also engage in non-suicidal self-injury (NSSI), there is a lack of studies on the cognitive function of BD patients with NSSI. This study aimed to evaluate cognitive functioning of BD patients with NSSI and provide a clinical basis for the differential diagnosis and treatment of BD and NSSI. MethodsA total of 60 BD patients with NSSI, 60 BD patients without NSSI, and 60 healthy controls (HC) were selected for the study. All participants met the inclusion criteria and were not taking any medications, excluding the potential effects of medication on cognitive functions. The following neurocognitive tests were used to measure the cognitive functions in areas such as speed of processing, reasoning and problem solving, attention/vigilance, working memory, visual learning, and verbal learning: The Trail Making Test (TMT), Category Fluency, Digit Symbol Coding Test (DSCT), Brief Visuospatial Memory Test-Revised (BVMT-R), The Neuropsychological Assessment Battery Mazes (NABM), Wechsler Memory Scale Third Edition Spatial Span Test (WMS III-SST), Hopkins Verbal Learning Test-Revised (HVLTR) and Continuous Performance Test and Identical Prs (CPT-IP). ResultsThe findings indicated that BD patients with NSSI exhibited cognitive impairment in all measured cognitive domains. On the other hand, BD patients without NSSI showed less pronounced impairment in terms of speed of processing, but exhibited significant cognitive impairment in the remaining five areas compared to the HC group. ConclusionThe study underscores the presence of cognitive impairment in BD, and the cognitive impairment is more severe in BD patients with NSSI compared to those without NSSI. In conclusion, both individuals with NSSI and those without NSSI in BD exhibit cognitive impairment, which provides ideas and strategies for using cognitive-behavioral therapy to treat BD and NSSI.

Association Study of a Comprehensive Panel of Neuropeptide-Related Polymorphisms Suggest Potential Roles in Verbal Learning and Memory.

Neuropeptides are mostly expressed in regions of the brain responsible for learning and memory and are centrally involved in cognitive pathways. The majority of neuropeptide research has been performed in animal models; with acknowledged differences between species, more research into the role of neuropeptides in humans is necessary to understand their contribution to higher cognitive function. In this study, we investigated the influence of genetic polymorphisms in neuropeptide genes on verbal learning and memory. Variants in genes encoding neuropeptides and neuropeptide receptors were tested for association with learning and memory measures using the Hopkins Verbal Learning Test-Revised (HVLT-R) in a healthy cohort of individuals (n = 597). The HVLT-R is a widely used task for verbal learning and memory assessment and provides five sub-scores: recall, delay, learning, retention, and discrimination. To determine the effect of candidate variants on learning and memory performance, genetic association analyses were performed for each HVLT-R sub-score with over 1300 genetic variants from 124 neuropeptide and neuropeptide receptor genes, genotyped on Illumina OmniExpress BeadChip arrays. This targeted analysis revealed numerous suggestive associations between HVLT-R test scores and neuropeptide and neuropeptide receptor gene variants; candidates include the SCG5, IGFR1, GALR1, OXTR, CCK, and VIPR1 genes. Further characterization of these genes and their variants will improve our understanding of the genetic contribution to learning and memory and provide insight into the importance of the neuropeptide network in humans.

The relationships between hippocampal cerebrovascular reactivity, hippocampal volume, and episodic memory in healthy ageing

AbstractBackgroundCerebrovascular biomarkers such as cerebrovascular reactivity (CVR) have previously been associated with episodic memory. However, the relationship between memory and regional CVR within the hippocampus is not well studied. Moreover, whether this association is affected by hippocampal volume remains to be investigated. This study investigated the associations between hippocampal physiology, structure, and memory in ageing.MethodData from 104 participants (Age: Mean = 77±4.9 years) of the ongoing Oxford Heart and Brain Study was analysed for this study. CVR was assessed by a compensatory change in the blood oxygenation level dependent magnetic resonance imaging (MRI) signal in response to a 5% CO2 challenge, hippocampus volume was measured by structural MRI, and episodic memory was assessed with the Hopkins Verbal Learning Test Revised (HVLT‐R).ResultMean hippocampal CVR decreased with age (β = ‐0.004, p = 0.006). Mean hippocampal CVR was positively associated with mean hippocampal volume (β = 0.11, p = 0.010), and this association was driven by the left hippocampus after correcting for age and sex. Higher hippocampal CVR was also associated with better performance on the HVLT (β = 13.8, p = 0.035). This association was fully mediated by hippocampal volume, suggesting a path from cerebrovascular reactivity to episodic memory (Sobel’s z = 2.16, p = 0.030, see Figure 1).ConclusionThis study presents novel findings showing that hippocampal CVR was associated with episodic memory, and this association was mediated by hippocampal volume. This suggests a pathway by which impairments in hippocampal CVR are associated with worse episodic memory via smaller hippocampal volumes.

Polysomnography results and cognitive performance in early‐stage Parkinson’s disease

AbstractBackgroundParkinson’s disease (PD) is a progressive neurological disorder that involves a range of motor and non‐motor symptoms. About 66% of individuals with PD report sleep disturbance impacts their quality of life. Sleep disorders may precede the cardinal motor features in PD and can influence motor and non‐motor symptom severity, including cognition. Yet current evidence of this association with objective assessments remains limited. The goal of this pilot study was to evaluate the associations between cognition and overnight polysomnography results in early‐stage PD.MethodsParticipants completed neuropsychological assessments and an overnight in‐clinic polysomnography. Associations between polysomnography results and cognitive performance were evaluated using partial correlations controlling for age and education.ResultsTwenty participants (mean age 69±8; 25% female) without dementia and with a diagnosis of early‐stage PD (Hoehn and Yahr stage 1‐2) were enrolled (Table 1). Table 2 displays the associations between polysomnography results and cognitive assessments. Greater percentage time in stage N1 sleep and increased duration of wakefulness time after sleep onset (WASO) were associated with poorer phonemic fluency (r = ‐0.626, p = .005 and r = ‐0.512, p = .030, respectively); whereas increased time spent in stage N2 sleep and higher sleep efficiency index were correlated with better phonemic fluency (r = 0.829, p &lt; .001 and r = 0.513, p = .029, respectively). Greater percentage in stage N2 was associated with better verbal learning (Hopkins Verbal Learning Test–Revised (HVLT‐R) Immediate Recall, r = 0.521, p = .027). Higher percent time in REM sleep was correlated with increased basic attention (Digit Span Forward, r = 0.483, p = .042). No associations were found between total sleep time and cognitive performance.ConclusionWhile total sleep time was not associated with cognition, higher percent time spent in Stage N2, Stage N3, and REM sleep were associated with better cognitive performance. In contrast, higher percentage of Stage N1 sleep and increased duration of WASO were associated with poorer verbal fluency. The preliminary results highlight the importance of increased time in deeper stages of sleep for cognition in adults with early‐stage PD. Future longitudinal studies will be necessary to evaluate long‐term cognitive trajectories and transition to dementia in association with diminished sleep quality in Parkinson’s disease.

Neurocognitive Outcomes over the First 3 Months after Chimeric Antigen Receptor T-Cell (CAR T) Therapy: Preliminary Findings from a Longitudinal Study

Introduction People treated with systemic therapies for cancer may exhibit changes in neurocognitive functioning over time, affecting domains such as memory, processing speed, and executive functioning. There is a need for prospective data regarding neurocognitive outcomes among patients treated with Chimeric Antigen Receptor T-Cell (CAR T) therapy. The purpose of this study was to investigate the trajectory of neurocognitive performance and self-reported cognitive functioning over the first 3 months of CAR T therapy. Methods As part of a larger cohort study of patients treated with CAR T, neurocognitive outcomes were assessed prior to starting CAR T and again at 1- and 3- months post-CAR T. Neurocognitive performance was measured using standardized neuropsychological tests including measures of verbal memory (Hopkins Verbal Learning Test-Revised (HVLT-R) - immediate recall, delayed recall, retention), processing speed (Trail-making Test - Part A (TMT-A)) and executive functioning (Trail-making Test Part B (TMT-B), Controlled Oral Word Association Test (COWAT)). Raw test scores were converted to z-scores (Mean 0, SD 1) based on norms adjusted for age, sex, and education, where applicable. Impairment on individual tests was defined by a z score ≤ -1.64. Participants were categorized as showing overall impairment if they had at least two tests with a z-score of ≤ -1.5 or a z-score ≤ -2.0 on one test. Self-reported cognitive functioning was measured using the Functional Assessment of Cancer Therapy - Cognition, Perceived Cognitive Impairment score (FACT-Cog3 PCI) and the European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire C-30, Cognitive Functioning scale (EORTC QLQ-C30 CF). Demographic and clinical data were collected through self-report and patient records. Frequencies of impairment were determined at each time point, with clinically significant changes on individual test scores in the first month determined based on z-score changes of ≥1.0 or minimal clinically important differences for self-report questionnaires. Linear mixed models were generated to estimate the trajectory of neurocognitive performance and self-reported cognitive functioning over time from baseline to 3 months. Results Neurocognitive outcomes were available for 37 participants at baseline, with follow-up data available for 29 patients at 1 month and 17 patients at 3 months. Participants were 54% male, had a mean age 58.4 years (sd 11.3) and a mean 15.5 years (sd 3.2) education. All patients had a diagnosis of non-Hodgkin lymphoma (53% diffuse large B-cell lymphoma (DLBCL), 31% transformed DLBCL from follicular lymphoma). Immune effector cell-associated neurotoxicity syndrome (ICANS) affected 32% of patients (5% Grade 4, 3% Grade 3, 8% Grade 2, 16% Grade 1). Cytokine release syndrome (CRS) affected 97% of patients (3% Grade 3, 76% Grade 2, 19% Grade 1). Frequency of overall impairment at each time point was 10/37 (27%) at baseline, 12/29 (41.4%) at 1 month, and 3/17 (17.6%) at 3 months. At each time point, impairment was most common on tests of executive functioning and memory. Based on individual test score changes between baseline and 1 month, rates of decline on individual tests of neurocognitive performance ranged from 11.5% (TMT-A) to 34.6% (COWAT). Decline on self-reported cognitive functioning was observed for 14.3% (FACT-Cog PCI) and 28.6% (EORTC QLQ-C30 CF) of participants. Based on mixed models (Table 1), there was a statistically significant decline in estimated mean z-scores on a test of executive function (COWAT: -0.52, 95% CI -0.89-(-0.16), p=0.007) at 1-month compared to baseline. At three months, there was a statistically significant improvement in estimated mean z-scores on memory (HVLT-R immediate recall: 0.56, 95% CI 0.11-1.01, p=0.017) and executive functioning (TMT-B: 0.87, 95% CI 0.17-1.57, p=0.019; COWAT: 0.68, 95% CI 0.19-1.16, p=0.009) compared to baseline. Conclusions Impairment is present in a subgroup of patients prior to starting CAR T therapy. Patients may demonstrate declines on performance-based measures and report worsening cognitive symptoms in the first month after CAR T therapy, but also improved performance in some domains by three months. Enrollment and long-term follow-up of patients in this study is ongoing. Future analyses will explore differences in trajectories among subgroups, such as those who have experienced ICANS and CRS.

BIOM-03. LACK OF CORRELATION OF MR-DETERMINED WHITE MATTER INJURY(WMI)WITH NEUROCOGNITIVE FUNCTION (NCF)6 MONTHS FOLLOWING WBRT+/-HIPPOCAMPAL AVOIDANCE(HA)+MEMANTINE:SECONDARY ANALYSIS OF NRG ONCOLOGY NRGCC001

Abstract PURPOSE Previous analysis of NRG-CC001 suggested pre-treatment WMI volume was a significant imaging-biomarker predictor of post-treatment neurocognitive decline at 4-and 12-months following HA-WBRT+Memantine. This suggested patients with greater pre-treatment WMI were more susceptible to neurocognitive decline, specifically when undergoing HA-WBRT, but not standard-WBRT. The current analysis examined the relationship between changes in MR-determined WMI and NCF 6-months following WBRT+memantine+/-HA. METHODS NCF-testing was performed at baseline, 2, 4, 6, and 12 months post-WBRT, and included Hopkins Verbal Learning Test–Revised (HVLT-R), Trail Making Test (TMT) Parts A and B, and Controlled Oral Word Association (COWA). Pre-treatment WMI was measured by FLAIR-volume corrected for whole brain volume and corrected for the FLAIR volume associated with metastases (met vol) (FLAIR-volume/(whole brain volume–met-vol). Pearson correlation coefficients were used to assess the correlation between pre-treatment WMI and change from baseline to 6-months for each standardized NCF score. RESULTS Of the 518 randomized patients, 443 (217 patients WBRT+Memantine and 226 HA-WBRT+Memantine) had WMI data available at baseline, and of those, 162 patients (89 patients WBRT+Memantine and 73 HA-WBRT+Memantine) had both baseline and 6-month imaging available. For these patients, there was only a trend toward significance for change in corrected FLAIR-volume from baseline to 6-months (p = 0.174) but no significant change in met-vol (p = 0.438) or whole brain volume (p = 0.977). The change in standardized TMT Part A and B and the change in composite 6-month change scores were moderately correlated with change in corrected FLAIR volume adjusted for met-vol but only in the WBRT+Memantine arm (rho=-0.35, -0.34, -0.39 and p-value = 0.003, 0.006, 0.001). CONCLUSIONS Despite an increase in post-WBRT MR-WMI at 6-months, analysis did not show strong correlation between NCF and MR-WMI as determined by FLAIR-volume change between baseline and 6-months. Similar analyses are underway for the NRG-CC003 imaging data.

34 Verbal Memory as a Language Function: Phonological Processing Contributes to Word List Recall in Persons with Multiple Sclerosis

Objective:Verbal memory deficits are present in multiple sclerosis (MS), but neither inflammatory T2 lesion volume nor cerebral atrophy (generalized or localized hippocampal atrophy) fully explain disease-related verbal memory changes. Importantly, the hippocampus does not function in a vacuum; memory encoding and retrieval requires interactions between the hippocampus and cortical areas where information is processed and represented. Indeed, we have previously shown that lexical access speed (a language function assessed by rapid automatized naming) independently predicted delayed recall of verbal information (word list) for persons with MS, even when controlling for total learning. Informed by this work and recent ultra high field (7.0 Tesla) MRI research reporting high cortical lesion count in regions associated with phonological processing (e.g., plenum temporale, superior temporal gyrus), we assessed whether phonological processing independently explains verbal memory deficits in persons with MS.Participants and Methods:Analyses were performed on a clinical sample of persons with MS aged 18 to 59 years (n=60: 49 relapsing, 11 progressive). Word-list memory was assessed by the Hopkins Verbal Learning Test, Revised (HVLT-R), which yielded scores for Total Learning (TL) and Delayed Recall (DR). Phonological processing was assessed with WIAT-4 Phonemic Proficiency. WIAT-4 Sentence Repetition was utilized as a non-phonological language control task, and WIAT-4 Word Reading was administered to control for premorbid verbal ability. CANTAB Paired Associate Learning served as a nonverbal memory comparison. Performance on tasks was standardized using published age-adjusted norms. Primary analyses used partial correlations to assess relationships between Phonemic Proficiency and (a) HVLT-R TL and DR controlling for WIAT-4 Word Reading, and (b) HVLT-R DR controlling for WIAT-4 Word Reading and HVLT-R TL. To assess specificity to phonological processing, the same partial correlations assessed relationships between Sentence Repetition and HVLT-R variables, and between Phonemic Proficiency and nonverbal memory (CANTAB PAL).Results:When controlling for premorbid verbal ability, Phonemic Proficiency performance accounted for 7.8% of the variance in HVLT-R TL (rpartial=0.28, p=0.031) and 16% of the variance in HVLT-R DR (rpartial=0.40, p=0.002). Moreover, when additionally controlling for HVLT-R TL, Phonemic Proficiency still accounted for 10% of the variance in HVLT-R DR (r partial— 0.32, p=0.016). Showing specificity to phonological processing ability, performance on Sentence Repetition was not significantly related to HVLT-R DR when controlling for premorbid verbal ability (WIAT-4 Word Reading) and HVLT-R TL (rpartial=0.09, p=0.510). Showing specificity to verbal memory, neither Phonemic Proficiency nor Sentence Repetition performance were reliably related to CANTAB PAL for any variance in performance in nonverbal memory (Ps&gt;0.9).Conclusions:Results suggest that language ability, specifically phonological processing, contributes to delayed recall of word lists independent of premorbid verbal ability and initial total learning scores in persons with MS. These findings demonstrate contributions of language ability to verbal memory and highlight the need for further research into language ability changes in persons with MS. This may have implications for verbal memory rehabilitation in MS.

60 Are all Embedded Measures Created Equal? A look at Embedded PVTs in Major Neurocognitive Disorder

Objective:Although performance validity is critical in determining the quality and accuracy of test data, research suggests not all neuropsychologists incorporate performance validity tests (PVTs) in dementia evaluations (McGuire et al., 2019). Furthermore, well-validated embedded measures, such as Reliable Digit Span (RDS) from the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV), have evidenced an unusually high number of failures in a dementia population when utilizing typical clinical cut-offs (Zenisek et al., 2016). The objective of this study is to explore performance on embedded PVTs among older adults who have a major neurocognitive disorder (MND), specifically among Alzheimer disease (AD) and non-AD patients.Participants and Methods:Archival data from outpatient neuropsychological evaluations were analyzed. All participants were at least 65 years of age, diagnosed with a MND, and completed Digit Span from the WAIS-IV, Brief Visuospatial Memory Test- Revised (BVMT-R), and Hopkins Verbal Learning Test-Revised (HVLT-R). In total, 84 participants, aged 67-96 (M=78.44, SD=6.11) with 6-20 years of education (M=13.47, SD=3.30), were included. The sample predominantly identified as female (n=60) and White (n=61). More individuals were diagnosed with AD (n=50) than non-AD dementia (n=34). Common non-AD diagnoses included Vascular (n=44), Lewy bodies (n=8), and Parkinson’s (n=2) dementias. Fisher’s Exact Test of Independence was used to account for the smaller sample to determine if there was a nonrandom association between diagnosis (AD vs non-AD) and embedded PVT performance: RDS&lt; 7, BVMT-R Hits&lt;4, BVMT-R Recognition Discrimination (RD) &lt; 4, and HVLT-R RD &lt; 5 (Bailey et al., 2018).Results:The Fisher’s Exact Test of Independence revealed a statistically significant association between neurocognitive diagnosis and RDS (p= .008), BVMT-R RD (p&lt;.001), and HVLT-R RD (p&lt;.001). BVMT-R Hits were not significantly associated with diagnosis (p = 0.10). These measures evidenced opposite patterns with RDS demonstrating a higher percentage of fails for the non-AD (63%) versus AD (20%) group. The AD group had a higher percentage of fails for BVMT-R RD (58% for AD and 13% for non-AD groups) and HLVT-R RD (66% for AD and 29% for non-AD group).Conclusions:The current study suggests performance on embedded PVTs vary across MND diagnoses. Individuals with a non-AD diagnosis were more likely to fail RDS than those with AD. This is likely secondary to attention and working memory demands that are mediated by the frontal-subcortical networks, which are less impacted by AD pathology (Bonelli &amp; Cummings, 2022; Loring et al., 2016). In contrast, AD patients were more likely to fail embedded PVTs within memory measures, which are largely mediated by the mesial temporal cortex associated with AD (Pluta, 2022). These results suggest embedded measures operate differently based on diagnosis and neuroanatomical systems affected. The clinical relevance of these findings includes potentially using alternative PVTs or different cut-offs based on diagnosis. Future research should attempt to better delineate more appropriate, as well as time efficient, PVTs among the dementia population.

54 Sleep and Circadian Rhythms in Premanifest Huntington’s disease: Relationship with Cognition

Objective:Huntington’s disease (HD) is a neurodegenerative disease characterised by motor, psychiatric and cognitive decline. Currently, no treatments have been identified in HD for slowing down cognitive decline or improving cognitive function. We are interested in identifying potentially modifiable factors in HD that can be targeted to improve or maintain cognitive function. Sleep and circadian disruption stand out as possible modifiable targets because sleep and circadian symptoms are common in HD, and such disruptions are known to impact cognition in the general population. Despite some emerging evidence that sleep quality correlates with cognition in manifest HD, whether these same relationships exist in the premanifest period is unknown. Further, whether circadian rhythms relate to cognition in premanifest HD remains open. Therefore, we aimed to determine whether sleep and circadian parameters relate to cognitive performance in premanifest HD.Participants and Methods:To date, we have recruited 27 premanifest HD participants to a two-week remote sleep study. During the study, participants wore an Actiwatch-2 and completed a sleep diary for 14 consecutive days to assess their sleep and rest-activity patterns. Participants also completed online sleep and mood questionnaires and a cognitive assessment using videoconference. We calculated Pearson correlations to examine whether cognitive performance relates to subjective sleep quality, objective sleep parameters and circadian rest-activity rhythms. Thus far, we have analysed data from 15 female participants with premanifest HD (Mage = 43.20, SD = 11.58).Results:Preliminary results indicate that measures of subjective sleep quality, insomnia severity, daytime sleepiness, and fatigue severity in premanifest HD do not correlate with cognitive performance. Increases in objectively measured sleep efficiency, however, strongly correlated with better performance on the Hopkins-Verbal Learning Test-Revised (HVLT-R) immediate (r = 0.562, p &lt; 0.05) and delayed recall trials (r = 0.597, p &lt; 0.05) and the Trail Making Test Part B (TMT-B; r = 0.550, p &lt; 0.05). More time spent awake (i.e., wake after sleep onset) was strongly linked to reduced performance on the TMT-B (r = -0.542, p &lt; 0.05) and Symbol Digit Modalities Test (r = -0.556, p &lt; 0.05). Further, increases in total sleep time were associated with better performance on the HVLT-R immediate (r = 0.682, p &lt; 0.05) and delayed recall trial (r = 0.616, p &lt; 0.05). For our circadian parameters, less fragmented day-today rest-activity rhythms (i.e., higher intra-daily variability) strongly correlated with higher scores on the HVLT-R immediate (r = 0.768, p &lt; 0.001) delayed recall trials (r = 0.7276, p &lt; 0.05) and TMT-B (r = 0.516, p &lt; 0.05), whereas consistent and stable day-to-day rest-activity rhythms (i.e., higher inter-daily stability) was associated with poorer performance on ERT (r = -0.587, p &lt; 0.05).Conclusions:Preliminary results suggest that fragmented sleep, sleep inefficiency, reduced total sleep time, rest-activity rhythm stability and fragmentation relate to poorer cognitive performance in people with premanifest HD. Should analysis of our whole sample confirm these preliminary findings, targeting sleep in HD (e.g., through sleep hygiene and/or psychoeducation) may be a useful strategy to improve or maintain cognition.

92 Teleneuropsychological Evaluation of Bariatric Surgery Candidates: Cognitive Profiles and Recommendations for Future Practice

Objective:Vascular complications, including elevated body mass index (BMI), are known risk factors for cognitive impairment. Obtaining a cognitive baseline is commonplace in pre-surgical protocols, including for Parkinson’s disease and epilepsy. Currently, routine evaluations for bariatric surgery candidates do not include neuropsychological assessment. This setting provides a unique opportunity to identify cognitive profiles of younger individuals at risk for cognitive impairment. Here, we argue for the standard implementation of a brief, online cognitive battery via telemedicine, to enhance existing protocols of bariatric pre-surgical evaluations.Participants and Methods:Nineteen bariatric surgery candidates were referred to a private neuropsychological assessment practice for pre-surgical cognitive/psychological evaluation. Assessments were conducted by a neuropsychologist and a psychology graduate student, via remote video conferencing, between April 2020 and June 2022. Candidates completed a clinical interview, intake form, and the Behavior Rating Inventory of Executive Function for Adults (BRIEF-A), and were administered a battery of cognitive measures: Wechsler Test of Adult Reading (WTAR), Hopkins Verbal Learning Test-Revised (HVLT-R); and select subtests from the TestMyBrain Digital Neuropsychology Toolkit: Trail Making Tests A and B (TMT-A/B), Matrix Reasoning (MR), Digit Span Forward and Backward (DSF, DSB), Gradual Onset Continuous Performance Test (CPT), and Simple and Choice Reaction Time (SRT, CRT). Descriptive statistics were conducted to analyze sample demographics. Raw scores on cognitive measures were converted to z-scores and averaged across the sample.Results:The average age at evaluation was 38.2 (9.6) years and average pre-surgical BMI was 46.6k/m2 (9.3), indicating morbid obesity (BMI&gt;40k/ m2). Ten (52.6%) candidates identified as female, 10 (52.6%) identified as White, 8 (42.1%) had 12 years of education or less, 4 (21.1%) were unemployed, and 9 (47.4%) had comorbid psychiatric diagnoses. BRIEF-A sub-scales were within the average range (T’s= 47.9 - 52.9, SD’s [10.1 - 12.8]). Estimated premorbid IQ was average at 102.7 (11.4). Neuropsychological data revealed group performance within the average range on DSF and DSB (z’s= 0.00), TMT-A (z= -0.16), MR (z= -0.53), CPT (z= -0.39), and HVLT-R False Positives (z= 0.05) and Recognition Discriminability (z= -0.44). SRT (z= -0.70), CRT Accuracy (z= -1.37), TMT-B (z= -0.79), HVLT-R Total Recall and Percent Retained (z’s= -0.88), and Delayed Recall and True Positives (z’s= -1.27) were low average.Conclusions:In this sample of pre-surgical bariatric candidates with average intelligence, baseline evaluations revealed mild deficits in reaction time accuracy, visual motoric set-shifting, and verbal learning/memory. These deficits may be the result of microvascular changes in the brain secondary to physical compromise. Results provide additional insight into potential early-onset executive dysfunction, psychomotor slowing, and verbal learning/memory difficulties. In addition to these relative areas of neuropsychological weakness, candidates demonstrated relative strengths in attention, working memory, and visuospatial functioning. These insights provide pre-surgical evaluators with additional information to tailor recommendations and treatment approaches that foster surgical success. With a remote, concise, easy-to-administer battery of tests, routine neuropsychological assessment for bariatric surgery candidates is both a feasible and a useful tool for identifying areas of cognitive strengths and weaknesses. Documenting a patients’ cognitive baseline can assist with monitoring long-term vascular risk-factors and potential cognitive impairment.

3 Optimizing Cognitive Rehabilitation of the Injured Warfighter

Objective:Many individuals who experienced a mild traumatic brain injury (mTBI) have persistent cognitive complaints. Traditional cognitive rehabilitation (TCR) interventions were primarily developed for severe neurological injury which has limited effectiveness in rehabilitation of active duty military personnel who have the goal of returning to full military operational status. To remain on active duty, warfighters must have sufficient mental competency to safely and effectively function in complex environments such as combat. There is need for a cognitive rehabilitation approach that addresses demands of military personnel to expedite return to duty. The Strategic Memory Advanced Reasoning Training (SMART) program is novel alternative to TCR. SMART is an evidence-based advanced reasoning protocol that enhances cognitive domains essential to military readiness (e.g., mental agility, strategic learning, problem solving, and focus) and requires less than half of the treatment time. The objective of this study was to assess the efficacy of SMART compared to TCR in terms of overall recovery as well as change in specific cognitive domains.Participants and Methods:Participants were recruited from a military treatment facility. All patients had at least one diagnosed mTBI as well as persistent cognitive complaints. Participants completed the Rey-15 to ensure performance validity. Final sample was SMART n = 28 and SCORE n = 19. Primary dependent measure was the Global Deficit Scale (GDS). GDS was calculated from: Hopkins Verbal Learning Test-Revised (HVLT-R); Delis Kaplan Executive Functioning System Color Word (CW) and Trail Making (TM), Paced Auditory Serial Addition Test (PASAT), and the Symbol Digit Modality Test (SDMT). Demographically corrected t-scores were converted to deficit scores as follows: &gt;40 = 0, 35-39 = 1, 30-34 = 2, 25-29 = 3, 20-24 = 4, &lt;20 = 5. Deficit scores were averaged to calculate GDS. For each measure, Hohen’s g was analyzed for effect size comparisons pre-post treatment.Results:Average number of treatment hours was significantly lower in the SMART condition (SMART: M = 18.47 hours, SD = 2.17; TCR: M = 42.42 hours, SD = 3.79, p &lt;.001). A repeated measures ANOVA showed a significant change on GDS post-treatment (F = 30.25, p &lt; .001) with a large effect size (n2 = .402); however, the interventions did not differ on GDS change. Impact on cognitive domains was relatively equivalent for processing speed (SMART h = 0.67 vs TCR h = -.54) and executive function (SMART h = -0.92 vs TCR h = -.85); however, SMART had a larger impact on memory (SMART h = -0.81 vs TCR h = -.39). SMART resulted in large improvements in retention and recognition memory which were minimally impacted by TCR.Conclusions:Both TCR and SMART had comparable effectiveness in improving cognitive impairment, though SMART was completed in less than half of the treatment time. Both interventions had large effect sizes on processing speed and executive functioning; however, SMART was more effective in improving long-term memory. Memory is an integral part of military readiness. Further investigation is required to determine the relative effectiveness of these two approaches to improving cognitive readiness of the warfighter.

19 Accuracy of Self- and Informant-Reported Domain-Specific Cognitive Ratings

Objective:Diagnostic criteria for mild cognitive impairment (MCI) include a report of cognitive decline from the patient or a close informant. It is therefore important to understand the relationship between self- and informant-rated cognition and actual patient performance. Furthermore, it is unknown whether the nature of the relationship between the patient and their informant impacts accuracy of subjective reports. This study aimed to determine the association between informant report, self-report and objective cognitive performance based on relationship factors. We predicted that informant report would be more closely associated with objective performance than self-report after controlling for demographics and mood (Geriatric Depression Scale [mean= 1.4, SD=2]), especially among those who live with the participant and those who are spouses/partners.Participants and Methods:Participants (n = 338; age= 73.5 ±6.7) of varying diagnoses and their respective informants were drawn from the longitudinal cohort of the Michigan Alzheimer’s Disease Research Center (MADRC). The majority of informants were spouses/significant others (55.6%), followed by 23.7% being other family members and 20.7% were non- family members; 58.9% of informants live with the participant. Both respondents completed the Cognitive Change Index (CCI) to rate the patient’s cognitive status (higher scores indicating worsening cognition) across three domains: memory (12 questions), language (1 question), and attention/executive functioning (7 questions). These domains were matched to objective cognitive performance measured using the MADRC neuropsychological battery. Executive functioning and attention were assessed using Number Span Test Forward and Backward (NSF, NSB) and Trail Making Test Part B and Trail- Making Test Part A and B ratio (TMTB, TMTB: A); memory was measured using Craft Story 21 (Immediate and Delayed), Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall, Delayed Recall, and Benson Complex Figure (BCF) Delayed Recall; and Language was measured by the Controlled Oral Word Association Test (COWAT) and Animal fluency.Results:Linear regression adjusted for sex, race, and mood indicated that both patient and informant CCI ratings were significantly (p&lt;.05) associated with objective cognitive performance. For every one unit increase on executive CCI items, there was a significant decline in executive functioning (NSF patient and informant ß= -0.09, NSB: [ßP= -.14; ßp-0.13]) and TMTB [ßP= 3.85; ß= 3.10 [% change]). Memory performance also declined per unit increase on CCI memory items: (Craft Story 21 Immediate [ßP=-0.32; ß= -0.37] and Delayed [ßP=-.40; ßp -.47], HVLT-R Total Recall [ßP= -.31; ßI=-.37] and Delayed Recall [ßP= -.16; ß=-.20], and BCF Delayed Recall [ßP= -.18; ß= -.23]. Similarly, one unit increase on the single CCI language item was associated with a decline in COWAT (ßP= -2.27; ß= -4.61) and Animal fluency (ßP= -1.88; ß= -3.03). Effect modification by participant-informant relationship type or participant-informant cohabitation was not significant.Conclusions:Patient and informant ratings are associated with objective measures of cognition regardless of the relationship between informant and patient or if they live together. This study was limited by a well-educated sample (mean= 16.1 years of education, SD= 2.4 years) with relatively limited diversity among participant-informant relationships. Future studies should replicate analyses across a larger and more diverse sample.

97 Evaluation of Video and Telephone-Based Administration of the Uniform Data Set Version 3 (UDS v3.0) Teleneuropsychological Measures

Objective:Telecommunication-assisted neuropsychological assessment (teleNP) has become more widespread, particularly in response to the COVID-19 pandemic. However, comparatively few studies have evaluated in-home teleNP testing and none, to our knowledge, have evaluated the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study compares in-home teleNP administration of the UDS v3.0, acquired while in-person activities were suspended due to COVID-19, with a prior in-person UDS v3.0 evaluation.Participants and Methods:210 participants from the Michigan Alzheimer’s Disease Research Center’s longitudinal study of memory and aging completed both an in-person UDS v3.0 and a subsequent teleNP UDS v3.0 evaluation. The teleNP UDS v3.0 was administered either via video conference (n = 131), telephone (n = 75), or hybrid format (n = 4) with approximately 16 months between evaluations (mean = 484.7 days; SD = 122.4 days; range = 320-986 days). The following clinical phenotypes were represented at the initial assessment period (i.e., the most recent in-person UDS v3.0 evaluation prior to the teleNP UDS v3.0): cognitively healthy (n = 138), mild cognitive impairment (MCI; n = 60), dementia (n = 11), and impaired not MCI (n = 1). Tests included both the in-person and teleNP UDS v3.0 measures, as well as the Hopkins Verbal Learning Test-Revised (HVLT-R) and Letter “C” Fluency.Results:We calculated intraclass correlation coefficients (ICC) with raw scores from each time point for the entire sample. Sub-analyses were conducted for each phenotype among participants with an unchanged consensus research diagnosis: cognitively healthy (n = 122), MCI (n = 47), or cognitively impaired (i.e., MCI, dementia, and impaired not MCI) (n = 66). Test-retest reliability across modalities and clinical phenotypes was, in general, moderate. The poorest agreement was associated with the Trail Making Test (TMT) - A (ICC = 0.00; r = 0.027), TMT - B (ICC = 0.26; r = 0.44), and Number Span Backward (ICC = 0.49). The HVLT-R demonstrated moderate reliability overall (ICC = 0.51-0.68) but had notably weak reliability for cognitively healthy participants (ICC = 0.12-0.36). The most favorable reliability was observed in Craft Story 21 Recall - Delayed (ICC = 0.77), Letter Fluency (C, F, and L) (ICC = 0.74), Multilingual Naming Test (MINT) (ICC = 0.75), and Benson Complex Figure – Delayed (ICC = 0.79).Conclusions:Even after accounting for the inherent limitations of this study (e.g., significant lapse of time between testing intervals), our findings suggest that the UDS v3.0 teleNP battery shows only modest relationships with its in-person counterpart. Particular caution should be used when interpreting measures showing questionable reliability, though we encourage further investigation of remote vs. in-person testing under more controlled conditions.

49 A Preliminary Neurocognitive Profile Characterization of Treatment Resistant Depression

Objective:Major Depressive Disorder (MDD) subtypes have been shown to differentially impact psychiatric symptom presentation, clinical features, and functional abilities. While there is extensive research regarding MDD subtypes and clinical characteristics, there has been limited information regarding the relationship between MDD subtypes and neurocognitive functioning. In particular, the neurocognitive impact of the subtype of treatment resistant depression (TRD), defined as MDD that is unresponsive to treatment, is unknown. The aim of this preliminary study was to address this gap by characterizing the neurocognitive profile of TRD. We characterized the performance of older adults with TRD on measures across multiple neurocognitive domains, and explored whether performance varied based on age and education.Participants and Methods:Data utilized were drawn from a broader NIMH-funded, randomized, controlled study conducted at the University of New Mexico that investigated the clinical and cognitive outcomes of varying pulse amplitudes during acute electroconvulsive therapy (ECT) in adults with MDD. Participants in the study were age 50+ with a diagnosis of MDD, and further delineated by subtype as TRD. For this analysis, we utilized demographic and baseline neurocognitive data collected prior to start of treatment for those diagnosed with MDD, recurrent, severe (TRD). Neurocognitive measures included the Delis Kaplan Executive Function System (D-KEFS) Verbal Fluency and Color-Word Interference Subtests, Hopkins Verbal Learning Test-Revised (HVLT-R), and the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) Digit Spans. Demographic-adjusted scaled scores were computed, and descriptive statistics were used to characterize the demographic and neurocognitive features of the sample. Multiple Analysis of Variance (MANOVA) was used to investigate difference in performance across neurocognitive measures based on level of education, with age as a covariate.Results:The sample (n = 42) had a mean age of 65 (SD=8), education level between12 and 14 years, 66.6% were female and 93% were Caucasian. DKEFS Verbal Fluency Category Switching Total Switching Accuracy fell in the Average range (Mean SS=9.5, SD=3.1), and Color Word Inhibition Total Completion Time fell in the Average range (Mean SS=8.5, SD=3.3). HVLT-R Total Recall Correct fell in the Mildly Impaired range (Mean T=35.5, SD=9.9) and Delayed Recall Correct fell in the Mildly to Moderately Impaired range (Mean T=32.9, SD=11.0). WAIS-IV Digit Span fell in the Average range (Mean SS=9.5, SD=2.2). Results indicated that age did not adjust outcomes on the neurocognitive variables, Wilks's λ=0.63, F(6, 23)=2.13, p=0.08. We found no evidence for significant effect of level of education on neurocognitive functioning when controlling for the covariate of age, Wilks's λ=-0.16, F(36, 103.7)=1.47, p=0.07.Conclusions:To our knowledge, this is one of two studies to examine neurocognitive functioning in patients with TRD. The analysis indicated generally intact performance in the neurocognitive domains of executive function (inclusive of verbal fluency, cognitive flexibility, and inhibition), auditory attention and working memory, and Impaired performance on indices of verbal learning and memory. Age did not impact performance on neurocognitive measures, and there was no significant effect for level of education. Further research is warranted to confirm these findings and further explicate the neurocognitive profile of TRD.