Sensory Impairment and Algorithmic Classification of Early Cognitive Impairment in Middle-Aged and Older Adults

Sensory function has been linked to cognitive impairment and dementia, but the link between multiple sensory impairments and early cognitive impairment (ECI) is unclear. Sensory function (vision, hearing, vestibular, proprioception, and olfaction) was measured in 390 BLSA participants (age=75±8 years; 57% women; 69% white) from 2012 to 2018 over a mean 3.6 years. ECI was defined based on 1 standard deviation below age-and race-specific means in Card Rotations or California Verbal Learning Test immediate recall. Cox proportional hazard models examined the risk of ECI for each sensory impairment and across categories of impairments. Vision impairment (vs. no vision impairment) was associated with a 70% greater risk of ECI (HR=1.70, p=0.05). Participants with 1 or ≥2 sensory impairments had triple the risk of ECI (HR=3.74 and 3.44, p=0.008 and 0.02, respectively) compared to those without impairment. Future studies are needed to examine whether treatment for sensory impairments can modify these risks.

Derivation and Validation of an Algorithmic Classification of Early Cognitive Impairment

The long prodromal period for dementia pathology demands valid and reliable approaches to detect cases before clinically recognizable symptoms emerge, by which time it may be too late to effectively intervene. We derived and compared several algorithms for early cognitive impairment (ECI) using longitudinal data on 1704 BLSA participants. Algorithms were based on cognitive impairment in various combinations of memory and non-memory tests, and the CDR. The best-performing algorithm was defined based on 1SD below age-and race-specific means in Card Rotations or California Verbal Learning Test immediate recall, two tests that in prior work show the earliest declines prior to dementia onset. While this ECI algorithm showed low concordance with concurrent adjudicated MCI/dementia (AUC: 0.63, sensitivity: 0.54, specificity: 0.73), it was among the best predictors of progression to MCI/dementia (HR: 3.65, 95% CI: 1.69,7.87). This algorithm may be useful in epidemiologic work to evaluate risk factors for early cognitive impairment.

Disease Correlates of Rim Lesions on Quantitative Susceptibility Mapping in Multiple Sclerosis

Quantitative susceptibility mapping (QSM), an imaging technique sensitive to brain iron, has been used to detect paramagnetic rims of iron-laden active microglia and macrophages in a subset of multiple sclerosis (MS) lesions, known as rim+ lesions, and are consistent with chronic active lesions. Because of their potential impact on disease progression and tissue damage, investigating the influence of rim+ lesions on disability and neurodegeneration is critical to establish the impact of these lesions on the disease course. This study aimed to explore the relationship between chronic active rim+ lesions, identified as having a hyperintense rim on QSM, and both clinical disability and imaging measures of neurodegeneration in patients with MS. The patient cohort was composed of 159 relapsing-remitting multiple sclerosis patients. The Expanded Disability Status Scale (EDSS) and Brief International Cognitive Assessment for Multiple Sclerosis, which includes both the Symbol Digit Modalities Test and California Verbal Learning Test-II, were used to assess clinical disability. Cortical thickness and thalamic volume were evaluated as imaging measures of neurodegeneration. A total of 4,469 MS lesions were identified, of which 171 QSM rim+ (3.8%) lesions were identified among 57 patients (35.8%). In a multivariate regression model, as the overall total lesion burden increased, patients with at least one rim+ lesion on QSM performed worse on both physical disability and cognitive assessments, specifically the Symbol Digit Modalities Test (p=0.010), California Verbal Learning Test-II (p=0.030), and EDSS (p=0.001). In a separate univariate regression model, controlling for age (p<0.001), having at least one rim+ lesion was related to more cortical thinning (p= 0.03) in younger patients (< 45 years). Lower thalamic volume was associated with older patients (p=0.038) and larger total lesion burden (p<0.001); however, the association did not remain significant with rim+ lesions (p=0.10). Our findings demonstrate a novel observation that chronic active lesions, as identified on QSM, modify the impact of lesion burden on clinical disability in MS patients. These results support further exploration of rim+ lesions for therapeutic targeting in MS to reduce disability and subsequent neurodegeneration.

Examining Delayed Recall in Cochlear Implant Users Using the Montreal Cognitive Assessment, California Verbal Learning Test, Third Edition, and Item Specific Deficit Approach: Preliminary Results

Purpose: Recent studies using the Montreal Cognitive Assessment (MoCA) suggest delayed recall is challenging for cochlear implant (CI) users. To better understand the underlying processes associated with delayed recall in CI users, we administered the MoCA and the California Verbal Learning Test, Third Edition (CVLT-3), which provides a more comprehensive assessment of delayed recall ability.Methods: The MoCA and CVLT-3 were administered to 18 high-performing CI users. For the CVLT-3, both the traditional scoring and a newer scoring method, the Item-Specific Deficit Approach (ISDA), were employed.Results: The original MoCA score and MoCA delayed recall subtest score did not relate to performance on any CVLT-3 measures regardless of scoring metric applied (i.e., traditional or ISDA). Encoding performance for both the CVLT-3 and ISDA were related. Consolidation, which is only distinctly defined by the ISDA, related to CVLT-3 cued delay recall performance but not free delay recall performance. Lastly, ISDA retrieval only related to CVLT-3 measures when modified.Conclusion: Performance on the MoCA and CVLT-3 in a high performing CI patient population were not related. We demonstrate that the ISDA can be successfully applied to CI users for the quantification and characterization of delayed recall ability; however, future work addressing lower performing CI users, and comparing to normal hearing controls is needed to determine the extent of potential translational applications. Our work also indicates that a modified ISDA retrieval score may be beneficial for evaluating CI users although additional work addressing the clinical relevance of this is still needed.

Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study

Background: Aerobic exercise training (physical activity for improving cardiorespiratory fitness) represents a promising approach for managing cognitive impairment in multiple sclerosis (MS). However, there is limited evidence that levels of physical activity and fitness are associated with cognition in progressive MS. Objective: We examined associations among cardiorespiratory fitness, moderate-to-vigorous physical activity (MVPA), and cognitive performance in a large, international progressive MS sample. Methods: Two hundred forty European and North American persons with progressive MS underwent cardiorespiratory fitness measurement on a recumbent stepper, wore an ActiGraph GT3X + accelerometer for 7 days for measuring MVPA, and underwent the Brief International Cognitive Assessment in MS. Results: Cardiorespiratory fitness was not significantly correlated with Symbol Digit Modalities Test (SDMT; r = −0.01; r = −0.04), California Verbal Learning Test-II (CVLT-II; r = 0.05; r = 0.05), or Brief Visuospatial Memory Test–Revised (BVMT-R; r = −0.14; r = −0.14) z-scores controlling for age, sex, and education. MVPA and SDMT ( r = 0.05), CVLT-II ( r = −0.07), and BVMT-R ( r = 0.01) z-scores were not significantly correlated. Conclusion: Cardiorespiratory fitness and MVPA were not associated with cognition in this large progressive MS sample, yet these outcomes represent critical manipulation checks for documenting the success of the CogEx trial. This highlights the importance of examining other exercise-related mechanisms-of-action for improving cognition in progressive MS.

The Comparison Between Neuropsychological Features of Psychogenic Non-epileptic Seizures and Epileptic Seizures

Background: Both epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) are often associated with some degree of cognitive impairment. Video electroencephalography (EEG) monitoring is the gold standard for diagnosing PNES. This diagnostic procedure is costly and available in specific tertiary centers. Neuropsychological assessment can provide clues for the differential diagnosis of PNES and ES and help clarify the nature and etiology of these two disorders. Objectives: Therefore, this study aimed to compare the neuropsychological profiles of PNES and ES patients. Methods: In this analytical cross-sectional study, 30 patients with ES and 31 patients with PNES were compared by neuropsychiatric tests, such as the Wechsler Adult Intelligence scale (WAIS), Addenbrooke’s Cognitive examination (ACE), and California Verbal Learning test (CVLT). Results: There was a female predominance in the PNES group (female-to-male ratio = 4.16/1, P = 0.003). In the PNES group, 77.4% of the patients had a psychiatric disorder versus 66.7% of the patients in the ES group; however, the difference was not statistically significant (P = 0.34). The mean score of total intelligence was higher in the PNES group (84.77 ± 16.94), compared to the ES group (83.63 ± 10.04); however, the difference was not significant (P = 0.75). Based on the mean subscale scores, the digit symbol score (WAIS-IV subscale) and memory score (ACE subscale) were significantly higher in the PNES group compared to the ES group (P = 0.037 and 0.032, respectively). Conclusions: This study showed that neuropsychological assessments might not differentiate ES from non-epileptic seizures.

A-143 Sorry, I Wasn’t Paying Attention. The Moderating Role of Auditory Attention on the Relationship between Age and Verbal Learning

Objective Attentional difficulties are known to negatively impact learning (Hervey et al., 2004; Alderson et al., 2013). This study builds upon previous work examining the effect of sustained visual attention as a moderator of age and learning (Thomas et al., 2019) by examining performance on an auditory attention measure as a moderator of the relationship between age and performance on a verbal list-learning task. Method Archival data from 424 adults (Mage = 36.01, SD = 15.13) were collected at an outpatient clinic. Auditory attention was assessed via the Brief Test of Attention (BTA) raw score. Learning was assessed via the California Verbal Learning Test (CVLT-II) total T-Score (Trials 1–5). Results Results of a hierarchical linear regression indicated a significant effect between BTA and learning, (β = 0.287, F(1, 422) = 17.993, p &lt; 0.001, ΔR2 = 0.078). There was no significant effect between age and learning, (β = 0.022, F(1, 422) = 0.204, p = 0.652, ΔR2 = 0.000). Additional results from a simple moderated regression analysis indicated a significant overall model between age, learning and BTA (F(3, 420) = 15.749, p &lt; 0.001, ΔR2 = 0.1011) with BTA having a significant positive interaction effect on the relation between age and learning (β = 0.816, F(1, 420) = 10.436, p = &lt; 0.001, ΔR2 = 0.022). Conclusion Sustained attention has been shown to be an important consideration when assessing verbal learning and memory performance. Present results demonstrate that when accounting for age, auditory attention is a significant positive predictor of performance on measures of verbal learning. Additionally, confirming prior research, performances on auditory attention and verbal learning measures are positively correlated.

Investigating the Residual Effects of Chronic Cannabis Use and Abstinence on Verbal and Visuospatial Learning

Rationale: Regular cannabis users have been shown to differ from non-using controls in learning performance. It is unclear if these differences are specific to distinct domains of learning (verbal, visuospatial), exacerbate with extent of cannabis exposure and dissipate with sustained abstinence.Objective: This study examines different domains of learning (verbal, visuospatial) in current and abstaining cannabis users, and the role of chronicity of use.Methods: In a cross-sectional design, we examined 127 psychiatrically healthy participants (65 female) with mean aged of 34 years. Of these, 69 individuals were current regular cannabis users (mean 15 years use), 12 were former cannabis users abstinent for ~2.5 yrs (after a mean of 16 years use), and 46 were non-cannabis using controls. Groups were compared on verbal learning performance assessed via the California Verbal Learning Test (CVLT-II) and for visuospatial learning measured with the Brown Location Test (BLT). We explored the association between CVLT/BLT performance and cannabis use levels in current and former users.Results: Current cannabis use compared to non-use was associated with worse performance on select aspects of verbal learning (Long Delay Cued Recall) and of visuospatial learning (Retroactive Interference and LD Rotated Recall). Prolonged abstinence was associated with altered verbal learning but intact visuospatial learning. There were non-significant correlations between distinct cannabis use measures, age and learning in both current and former users.Conclusions: Our findings suggest cannabis use status (current use, former use) affects different domains of learning (verbal and visuospatial) in a distinct fashion. These findings might be accounted for in the design of cognitive interventions aimed to support abstinence in cannabis users.