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An acquired brain injury (ABI) is a neurological pathology that generates a physical injury in the brain. These include cerebrovascular accidents (CVA) and traumatic brain injuries (TBI). Brain injuries can cause cognitive, emotional, and social problems, which have the potential to severely alter a person’s independence and quality of life. Loneliness, thesubjective experience of social isolation, has been shown to be the best predictor of mental health problems and poorquality of life in patients with ABI. This study aimed to explore the relationship between cognitive, emotional, and social determinants and loneliness in Puerto Ricans with ABI in the chronic phase.
Participants and Methods:
Cross-sectional, exploratory, and correlational methods were implemented. Assessments included the Frontal Systems Behavioral Scale - Spanish version (FrSBe-SP), Perth Emotional Reactivity Scale -Spanish version (PERS), Anticipated Stigma and Concealment (ASC), and the University of California Los Angeles - Loneliness Scale (UCLA-LS).
Results:
A total of seventeen participated (n=17). Twenty-nine percent of participants were female. Forty-seven percent had history of previous CVA and fifty-two percent had history of TBI. Correlational analyses suggest a positive and significant relationship between executive dysfunction (FrSBe-SP) and feelings of loneliness (UCLA-LS) (p=.601), as well as a positive and significant relationship between neuroticism-negative emotional reactivity (PERS) and feelings of loneliness (UCLA-LS) (p=.736). Correlational analysis suggests there is no significant relationship between anticipated stigma (ASC) and feelings of loneliness (UCLA-LS) (p=.282).
Conclusions:
Our findings suggest that there is a significant relationship between cognitive determinants (executive functions) and emotional determinants (neuroticism) with feelings of loneliness in people with a history of ABI. These results support the connection between executive dysfunction, the tendency to experience negative emotions, and the subjective experience of loneliness, consistent with previous studies. However, our study did not find any significant relationship between interactional determinants, such as stigma and concealment, and loneliness. Understanding the role of cognition, emotions, and social variables in reported feelings of loneliness is important for clinical neuropsychological assessment and rehabilitation interventions.
Executive function (EF) is a self-regulatory construct well-established as a predictor of long-term academic achievement and socioemotional functioning in children (Best et al., 2009; Diamond, 2013; Zelazo & Carlson, 2020). Traumatic brain injury (TBI) in childhood frequently results in EF deficits (Beauchamp & Anderson, 2013; Levin & Hanten, 2005). In comparison to adults (Okonkwo et al., 2013), there is an absence of viable blood biomarkers for pediatric TBI to assist in diagnosis and prognosis. Osteopontin (OPN), an inflammatory cytokine, has recently been identified as a putative pediatric TBI blood biomarker (Gao et al., 2020). However, more work is needed to establish OPN’s utility in predicting functional outcomes. Thus, the present study aimed to test relations between OPN measured during the first 72 hours of hospitalization and EF 6-12 months post injury among a sample of pediatric TBI patients.
Participants and Methods:
Sample consisted of 38 children (age at injury = 4.60-16.67 years, M age = 10.61 years, 65.8% male, lowest Glasgow Coma Scale [GCS] score = 3-15, M gcs= 9.97) with TBI whose parents completed the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2; Gioia et al., 2015) 6-12 months post injury. Plasma OPN was measured at hospital admission, 24 hours after admission, 48 hours after admission, and 72 hours after admission. 7-scores for each BRIEF-2 clinical scale (Inhibit, Self-Monitor, Shift, Emotional Control, Initiate, Working Memory, Plan/Organize, Task-Monitor, Organization of Materials) and composite index (Behavior Regulation Index, Emotion Regulation Index, Cognitive Regulation Index, Global Executive Composite) were used in analyses.
Results:
Correlation analyses revealed large positive associations (rs = .50-.73, ps = <.001.039) between 48-hour OPN and all BRIEF-2 scales/indices except Initiate. OPN at 24 hours positively correlated with Task-Monitor (r = .40, p = .037). Bivariate logistic regression analyses testing whether OPN predicted at least mildly elevated BRIEF-2 t-scores (>60) did not yield significant associations. Additional supplementary analyses testing whether alternative injury markers - glial fibrillary acidic protein (GFAP), ubiquitin C-terminal Hydrolase-L1 (UCH-L1), S100 calcium binding protein B (S100B) - measured at all time points as well as lowest GCS score correlated with EF revealed the following: admission S100B positively correlated with Inhibit (r = .34, p = .045), 48-hour UCH-L1 negatively correlated with Initiate (r = -.49, p = .041) and Cognitive Regulation Index (r = -.48, p = .044), and 72-hour UCH-L1 negatively correlated with Initiate (r = -.47, p = .048).
Conclusions:
Findings showed higher OPN at 48 hours post admission was broadly related to worse parent-reported EF 6-12 months later, with 24-hour OPN also showing limited associations. Higher levels of alternative injury markers likewise showed limited associations with EF outcomes. Null logistic regression findings may be due to few participants having elevated BRIEF-2 scores. Disrupted EF development may be more noticeable after longer time periods as children age and self-regulatory demands increase. Overall, OPN was found to more consistently predict EF outcomes than GCS score and other injury markers. This could be because OPN is a marker of inflammation, which may be particularly predictive of TBI cognitive outcomes.
Assessment of medication management, an instrumental activity of daily living (IADL), is particularly important among Veterans, who are prescribed an average of 2540 prescriptions per year (Nguyen et al., 2017). The Pillbox Test (PT) is a brief, performance-based measure that was designed as an ecologically valid measure of executive functioning (EF; Zartman, Hilsabeck, Guarnaccia, & Houtz, 2013), the cognitive domain most predictive of successful medication schedule management (Suchy, Ziemnik, Niermeyer, & Brothers, 2020). However, a validation study by Logue, Marceaux, Balldin, and Hilsabeck (2015) found that EF predicted performance on the PT more so than processing speed (PS), but not the language, attention, visuospatial, and memory domains combined. Thus, this project sought to increase generalizability of the latter study by replicating and extending their investigation utilizing a larger set of neuropsychological tests.
Participants and Methods:
Participants included 176 patients in a mixed clinical sample (5.1% female, 43.2% Black/African American, 55.7% white, Mage = 70.7 years, SDage = 9.3, Medu = 12.6 years, SDedu = 2.6) who completed a comprehensive neuropsychological evaluation in a VA medical center. All participants completed the PT where they had five minutes to organize five pill bottles using a seven-day pillbox according to standardized instructions on the labels. Participants also completed some combination of 26 neuropsychological tests (i.e., participants did not complete every test as evaluations were tailored to disparate referral questions). Correlations between completed tests and number of pillbox errors were evaluated. These tests were then combined into the following six domains: language, visuospatial, working memory (WM), psychomotor/PS, memory, and EF. Hierarchical multiple regression was completed using these domains to predict pillbox errors.
Results:
Spearman’s correlation coefficients indicated that 25 tests had a weak to moderate relationship with PT total errors (rs = 0.23 -0.51); forward digit span was not significantly related (rs = 0.13). A forced-entry multiple regression was run to predict PT total errors from the six domains. The model accounted for 29% of the variance in PT performance, F(6, 169) = 11.56, p < .001. Of the domains, psychomotor/PS made the greatest contribution, f(169) = 2.73, p = .007, followed by language, f(169) = 2.41, p = .017, and WM, f(169) = 2.15, p = .033. Visuospatial performance and EF did not make significant contributions (ps>.05). Next, two hierarchical multiple regressions were run. Results indicated that EF predicted performance on the PT beyond measures of PS, AR2 = .02, p = .044, but not beyond the combination of all cognitive domains, AR2 = .00, p = .863.
Conclusions:
Results of this study partially replicated the findings of Logue et al. (2015). Namely, EF predicted PT performance beyond PS, but not other cognitive domains. However, when all predictors were entered into the same model, visuospatial performance did not significantly contribute to the prediction of pillbox errors. These results suggest that providers may benefit from investigating medication management abilities when deficits in PS, WM, and/or language are identified. Further research is needed to better understand which domains best predict PT failure.
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that results in progressive decline in motor function in all patients and cognitive impairment in a subset of patients. Evidence suggests that cognitive reserve (CR) may protect against cognitive and motor decline in ALS, but less is known about the impact of specific occupational skills and requirements on clinical outcomes in ALS. We expected that a history of working jobs with more complex cognitive demands would protect against cognitive decline, while jobs that require fine and complex motor skills would protect against motor dysfunction.
Participants and Methods:
Participants were 150 ALS patients recruited from the University of Pennsylvania’s Comprehensive ALS Center. Participants underwent clinical and neuropsychological evaluations within 1 year of ALS diagnosis. Cognitive performance was measured using the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), which includes ALS-Specific (e.g., verbal fluency, executive functions, language, social cognition) and NonSpecific (e.g., memory, visuospatial functions) composite scores. Motor functioning was measured using the Penn Upper Motor Neuron (UMN) scale and the ALS Functional Rating Scale (ALS-FRS). Occupational skills and requirements for each participant were assessed using data from the Occupational Information Network (O*NET) Database. O*NET data were assessed using principal components analysis, and 17 factor scores were derived representing distinct worker characteristics (n=5), occupational requirements (n=7), and worker requirements (n=5). These scores were entered as independent variables in multiple linear regression models using ECAS, UMN, and ALS-FRS scores as dependent variables covarying for education.
Results:
Preserved ECAS ALS-Specific performance was associated with jobs that involve greater reasoning abilities (ß=2.03, S.E.=0.79, p<.05), analytic skills (ß=3.08, S.E.=0.91, p<.001), and humanities knowledge (ß=1.20, S.E.=0.58, p<.05), as well as less exposure to environmental hazards (ß=-2.42, S.E.=0.76, p<.01) and fewer demands on visualperceptual (ß=-1.75, S.E.=0.73, p<.05) and technical skills (ß=-1.62, S.E.=0.63, p<.05). Preserved ECAS Non-Specific performance was associated with jobs that involve greater exposure to conflict (ß=0.82, S.E.=0.33, p<.05) and social abilities (ß=0.65, S.E.=0.29, p<.05). Jobs involving greater precision skills (ß=1.92, S.E.=0.79, p<.05) and reasoning ability (ß=2.10, S.E.=0.95, p<.05) were associated with greater disease severity on the UMN, while jobs involving more health services knowledge were associated with worse motor functioning on the ALS-FRS (ß=-1.30, S.E.=0.60, p<.05).
Conclusions:
Specific occupational skills and requirements show protective effects on cognitive functioning in ALS, while others confer risk for cognitive and motor dysfunction. Preserved cognitive functioning was linked to a history of employment in jobs requiring strong reasoning abilities, social skills, and humanities knowledge, while poorer cognitive functioning was linked to jobs involving a high risk of exposure to environmental hazards and high visuo-perceptual and technical demands. In contrast, we did not find evidence of motor reserve, as no protective effects of occupational skills and requirements were found for motor symptoms, and jobs involving greater precision skills, reasoning abilities, and health services knowledge were linked to worse motor functioning. Our findings offer new insights into how occupational history may protect against cognitive impairment or confer elevated risk for cognitive and motor dysfunction in ALS.
Existing research has demonstrated that neuropsychiatric/behavioral-psychological symptoms of dementia (BPSD) frequently contribute to worse prognosis in patients with neurodegenerative conditions (e.g., increased functional dependence, worse quality of life, greater caregiver burden, faster disease progression). BPSD are most commonly measured via the Neuropsychiatric Inventory (NPI), or its briefer, informant-rated questionnaire (NPI-Q). Despite the NPI-Q’s common use in research and practice, there is disarray in the literature concerning the NPI-Q’s latent structure and reliability, possibly related to differences in methods between studies. Also, hierarchical factor models have not been considered, even though such models are gaining favor in the psychopathology literature. Therefore, we aimed to compare different factor structures from the current literature using confirmatory factor analyses (CFAs) to help determine the best latent model of the NPI-Q.
Participants and Methods:
This sample included 20,500 individuals (57% female; 80% White, 12% Black, 8% Hispanic), with a mean age of 71 (SD = 10.41) and 15 average years of education (SD = 3.43). Individuals were included if they had completed an NPI-Q during their first visit at one of 33 Alzheimer Disease Research Centers reporting to the National Alzheimer Coordinating Center (NACC). All CFA and reliability analyses were performed with lavaan and semTools R packages, using a diagonally weighted least squares (DWLS) estimator. Eight single-level models using full or modified versions of the NPI-Q were compared, and the top three were later tested in bifactor form.
Results:
CFAs revealed all factor models of the full NPI-Q demonstrated goodness of fit across multiple indices (SRMR = 0.039-0.052, RMSEA = 0.025-0.029, CFI = 0.973-0.983, TLI = 0.9670.977). Modified forms of the NPI-Q also demonstrated goodness of fit across multiple indices (SRMR = 0.025-0.052, RMSEA = 0.0180.031, CFI = 0.976-0.993, TLI = 0.968-0.989). Top factor models later tested in bifactor form all demonstrated consistently stronger goodness of fit regardless of whether they were a full form (SRMR = 0.023-0.035, RMSEA = 0.015-0.02, CFI = 0.992-0.995, TLI = 0.985-0.991) or a modified form (SRMR = 0.023-0.042, RMSEA = 0.015-0.024, CFI = 0.985-0.995, TLI = 0.9770.992). Siafarikas and colleagues’ (2018) 3-factor model demonstrated the best fit among the full-form models, whereas Sayegh and Knight’s (2014) 4-factor model had the best fit among all single-level models, as well as among the bifactor models.
Conclusions:
Although all factor models had adequate goodness of fit, the Sayegh & Knight 4-factor model had the strongest fit among both single-level and bifactor models. Furthermore, all bifactor models had consistently stronger fit than single-level models, suggesting that BPSD are best theoretically explained by a hierarchical, non-nested framework of general and specific contributors to symptoms. These findings also inform consistent use of NPI-Q subscales.
The accurate assessment of instrumental activities of daily living (iADL) is essential for those with known or suspected Alzheimer's disease or related disorders (ADRD). This information guides diagnosis, staging, and treatment planning, and serves as a critical patient-centered outcome. Despite its importance, many iADL measures used in ADRD research and practice have not been sufficiently updated in the last 40-50 years to reflect how technology has changed daily life. For example, digital technologies are routinely used by many older adults and those with ADRD to perform iADLs (e.g., online financial management, using smartphone reminders for medications.) The purpose of the current study was to a) asses the applicability of technology-related iADL items in a clinical sample; b) evaluate whether technology-based iADLs are more difficult for those living with ADRD than their traditional counterparts; and c) test if adding technology-based iADL items changes the sensitivity and specificity of iADL measures to ADRD.
Participants and Methods:
135 clinically referred older adults (mean age 75.5 years) undergoing neuropsychological evaluation at a comprehensive multidisciplinary memory clinic were included in this study [37% with mild cognitive impairment (MCI) and 51.5% with dementia]. Collateral informants completed the Functional Activities Questionnaire (FAQ; Pfeffer, 1982) as well as 11 items created to parallel the FAQ wording that assessed technology-related iADLs such as digital financial management (i.e. online bill pay), everyday technology skills (i.e. using a smartphone; remembering a password), and other technology mediated activities (i.e. visiting internet sites; online shopping).
Results:
Care partners rated tech iADLs items as applicable for the majority of items. For example, technology skill items were applicable to 90.4% of the sample and online financial management questions were applicable for 76.4% of participants. Applicability ratings were similar across patients in their 60's and 70's, and lower in those over age 80. Care partners indicated less overall impairment on technology-related iADLs (M =1.22, SD =.88) than traditional FAQ iADLs (M =1.36, SD = .86), t(129) = 3.529, p =.001). A composite of original FAQ paperwork and bill pay items (M = 1.62, SD = 1.1) was rated as more impaired than digital financial management tasks (M = 1.30, SD = 1.09), t(122) = 4.77, p <.001). In terms of diagnostic accuracy, tech iADL items (AUC= .815, 95% CI [.731, -.890]) appeared to perform comparably to slightly better than the traditional FAQ (AUC =.788, 95% CI [.705, .874]) at separating MCI and dementia, though the difference between the two was not statistically significant in this small pilot sample.
Conclusions:
Technology is rapidly changing how older adults and those with ADRD perform a host of iADLs. This pilot study suggests broad applicability of tech iADL to the lives of those with ADRD and highlights how measurement of these skills may help identify trends in iADL habits that may help to mitigate the impact of ADRD on daily functions. Further, this data suggests the need to refine and improve upon existing iADL measures to validly capture the evolving technological landscape of those living with ADRD.
Accumulating evidence suggests that corpus callosum development is critically involved in the emergence of behavioral and cognitive skills during the first two years of life and that structural abnormalities of the corpus callosum are associated with a variety of neurodevelopmental disorders. Indeed by adulthood ∼30% of individuals with agenesis of the corpus callosum (ACC), a congenital condition resulting in a partial or fully absent corpus callosum, exhibit phenotypic features consistent with autism spectrum disorder (ASD). However, very little is known about developmental similarities and/or differences among infants with ACC and infants who develop ASD. This study describes temperament in infants with ACC during the first year of life in comparison with a neurotypical control group. Additionally, it examines the potential contribution of disrupted callosal connectivity to early expression of temperament in ASD through comparison to children with high familial likelihood of ASD.
Participants and Methods:
Longitudinal ratings of positive and negative emotionality were acquired at 6 and 12 months on the Infant Behavior Questionnaire-Revised across four groups of infants: isolated complete and partial ACC (n=104), high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=81, HL- n=282), and low-likelihood controls (LL- n=152).
Results:
Overall, the ACC group demonstrated blunted affect, with significantly lower positive and negative emotionality than LL controls at both timepoints. Specifically, the ACC group exhibited lower activity and approach dimensions of positive emotionality at both timepoints, with lower high-intensity pleasure at 6 months and lower vocal reactivity at 12 months. On negative emotionality subscales, the ACC group exhibited lower distress to limitations and sadness at both timepoints, as well as lower falling reactivity at 6 months. The ACC and HL groups did not differ significantly on positive emotionality at either timepoint. However, negative emotionality was lower in the ACC group than the HL- group at both timepoints and lower than the HL+ group at 12 months, with lower distress to limitations and sadness ratings than both HL groups at both timepoints.
Conclusions:
These findings highlight the importance of interhemispheric connections in facilitating active engagement and pursuit of pleasurable activities during the first year of life, as well as expression of sadness and distress to limitations. Notably, similarities between infants with ACC and infants at elevated familial risk of ASD suggest that disrupted callosal connectivity may specifically contribute to reductions in positive emotionality.
Risk factors that contribute to brain pathology and cognitive decline among older adults include demographic factors (e.g., age, educational attainment), genetic factors, health factors, and depression (Plassman et al., 2010). Variability within an individual’s performance across cognitive tasks is referred to as dispersion (Hultsch et al., 2002), which appears sensitive to subtle cognitive impairments associated with neurodegenerative pathology in older adults (Bangen et al., 2019; Kälin et al., 2014). Thaler and colleagues (2015) found that dispersion across domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was a useful indicator of cognitive changes associated with cardiovascular disease and mortality. Also, research by Manning and colleagues (2021) found that elevated ratings of depression and anxiety in older adults was associated with greater dispersion across neuropsychological testing. The present study aimed to replicate findings that greater dispersion in neuropsychological performance is associated with impaired neurocognitive performance and greater self-reported depression among older adults who present for neuropsychological evaluation with cognitive concerns.
Participants and Methods:
Neuropsychological testing data was obtained from a university hospital. Chart reviews were conducted on 369 participants who met initial criteria (60 years or older with testing data from the RBANS Form A, Wechsler Test of Adult Reading, and Geriatric Depression Scale [GDS]). Retrospective analyses were conducted on a final sample of 293 participants from 60 to 94 years old (Mage = 74.41, SDage = 7.43; 179 females, 114 males). Diagnoses were used for group comparisons between cognitively intact individuals with subjective cognitive complaints (SCC, n = 49), persons with Mild Neurocognitive Disorder (mND, n =137), and persons with Major Neurocognitive Disorder (MND, n = 107).
Results:
As expected, results indicated that higher dispersion was related to lower Total RBANS Scores (r = -0.54, p < .001) and significant differences across diagnostic groupings (F(2, 289) = 29.19, p < 0.001; SCC, mND, MND) indicated that variability in performance was an indicator of greater neurocognitive impairment. Contrary to expectations, greater dispersion was very weakly associated with lower reported depressive symptomatology (r = -0.13, p = 0.03). A three-stage hierarchical linear regression was conducted with the RBANS Coefficient of Variation (CoV) as the dependent variable and three predictor variables (Age, Total RBANS, Total GDS). The regression analysis results indicated that age was not a significant predictor, but both Total RBANS and GDS Scores were. The most important predictor was Total RBANS Scores which uniquely explained 21% of the variation in dispersion.
Conclusions:
This study adds to the current literature regarding the clinical utility of dispersion in neuropsychological performance as an indicator of early and subtle neurocognitive impairment. Depressive symptom reporting was expected to help predict the degree of variability, but this factor was only weakly associated with the RBANS CoV.
Limitations of this study include its retrospective use of archival data and the restricted range on some variables of interest. Further research is needed to examine the relative utility of different measures of dispersion and why increased cognitive performance variability is related to neurocognitive impairment and decline.
As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).
Participants and Methods:
The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.
Results:
The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.
Conclusions:
Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.
To investigate the informative value of nightmares on neurobehavioral functioning in individuals with mild traumatic brain injury (mTBI) beyond general sleep disturbance.
Participants and Methods:
A sample of 146 adults with mTBI (mean age = 45.1±16.0), recruited from a specialized concussion treatment center, underwent an assessment of neurobehavioral functioning using the Behavioral Assessment Screening Tool (BAST), self-reported habitual sleep disturbance and quality (via the Pittsburgh Sleep Quality Index; PSQI), and reported nightmare frequency in the past two weeks.
Results:
Nightmare frequency was the strongest predictor of negative affect (ß = .362, p <.001), anxiety (ß = .332, p <.001), and impulsivity (ß = .270, p <.001) after controlling for sex and age. Sleep disturbance accounted for the greatest variance in depression (ß = .493, p <.001), burden from concussion (ß = .477, p <.001), and fatigue (ß = .449, p <.001) after controlling for sex and age.
Conclusions:
Nightmares independently associate with neurobehavioral symptoms and likely have differential etiology from reported sleep disturbance. Nightmare frequency was more strongly related to positive neurobehavioral symptoms (i.e., added factors that impact functioning, e.g., anxiety), while general sleep disturbance was associated with negative neurobehavioral symptoms (i.e., factors taken away that impact functioning, e.g., lack of energy). Our findings suggest that neuropsychological evaluations of individuals with mTBI should assess for sleep disturbance and nightmare frequency as risk factors for neurobehavioral barriers to functioning.
Alzheimer’s disease (AD), a leading cause of dementia worldwide, affected an estimated 47 million people in 2015, placing a burden of over $1 trillion on health systems. Subclinical markers of AD pathology are seen many years before the clinical onset of dementia, suggesting that steps could be taken to prevent progression to disease in healthy individuals. Sleep optimizes cognition by creating a window of opportunity to consolidate memories, prune synaptic networks, and clear waste products. Studies that characterize the relationship between sleep and cognitive function prior to the onset of clinical AD could guide research into effective methods of delaying AD onset or preventing it altogether. The objective of our study is to describe how sleep quality and quantity correlate with performance on cognitive assessments within a healthy, aging population.
Participants and Methods:
Seventeen participants, between 62-82 years of age enrolled in an ongoing clinical trial assessing the effects of melatonin (5mg daily) versus placebo, were included in our study. Participants were observed over a 2-month period, during which no experimental interventions were administered. At study entry, participants underwent a comprehensive neuropsychological evaluation evaluating cognitive domains of attention, memory, speed of information processing, language, executive functioning, and mood. Afterwards, all participants wore a watch that measured actigraphy and light data (Philips Actiwatch Spectrum Pro actigraphy monitor) for 8 weeks to evaluate their sleep habits. Pearson and Spearman partial correlations were used to evaluate relationships between objective sleep parameters and baseline cognitive function test scores.
Results:
Aberrations of sleep length, sleep fragmentation, and daytime activity measures significantly correlated with cognitive performance on memory, language, visuospatial skills, and speed of processing tests (p = <0.05). Greater variability of awakenings at nighttime associated with better scores on memory tests but worse scores on language tests. Longer sleep times associated with worse language scores, while greater variability in daily activity correlated with poorer scores on visuospatial skills tests and speed of processing tests.
Conclusions:
This study establishes a framework for obtaining longitudinal sleep data in conjunction with serial cognitive function testing, encouraging further exploration into how sleep metrics affect specific domains of cognitive function. Findings suggest that having a less consistent sleep routine correlates with poorer cognitive function across multiple domains. The authors recommend broader analysis of actigraphy and cognitive function testing as objective measures of sleep and cognition in research and clinical practice.
Despite the rise in literacy, 773 million of the global population is estimated to be illiterate. The rate of illiteracy is even higher among women and older adults (OA). Literacy has been well documented to impact cognitive skills, and most neuropsychological tests developed are for individuals with higher education. Moreover, there is sparse research on cognitive process and performance of illiterate individuals across cognitive domains.
Per a 2011 census, the illiteracy rate in the Indian older adult population was as high as 56%, and within this group, women and older adults in rural regions were especially vulnerable. Thus, it is important to understand cognitive performance of illiterate Indian older adult population, especially when they are being assessed for neurodegenerative disorders.
Participants and Methods:
This study used subset of data from Harmonized Longitudinal Aging Study of India, Diagnostic Assessment of Dementia (LASI DAD), which was developed by the Gateway to Global Aging Data. A sample of cognitive healthy OA (n = 715) was selected based on Hindi Mental Status Exam score of >19 and a Clinical Dementia Rating Scale of 0 (literate = 419, illiterate = 296). Given the heterogeneity of the population, adapted cognitive instruments were used. This study compared memory performances, using word list and constructional praxis with delayed recall tasks, of OA based on their literacy status (illiterate vs. literate).
Results:
Literate cognitive healthy OA (M = 15.27, SD = 3.9) learned more words over three trials than illiterate OA (M = 12.17, SD = 3.7) on a world list task, a statistically significant difference (M = 3.1, 95% CI [2.5, 3.6], t (713) = 10.62, p<0.05. Literate OA (M = 8.7, SD = 2.2) had higher scores on task of copy of simple geometrical figures than illiterate OA (M = 5.3, SD = 2.8), a statistically significant difference (M = 3.3, 95% CI [2.9, 3.7], t (713) = 7.1, p<0.05. Literate OA (M = 4.5, SD = 1.8) also recalled more words than illiterate OA (M = 3.6, SD = 2.1) after a delay. Recall of geometric figures after a delay was higher for literate OA (M = 5, SD = 2.9) as well compared to illiterate OA (M = 2.4, SD = 2.5).
Conclusions:
Conclusion: In a sample of cognitively healthy Indian older adults, literate OA consistently performed better than illiterate OA on both verbal and nonverbal memory measures. This is consistent with past literature which shows that illiterate individuals take longer to learn verbal information and have lower recall. Additionally, use of geometric figure may be complicated for these individuals. These are important considerations when assessing an OA for memory problems with low or no education. Next steps would be to look at differences across other cognitive domains and also examining if cognitive differences exist in illiterate OA based on gender.
This study aimed to provide information about pathways to care and clinical response to community-based brief interventions for improving youth mental health through evaluating the Mindspace Mayo service.
Methods:
Participants were 1,184 individuals aged 12–25 years (Mean = 17.92, SD = 2.66) who engaged with the Mindspace service. Demographic information included gender, age and living situation. The Clinical Outcome in Routine Evaluation (CORE) was used to measure psychological distress before and after attending the Mindspace service between February 2015 and 2022.
Results:
On average, individuals received six sessions of therapeutic support. Analyses indicated that most referrals were made by either a parent (40%) or self-referral (38%). The most frequent reason for referral was mood and anxiety-related issues. Across the entire sample, reductions in CORE scores were both statistically and clinically significant. Neither the source of the referral nor living situation significantly predicted intervention response. Complexity of issues presented at referral significantly predicted a reduction in psychological distress post-intervention in young people aged over 17 years.
Conclusions:
This study highlighted the value of primary care mental health services for young people aged 12–25 years, and underlined the importance of recording electronic data to track referral pathways, reasons for referral and the intervention outcomes over time.
Parkinson’s disease (PD) is a neurodegenerative disorder affecting over 10 million people worldwide. PD is characterized by both motor (e.g., tremor, rigidity, and bradykinesia) and non-motor (including cognitive impairment and neuropsychiatric symptoms such as apathy, disinhibition, executive dysfunction) symptoms. Caregiver burden is prevalent in those providing care for patients with PD and can result in negative health complications. Past work shows associations between motor symptoms, cognitive impairment, neuropsychiatric symptoms, and caregiver burden in PD. However, their relative contributions are poorly understood. This study examined these relationships, hypothesizing that while motor symptoms, cognitive impairment, and neuropsychiatric symptoms would all affect caregiver burden, neuropsychiatric symptoms would predict burden above and beyond the contribution of the other factors
Participants and Methods:
Participants were 42 people living with PD who were assessed at a hospital-based tertiary movement disorders specialty clinic for deep brain stimulation (DBS) candidacy evaluation with their caregiver. Motor exam was assessed by a PD specialist using the Unified Parkinson’s Disease Rating Scale (UPDRS). The Mini Mental State Examination (MMSE) assessed global cognition. Frontal Systems Behavior Scale (FrSBe) Family Form captured caregiver ratings of neuropsychiatric symptoms under 3 subscales: apathy, disinhibition, and executive dysfunction. The Multidimensional Caregiver Strain Index (MCSI) captured caregiver burden. Linear regression analyses examined relationships between caregiver burden (MCSI) and motor symptoms (UPDRS), cognitive impairment (MMSE), and neuropsychiatric symptoms (FrSBe).
Results:
Using linear regression analyses, cognitive impairment (R2=0.08, F(1,41)=4.42, p=0.04) and neuropsychiatric symptoms (R2=0.35, F(1, 41)=21.0, p<0.01) predicted caregiver burden but motor symptoms did not (R2=0.03, F(1,41)=1.30, p=0.26). Hierarchical linear regression revealed that neuropsychiatric symptoms predicted caregiver burden above and beyond the contribution of cognitive impairment (AR2=0.28, AF(1)=12.7, p=0.001), accounting for an additional 28% of the variance in caregiver burden. Follow-up linear regression to examine the relationships between caregiver burden and the FrSBe subscales indicated that apathy (p<0.001), versus disinhibition (p=0.16) and dysexecutive behaviors (p=0.80), was the driver of the significant relationship.
Conclusions:
Consistent with our hypothesis, results revealed that cognitive impairment and neuropsychiatric symptoms (specifically apathy) were independent predictors of caregiver burden, with neuropsychiatric symptoms predicting caregiver burden above and beyond the contribution of cognitive impairment. Somewhat surprisingly, motor symptoms were not a predictor of caregiver burden contrary to some previous research, though findings are mixed. Results highlight the importance of assessing for neuropsychiatric symptoms in PD, which may be overlooked by care providers relative to motor or cognitive symptoms, but which appear stressful to caregivers. Future directions include reexamining results in a larger more heterogenous sample including people living with PD at different disease stages (i.e., everyone in the present sample had severe enough symptoms to be considering DBS). Cognitive measures of executive functioning (which are more specific to PD than measures of global cognition) should also be included in future works. Development of supportive caregiver interventions specifically targeting apathy in PD may be useful. Longitudinal designs would be helpful to reexamine relationships following DBS surgery, as there are some reports of increased neuropsychiatric symptoms following the procedure.
Traumatic brain injury (TBI) is a prevalent cause of long-term morbidity in children and adolescents and can lead to persistent difficulties with social and behavioral function. TBI may impact brain structures that support social cognition, social perception, and day-to-day social interactions—termed the social brain network (SBN). We examined differences in links among the SBN and regions of interest from other neural networks thought to support social outcomes, i.e., the default mode network (DMN) and salience network (SN). Furthermore, we examined how differences in co-activation among the SBN and these other key networks were associated with ratings of social and day-to-day adaptive outcomes.
Participants and Methods:
Participants included children and adolescents with moderate to severe TBI (msTBI; n=11, Mage=11.78, 6 male), complicated-mild TBI (cmTBI; n=12, Mage=12.59, 9 male), and orthopedic injury (OI; n=22, Mage=11.69, 15 male). Participants underwent resting-state functional MRI on a 3Tesla Siemens Prisma scanner. Parents rated their child’s social and adaptive function on the Child Behavior Checklist (CBCL) and Adaptive Behavior Assessment System-Third Edition (ABAS-3). Resting-state connectivity was assessed using the CONN Toolbox, including preprocessing, denoising, and alignment to the participants’ processed T1 MPRAGE sequence followed by seed-to-voxel analysis using a SBN mask and targeted regions of interest within the DMN and SN. Individual-level r-to-z correlations were extracted from resulting clusters of co-activation with the SBN mask and exported into SPSSv28.0 for integration with behavioral data.
Results:
One-way ANOVAs used to examine group differences in social and adaptive outcome revealed significant group differences in CBCL Social Competence (F=4.49, p=.019) and all composite scores on the ABAS-3 (Fs=3.78 to 5.17, ps=.031 to .010). In each domain, children with msTBI were rated as having elevated difficulties relative to cmTBI or OI, whereas cmTBI and OI groups did not differ. Connectivity also differed significantly between groups, with children with OI demonstrating greater connectivity between the SBN and the anterior cingulate cortex of the SN (t=5.19, p(FDR)<.0001) and posterior cingulate cortex of the DMN (f=4.30, p(FDR)<.001) than children with msTBI. Children with cmTBI also showed greater connectivity between the SBN and left temporal pole of the DMN (t=7.45, p(FDR)<.000001) than children with msTBI. Degree of connectivity between the SBN and posterior cingulate was significantly positively correlated across all domains of adaptive function (rs=.451 to .504, ps=.010 to .003), whereas degree of connectivity between the SBN and left temporal pole was strongly positively related to Social Competence (a=.633, p=.006) and conceptual adaptive skills on the ABAS (A=.437, p=.037).
Conclusions:
Our findings provide insights into the neural substrates of social and adaptive morbidity after pediatric TBI, particularly msTBI, by linking alterations in connectivity among the SBN, DMN, and SN with measures of social and adaptive outcome. While the posterior cingulate was broadly associated with adaptive outcome, the temporal pole was particularly strongly associated with social competence. This may reflect the diverse functions and high degree of interconnectivity of the posterior cingulate, which contributes to various cognitive and attentional processes, relative to the strong amygdala/limbic connections of the temporal pole.
Cognitive difficulties among diffuse glioma survivors are common in survivorship due to cancer treatment effects (i.e., surgery, chemotherapy, and/or radiation therapy), which can diminish quality of life. Routine monitoring of cognitive symptoms in survivorship is recommended and can help address patient needs and inform clinical interventions (e.g., cognitive rehabilitation). While several patient-reported outcome (PRO) measures have been used in brain tumor populations, there has been few studies comparing the performance of these PROs in patients with diffuse glioma. In order to better understand the value of different PROs, we conducted preliminary analyses associating cognitive PROs with neuropsychological impairment in a well-characterized sample of patients with diffuse glioma.
Participants and Methods:
23 glioma patients (mean aged 44.26 ± 12.24), six or more months after completing cancer treatment, underwent comprehensive psychosocial and neuropsychological assessments. The neuropsychological battery included the Hopkins Verbal Learning Test - Revised, Brief Visuospatial Memory Test - Revised, Wechsler Adult Intelligence Scale-IV tests of Coding and Digit Span, Trail-Making Test, Stroop Test, FAS, Animals, Boston Naming Test, and Rey-Osterrieth Complex Figure (copy). Completed cognitive PROs included the Functional Assessment of Cancer - Cognitive Function and Brain questionnaires (FACT-Cog; FACT-Br), the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire for Brain Neoplasms (EORTC QLQ-BN20), and the Multidimensional Fatigue Symptom Inventory, short form (MFSI-SF) Mental subscale. Based on published norms, we divided the sample into cognitively impaired and non-impaired groups (two or more primary neuropsychological test scores <= -2 z-score). We compared PRO scores between impaired and non-impaired groups using Mann-Whitney U tests. Higher medians equate to better cognitive functioning for all PROs, except for the MSFI-SF.
Results:
We found significantly worse scores in the impaired group compared to non-impaired group on the FACT-Cog subscales of perceived cognitive ability (PCA), [Non-Impaired (Mdn = 21, n = 11), Impaired (Mdn = 10, n = 12), U = 22.5, z = -2.68, = 0.007], perceived cognitive impairment (PCI), [Non-Impaired (Mdn = 59, n = 11), Impaired (Mdn = 44, n = 12), U = 32.5, z = -2.06, p=0.039]. The impaired group also trended towards worse scores on the FACT-Br additional concerns subscale [Non-Impaired (Mdn = 79.5, n = 10), Impaired (Mdn = 61, n = 12), U = 32.5, z = -1.81, p=0.07]. Group differences were not observed on the MSFI-SF [Non-Impaired (Mdn = 5, n = 11), Impaired (Mdn = 7, n = 12), U = 40.5, z = -1.57, p=0.12], or EORTC Cognitive Functioning subscale [Non-Impaired (Mdn = 83.33, n = 10), Impaired (Mdn = 75, n = 12), U = 42, z = -1.23, p=0.218].
Conclusions:
The preliminary findings suggest that the FACT-Cog, especially the PCA and PCI correspond with neuropsychological impairment among diffuse glioma survivors better than other cognitive PROs. The FACT-Br subscale was somewhat effective. The MFSI-SF Mental and EORTC Cognitive Functioning subscales did not correspond to impairment status. The FACT-Cog is a promising instrument and future work is needed to better determine relative utility of cognitive PROs in this population.
Discrimination on the basis of race, gender identity, and age, among others, has been associated with negative cognitive outcomes. However, the mechanisms by which perceived discrimination impacts cognition are not yet well understood. Discrimination can lead to chronic stress, which disrupts glucocorticoid pathways and induces susceptibility to metabolic dysregulation. On the basis of this prior work, and the known associations between metabolic syndrome and cognition, the current study examined the hypothesis that metabolic syndrome mediates the relationship between discrimination and cognition.
Participants and Methods:
1,063 adults (Mean age = 54.92 years, SD = 11.68) who participated in the Midlife in the United States project were included. Confirmatory factor analysis was used to examine the acceptability of a bifactor model of metabolic syndrome using four subfactors (insulin resistance, adiposity, dyslipidemia, and blood pressure). The mediating effect of the metabolic syndrome latent factor on the association between discrimination and cognition was tested using PROCESS (Hayes, 2013). Exploratory analyses were conducted to examine which cognitive domains and which metabolic syndrome subfactors were driving these relationships. Mediation analyses adjusted for age, race, sex, and education.
Results:
The three most frequently reported reasons for discrimination were gender (n = 209), age (n = 174), and race (n = 129). The CFA of metabolic symptoms was deemed acceptable based on previously outlined goodness of fit criteria (CFI = 0.986, TLI = 0.976, RMSEA = 0.040, SRMR = 0.034). Results of the mediation analysis indicated a significant indirect effect of major events discrimination on the total cognition composite through the general metabolic syndrome factor (B = -0.0029, 95% CI [-0.0016, -0.0066]). Further examination revealed that this relationship was driven through an indirect path of metabolic syndrome on the relationship between discrimination and executive functioning (B = -0.0024, 95% CI -0.0059, -0.0001]). We examined which subfactors were driving these relationships and found that there were significant indirect effects of major events discrimination on total cognition through the insulin resistance (B = -0.0028, 95% CI -0.0065, -0.0003]) and dyslipidemia factors (B = -0.0026, 95% CI -0.0064, -0.0002]).
Conclusions:
Our findings provide evidence that metabolic syndrome can help explain differences in cognitive functioning based on experiences of discrimination, even after adjusting for relevant demographic factors. Results from this study suggest that understanding the impact of perceived discrimination on metabolic syndrome and developing lifestyle interventions that can improve metabolic syndrome may be helpful in reducing stress-related cognitive disparities.
Improving the timeline for intervention in Alzheimer's disease (AD) has considerable potential to delay and mitigate disability and suffering. Neuropsychological assessment is useful for distinguishing AD from normal aging and other dementias but is less useful in preclinical detection due to its limited sensitivity. The N400 (N4), a language-based EEG event-related potential (ERP) related to semantic functioning, is a promising candidate marker of AD with potential to improve early detection and monitoring of AD. For example, studies have shown that individuals with AD show a reduced N4 "effect"—a smaller difference in the size of the N4 to semantically congruent vs. incongruent word-pairs. The goal of this study is to assess the presence of the N4 effect in healthy seniors, and those with amnestic mild cognitive impairment (MCI) or mild AD, and to evaluate associations between performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the N4 across these samples.
Participants and Methods:
Fifty older adults (intact=27, combined MCI/mild AD group=23; "impaired") completed neuropsychological testing, including the RBANS, as part of a larger study. Participants were re-contacted and returned for EEG assessment between several weeks to one year later. During EEG recording, participants completed a word-pair judgement paradigm, which involved distinguishing between semantically congruent and incongruent word-pairs. Data was collected and analyzed according to customized N4 analysis scripts provided as part of ERPCORE, an online resource for acquiring and analyzing common ERP components (Kappenman et al., 2021; https://osf.io/thsqg/). The change in N4 amplitude between congruent and incongruent trials (the N4 effect) was used as an index of participants' semantic functioning. Participants' N4 effect was quantified using the mean amplitude from 300-550 milliseconds poststimulus at electrode Cz.
Results:
Repeated measures ANOVAs indicated a significant effect of trial type on the N400 amplitude in the intact individuals (F(1, 26)=77.66, p<.001), which remained significant in the sample as a whole (F(1, 48)=65.18, p<.001). Although intact participants numerically showed a larger N4 effect (intact: M=-4.02, SD=2.37; impaired: M=-2.60, SD=3.40), the expected group-by-trial interaction was not significant (F(1, 48)=3.01, p=.089). Correlational analyses revealed no significant associations between the N4 effect and the RBANS Total Scale scores (r=-.14, p=.32), nor for the Immediate Memory (r=-.002, p=.99), Visuospatial/Constructional (r=-.069, p=.63), Language (r=-.15, p=.30) Attention (r=-.21, p=.14), or Delayed Memory (r=-.18 p=.58) indexes.
Conclusions:
Results confirmed the presence of the N4 effect in intact participants and in the sample as a whole. Although the N4 effect was numerically smaller in the impaired group as expected, this difference was not significant in the present sample. Likewise, we observed no evidence for associations between the size of N4 effect and performance on RBANS indexes. Overall, the present study provides mixed evidence for the utility of the N4 as a biomarker in mild AD. Factors that may have contributed to the lack of associations between the N4 effect and the RBANS include the limited sample size and variable lengths of time between participants' initial cognitive assessments and EEG testing.
Limitations of traditional neuropsychological assessment include testing in a highly controlled environment designed to minimize distraction. While informative, it may not fully capture real-world cognitive functioning. This may be particularly important for individuals with mild traumatic brain injury (mTBI), a subset of whom report subtle challenges with complex cognitive functioning that are not consistently captured by neuropsychological assessment. The objective of this study was to extend previous work examining cognitive correlates of performance on functional assessment tool, the Goal Processing Sale (GPS), in a larger sample of Veterans with mTBI.
Participants and Methods:
46 Veterans with chronic mTBI completed GPS and neuropsychological measures (mean age = 43.5; education = 15 years; 89% male). 93% of participants had clinically significant PTSD (PCL-M > 31). The GPS is an ecologically valid assessment in which participants plan and execute a complex task following specified rules under a time constraint. Performance is rated on a 0 (not able) to 10 (absolutely not a problem) scale in 8 domains: 1) Planning, 2) Initiation, 3) Self-Monitoring, 4) Maintenance of Attention, 5) Sequencing and Switching of Attention, 6) Flexible Problem Solving, 7) Task Execution, and 8) Learning and Memory. The GPS Overall Performance is average of 8 domain scores. Neuropsychological assessment data were scored using standardized norms and transformed into z-scores. Scores were averaged into 2 domains: 1) Overall Attention/Executive Function (4 subdomains: Working Memory [Auditory Consonant Trigrams, WAIS-III Letter Number Sequencing], Sustained Attention [Digit Vigilance Test], Inhibition [D-KEFS Stroop Inhibition], Mental Flexibility [Trail Making Test B, D-KEFS Stroop Inhibition Switching, Design Fluency Switching, Verbal Fluency Switching]) and 2) Overall Memory (2 subdomains: Total Recall [HVLT-R, BVMT-R], and Delayed Recall [HVLT-R, BVMT-R]).
Pearson correlation coefficients were used to determine relation between overall GPS and overall executive function performance, as well as 8 GPS subdomain and 8 neuropsychological domain/subdomain scores. To adjust for multiple comparisons, p < .01 was used.
Results:
Overall GPS performance was statistically significantly related to Overall Attention/Executive Functioning and Overall Memory. Investigating further, multiple significant subdomain relations emerged. GPS Planning was related to Inhibition. GPS Self-Monitoring and GPS Task Execution were related to Mental Flexibility. GPS Maintenance of Attention and GPS Flexible Problem Solving were related to Mental Flexibility and Inhibition. GPS Sequencing and Switching of Attention was related to Mental Flexibility and Total Recall.
GPS Learning and Memory was related to Working Memory, Mental Flexibility, and Inhibition. GPS Initiation was not related to neuropsychological measures.
Conclusions:
Current findings build upon prior work establishing validity of GPS functional assessment measure (Novakovic-Agopian et al., 2012). Seven of 8 GPS subdomains were related to at least one aspect of executive functioning assessed with neuropsychological measures, with the majority related to mental flexibility. Taken together, findings suggest that the GPS converges with traditional measures, offering a method to capture multiple aspects of executive functioning applied together. Further, it may also be useful tool capturing aspects of executive functioning in complex, ecologically-valid settings often not captured with traditional neuropsychological assessment.