Neuropsychological Test Performance Research Articles

Single-value brain activity scores reflect both severity and risk across the Alzheimer's continuum.

Single-value scores reflecting the deviation from (FADE score) or similarity with (SAME score) prototypical novelty-related and memory-related functional magnetic resonance imaging (fMRI) activation patterns in young adults have been proposed as imaging biomarkers of healthy neurocognitive aging. Here, we tested the utility of these scores as potential diagnostic and prognostic markers in Alzheimer's disease (AD) and risk states like mild cognitive impairment (MCI) or subjective cognitive decline (SCD). To this end, we analyzed subsequent memory fMRI data from individuals with SCD, MCI, and AD dementia as well as healthy controls (HC) and first-degree relatives of AD dementia patients (AD-rel) who participated in the multi-center DELCODE study (N = 468). Based on the individual participants' whole-brain fMRI novelty and subsequent memory responses, we calculated the FADE and SAME scores and assessed their association with AD risk stage, neuropsychological test scores, CSF amyloid positivity, and ApoE genotype. Memory-based FADE and SAME scores showed a considerably larger deviation from a reference sample of young adults in the MCI and AD dementia groups compared to HC, SCD and AD-rel. In addition, novelty-based scores significantly differed between the MCI and AD dementia groups. Across the entire sample, single-value scores correlated with neuropsychological test performance. The novelty-based SAME score further differed between Aβ-positive and Aβ-negative individuals in SCD and AD-rel, and between ApoE ε4 carriers and non-carriers in AD-rel. Hence, FADE and SAME scores are associated with both cognitive performance and individual risk factors for AD. Their potential utility as diagnostic and prognostic biomarkers warrants further exploration, particularly in individuals with SCD and healthy relatives of AD dementia patients.

Cardiopulmonary rehabilitation’s influence on cognitive functions, psychological state, and sleep quality in long COVID-19 patients: A randomized controlled trial

ABSTRACT Background: Cognitive impairment, brain fog, depressive symptoms, and sleep disturbance are prevalent symptoms among individuals with long COVID, for which there currently is no treatment. Aim: To assess the effectiveness of an eight-week cardiopulmonary rehabilitation programme on cognition, psychological well-being, and sleep quality in individuals with long COVID-19. Methods: Forty participants diagnosed with long COVID-19 (26 female, 14 male participants; mean age 53 ± 11 years) were randomly assigned to a rehabilitation group or to a control group. The control group maintained their regular daily habits, while the rehabilitation group was prescribed an individualized clinical programme consisting of three sessions per week. Each session involved light to moderate aerobic exercise, resistance training, and respiratory exercises. Neuropsychological tests evaluating executive function, memory, and processing speed were administered at baseline and at study completion. Participants also completed questionnaires on their psychological state and sleep quality at both time points. Results: No difference between groups was observed for neuropsychological test performance, however significant group differences in perceived stress and depression were found post-intervention. Conclusion: Cardiopulmonary rehabilitation was shown to be effective in individuals suffering from long COVID in terms of decreasing perceived stress and depression levels but not for neuropsychological test performance. ClinicalTrials.gov NCT05035628. Trial registration: ClinicalTrials.gov identifier: NCT05035628..

145 Encoding Brain Dynamics: Neuropsychological Test Scores as Predictors of iEEG Spectral Features in Epilepsy

INTRODUCTION: Intracranial EEG is a valuable tool for investigating the neural mechanisms underlying medically refractory epilepsy (MRE). Despite the advances made in understanding the condition, there is a lack of research exploring the relationship between iEEG data and neuropsychological test performance in MRE patients. METHODS: We performed a retrospective analysis of resting-state iEEG data from 70 MRE patients, extracting spectral features from 4.4 million 10-second time windows across 5201 electrodes. Using MATLAB and FieldTrip toolbox, we processed the data and used two brain atlases for probabilistic electrode assignment. Neuropsychological test scores were corrected for demographic factors. Relationships between preoperative neuropsychological test scores and spectral features were explored using nested hierarchical generalized linear mixed effects (GLME) models, focusing on the hippocampus. RESULTS: We found significant associations between neuropsychological tests and hippocampal power spectral densities (PSDs). Rey Auditory verbal learning test (RAVLT) recognition correct and short-term retention percentages were significantly associated with relative power (RP) in the beta-range (p < 0.05, FDR-corrected). The Boston naming test and Trail Making Test (TMT)-A finishing time showed significant associations with high-beta/low-gamma PSD (p < 0.05, FDR-corrected). TMT-B errors are positively correlated with delta/theta RP (p < 0.05, FDR-corrected). CONCLUSIONS: Our study provides novel insights into the relationship between iEEG spectral features and neuropsychological test performance in MRE patients. The findings suggest that the heterogeneity in spectral features may explain relevant cognitive performance, highlighting the biological basis and circuits of neuropsychological testing.

Cancer-related cognitive impairment and wellbeing in patients with newly diagnosed aggressive lymphoma compared to population norms and healthy controls: an exploratory study

PurposeThere has been little dedicated research on cancer-related cognitive impairment in patients with aggressive lymphoma. We describe and compare patients’ cognitive function with that of healthy controls and patients’ wellbeing and distress with general population values. We also explore associations between patients’ neuropsychological test performance and self-reported cognitive function and distress.MethodsSecondary analysis of data from a feasibility study of 30 patients with newly diagnosed aggressive lymphoma and 72 healthy controls. Patients completed neuropsychological tests and self-report measures before and 6–8 weeks after chemotherapy. Healthy controls completed neuropsychological tests and the FACT-Cog at enrolment and 6 months later. Mixed models were used to analyze neuropsychological test and FACT-Cog scores. One-sample t-tests were used to compare patients’ self-reported wellbeing and distress with population norms. Associations were explored with Kendall’s Tau b.ResultsPatients and healthy controls were well matched on socio-demographics. Differences between neuropsychological test scores were mostly large-sized; on average, patients’ scores on measures of information processing speed, executive function, and learning and memory were worse both before and after chemotherapy (all p ≤ 0.003). The same pattern was observed for impact of perceived cognitive impairment on quality-of-life (both p < 0.001). Patients’ physical and emotional wellbeing scores were lower than population norms both before and after chemotherapy (all p ≤ 0.018). Associations between neuropsychological performance and other measures were mostly trivial (all p > 0.10).ConclusionFor many patients with aggressive lymphoma, impaired neuropsychological test performance and impact of perceived impairments on quality-of-life precede chemotherapy and are sustained after chemotherapy. Findings support the need for large-scale longitudinal studies with this population to better understand targets for interventions to address cognitive impairments.

Reliability of clinical judgment for evaluation of informed consent in mental health settings and the validation of the Evaluation of Informed Consent to Treatment (EICT) scale.

The competence assessment to give informed consent in the legal and healthcare settings is often performed merely through clinical judgment. Given the acknowledged limited reliability of clinician-based evaluation in the mental health sector, particularly for the assessment of competence to consent, our objective was to ascertain the dependability of clinical judgment when evaluating the ability of schizophrenia patients to make choices about their health. The potential convergence between clinical evaluation and scores from a new standardized assessment (the "Evaluation of Informed Consent to Treatment" - "EICT" scale) was therefore tested. The scale assesses four dimensions of competence, specifically how patients normally understand information relating to care (Understanding); how they evaluate the choice of treatment in terms of risk/benefit ratio (Evaluating); how they reason coherently in the decision-making process (Reasoning); and, finally, their ability to make a choice between treatment alternatives (Expressing a choice). Thirty-four outpatients with schizophrenia were evaluated for their competence to consent by five referring clinicians with different backgrounds (psychiatrist, forensic psychiatrist, geriatrician, anesthetist, and medico-legal doctor). Inter-raters variability was tested through correlation analyses between the scores obtained by the clinicians on a modified version of the Global Assessment of Functioning scale (GAF) designed specifically to subjectively assess functioning in each of the four competence dimensions. Two validated competence scales (Mac-CAT-T, SICIATRI-R), and a neuropsychological battery were also administered along with scales for evaluating neuropsychiatric symptoms severity and side effects of medication. Clinical judgments of the individual specialists showed great inter-rater variability. Likewise, only weak/non-significant correlations were found between the EICT subscales and the respective clinicians-rated GAF scales. Conversely, solid correlations were found between the EICT and MacCAT-T subscales. As expected, healthy controls performed better in the ability to give informed consent to treatment, as measured by the three scales (i.e., EICT, MacCAT-T, and SICIATRI-R), and neuropsychological test performance. In the comparisons between patients who, according to the administered EICT, were able or not able to give informed consent to treatment, significant differences emerged for the Phonemic verbal fluency task (p = 0.038), Verbal judgments (p = 0.048), MacCAT-T subscales, and SICIATRI-R total score. Moreover, EICT exhibited excellent internal consistency (Cronbach's alphas ranging from 0.96 to 0.98 for the four subscales) while the Item Analysis, by measuring the correlation between each item of the EICT and the total score, was excellent for all items of all subscales (alphas ranging from 0.86 to 0.98). In conclusion, our findings highlighted that the assessment of competence exclusively through clinical judgment is not fully reliable and needs the support of standardized tools. The EICT scale could therefore be useful in assessing general competence to consent both in healthcare and legal contexts, where it might be necessary to evaluate the effective competence of patients with psychiatric disorders. Finally, this scale could serve as a valuable tool for decisions regarding whether and to what extent a patient needs support.

The influence of early life socio-environmental factors on executive performance in a healthy adult sample.

Attempts have been made (with research efforts encouraged) to deconstruct the "race" concept into language, cultural, and life experience variables that can help explain performance differences found between ethnic groups (Romero et al., 2009). The extant empirical literature reveals that early environmental factors and life experiences (e.g., socioeconomic status) are related to cognitive test performance in adulthood (Byrd et al., 2006). This study examined the explanatory value of early life childhood resources in the relationship between ethnicity and neuropsychological test performance in adulthood. Neurologically and psychologically healthy African American (n = 40), Caucasian (n = 14), and Hispanic (n = 107) college students ranging from 19-38 years of age. On average, participants had completed around 13 years of education, indicating that the majority were in the early stages of their undergraduate studies and mostly consisted of females (72%). Each participant completed a comprehensive neuropsychological battery that included tests of executive function and an extensive background questionnaire. A one-way analysis of variance (ANOVA) revealed that the CA group was significantly older (F (2, 160) = 18.38, p = .045) compared to the AA and H groups, but the groups did not differ in terms of number of years of educations or gender. Also, an ANOVA revealed significant group test performance differences on the Stroop-C [F (2, 160) = 1.53, p = .047], but not on the TMT-B and COWAT. Furthermore, a Tukey post hoc revealed that there were no significant differences in test performance on Stroop-C between the groups. Hierarchical multiple regression analyses revealed that group performance differences on executive function tests were medium or non-existent and only partially explained by years of education and early life financial resources. The results are discussed in light of the existing literature, study strengths and limitations, as well as directions for future research. This research can aid in pinpointing variables crucial for interpreting differences in neuropsychological assessments among diverse populations, holding potential implications for intervention research and policy settings. It is particularly relevant in the context of the continuously evolving social, political, and economic landscapes of societies.

Micro-RNA profiles of pathology and resilience in posterior cingulate cortex of cognitively intact elders.

The posterior cingulate cortex (PCC) is a key hub of the default mode network underlying autobiographical memory retrieval, which falters early in the progression of Alzheimer's disease (AD). We recently performed RNA sequencing of post-mortem PCC tissue samples from 26 elderly Rush Religious Orders Study participants who came to autopsy with an ante-mortem diagnosis of no cognitive impairment but who collectively displayed a range of Braak I-IV neurofibrillary tangle stages. Notably, cognitively unimpaired subjects displaying high Braak stages may represent cognitive resilience to AD pathology. Transcriptomic data revealed elevated synaptic and ATP-related gene expression in Braak Stages III/IV compared with Stages I/II, suggesting these pathways may be related to PCC resilience. We also mined expression profiles for small non-coding micro-RNAs (miRNAs), which regulate mRNA stability and may represent an underexplored potential mechanism of resilience through the fine-tuning of gene expression within complex cellular networks. Twelve miRNAs were identified as differentially expressed between Braak Stages I/II and III/IV. However, the extent to which the levels of all identified miRNAs were associated with subject demographics, neuropsychological test performance and/or neuropathological diagnostic criteria within this cohort was not explored. Here, we report that a total of 667 miRNAs are significantly associated (rho > 0.38, P < 0.05) with subject variables. There were significant positive correlations between miRNA expression levels and age, perceptual orientation and perceptual speed. By contrast, higher miRNA levels correlated negatively with semantic and episodic memory. Higher expression of 15 miRNAs associated with lower Braak Stages I-II and 47 miRNAs were associated with higher Braak Stages III-IV, suggesting additional mechanistic influences of PCC miRNA expression with resilience. Pathway analysis showed enrichment for miRNAs operating in pathways related to lysine degradation and fatty acid synthesis and metabolism. Finally, we demonstrated that the 12 resilience-related miRNAs differentially expressed in Braak Stages I/II versus Braak Stages III/IV were predicted to regulate mRNAs related to amyloid processing, tau and inflammation. In summary, we demonstrate a dynamic state wherein differential PCC miRNA levels are associated with cognitive performance and post-mortem neuropathological AD diagnostic criteria in cognitively intact elders. We posit these relationships may inform miRNA transcriptional alterations within the PCC relevant to potential early protective (resilience) or pathogenic (pre-clinical or prodromal) responses to disease pathogenesis and thus may be therapeutic targets.

Neuropsychological characteristics of drug resistant epilepsy patients with and without comorbid functional seizures

IntroductionNeuropsychological testing is a mandatory component in the evaluation of drug resistant epilepsy. The results of testing may assist with both the localization of an epilepsy as well as assessment of surgical risk. Previous studies have demonstrated differences in the neuropsychological performance of patients with epilepsy and functional seizures. We hypothesized that comorbid functional seizures could potentially influence neuropsychological test performance. Therefore, we evaluated whether there is a difference in the neuropsychological test results between drug resistant epilepsy patients with and without comorbid functional seizures. MethodNeuropsychological test results were compared between 25 patients with drug resistant focal epilepsy and 25 patients that also had documented functional seizures. Univariate analyses and multiple logistic regression models were used to both assess performance differences between the groups and to assess whether test results could be used to accurately identify which patients had comorbid functional seizures. ResultsEpilepsy patients with comorbid functional seizures performed significantly worse on the FAS Verbal Fluency Test compared to ES patients (p = 0.047). Digit Span Backwards (p = 0.10), Digit Span Forwards (p = 0.14) and Working Memory Index (p = 0.10) tended to be lower in the epilepsy and functional seizures group but was not statistically significant. A multiple logistic regression model using the results of four neuropsychological tests was able to identify patients with comorbid functional seizures with 83.33% accuracy. ConclusionsThere are appeared to be some differences in the neuropsychological performance among drug resistant epilepsy patients based on whether they have comorbid functional seizures. These findings may have relevant implications for the interpretation of neuropsychological test results.

A network approach to subjective cognitive decline: Exploring multivariate relationships in neuropsychological test performance across Alzheimer's disease risk states

Subjective cognitive decline (SCD) is characterized by subjective concerns of cognitive change despite test performance within normal range. Although those with SCD are at higher risk for developing further cognitive decline, we still lack methods using objective cognitive measures that reliably distinguish SCD from cognitively normal aging at the group level. Network analysis may help to address this by modeling cognitive performance as a web of intertwined cognitive abilities, providing insight into the multivariate associations determining cognitive status. Following previous network studies of mild cognitive impairment (MCI) and Alzheimer's dementia (AD), the current study centered upon the novel visualization and analysis of the SCD cognitive network compared to cognitively normal (CN) older adult, MCI, and AD group networks. Cross-sectional neuropsychological data from CIMA-Q and COMPASS-ND cohorts were used to construct Gaussian graphical models for CN (n = 122), SCD (n = 207), MCI (n = 210), and AD (n = 79) groups. Group networks were explored in terms of global network structure, prominent edge weights, and strength centrality indices. CN and SCD group networks were contrasted using the Network Comparison Test. Results indicate that CN and SCD groups did not differ in univariate cognitive performance or global network structure. However, measures of strength centrality, principally in executive functioning and processing speed, showed a CN-SCD-MCI gradient where subtle differences within the SCD network suggest that SCD is an intermediary between CN and MCI stages. Additional results may indicate a distinctiveness of network structure in AD, a reversal in network influence between age and general cognitive status as clinical impairment increases, and potential evidence for cognitive reserve. Together, these results provide evidence that network-specific metrics are sensitive to cognitive performance changes across the dementia risk spectrum and can help to objectively distinguish SCD group cognitive performance from that of the CN group.

Change in Neuropsychological Test Performance Seen in a Longitudinal Study of Patients With Post-acute Sequelae of COVID-19: A 6-Month Follow-up Study

BackgroundPost-acute sequelae of COVID-19 (PASC) may include physical, psychiatric, and neurocognitive symptoms. Few studies of cognitive symptoms have been longitudinal, with many following participants briefly after infection, relying on subjective complaints, screening instruments, or computerized testing. This group previously reported diminished neuropsychological (NP) test performance in over half of 60 individuals tested in-person 7 months post-COVID-19, particularly those seeking care for cognitive complaints. The current study describes the intial and 6-month follow-up results of an expanded cohort of 75 participants. MethodsParticipants underwent NP, psychiatric, and medical assessments approximately 7 months after acute COVID-19 infection. Sixty-three (84%) returned approximately 6 months later for repeat evaluation. ResultsAt the initial visit, 29 (38.7%) met criteria for low NP performance and 16 (21.3%) met criteria for extremely low NP performance. At 6-month follow-up, several NP domains which were significantly below normative values at the initial visit were no longer abnormal, with the exception of language. Only measures of delayed memory and fatigue showed significant improvements between the two time points. Discussion/ConclusionA substantial proportion of individuals recovered from acute COVID-19 infection have persistent neuropsychiatric symptoms over 1 year after infection. While the overall sample in this study showed some improvement in NP test performance relative to norms, only fatigue and delayed memory improved significantly between times one and two. No individual declined in NP test performance, though relatively few individuals made significant clinical improvement, indicating the need for serial neuropsychiatric assessment and treatment supports. Longitudinal follow-up of this cohort is in progress.

Behavior Rating Inventory of Executive Function in Preschool (BRIEF-P) and Attention-Deficit and Hyperactivity Disorders (ADHD): A Systematic Review and Meta-Analysis of Floor and Ceiling Effects.

ADHD is a neurodevelopmental disorder that is accompanied by executive challenges. To obtain evidence of the usefulness of the BRIEF-P and to analyze the possible ceiling and floor effect of its scores in the assessment of executive function in preschoolers with signs compatible with a possible diagnosis of ADHD. A search was performed in Science Direct, NCBI (PubMed), and ProQuest Education Journals during the period 2012-2022. We included studies that evaluated samples of individuals with symptomatology compatible with ADHD, with an age range between 2 and 6 years, published in English or Spanish. Of a total of 2538 articles, only seven met the inclusion criteria. The risk of bias was assessed using the QUADAS-2 questionnaire. The main variables were age and executive functioning. Executive deficits in early-age individuals with symptoms compatible with ADHD are more extensive than just deficits in working memory. A floor effect has been found in tests associated with hot executive functions and a ceiling effect in cold executive functions. This makes it necessary to use different tests to assess executive performance in preschoolers with ADHD-compatible symptomatology and to design intervention proposals accordingly. The BRIEF-P is an instrument that facilitates obtaining a sensitive and discriminative executive profile, although it should be used in combination with other neuropsychological performance tests.

Examining the validity of the Mini-Mental State Examination (MMSE) and its domains using network analysis.

The Mini-Mental State Examination (MMSE) is the most widely used standardised screener for impairments across a range of cognitive domains. However, the degree to which its domains (orientation, registration, attention, recall, language, and visuospatial) capture cognitive functioning measured using standardised neuropsychological tests is unclear. A longitudinal research design with four biannual assessments over a 6-year period was used with an initial sample of 1037 older adults (aged above 70 years). Participants completed MMSE and neuropsychological tests at each assessment. Network analysis was utilised to investigate unique associations among the MMSE and its domains and neuropsychological test performance at each time point. The total MMSE and two of its domains, language and recall, were associated with neuropsychological memory performance. The MMSE orientation, registration and visuospatial domains did not have any unique associations with neuropsychological performance. No stable internal interconnections between MMSE domains were found over time. The association of total MMSE as well as its recall domain with neuropsychological memory performance remained very similar over the 6-year period. The present study adds evidence to the validity of the MMSE and supports the clinical usage of the MMSE, whereby the total score is used for screening patients with or without cognitive impairments, with repeated administration to monitor cognitive changes over time, to inform intervention. However, the tool is not able to diagnose the cases for changes in specific cognitive domains and as such, should not replace a complete neuropsychological assessment.

Bilingual neurocognitive resiliency, vulnerability, and Alzheimer’s disease biomarkers in Latino older adults enrolled in the Health and Aging Brain Study‐Health Disparities (HABS‐HD)

AbstractBackgroundAlthough bilingualism has been associated with cognitive reserve and a later age of dementia onset (e.g., Alladi et al., 2013, 2017; Bialystok et al., 2007, 2010; de Leon et al., 2020), the effects of bilingualism on neuropsychological test performance in bilinguals with and without cognitive impairment have not yet been thoroughly investigated (e.g., Briceño et al., 2021; Cherner et al., 2021; Padilla et al., 2016).MethodThe present study explored patterns of cognitive performance and impairment across a large sample of bilingual and monolingual Latino older adults from the Health and Aging Brain: Health Disparities cohort (O’Bryant et al., 2021). In addition to examining differences between bilinguals and monolinguals, the associations between specific bilingual factors (i.e., dominance and age of acquisition) and cognitive performance were examined in order to elucidate which components of the bilingual experience explain such associations.ResultBilingual speakers demonstrated a pattern of cognitive resiliency in the form of better performance on attention/processing speed that can be observed across the cognitively unimpaired (Trails A, p = .001; Trails B, p = .02; Digit Substitution p = .004, and Logical Memory I p = .04) and mild cognitive impairment (Trails A, p &lt; .001 and Digit Substitution, p &lt; .02) diagnostic spectrum. In contrast, bilingual speakers demonstrated a pattern of cognitive vulnerability in the form of poorer performance and higher rates of impairment on a language measure that is only evident in the MCI phase (letter fluency, p = .001). Follow‐up analyses revealed bilinguals that 1) had a later age of language acquisition or 2) unbalanced language dominance performed more poorly on cognitive testing (Table 1) and had higher rates of impairment (Table 2). Exploratory analyses revealed that bilinguals with impaired language scores demonstrated lower levels of plasma Ab 42/40 relative (indicative of greater AD pathology) to unimpaired bilinguals (p = .02; Figure 1).ConclusionResults suggest that patterns of cognitive performance and impairment differ as a function of bilingualism. Bilingual factors must be considered in clinical and research investigations centered on evaluating cognitive outcomes of Latino older adults.

Examination of plasma YKL‐40 as a clinical biomarker for Alzheimer’s disease

AbstractBackgroundBlood biomarkers represent a potential non‐invasive and cost‐effective strategy for the clinical detection and monitoring of neurodegenerative conditions including Alzheimer’s disease (AD). YKL‐40 is a secreted glycoprotein associated with inflammatory processes, and elevated cerebrospinal fluid levels have been observed in AD and other neurodegenerative conditions. Fewer studies have examined plasma YKL‐40. We examined relationships between plasma YKL‐40 and clinical indices of AD in a large cross‐sectional sample from a clinical cohort registry.MethodThe sample included 569 participants from the Boston University Alzheimer’s Disease Research Center, including participants with normal cognition (NC; n = 235), mild cognitive impairment due to suspected AD (MCI; n = 181), and AD dementia (n = 153). Blood plasma samples were analyzed using standard ELISA methods; values were log transformed and standardized into z‐scores. Cross‐sectional analyses investigated the relationships between YKL‐40 and clinical indices of functioning including diagnostic status, dementia severity (on the Clinical Dementia Rating scale [CDR]), and neuropsychological test performance. Age, sex, education, race, and APOE ε4 carrier status were included as covariates in all analyses.ResultNo significant differences in plasma YKL‐40 were observed between participants with NC, MCI, and AD dementia after accounting for covariates. The comparison between MCI and dementia was marginally significant (p = .07), with an adjusted mean difference of Z = 0.19. For participants with dementia (CDR scores 1‐3), non‐significant trends were observed for relationships between plasma YKL‐40 values and dementia severity, including for Sum of Boxes (Pearson partial correlation: r = .14, p = .10) and Total Score (ordinal logistic regression: OR = 1.38; 95% CI: [0.98,1.93]), p = .06. Modest but significant correlations were observed between YKL‐40 and performance on 4/12 neuropsychological tests including Animal Fluency (r = ‐.10), Vegetable Fluency (r = ‐.09), and Neuropsychological Assessment Battery List Learning Trials 1‐3 (r = ‐.10) and Short Delay (r = ‐.12).ConclusionPlasma YKL‐40 biomarker levels were modestly related to neuropsychological assessments of language and memory but not significantly related to cognitive diagnosis of AD or dementia severity. This biomarker may reflect underlying inflammatory processes in the context of AD. However, the use of plasma YKL‐40 to assess the presence and severity of AD in a larger cross‐sectional sample size, and using a multiple biomarker approach, warrant further study.

Toward optimizing measurement of self‐perceived cognitive function ‐ a global expert survey on behalf of the SCD‐I Working Group

AbstractBackgroundAssessment of self‐perceived cognitive decline (SCD) is relevant in the context of Alzheimer’s disease and related disorders, but heterogeneity in measurement limits its interpretability and usability. Selection of optimal content for a questionnaire measuring SCD requires statistical information and expert opinion to ensure reliability as well as acceptability and feasibility. This study aims to survey experts about their perspectives on essential features of SCD measurement.MethodThe survey was distributed through the ISTAART Subjective Cognitive Decline PIA, International Neuropsychological Society’s Dementia Special Interest Group, and authors’ professional networks. Targeted experts included professionals working with older adults with SCD through research and/or clinical practice. Main topics were item content, item format, and questionnaire features. Topics were evaluated with multiple choice questions and open‐ended questions. Furthermore, experts were shown items from existing SCD questionnaires with relatively high information value as identified in a previous statistical harmonization effort using Item Response Theory analyses (see Rabin et al., 2021), and asked to select items they viewed as most relevant. Frequency analyses were performed.ResultNinety‐one experts (66% female) across four continents completed the questionnaire (Table 1). Thirty‐nine experts (43%) indicated routinely using an instrument to assess SCD (17 different instruments were mentioned). Seventy‐nine experts (87%) perceived a need for a harmonized SCD instrument. Whereas most experts (72%) responded that a questionnaire should measure both current ability and change in ability, views on the most relevant timeframe varied substantially (top choices: past year (33%) and past six months (25%)). Figure 1a and 1b show that items with the highest statistical information value were not necessarily selected as most relevant by experts. Preferred practical features of a questionnaire were availability of an informant version and coverage of multiple cognitive domains (chosen by 13% and 14% respectively). Preferred validation approaches were distinguishing psychiatric illness from neurodegenerative disorders and the correlation with neuropsychological test performance (both chosen by 20%).ConclusionDespite agreeing on the need for a harmonized SCD instrument, experts express varying views on optimal content, format, and validation approaches. The complementary information derived from statistical results and expert opinion can facilitate more comprehensive measurement of SCD.

Subtypes of complex regional pain syndrome-a systematic review of the literature.

To systematically identify and summarize possible subtypes of complex regional pain syndrome (CRPS), we searched MEDLINE, Embase, Cochrane, Scopus, and Web of Science for original studies reporting or investigating at least one subtype within a group of patients with CRPS. The search retrieved 4239 potentially relevant references. Twenty-five studies met our inclusion criteria and were included in the analysis. Complex regional pain syndrome phenotypes were investigated based on the following variables: clinical presentation/sensory disturbances, dystonia, skin temperature, disease duration, onset type, CRPS outcome, and neuropsychological test performance. Support was found for the following CRPS subtypes: CRPS type I, CRPS type II, acute CRPS, chronic CRPS, centralized CRPS, cold CRPS, warm CRPS, inflammatory CRPS, dystonic CRPS, nondystonic CRPS, familial CRPS, and nonfamilial CRPS. It is unclear whether these are distinct or overlapping subtypes. The results of this comprehensive review can facilitate the formulation of well-defined CRPS subtypes based on presumed underlying mechanisms. Our findings provide a foundation for establishing and defining clinically meaningful CRPS subtypes, with the ultimate goal of developing targeted and enhanced treatments for CRPS.

Bilingualism in the Clinical Diagnosis of Mild Cognitive Impairment and Dementia

AbstractBackgroundNeuropsychological assessments determine the presence of cognitive impairment in Alzheimer’s Disease and Related Dementias (ADRD). These tests are susceptible to the influence of cultural and linguistic variables. Bilingualism is a potential contributor to cognitive reserve in elderly individuals. Positive effects of bilingualism have been observed in executive function tasks, while negative effects have been reported on verbal fluency tests. Maintaining two active languages may modify cognitive and brain reserve among bilinguals, but evidence is inconsistent and contradictory. We investigated the relationship between bilingualism and neuropsychological test performance in aging participants from the 1Florida ADRC using a longitudinal design.MethodsWe studied 238 Latino older adults (age 71.79 ± 8.01 years old, 65% female). 158 Latino participants were Spanish‐English bilinguals; 80 were Spanish monolinguals. Bilingualism was assessed by a proficiency questionnaire. Six cognitive composites were developed (Figure 1). We investigated cognitive test change scores between language group, visit (2 visits: M = 14.61 months; SD = 3.52), and diagnosis (normal, MCI, dementia) using 2×2×3 repeated measures ANCOVAs (age and level of education). Cognitive scores were correlated with frontal and temporal brain volumes in bilinguals and monolinguals separately.ResultsMain effects of the diagnostic group and visit were significant for all composites (ps &lt; .001), with the dementia group showing the lowest scores. No significant main effect of Bilingualism was observed for any of the composites. An interaction between visit and bilingualism was seen for the Trail Making Test B‐ A. Three‐way interactions were found between diagnostic groups, visit, and bilingualism for the Verbal composite and the Logical Memory delay subtest (part of the Memory composite). A more significant decline in the monolingual groups was observed, more so in the dementia group. Significant correlations were found between most composites in both language groups, being more related to the temporal than frontal lobe areas, using MRI volumetric measures.ConclusionBilingualism seems to interact with cognitive decline in aging. It is essential to consider the individual’s level of bilingualism to obtain an accurate assessment of cognitive impairment. The interaction of bilingualism with other sociodemographic and cognitive variables will be discussed.

S16: Post-Acute Covid-19 Cognitive Sequelae in an Aging Population

S16: Post-Acute Covid-19 Cognitive Sequelae in an Aging Population

Cross‐cultural properties of the Cross‐cultural Dementia Screening test and the European Cross‐Cultural Neuropsychological Test Battery

AbstractBackgroundCross‐cultural neuropsychological tests are essential to avoid potential cultural biases during the performance and score interpretation in diverse populations. We aimed to compare the performance of healthy controls in the Cross‐cultural Dementia Screening test and the European Cross‐Cultural Neuropsychological Test Battery in the majority and minority populations living in Spain.MethodThree hundred cognitively healthy participants were enrolled (58% women, age range 18‐90). One hundred from majority population (Spaniards), one hundred from minority population from Colombia, and one hundred from different minority populations, including participants from Latin America (66%, excluding participants from Colombia), Spaniards of Romani (gipsy) ethnicity (14%), Arab League (10%), and East Europe (10%). We matched the three groups controlling for sex, age, and level of education. All scores on CCD and CNTB were compared and correlated with an acculturation scale, controlling for age and years of education.ResultThere were no differences between groups in most of the items. Only processing speed measures of the CCD (Sun‐Moon test) and verbal fluency tasks of the CNBT showed statistically significant differences between groups. Scores on the acculturation scale were not associated with the neuropsychological test performance of all participants.ConclusionThe absence of differences between groups or acculturation influence on the scores supports the favourable cross‐cultural properties of the CCD and the CNTB. However, some tasks could still be more influenced, especially those associated with processing speed and verbal fluency, which suggests the need to further study and develop new tests and paradigms with better cross‐cultural properties.

Neuroticism is associated with entorhinal cortex volume in cognitively unimpaired older adults

AbstractBackgroundNeuroticism, the tendency toward negative mood states, is associated with Alzheimer’s Disease (AD) and tau pathology within entorhinal cortex (EC) in mild cognitive impairment and healthy older adults. However, studies of the link between neuroticism and structural neurodegeneration of EC have been negative. This may result from failure to account for subsyndromal affective symptoms or previous psychiatric history, as neuroticism is closely related to mood conditions that in turn, affect similar brain regions vulnerable to AD. We examined the association between neuroticism and EC volume while accounting for cognition, affective symptoms, and other personality traits in cognitively unimpaired (CU) older adults without history of major psychiatric conditions.Method42 CU adults (age = 71.1 years, 27 females) with normal neuropsychological test performance and no known neurological conditions and current or past psychiatric disorders completed Geriatric Depression Scale, State‐Trait Anxiety Inventory, NEO Five‐Factor Inventory‐3 which assesses neuroticism, openness, conscientiousness, extraversion, and agreeableness, Montreal Cognitive Assessment (MoCA), and structural magnetic resonance imaging of whole brain at 3T. Regression analyses examined the unconditional ability of neuroticism to predict bilateral EC volume, and while considering the potential contribution of cognition (MoCA, California Verbal Learning Test Delayed Recall), affective state, other personality traits, and age, gender, and education. P&lt;.10 was set as the significance threshold for β estimates.ResultIn univariable modelling, neuroticism was predictive of left EC volume (β = ‐17.4, p = .025), explaining 9.8% of its variability [F(1, 40) = 5.45, p = .025]. Neuroticism remained a significant predictor of left EC volume (β = ‐1.9, p = .045) after factoring in demographic, cognitive and affective/personality variables. Additional left EC predictors were extraversion and state anxiety (β = ‐2.61, p = .01; β = 1.71, p = .045 respectively). Neuroticism was not predictive of right EC in univariable or multivariable modelling, but agreeableness emerged as a significant predictor (β = ‐1.68, p = .091).ConclusionNeuroticism was predictive of left EC volume in CU adults without current or past history of psychiatric disorders, independent of cognition, affect, and other personality traits. These findings, which have not been previously reported, extend previous epidemiological evidence of increased AD risk due to neuroticism and suggest the importance of considering the impact of mood symptoms and psychiatric history in this context.