Hopkins Verbal Learning Test-Revised Research Articles

Effect of Esketamine Nasal Spray on Cognition in Patients with Treatment-Resistant Depression: Results from Four Phase-3 Studies.

While esketamine is effective in treatment-resistant depression (TRD), detailed information about the effect of esketamine on cognition is relatively scarce. This analysis assessed the effect of short-term (three double-blind [DB] studies; DB1, DB2, and DB4) or long-term maintenance treatment (DB3) with esketamine nasal spray (ESK) compared to an active-comparator+placebo (PBO), on cognition in patients with TRD. Patients (DB1/DB2/DB3: [18-64years, n=747]; DB4: [≥65years, n=137]) with TRD received ESK (DB1/DB2/DB3:56/84mg; DB4:28/56/84mg) or PBO+newly initiated oral antidepressant (OAD) as per treatment schedules. Cognitive assessments- Cogstate battery and Hopkins Verbal Learning Test-Revised, were administered at baseline, Day-28/early withdrawal, and follow-up visits in DB1/DB2/DB4 and at 12-week intervals in DB3 maintenance phase. Descriptive statistics were used to analyze ESK effects on cognition with effect sizes and 95% confidence intervals (CIs) used to express the nature/magnitude of treatment effects relative to active-comparator+PBO. Correlation between depression severity (MADRS scores) and cognition was assessed at baseline and endpoint(s). At baseline, mild-to-moderate impairment in psychomotor function, attention, and memory (working/episodic) were evident. For each DB1/DB2/DB4, group mean performance in z-scores for ESK+OAD and OAD+PBO groups on all cognitive tests remained similar/slightly improved from, baseline at endpoint (Day-28) and follow-up assessments. Similarly, in DB3(limited to participants ≥65years), both groups generally showed improvement in cognitive performance at endpoint(s). Correlations between MADRS scores and performance on the cognitive test battery were small at baseline and endpoint(s). This analysis did not identify evidence of negative effects on cognition following short-term or long-term maintenance treatment with ESK+OAD in patients with TRD.

Implementing the optimized hippo-avoidance prophylactic cranial irradiation for limited-stage small cell lung cancer by tomotherapy and volumetric modulated arc therapy.

Hippo-avoidance prophylactic cranial irradiation (HA-PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall-off and compensate for setup errors. Most studies recommend a 5-mm margin, while it could be optimized to a 2-mm expansion. Here, we showed the details of optimized HA-PCI for limited-stage small cell lung cancer (LS-SCLC). This cohort study reviewed patients with LS-SCLC receiving optimized HA-PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo-related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test-Revised (HVLT-R) scores in different time points was conducted. The Kaplan-Meier method was used to calculate the survival rates. A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40-7.44) and 7.63 Gy (IQR: 7.14-8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric-modulated arc therapy [VMAT]). The decline of HVLT-R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow-up of 52 months (95% CI: 47.2-56.7), the 2-year overall survival and progression-free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus. Optimized HA-PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity.

B - 137 Analyzing Completion Time on a Created Forced Choice Trial of the Hopkins Verbal Learning Test – Revised (HVLT-R) to Measure Engagement in a Mixed Clinical Sample

Abstract Objective We created a forced choice recognition trial (FCR) for the HVLT-R, including recording completion time (FCompT), to evaluate the utility of combining completion time with accuracy scores when using performance validity tests (PVTs). Method Participants included 29 clinically referred patients at a large medical center who completed the HVLT-R in addition to multiple free-standing and embedded PVTs including the TOMM, Word Choice Test (WCT), Reliable Digit Span (RDS), and the Dot Counting Test (DCT) as part of a larger battery of neuropsychological tests in an outpatient setting. Data from the sample (M age = 64.79, SD = 13.86; M education = 15.65, SD = 2.47; 62.1% females) were analyzed using correlation and linear regression. Results The HVLT-R FCR trial correlated with the TOMM-10, r(19) = 0.75, p = &amp;lt;0.001, TOMM trial 1, r(17) = 0.75, p = &amp;lt;0.01, the DCT r(12) = −0.71, p = &amp;lt;0.01, and the FCompT, r(29) = −0.72, p = &amp;lt;0.001. The FCompT was correlated with RDS, r(28) = −0.46, p = 0.03, TOMM-10, r(19) = −0.64, p = &amp;lt;0.01, and TOMM trial 1, r(17) = −0.61, p = &amp;lt;0.01. FCompT significantly predicted FCR accuracy b = −0.72, t(29) = −5.41, p &amp;lt; 0.001. Conclusions The HVLT-R FC and FCompT strongly correlated with free-standing and embedded PVTs. Data demonstrates that a longer completion time predicts poorer performance on FCR. Results demonstrate the value of measuring completion time for specific PVTs, in addition to providing support for the addition of a FCR trial to the HVLT-R.

A - 74 Comparing HVLT-R Performance in Monolingual Vs. Spanish/English Bilingual Veterans

Abstract Objective Norms developed in monolingual populations may not be appropriate for use with bilingual patients. This study examined the impact of Spanish-English bilingualism on rote verbal memory using the Hopkins Verbal Learning Test-Revised (HVLT-R). Methods Clinically-referred veterans (86 monolingual; 30 bilingual) completed HVLT-R (English) during a comprehensive neuropsychological evaluation. Chi square analyses and independent samples t-tests were used to examine group demographic differences. Verbal fluency scores and HVLT-R scores were compared between groups using independent samples t-tests. Results Groups did not differ significantly in age (monolingual-M = 62.62; bilingual-M = 65.67) or education (monolingual-M = 13.9; bilingual-M = 13.2). Self-reported race/ethnicity was mostly White for the monolingual sample, while the bilingual sample was predominantly Hispanic. Groups also differed in gender composition (bilingual: 100% male; monolingual: 84% male). Groups did not differ in their speeded English phonemic word generation, t(108) = 0.311, p = 0.757, or speeded semantic word generation, t(109) = 1.931, p = 0.056, suggesting the current bilingual sample had high English proficiency. Cognitively unimpaired monolingual and bilingual veterans did not differ in their raw total recall, t(114) = 1.228, p = 0.222, delayed free recall, t(114) = 0.331, p = 0.741, percent retention, t(114) = 0.240, p = 0.811, or recognition discrimination, t(114) = 0.521, p = 0.603, for target words. Groups did not differ in their age-corrected T-scores in any of the above scores. Conclusions Results support the use of existing HVLT-R normative data for assessment of rote verbal memory in Spanish/English bilinguals with high English proficiency.

The Association of Cerebral Autoregulation Dysfunction and Postoperative Memory Impairment in Cardiac Surgery Patients.

Background and Objectives: Cardiac surgery is associated with various durations of cerebral autoregulation (CA) impairment and can significantly impact cognitive function. Cognitive functions such as memory, psychomotor speed, and attention are significantly impacted after cardiac surgery, necessitating prioritization of these areas in cognitive function tests. There is a lack of research connecting cerebral autoregulation impairment to specific cognitive function domains after cardiac surgery. This study aimed to determine if impaired cerebral autoregulation is associated with postoperative memory impairment and to test the hypothesis that the duration of this impairment affects the development of postoperative memory issues. Materials and Methods: A prospective study was conducted in 2021-2023. After approval of the Ethics Committee and with patient's written consent, 83 adult patients undergoing elective on-pump coronary artery bypass graft (CABG) surgery were enrolled. All patients were assessed for cognitive function 1 day before surgery using the Mini-Mental state examination (MMSE-2) test as a screening tool and the Hopkins Verbal Learning Test-Revised (HVLT-R) to assess memory specifically. To diagnose possible memory impairment (IM), all patients underwent a repeat assessment of cognitive function on the 7th-10th postoperative day. Cerebral autoregulation monitoring using transcranial Doppler was performed. Cerebral autoregulation status index (Mx) was recorded using Intensive Care Brain Monitoring System software, 9.1.5.23 (Cambridge, UK). Results: According to our research, the incidence of postoperative memory impairment is 30.1%. Temporary cerebral autoregulation impairment occurs in all patients undergoing elective in-pump CABG surgery. The duration of the single longest CA impairment event in seconds (LCAI) and the LCAI dose were higher in patients with postoperative memory impairment, p = 0.006 and p < 0.007, respectively. Conclusions: Cerebral autoregulation impairment is important in developing memory loss after cardiac surgery. The duration and dose of the LCAI event are predictive of postoperative memory impairment.

Association of Serum Biomarkers With Neurocognitive Decline After PCI in Small Cell Lung Cancer: An Exploratory Study of the Phase III NCT01780675 Trial

IntroductionBlood samples were collected to explore potential serum biomarkers associated with neurocognitive function in small-cell lung cancer (SCLC) patients who received prophylactic cranial irradiation (PCI). MethodsThis pre-specified study included patients with blood samples available, who participated in a phase III trial (NCT01780675). Blood samples were collected before PCI and 3-days post-initiating PCI. Neurocognitive decline was defined as a decrease of ≥ 5 points on total recall in the Hopkins Verbal Learning Test—Revised (HVLT-R) assessed from pre-PCI to 4-months post-PCI. Biomarkers were screened using univariate logistic regression analysis. P < .1 was considered statistically significant. ResultsForty-eight enrolled patients who had blood samples at baseline were included and 27 were available for analysis as the other 21 did not assess neurocognitive function at 4-months. Lower levels of Tie-2 (OR = 0.999, 90% CI 0.998-1.000, P = .062), and higher levels of MIP-1b (OR = 1.022, 90% CI 1.000-1.044, P = .093), CCL-17 (OR = 1.004, 90% CI 1.001-1.006, P = .029), and IL-1α (OR = 1.597, 90% CI 1.077-2.367, P = .05) before PCI were correlated with neurocognitive decline at 4-months. Decrease of VEGF-C (OR = 0.972, 90% CI 0.949-0.996, P = .055), CCL-17 (OR = 0.993, 90% CI 0.988-0.999, P = .036), IL-1α (OR = 0.788, 90% CI 0.635-0.979, P = .071), and VEGF (OR = 0.981, 90% CI 0.965-0.997, P = .051) 3-days post-initiating PCI were also associated with neurocognitive decline at 4-months. ConclusionsBiomarker levels before PCI and changes in their levels 3-days post-initiating PCI may be linked to subsequent neurocognitive decline at 4-months. If validated, these biomarkers could be used to predict the risk of neurocognitive decline and act as a decision aid for personalized PCI in SCLC.

Hippocampal avoidance whole-brain radiotherapy with simultaneous integrated boost in lung cancer brain metastases and utility of the Hopkins verbal learning test for testing cognitive impairment in Chinese patients: a prospective phase II study

BackgroundThis study aimed to evaluate the efficiency of hippocampal avoidance whole-brain radiotherapy with a simultaneous integrated boost (HA-WBRT-SIB) treating brain metastases (BM) and utility of the Hopkins Verbal Learning Test-Revised (HVLT-R) (Chinese version) in Chinese lung cancer patients.MethodsLung cancer patients with BM undergone HA-WBRT-SIB at our center were enrolled. Brain magnetic resonance imaging, The HVLT total learning score, and side effects were evaluated before radiotherapy and 1, 3, 6, and 12 months after radiotherapy. This study analyzed the overall survival rate, progression-free survival rate, and changes in HVLT-R immediate recall scores.ResultsForty patients were enrolled between Jan 2016 and Jan 2020. The median follow-up time was 14.2 months. The median survival, progression-free survival, and intracranial progression-free survival of all patients were 14.8 months, 6.7 months and 14.8 months, respectively. Multivariate analysis indicated that male sex and newly diagnosed stage IV disease were associated with poor overall survival and progression-free survival, respectively. HVLT-R scores at baseline and 1, 3, and 6 months after radiotherapy were 21.94 ± 2.99, 20.88 ± 3.12, 20.03 ± 3.14, and 19.78 ± 2.98, respectively. The HVLT-R scores at 6 months after radiotherapy decreased by approximately 9.8% compared with those at baseline. No grade 3 toxicities occurred in the entire cohort.ConclusionsHA-WBRT-SIB is of efficiency and cognitive-conserving in treating Chinese lung cancer BM.Trial registrationThis study was retrospectively registered on ClinicalTrials.gov in 24th Feb, 2024. The ClinicalTrials.gov ID is NCT06289023.

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.

A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1–10 Brain Metastases

AimsTo assess in patients with 1–10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. Materials and methodsA multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. ResultsThe trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. ConclusionA phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.

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.

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 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) postradiotherapy. 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 test, Hopkins verbal learning test-revised, and trail making test were used to objectively measure ND. A comprehensive set of potential clinical and dose-volume measures on several brain structures were considered for statistical modeling. 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. Fifty percent, 44.5%, and 42.7% of the patients developed ND at 6-month, 1-year, and 2-year time points, respectively. The 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 V20 Gy ≥ 20% (OR = 3.53), brainstem volume ≥ 26 cc (OR = 0.39), and hypothalamus volume ≥ 0.5 cc (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) time points. 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.