California Verbal Learning Test-II Research Articles

The influence of depression and anxiety on cognition in people with multiple sclerosis: a cross-sectional analysis.

There are conflicting findings about the relationships between depression, anxiety, and cognitive dysfunction in people with multiple sclerosis (MS), and a paucity of research has examined the cumulative influence on cognition of depression plus anxiety. This study aimed to determine whether elevated symptoms of depression and anxiety alone or in combination are associated with worse cognition in people with MS. In this cross-sectional analysis, people with MS consecutively seen at a tertiary neuropsychiatry clinic completed the Hospital Anxiety and Depression Scale for symptoms of depression (HADS-D) and anxiety (HADS-A), and the Minimal Assessment of Cognitive Function in MS for cognitive indices. Accounting for covariates, regression models predicted cognitive indices from scores for HADS-D, HADS-A, and the interaction. Of 831 people with MS, 72% were female, mean age was 43.2years, and median Expanded Disability Status Scale score was 2.0. Depressive symptoms were independently predictive of lower verbal fluency (Controlled Oral Word Association Test, p < 0.01), verbal learning (California Verbal Learning Test-II (CVLT-II) total learning, p = 0.02), verbal delayed recall (CVLT-II delayed recall, p < 0.01), and processing speed (Symbol Digit Modalities Test, p < 0.01; three-second Paced Auditory Serial Addition Test (PASAT), p = 0.05; two-second PASAT, p = 0.01). Anxiety in people with depression predicted decreased visuospatial function (Judgment of Line Orientation, p = 0.05), verbal learning (p < 0.01), verbal delayed recall (p < 0.01), visuospatial recall (Brief Visuospatial Memory Test-Revised, p = 0.02), and executive function (Delis-Kaplan Executive Function System, p < 0.01). Anxiety alone was not independently predictive of cognition. In conclusion, depression, especially with comorbid anxiety, is associated with cognitive dysfunction in people with MS.

White matter lesion load and location in relation to cognitive impairment in relapsing–remitting multiple sclerosis

Abstract Background In relapsing–remitting multiple sclerosis (RRMS) the connection between cognitive impairment (CI) and white matter lesion load (WM-LL) and location is still unclear. This study aimed to identify the relationship between CI in RRMS patients and WM-LL and locations using a fully automated platform. CI and WM-LL were evaluated in 90 patients with RRMS using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) and Automated MRI volumetric measures of WM-LL and lesion distribution. Regression analysis of BICAMS as a dependent variable with different clinical and radiological parameters was performed. Results Data were obtained from 90 patients with RRMS who had a mean age of 32.74 ± 8.43 years and a female-to-male ratio of 3:1. The mean (± SD) cognitive rating scores for the BICAMS subtests were 28.07 ± 11.78 for the Symbol Digit Modalities Test (SDMT), 42.32 ± 12.46 for the California Verbal Learning Test-II (CVLT-II), and 16.13 ± 8.17 for the Brief Visuospatial Memory Test-Revised (BVMT-R). According to the BICAMS criteria, 29 cases (32.2%) had CI. BICAMS scores were significantly correlated with age, education level, relapse frequency, disease duration, and time to start disease-modifying therapies. Whole WM-LL and periventricular lesion load were significantly associated with CI. After controlling for age, sex, and education, logistic regression analysis revealed that total WM-LL was the best predictor for CI together with duration of illness and years of education. The cut-off value of 12.85 cc for total WM-LL predicted CI. Conclusions Whole WM-LL and periventricular lesion load are the best anatomical predictors for CI probably due to the effect on the anterior commissural fibers while years of education and duration of disease are the best demographic predictors for CI.

Use of perceptual memory as a performance validity indicator: initial validation with simulated mild traumatic brain injury

ABSTRACT Introduction Many commonly employed performance validity tests (PVTs) are several decades old and vulnerable to compromise, leading to a need for novel instruments. Because implicit/non-declarative memory may be robust to brain damage, tasks that rely upon such memory may serve as an effective PVT. Using a simulation design, this experiment evaluated whether novel tasks that rely upon perceptual memory hold promise as PVTs. Method Sixty healthy participants were provided instructions to simulate symptoms of mild traumatic brain injury (TBI), and they were compared to a group of 20 honest responding individuals. Simulator groups received varying levels of information concerning TBI symptoms, resulting in naïve, sophisticated, and test-coached groups. The Word Memory Test, Test of Memory Malingering, and California Verbal Learning Test-II Forced Choice Recognition Test were administered. To assess perceptual memory, selected images from the Gollin Incomplete Figures and Mooney Closure Test were presented as visual perception tasks. After brief delays, memory for the images was assessed. Results No group differences emerged on the perception trials of the Gollin and Mooney figures, but simulators remembered fewer images than the honest responders. Simulator groups differed on the standard PVTs, but they performed equivalently on the Gollin and Mooney figures, implying robustness to coaching. Relying upon a criterion of 90% specificity, the Gollin and Mooney figures achieved at least 90% sensitivity, comparing favorably to the standard PVTs. Conclusions The Gollin and Mooney figures hold promise as novel PVTs. As perceptual memory tests, they may be relatively robust to brain damage, but future research involving clinical samples is necessary to substantiate this assertion.

Internet-delivered lifestyle physical activity intervention for cognitive processing speed in multiple sclerosis

BackgroundWe propose a randomized controlled trial(RCT) of a Social Cognitive Theory-based(SCT), Internet-delivered behavioral intervention targeting lifestyle physical activity(LPA) for yielding improvements in cognitive processing speed(CPS), learning and memory(L/M), symptoms, and quality of life(QOL) among persons with mild multiple sclerosis(MS)-related ambulatory impairment who have impaired CPS. Methods/designThe study involves a Phase-II, parallel group, RCT design. Participants with MS(N = 300) will be randomly assigned on an equal basis(1:1) into behavioral intervention(n = 150) or attention and social contact control(n = 150) conditions. The conditions will be administered over 6-months by trained behavior coaches who will be uninvolved in screening, recruitment, random assignment, and outcome assessment. We will collect outcome data remotely every 6-months over the 12-month period(baseline, immediate follow-up, and 6-month follow-up) using a treatment blinded assessor. The primary outcome is the raw, oral Symbol Digit Modalities Test as a neuropsychological measure of CPS. The secondary outcomes include the California Verbal Learning Test-II as an objective measure of L/M, and patient-reported outcomes of fatigue, depressive symptoms, anxiety, pain, and QOL. The tertiary outcome is accelerometry as an objective, device-based measure of steps/day for generating a minimal clinically important difference(MCID) value that guides the prescription of LPA for improving CPS in clinical practice. The primary data analyses will involve intent-to-treat principles, and mixed-effects models and logistic regression. DiscussionIf successful, the proposed study will provide Class I evidence for the efficacy of a theory-based, Internet-delivered behavioral intervention focusing on LPA for improving CPS and mitigating its negative impact on other outcomes in persons with MS.Clinicaltrials.gov: NCT04518657

The impact of race and other demographic factors on the false positive rates of five embedded Performance Validity Tests (PVTs) in a Veteran sample

ABSTRACT Introduction It is common to use normative adjustments based on race to maintain accuracy when interpreting cognitive test results during neuropsychological assessment. However, embedded performance validity tests (PVTs) do not adjust for these racial differences and may result in elevated rates of false positives in African American/Black (AA) samples compared to European American/White (EA) samples. Methods Veterans without Major Neurocognitive Disorder completed an outpatient neuropsychological assessment and were deemed to be performing in a valid manner (e.g., passing both the Test of Memory Malingering Trial 1 (TOMM1) and the Medical Symptom Validity Test (MSVT), (n = 531, EA = 473, AA = 58). Five embedded PVTs were administered to all patients: WAIS-III/IV Processing Speed Index (PSI), Brief Visuospatial Memory Test-Revised: Discrimination Index (BVMT-R), TMT-A (secs), California Verbal Learning Test-II (CVLT-II) Forced Choice, and WAIS-III/IV Digit Span Scaled Score. Individual PVT false positive rates, as well as the rate of failing two or more embedded PVTs, were calculated. Results Failure rates of two embedded PVTs (PSI, TMT-A), and the total number of PVTs failed, were higher in the AA sample. The PSI and TMT-A remained significantly impacted by race after accounting for age, education, sex, and presence of Mild Neurocognitive Disorder. There were PVT failure rates greater than 10% (and considered false positives) in both groups (AA: PSI, TMT-A, and BVMT-R, 12–24%; EA: BVMT-R, 17%). Failing 2 or more PVTs (AA = 9%, EA = 4%) was impacted by education and Mild Neurocognitive Disorder but not by race. Conclusions Individual (timed) PVTs showed higher false positive rates in the AA sample even after accounting for demographic factors and diagnosis of Mild Neurocognitive Disorder. Requiring failure on 2 or more embedded PVTs reduced false positive rates to acceptable levels across both groups (10% or less) and was not significantly influenced by race.

Frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico.

Between 29% and 67% of neuromyelitis optica spectrum disorder patients have cognitive alterations. To assess the frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico using the Brief International Cognitive Assessment for Multiple Sclerosis. We evaluated 40 neuromyelitis optica spectrum disorder patients and 40 healthy controls from Mexico. 28 (70.0%) patients with neuromyelitis optica spectrum disorder had cognitive impairment in two or more cognitive domains. Student´s T test showed statistically poor performance by neuromyelitis optica spectrum disorder patients compared to healthy controls on all three neuropsychological test scores. This significant difference was observed on the Symbols Digit Modalities Test (t = 8.875; p ≤ 0.001); California Verbal Learning Test-II memory (t = 10.418; p ≤ 0.001); and Brief Visuospatial Memory Test Revised (t = 6.123; p ≤ 0.001). This study showed that 70% of neuromyelitis optica spectrum disorder patients exhibited cognitive impairment in two or more cognitive domains. Determining the frequency of cognitive impairment will guide the decision of Neuropsychologists in planning cognitive rehabilitation across various domains.

Effects of healthy aging and mnemonic strategies on verbal memory performance across the adult lifespan: Mediating role of posterior hippocampus.

In this study, we aimed to understand the contributions of hippocampal anteroposterior subregions (head, body, tail) and subfields (cornu ammonis 1-3 [CA1-3], dentate gyrus [DG], and subiculum [Sub]) and encoding strategies to the age-related verbal memory decline. Healthy participants were administered the California Verbal Learning Test-II to evaluate verbal memory performance and encoding strategies and underwent 4.7 T magnetic resonance imaging brain scan with subsequent hippocampal subregions and subfields manual segmentation. While total hippocampal volume was not associated with verbal memory performance, we found the volumes of the posterior hippocampus (body) and Sub showed significant effects on verbal memory performance. Additionally, the age-related volume decline in hippocampal body volume contributed to lower use of semantic clustering, resulting in lower verbal memory performance. The effect of Sub on verbal memory was statistically independent of encoding strategies. While total CA1-3 and DG volumes did not show direct or indirect effects on verbal memory, exploratory analyses with DG and CA1-3 volumes within the hippocampal body subregion suggested an indirect effect of age-related volumetric reduction on verbal memory performance through semantic clustering. As semantic clustering is sensitive to age-related hippocampal volumetric decline but not to the direct effect of age, further investigation of mechanisms supporting semantic clustering can have implications for early detection of cognitive impairments and decline.

When Failing One Performance Validity Test Matters

There appears to be a lack of consensus regarding how best to interpret cognitive test findings when there is a failure on only one Performance Validity Test (PVT). The current study examined the impact of failing one freestanding, forced-choice, memory-based (Fr-FC-MB) PVT across two memory measures in a large sample of veterans (N = 1,353). The impact of failing zero, one, or two Fr-FC-MB PVTs (Test of Memory Malingering Trial 1 or the Medical Symptom Validity Test) on subsequent memory measures was examined (California Verbal Learning Test-II [CVLT-II], Brief Visuospatial Memory Test-R [BVMT-R]). Compared to those failing zero PVTs, those failing one PVT showed significant declines across all memory indices with large average effect sizes (BVMT-R, d = −0.9, CVLT-II, d = −1.0). Those failing one PVT had memory scores more similar to those failing two PVTs. There is a need for greater nuance and flexibility when determining invalid test performance. The current findings, along with a brief review of the literature, find that failing even one Fr-FC-MB PVT dramatically (negatively) impacts memory performance. Results suggest that including individuals failing one Fr-FC-MB PVT into a credible group should be more closely scrutinized.

Larger hippocampal and temporal lobe volume may associate with early rapid forgetting in cognitively healthy individuals with a predisposition to Alzheimer’s disease

AbstractBackgroundGrowing need exists to link volumetric brain analysis to functional cognitive performance in early prediction of Alzheimer’s disease.MethodIn cognitively healthy older adults (N = 40; M age = 71.7±7.7 years), we established amyloid/tau ratios from cerebrospinal fluid, thus finding a small group with pathological amyloid/tau ratios (PAT, n = 11) and normal ratio (NAT, n = 29). Approximately 40% of the PAT group were expected to convert to mild cognitive impairment within 4 years. It was hypothesized that reduced performance on the California Verbal Learning Test‐II (CVLT‐II) Short Delay Free (SDFR) and Cued Recall (SDCR) task would be associated with smaller hippocampal and temporal lobe volume (obtained via NeuroQuant).ResultHippocampal total, left, and right percentiles were found to be negatively associated with SDFR in the PAT group, r(38) = ‐.67*, ‐.66*, and ‐.63*, but not in the NAT group, r(38) = ‐.21, ‐.04, and ‐.35, such that a larger hippocampus was associated with fewer remembered words after a short delay on a list learning task in those with pathological amyloid/tau ratios. Temporal lobe volume was also found to be negatively associated with SDFR and SDCR in the PAT group, r(38) = ‐.67* and ‐.69*, but not in the NAT group, r(38) = ‐.36 and ‐.34, such that a larger temporal lobe was associated with fewer remembered words after a short delay on a list learning task (even when cued) in those with smaller amyloid/tau ratios. Two hierarchical multiple regression analyses, one including amyloid/tau ratio and the other including amyloid only, found that age and sex associate with ∼20.4% variance of the performance on the CVLT‐II SDFR task while temporal lobe volume increased associative value by 16.1% in the former [F (1, 35) = 8.871, p &lt; .05] and by 15.4% in the latter [F (1, 35) = 8.430, p &lt; .05].ConclusionOur findings suggest there may be early compensation in brain structures among cognitively healthy individuals whose CSF biomarker suggest increased risk for the development of symptomatic Alzheimer’s disease, such that hippocampi and temporal lobes increase in size during early pre‐Alzheimer’s stages despite reduced performance on memory tasks.

Low serum 25‑hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis.

Cognitive impairment frequently affects people with multiple sclerosis (MS). Low vitamin D has been associated with cognitive dysfunction in different neurodegenerative diseases, and, in MS, with motor disability and disease activity. We aim to investigate associations between vitamin D and cognitive status in MS. In this cross-sectional study, we included 181 MS patients, recruited consecutively at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, between January and April 2022, with serum 25‑hydroxy (25-OH) vitamin D measurements using Chemiluminescence-ImmunoAssay, and cognitive assessment using the Brief International Cognitive Assessment for MS (BICAMS), which includes Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). We collected demographics (age, sex, education), and clinical variables (disease duration, disease subtype, expanded disability status scale (EDSS), disease modifying treatment, relapses in previous 12 months, vitamin D supplementation, comorbidities). For a subset of patients (n=41, 23.2% of the total sample), we collected Beck Depression Inventory-II, Beck Anxiety Inventory, and Modified Fatigue Impact Scale. At univariable linear regression models, serum 25-OH-vitamin D levels were 0.9ng/mL higher for each unit increase of SDMT adjusted scores (Coeff=0.93; 95%CI=0.81, 1.04; p<0.01), 0.7ng/mL higher for each unit increase of CVLT-II adjusted scores (Coeff=0.68; 95%CI=0.53, 0.83; p<0. 01), 0.6ng/mL higher for each unit increase of BVMT-R adjusted scores (Coeff=0.58; 95%CI=0.43, 0.73; p<0.01), -9.63ng/mL lower for each impaired BICAMS test (Coeff=-9.63; 95%CI=-11.48, -7.79; p<0.01), and -2.2ng/mL lower for each unit increase of EDSS (Coeff=-2.16; 95%CI=-3.57, -0.75; p<0.01). At multivariable linear regression models, we confirmed associations between 25-OH-vitamin D and EDSS (Coeff=-2.09; 95%CI=-4.45, -0.43; p<0.01), SDMT (Coeff=0.75; 95%CI=0.60, 0.90; p<0.01), and CVLT-II (Coeff=0.14; 95%CI=0.01, 0.28; p=0. 04). Results remained unchanged when including depression, anxiety and fatigue scores. Lower serum 25-OH-vitamin D was associated with worse cognitive function in MS. Future studies should consider longitudinal variations in cognitive function in relation to vitamin D supplementation.

6 The Moderating Role of Physical Activity on Hippocampal Iron Deposition and Memory Outcomes in Typically Aging Older Adults

Objective:Quantitative Susceptibility Mapping (QSM) is an MRI-based technique that sensitively measures in-vivo iron deposition via relaxation and magnetic susceptibility of brain tissue. Iron is essential for brain homeostasis, including oxidative metabolism, formation and maintenance of neural networks, and myelin synthesis. While increased levels of iron deposition occur during normal aging, high levels may have detrimental effects. Previous work has linked excessive brain iron accumulation to oxidative stress, beta-amyloid and tau toxicity, neurodegeneration, and cognitive dysfunction, particularly memory loss. Physical activity, on the other hand, correlates with higher synaptic integrity and memory performance, even in the presence of neuropathology. To date, it is unknown how physical activity may affect iron deposition-related cognition changes. We examined the moderating role of physical activity on the relationship between QSM hippocampal iron deposition and verbal memory in typically aging adults.Participants and Methods:62 cognitively unimpaired older adults from the UCSF Memory and Aging Center (age mean(SD) = 78.34(7.28) years; 56% women; education mean(SD) = 17.94(1.72) years; 85% non-Hispanic White) completed neuropsychological testing and brain MRI during annual research visits, followed by Fitbit™ physical activity monitoring for 30 days. Average total daily steps were aggregated. Participants completed 3T Prisma neuroimaging with QSM, and regional iron deposition levels were quantified. All subjects also underwent diffusion tensor imaging (fractional anisotropy). Verbal memory was assessed via long delay free recall scores from the California Verbal Learning Test II (CVLT-II). Linear regression examined verbal memory as a function of hippocampal QSM (bilateral), physical activity, and their interaction. Models covaried for age, sex, and education. Additional models separately examined left and right hippocampal QSM, as well as subcortical QSM to determine lateralization and specificity of verbal memory effects to hippocampal iron deposition, respectively.Results:Univariably, higher bilateral hippocampal QSM correlated with worse verbal memory (r= 0.35; p= 0.015). Adjusting for demographics, physical activity moderated the relationship between bilateral hippocampal QSM and verbal memory (ß= 0.41, p= 0.011), such that at higher levels of physical activity, the negative relationship between hippocampal QSM and verbal memory was significantly attenuated. Results persisted when adjusting for DTI integrity of the uncinate fasciculus and fornix white matter tracts. Lateralization models were both significant, suggesting that results were not dominantly driven by either left (ß= 0.34, p= 0.048), or right (ß=0.31, p= 0.035) hippocampal QSM. In contrast, subcortical QSM did not correlate with memory performance (r= 0.13, p &gt; 0.05) or interact with physical activity on verbal memory outcomes (p &gt; 0.05).Conclusions:Physical activity significantly moderated the negative relationship between hippocampal QSM and verbal memory performance. Higher exercise engagement may buffer the adverse effect of hippocampal iron deposition on memory, potentially through its role in maintenance of myelin and synaptic integrity and/or protecting against other neurotoxic events (e.g., oxidative stress, neuronal cell death). Our results support that physical activity continues to be a modifiable risk factor that may offer a protective role in neurobiological pathways of memory and cognitive decline.

5 Rejuvenating Blood Factor TIMP2 Relates to Physical Activity and Cognitive Functioning in Older Adults on The Alzheimer’s Disease Continuum

Objective:Tissue inhibitor of metalloproteinases 2 (TIMP2) is produced peripherally, crosses the blood-brain barrier, and improves synaptic plasticity and hippocampal-dependent cognition in aged mice; however, the role of TIMP2 in human cognitive aging is unclear. We examined associations of circulating TIMP2 levels in blood with a known plasticity-inducing behavior, physical activity, and cognitive functioning among older adults along the Alzheimer’s disease continuum.Participants and Methods:Participants included 84 community-dwelling older adults (meanage = 78.8; 57% female; 82% cognitively normal; 14% MCI; 4% mild dementia; 35% PET Aß+) enrolled in the UC San Francisco Memory and Aging Center. All participants completed 30 days of observational FitbitTM monitoring to quantify physical activity (average daily steps), as well as a comprehensive in-person visit including blood draw (proteins assayed on SOMAscan platform), [18F]AV-45 positron emission tomography (PET) to quantify brain beta-amyloid (centiloids), and neuropsychological assessment. Composite cognitive z-scores were calculated for memory (California Verbal Learning Test-II [CVLT-II] and Benson Figure Recall), semantic processing (animal fluency and Boston Naming Test), and executive functioning (digits backwards span, Stroop inhibition, modified trail making test, lexical fluency, and design fluency). Multiple linear regression examined TIMP2 as a function of physical activity, covarying for age and PET centiloids. Additional regression models separately examined cognitive z-scores as a function of TIMP2, covarying for age, sex, education, PET centiloids, and body mass index (BMI).Results:TIMP2 was not significantly correlated with age, sex, education, or PET centiloids (ps &gt; 0.05); however, TIMP2 was negatively correlated with BMI (r = -0.23, p = 0.036). Greater average daily steps related to higher levels of TIMP2 (b = 0.30, 95%CI = 0.04-0.55, p = 0.022). TIMP2 also related to better semantic processing (b = 0.28, 95%CI = 0.04-0.51, p = 0.021) and executive functioning (b = 0.26, 95%CI = 0.03-0.49, p = 0.028). TIMP2 did not significantly relate to memory (p &gt; 0.05).Conclusions:Greater physical activity was associated with higher concentrations of blood factor TIMP2, which in turn related to better cognitive functioning independent of Alzheimer’s disease pathology burden. These results support previous mouse models by broadly replicating relationships between TIMP2 and cognition in humans, while also uniquely demonstrating an association between TIMP2 and physical activity, a modifiable protective factor in both typical and diseased cognitive aging. Our domain-specific results, however, suggest that benefits of TIMP2 in humans may involve a broader neuroanatomical network than the hippocampal-specific effects previously shown in mice. Although exact mechanisms of TIMP2 need further examination, TIMP2 is known to be enriched in human umbilical cord plasma, has been shown to be involved in cell-growth promoting activities, and may relate to increased neural plasticity in older age. Further examination of TIMP2 and other novel blood-based proteins as potential therapeutic targets for improved cognitive aging, including in the presence of Alzheimer’s disease, is warranted.

47 Amyloid/Tau Ratio and Early Predictors of Alzheimer's Disease

Objective:Early cognitive signs of Alzheimer's disease are often subtle and go unnoticed until they become more prominent and debilitating. Thus, symptoms begin long before an actual Alzheimer's diagnosis is given. However, it is known that cognitively healthy older individuals with lower amyloid/tau ratios (PAT) are more likely to develop Alzheimer's disease than those with higher amyloid/tau ratios (NAT). Therefore, we explored whether this ratio can be used in conjunction with neuropsychological tests to isolate cognitive predictors of Alzheimer's disease amongst cognitively healthy older adults. We were interested in potential group differences on the California Verbal Learning Test, Second Edition (CVLT-II) Long Delay Free Recall scores and Cued Recall scores. We hypothesized that: (a) individuals in the PAT group would have weaker CVLT-II Long Delay Free Recall scores than individuals in the NAT group; and (b) individuals in the PAT group would recall fewer words on the CVLT-II Long Delay Cued Recall trial than individuals in the NAT group.Participants and Methods:There were 115 older individuals recruited via Huntington Medical Research Institutes and the University of Southern California who had their cerebral spinal fluid extracted to measure amyloid/tau ratios. They completed the California Verbal Learning Test-II as part of a larger neuropsychological battery and were determined to be cognitively healthy. The mean age of these participants was 74.5 years (SD = 8.3), and there were 36 who met the threshold for the amyloid/tau ratio associated with Alzheimer's disease (PAT) while the other 79 did not (NAT). A hierarchical linear regression tested the hypotheses, with two blocks used for the analyses. Block 1 for both analyses contained variables to control for the potential effects of various factors in performance on the Long Delay tasks. Block 2 consisted of the amyloid groups (NAT vs. PAT).Results:After controlling for age, sex, education, body mass index, Montreal Cognitive Assessment scores, and depression, we found no significant difference between CVLT-II Long Delay Free Recall scores or Long Delay Cued Recall scores for the two groups.Conclusions:While no significant difference was found on the long delay trials of the CVLT-II, it is important to note that it is unclear at what stage Alzheimer's related decline begins or can be detected using cognitive testing. Longitudinal studies would help to better understand if this lack of association holds true over time. Other aspects of the CVLT-II, such as intrusions and repetitions, would also help to better understand the different ways that symptoms of Alzheimer's disease can manifest early on.

H - 37 Impact of Barriers to Healthcare Access on Cognition and Accelerated Brain Aging in Diverse Persons with Multiple Sclerosis: Preliminary Pilot Data.

Racially/ethnically diverse persons with multiple sclerosis (pwMS) have worse outcomes than their white counterparts. Barriers to healthcare access may contribute to these disparities, though much remains unknown. The current pilot study investigates the impact of barriers to healthcare on cognition and accelerated brain aging in diverse pwMS. We hypothesize that greater barriers to healthcare will be associated with poorer cognitive performance and increased brain aging. Eighteen middle-aged pwMS (40-60years) were included. Barriers to healthcare access was evaluated using total and subscale (skills, marginalization, expectations, knowledge, and pragmatics) scores of the modified Barriers to Care Questionnaire. Cognition was measured using raw scores from the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and California Verbal Learning Test-II (CVLT-II). Accelerated brain aging was calculated by subtracting chronological age from predicted brain age based on the brainageR paradigm. Given established directional hypotheses, one tailed correlations were conducted. Greater marginalization-related barriers to healthcare were associated with poorer performance on the SDMT (r = -0.409, p = 0.046). Greater knowledge-based barriers to healthcare were associated with increased brain aging (r = -0.615, p = 0.004). Lastly, brain age was significantly related to immediate (r = -0.653, p = 0.003) and delayed (r = -0.549, p = 0.014) visual memory, such that increased brain age was associated with poorer visual memory. To the authors' knowledge, this is among the first studies to examine the impact of barriers to healthcare on cognition and brain health in diverse pwMS. It demonstrates the importance of sociocultural determinants when examining outcomes in MS. This work has implications for culturally informed research and clinical care.

A - 123 Depression and Negative Symptoms Predicting Memory and Verbal Fluency in Psychotic Major Depression.

Although substantial research exists regarding negative symptoms and depression impacting cognitive functioning in schizophrenia, research in major depression with psychotic features (psychotic major depression; PMD) is limited (Calderon-Mediavilla et al., 2021). This study investigates if negative symptoms can predict delayed verbal memory and verbal fluency in individuals with PMD, after controlling for depression severity. As part of a larger study, 49 adults with PMD (57% female; Mage = 37.7years) were administered the following measures. The Hamilton Depression Rating Scale measured depression severity. A negative symptoms composite score was made with items from the Brief Psychiatric Rating Scale. The California Verbal Learning Test-II measured verbal memory. The Controlled Oral Word Association Test measured verbal fluency. Depression and negative symptoms were not significantly correlated (r = 0.08, p > 0.05). After controlling for depression severity, negative symptoms explained an additional 8.5% of the variance in long-delay free recall (Adjusted R2 = 12%, p < 0.05). Depression and negative symptoms were significant unique predictors (β= 0.302, β= -0.29, respectively; ps < 0.05). After controlling for depression severity (which was not a significant predictor), negative symptoms explained 14.9% of the variance in verbal fluency (p < 0.05). Negative psychotic symptoms are just as important or more important than depression severity in predicting verbal fluency and memory for individuals with depression who experience psychotic symptoms during a depressive episode. These findings improve the understanding of cognitive functioning in individuals with PMD, which can impact treatment planning.

One-year regional brain volume changes as potential predictors of cognitive function in multiple sclerosis: a pilot study

BackgroundThe most reliable magnetic resonance imaging (MRI) marker of cognitive dysfunction in multiple sclerosis (MS) is brain atrophy. However, 1-year volumetric changes prior to cognitive assessment were never studied as potential predictors of cognition, which we aim to assess with this pilot work.MethodsTwenty-two MS patients were submitted to a baseline measure of 83 regional brain volumes with MRI and re-evaluated 1 year later; they were also tested with the Brief International Cognitive Assessment for MS (BICAMS): sustained attention and processing speed were examined with the Symbol Digit Modalities Test (SDMT), verbal and visuo-spatial learning and memory with the learning trials from the California Verbal Learning Test-II (CVLT) and the Brief Visuo-spatial Memory Test-revised (BVMT), respectively. Controlling for age, sex, and years of education, a multivariate linear regression model was created for each cognitive score at 1-year follow-up in a backward elimination manner, considering cross-sectional regional volumes and 1-year volume changes as potential predictors.ResultsDecreases in the volumes of the left amygdala and the right lateral orbitofrontal cortex in the year prior to assessment were identified as possible predictors of worse performance in verbal memory (P = 0.009) and visuo-spatial memory (P = 0.001), respectively, independently of cross-sectional brain regional volumes at time of testing.ConclusionOur work reveals novel 1-year regional brain volume changes as potential predictors of cognitive deficits in MS. This suggests a possible role of these regions in such deficits and might contribute to uncover cognitively deteriorating patients, whose detection is still unsatisfying in clinical practice.

Patterns of proactive interference in CVLT-II: evidence of a low-organized, disorganized, and highly organized learning style

ABSTRACT Objective Previous studies have interpreted proactive interference (PI) either as indicating executive dysfunction or a normal process indicating deep level encoding. We investigated these competing models of PI in a large clinical sample using cluster analyses. We expected to find clusters defined by high PI but otherwise characterized by either EF impairment or of good memory performance. Method File records of 731 patients with neurological or psychiatric disorders were analyzed. PI-scores, false positive recognition errors, and semantic organization scores on the California Verbal Learning Test-II (CVLT-II) were subjected to cluster analyses. Clusters were compared regarding buildup and release from PI, memory performance and strategy measures, measures of intelligence, EF, and processing speed. Results The analyses revealed six analyzable clusters. Two clusters showed no buildup of PI and normal release from PI. Discriminability was impaired both in List A and B. Learning acquisition and speeded measures of EF were reduced. One cluster showed both buildup of PI and problems with releasing from PI, and particularly impaired discriminability of List B. Semantic organization was low. Learning consolidation and EF speeded measures were impaired. Two other clusters showed buildup of PI, but no problem with release. Learning was highly organized, and they showed good memory and normal neuropsychological performance. Conclusions Results shows differentiation between a low organized EF dysfunction pattern with no PI, a disorganized PI pattern also indicating EF dysfunction and a highly organized pattern where PI seems to be the price to pay for high effort put into the learning process.

Sleep-disordered breathing and neurocognitive function in multiple sclerosis: Differential associations across cognitive domains

Background: Sleep disorders are common in people with multiple sclerosis (PwMS) and could contribute to cognitive dysfunction. However, effects of pathological sleep on cognitive domains are insufficiently characterized. Objective: To evaluate associations between cognitive performance and polysomnographic (PSG)-based sleep disturbances in PwMS. Methods: PwMS with known/suspected untreated obstructive sleep apnea (OSA, N = 131) underwent PSG and cognitive tests: Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test-II (CVLT-II), Brief Visuospatial Memory Test-Revised (BVMT-R Total and Delayed), Judgment of Line Orientation (JLO), Controlled Oral Word Association Test (COWAT), Trail Making Test, Go/No-Go, and Nine-Hole Peg Test (NHPT). Results: Apnea severity measures were associated with worse processing speed, attention, and working memory (SDMT); immediate and delayed visual memory (BVMT-R Total and Delayed); attention, psychomotor speed, and cognitive flexibility (Trails); and manual dexterity and visuomotor coordination (NHPT) (ps ⩽ 0.011). Sleep macrostructure measures showed stronger associations with verbal memory and response inhibition (CVLT-II Total Recognition Discriminability Index), and immediate visual memory (BVMT-R Total) (ps ⩽ 0.011). Conclusions: Pathological sleep, including hypoxia, sleep fragmentation, and disturbances in sleep/wake states, are differentially associated with worse cognitive performance in PwMS. These findings could inform future personalized approaches to cognitive impairment in PwMS with sleep disorders. Trial registration: ClinicalTrials.gov identifier: NCT02544373 (https://clinicaltrials.gov/ct2/show/NCT02544373).

Episodic memory deficit in HIV infection: common phenotype with Parkinson’s disease, different neural substrates

Episodic memory deficits occur in people living with HIV (PLWH) and individuals with Parkinson’s disease (PD). Given known effects of HIV and PD on frontolimbic systems, episodic memory deficits are often attributed to executive dysfunction. Although executive dysfunction, evidenced as retrieval deficits, is relevant to mnemonic deficits, learning deficits may also contribute. Here, the California Verbal Learning Test-II, administered to 42 PLWH, 41 PD participants, and 37 controls, assessed learning and retrieval using measures of free recall, cued recall, and recognition. Executive function was assessed with a composite score comprising Stroop Color-Word Reading and Backward Digit Spans. Neurostructural correlates were examined with MRI of frontal (precentral, superior, orbital, middle, inferior, supplemental motor, medial) and limbic (hippocampus, thalamus) volumes. HIV and PD groups were impaired relative to controls on learning and free and cued recall trials but did not differ on recognition or retention of learned material. In no case did executive functioning solely account for the observed mnemonic deficits or brain-performance relations. Critically, the shared learning and retrieval deficits in HIV and PD were related to different substrates of frontolimbic mnemonic neurocircuitry. Specifically, diminished learning and poorer free and cued recall were related to smaller orbitofrontal volume in PLWH but not PD, whereas diminished learning in PD but not PLWH was related to smaller frontal superior volume. In PD, poorer recognition correlated with smaller thalamic volume and poorer retention to hippocampal volume. Although memory deficits were similar, the neural correlates in HIV and PD suggest different pathogenic mechanisms.

A virtual reality program to assess cognitive function in multiple sclerosis: A pilot study.

Introduction: Cognitive impairment is a debilitating symptom in people with multiple sclerosis (MS). Most of the neuropsychological tasks have little resemblance to everyday life. There is a need for ecologically valid tools for assessing cognition in real-life functional contexts in MS. One potential solution would involve the use of virtual reality (VR) to exert finer control over the task presentation environment; however, VR studies in the MS population are scarce. Objectives: To explore the utility and feasibility of a VR program for cognitive assessment in MS. Methods: A VR classroom embedded with a continuous performance task (CPT) was assessed in 10 non-MS adults and 10 people with MS with low cognitive functioning. Participants performed the CPT with distractors (i.e., WD) and without distractors (i.e., ND). The Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II), and a feedback survey on the VR program was administered. Results: People with MS exhibited greater reaction time variability (RTV) compared to non-MS participants, and greater RTV in both WD and ND conditions was associated with lower SDMT. Conclusions: VR tools warrant further research to determine their value as an ecologically valid platform for assessing cognition and everyday functioning in people with MS.