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Infant motor development is a robust predictor of long-term developmental outcomes, especially in infants at high risk for neurodevelopmental impairments, such as those born preterm (PT, gestational age [GA] <37 weeks). Although direct assessments of motor development are available, they are infrequently applied by pediatricians in routine screening of the broader population of infants born preterm. Parent ratings, such as the Ages and Stages Questionnaire, 3rd Ed., can be used to screen for motor delays. However, this and other existing screening measures focus on whether children have reached milestones based on pre-established cutoffs, rather than on assessing development along a continuum of ability. The present study examined the validity of the Motor domain of the recently developed caregiver report screening tool, PediaTracTM, in distinguishing infants born PT from infants born full term (FT, GA ^37 weeks) across the first 6 months of life. The reliability and factor structure of this motor scale were also evaluated.
Participants and Methods:
PediaTracTM is a web-based caregiver report assessing infant development across multiple domains, including motor functioning. This study reports on results from the PediaTracTM Motor domain for the study sample of 571 caregiver-infant dyads (240 PT, 331 FT). Caregivers rated their infants on age-targeted motor skills during the newborn period (NB, defined as term equivalent for the PT group) and at 2-, 4-, and 6-months after the NB period. Item Response Theory (IRT) methods were applied to assess the reliability (i.e., information) of caregiver-reported motor skills at each age. Using the IRT item parameters of discrimination and difficulty, items were selected for inclusion and to estimate theta, an index of the latent trait, motor ability, for each infant. Analyses conducted at each age assessed the effects of group, sex, and group x sex on the motor trait. Scale reliabilities and factor structure were also examined.
Results:
The PT group had significantly higher scores than the FT group on the motor trait at the NB period but significantly lower scores by 4 and 6 months, suggesting slower development of motor skills in the PT group. Means (SD) theta scores (similar to z scores) for the PT and FT groups, respectively, were .14 (.88) and -.05 (.91) for the NB period, -.01 (.90) and .01 (.91) for 2 months, .20 (.90) and .36 (88) for 4 months, and .46 (78) and .66 (.89) for 6 months. Effects for sex and group x sex interactions were not significant. Reliabilities, estimated at a point close to mean theta, were .94, .93, .96, and .98 at the NB, 2-, 4-, and 6-month periods, respectively. Exploratory factor analyses revealed evidence for a single primary motor factor and multiple second-order factors at each age.
Conclusions:
Findings provide strong support for applications of the caregiver reported PediaTracTM motor scales in screening infants born PT and other at-risk populations for early delays or abnormalities in motor development. Advantages of this method include its ease of administration, sensitivity to developmental change, and promise in assessing subdomains of motor skill.
Cannabis is classified as a class B drug in the UK with penalties for possession of up to 5 years in prison, an unlimited fine or both. Nevertheless it is widely available and is the most commonly used drug in the UK with approximately 2.6 million (7.6%) of adults reporting that they sometimes or regularly use it. It is not uncommon for people who present in our epilepsy clinic to report regular use of cannabis; some use it recreationally whilst others report ‘self-medicating’ based on the belief that it has a beneficial impact on their seizures. The aim of this study was to establish the prevalence of cannabis use in people with epilepsy referred for a neuropsychological assessment and to examine the impact of cannabis use on cognitive function in this group.
Participants and Methods:
All patients who attend for a neuropsychological assessment are routinely asked about illegal drug use in their clinical interview. This information is also captured in the medical and neuropsychiatric assessments they undergo when assessed by the multidisciplinary team. The electronic medical records of 800 consecutive patients who had undergone a neuropsychological assessment between 2019 and 2022 were searched for references to cannabis use. The neuropsychological profiles of patients reporting cannabis use were compared to those seen in the larger series across multiple cognitive domains.
Results:
Seventy (8.75%) of the patients in the series reported past or present cannabis use. Cannabis users were more likely to be male (p<0.01) and were younger (p<0.01) than those who did not report use. Reading IQ was significantly lower in the cannabis group (p<0.001). Patients who were regularly using cannabis at the time of the neuropsychological assessment did not differ from the rest of the cohort on tests of processing speed, working memory, naming or verbal fluency. There were no differences between the groups in their performance on an embedded measure of performance validity. However the patients who were regularly using cannabis at the time of their neuropsychological assessments scored significantly lower on tests of verbal learning (p<0.05) and reported significantly greater subjective memory problems in everyday life (p=0.02) than the non-cannabis group. The group using cannabis also scored significantly more highly on the depression (p<0.01) and anxiety scales (p=0.02) on the Hospital Anxiety and Depression Scale.
Conclusions:
The prevalence and patterns of cannabis use in the epilepsy population mirror those seen in the wider population. The impact on regular cannabis use on neuropsychological function appears to be most evident on measures of new learning and subjective measures of memory disturbance. Cannabis use is significantly associated with lower levels of cognitive reserve and elevated levels of anxiety and low mood. Whilst caution must be employed with respect to any direct attribution in these complex clinical presentations, these findings may be helpful in the interpretation of neuropsychological test scores and the planning of interventions, particularly with respect to subjective memory complaints in this group.
Although health problems are often a natural consequence of aging, many older adults struggle to manage their health care problems. Health literacy refers to the ability to access, process, and use health information to make appropriate decisions to promote good overall health. Low levels of health literacy are associated with a host of negative outcomes such as less efficient use of healthcare services, higher healthcare costs, increased mortality, and poorer self-rated health. In those with medical conditions (e.g., diabetes), lower health literacy is linked with higher levels of depression. It is important to investigate whether mental health is linked to health literacy as understanding these links has the potential to identify those at risk for negative outcomes and thus implement protective strategies. Therefore, the current study sought to determine the extent to which various mental health constructs such as happiness, well-being, anxiety and depression are related to health literacy in a community-based sample of cognitively healthy individuals. We hypothesized that higher levels of health literacy would be associated with higher self-reported well-being, happiness, and lower anxiety and depression.
Participants and Methods:
Design - Cross-sectional, prospective study. Setting - Community-based. 93 individuals were included with mean age=59.02 years (SD=15.12) and mean education=15.70 (SD=2.39). 60% were women, the majority were White (55%) while 38% were Black and 7% belonged to other races; 90% were non-Hispanic.
Measures:
Health Literacy - Health literacy was measured by an 8-item instrument in the Rush Memory and Aging Project that examined the participant’s understanding of health care, treatment, and related behaviors. Happiness - Happiness was measured by 5 items from the Satisfaction with Life Scale using a 7-point scale (1 = strongly agree; 7 = strongly disagree). Higher scores indicated lower levels of happiness. Well-being - Well-being was measured with an 18-item instrument from the Rush Memory and Aging project, with higher scores indicating better well-being. Statistics: Bivariate correlations between age, education, and mental health measures and health literacy were examined.
Results:
Higher level of health literacy was significantly associated with age (r = .282 p = .009) and education (r = .228 p = .039). Contrary to our hypothesis, health literacy was not significantly associated with happiness (r = .002 p = .987), well-being (r = .037 p = .742), depression (r = .005 p = .962) or anxiety (r = -.064 p = .568). Even after controlling for age and education, these associations remained significant.
Conclusions:
Higher level of healthy literacy was associated with older age and higher level of education. However, no significant association was found between health literacy and mental health measures of happiness, well-being, depression, and anxiety in cognitively healthy individuals, even after controlling for demographics. The lack of such associations in this study was unexpected and suggests that other factors such as the presence of health conditions (e.g., diabetes, cancer) might critically contribute to such associations. Future studies should examine these associations in a larger context to better understand how to promote healthy self-care behaviors.
Interventions using a cognitive training paradigm called the Useful Field of View (UFOV) task have shown to be efficacious in slowing cognitive decline. However, no studies have looked at the engagement of functional networks during UFOV task completion. The current study aimed to (a) assess if regions activated during the UFOV fMRI task were functionally connected and related to task performance (henceforth called the UFOV network), (b) compare connectivity of the UFOV network to 7 resting-state functional connectivity networks in predicting proximal (UFOV) and near-transfer (Double Decision) performance, and (c) explore the impact of network segregation between higher-order networks and UFOV performance.
Participants and Methods:
336 healthy older adults (mean age=71.6) completed the UFOV fMRI task in a Siemens 3T scanner. UFOV fMRI accuracy was calculated as the number of correct responses divided by 56 total trials. Double Decision performance was calculated as the average presentation time of correct responses in log ms, with lower scores equating to better processing speed. Structural and functional MRI images were processed using the default pre-processing pipeline within the CONN toolbox. The Artifact Rejection Toolbox was set at a motion threshold of 0.9mm and participants were excluded if more than 50% of volumes were flagged as outliers. To assess connectivity of regions associated with the UFOV task, we created 10 spherical regions of interest (ROIs) a priori using the WFU PickAtlas in SPM12. These include the bilateral pars triangularis, supplementary motor area, and inferior temporal gyri, as well as the left pars opercularis, left middle occipital gyrus, right precentral gyrus and right superior parietal lobule. We used a weighted ROI-to-ROI connectivity analysis to model task-based within-network functional connectivity of the UFOV network, and its relationship to UFOV accuracy. We then used weighted ROI-to-ROI connectivity analysis to compare the efficacy of the UFOV network versus 7 resting-state networks in predicting UFOV fMRI task performance and Double Decision performance. Finally, we calculated network segregation among higher order resting state networks to assess its relationship with UFOV accuracy. All functional connectivity analyses were corrected at a false discovery threshold (FDR) at p<0.05.
Results:
ROI-to-ROI analysis showed significant within-network functional connectivity among the 10 a priori ROIs (UFOV network) during task completion (all pFDR<.05). After controlling for covariates, greater within-network connectivity of the UFOV network associated with better UFOV fMRI performance (pFDR=.008). Regarding the 7 resting-state networks, greater within-network connectivity of the CON (pFDR<.001) and FPCN (pFDR=. 014) were associated with higher accuracy on the UFOV fMRI task. Furthermore, greater within-network connectivity of only the UFOV network associated with performance on the Double Decision task (pFDR=.034). Finally, we assessed the relationship between higher-order network segregation and UFOV accuracy. After controlling for covariates, no significant relationships between network segregation and UFOV performance remained (all p-uncorrected>0.05).
Conclusions:
To date, this is the first study to assess task-based functional connectivity during completion of the UFOV task. We observed that coherence within 10 a priori ROIs significantly predicted UFOV performance. Additionally, enhanced within-network connectivity of the UFOV network predicted better performance on the Double Decision task, while conventional resting-state networks did not. These findings provide potential targets to optimize efficacy of UFOV interventions.
To test whether adherence to treatment in patients with MS is influenced by cognitive variables (executive functions), personality, and social support.
Participants and Methods:
This is a pilot observational, descriptive, cross-sectional study. 60 patients with Relapsing remitting MS ( 73.33% female; age: 41.41 ±14.00) undergoing medical treatment ( 28 dymethilfumarate, 7 ocrelizumab/ rituximab, 6 fingolimod, 5 interferon, 5 natalizumab, 4 cladribine, 3 teriflunomide, 1 alemtuzumab, 1 glatiramer acetate) underwent a comprehensive multi-component evaluation including : cognition, social support (using the self-reported record of social support scale), personality (using the NEO-FFI questionnaire) and evaluation of treatment adherence using the Morisky Green Levine Medication Adherence Scale Participants were divided into two groups according to their adherence to medical treatment, low vs. high adherence was defined using a cutoff score of 4. Differences between groups were evaluated using Student's t-test with a significance level of p<0.05, the effect size was calculated with Cohen's d test.
Results:
Groups did not differ significantly in age, sex, type of treatment, Montreal Cognitive Assesments (MoCA) or neuropsychiatric scales of depression and anxiety. Regardless of treatment type, 63.33% of the patients had high treatment adherence. Significant differences between groups were found in the Global Index of Social Support (p=0.016, Cohen's d= 0.73) and the responsibility factor of the NEO-FFI (p=0.048, Cohen's d= 0.20). Conversely, no significant differences were found in executive functions (p=0.8), Openness (p=0.062), Extraversion (p=0.5), Neuroticism (p=0.4) and Agreeableness (p=0.8).
Conclusions:
Social support and the responsibility factor of personality are significantly different between MS patients with high and low adherence to medical treatment. The study of social support and personality may be a key component in improving adherence strategies.
Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there is variability in the level of cognitive gains after cognitive training across studies. One potential explanation for this variability could be moderating factors. Prior studies suggest variables moderating cognitive training gains share features of the training task. Learning trials of the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) recruit similar cognitive abilities and have overlapping neural correlates with the UFOV task and speed-ofprocessing/working memory tasks and therefore could serve as potential moderators. Exploring moderating factors of cognitive training gains may boost the efficacy of interventions, improve rigor in the cognitive training literature, and eventually help provide tailored treatment recommendations. This study explored the association between the HVLT-R and BVMT-R learning and the UFOV task, and assessed the moderation of HVLT-R and BVMT-R learning on UFOV improvement after a 3-month speed-ofprocessing/attention and working memory cognitive training intervention in cognitively healthy older adults.
Participants and Methods:
75 healthy older adults (M age = 71.11, SD = 4.61) were recruited as part of a larger clinical trial through the Universities of Florida and Arizona. Participants were randomized into a cognitive training (n=36) or education control (n=39) group and underwent a 40-hour, 12-week intervention. Cognitive training intervention consisted of practicing 4 attention/speed-of-processing (including the UFOV task) and 4 working memory tasks. Education control intervention consisted of watching 40-minute educational videos. The HVLT-R and BVMT-R were administered at the pre-intervention timepoint as part of a larger neurocognitive battery. The learning ratio was calculated as: trial 3 total - trial 1 total/12 - trial 1 total. UFOV performance was measured at pre- and post-intervention time points via the POSIT Brain HQ Double Decision Assessment. Multiple linear regressions predicted baseline Double Decision performance from HVLT-R and BVMT-R learning ratios controlling for study site, age, sex, and education. A repeated measures moderation analysis assessed the moderation of HVLT-R and BVMT-R learning ratio on Double Decision change from pre- to post-intervention for cognitive training and education control groups.
Results:
Baseline Double Decision performance significantly associated with BVMT-R learning ratio (β=-.303, p=.008), but not HVLT-R learning ratio (β=-.142, p=.238). BVMT-R learning ratio moderated gains in Double Decision performance (p<.01); for each unit increase in BVMT-R learning ratio, there was a .6173 unit decrease in training gains. The HVLT-R learning ratio did not moderate gains in Double Decision performance (p>.05). There were no significant moderations in the education control group.
Conclusions:
Better visuospatial learning was associated with faster Double Decision performance at baseline. Those with poorer visuospatial learning improved most on the Double Decision task after training, suggesting that healthy older adults who perform below expectations may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes.
Nearly 85% of adults on the autism spectrum are unemployed, although nearly 70% of those who are unemployed express a desire and willingness to work. The job interview has been identified as a significant obstacle to obtaining employment by young adults on the spectrum. A growing field of research has been focused on evaluating innovative training tools to improve interview skills. Our previous work shows that a virtual reality job interview training (VR-JIT) tool improves certain job interview skills (such as sounding professional, establishing rapport), but does not improve the ability to speak about personal strengths and abilities. The current study combined VR-JIT with a new training tool: Kessler Foundation Strength Identification and Expression (KF-STRIDE), an intervention grounded in principles of positive psychology. KF-STRIDE targets identification of personal character strengths and expressing those strengths to employers in a socially appropriate way.
Participants and Methods:
The current study evaluated data from 20 autistic youth, randomized to an experimental group (n=10) and a services-as-usual (SAU) control group (n=10). Those in the experimental group participated in a 12 session intervention (9 sessions using VR-JIT and 3 sessions in KF-STRIDE). Each session was roughly one hour. Job interview performance was assessed by video-recorded mock job interviews rated by blinded assessors pre- and post- the intervention. Paired samples t-tests were conducted to examine differences in job interview skills from baseline to follow up in both groups.
Results:
The intervention group showed a significant improvement from baseline to follow-up in job interview skills in general (p = .004), and specifically sharing strengths about themselves to a future employer (p = .004). No significant differences were seen from baseline to follow-up in the SAU group. Conclusions: Individuals on the autism spectrum are significantly underemployed, which negatively impacts one’s ability to lead an independent life. Two innovative tools: VR-JIT and KF-STRIDE successfully improved job interview skills, including the ability to identify and express personal strengths. These findings indicate that these combined tools may help to improve employment skills for individuals on the autism spectrum.
The aim of the present study was to analyse the effects of the transcranial random noise stimulation (tRNS) technique when placed on the left dorsolateral prefrontal cortex (L-DPFC) and left inferior frontal gyrus (L-IFG), for the improvement of verbal fluency performance and creativity skills in a group of multilingual healthy adults.
Participants and Methods:
Fifty healthy adults, aged 18-47 years, participated in the study. All of them were native Spanish speakers of which three were bilingual (Spanish and English) and 47 were multilingual (Spanish, Basque and English). The study had a randomized, counterbalanced, double-blind, sham-controlled design. The participants were randomly allocated to either a tRNS active group or a placebo-control group. All participants were tested individually in one session divided into three parts: (1) baseline, (2) online, and (3) offline assessment. In the active condition, a 1.5mA current (100-500 Hz) was delivered for 20 minutes (online phase). Participants’ verbal fluency was assessed through semantic and phonemic verbal fluency tasks in three different languages (Spanish, Basque and English), while creativity was assessed in their native language with the Remote Associations Test (RAT, pre and post forms) for convergent thinking, and with the Unusual Uses subtest (UU, pre and post forms) for divergent thinking. In addition, the linguistic profile of the participants was evaluated with the Language Experience and Proficiency Questionnaire (LEAP-Q), and their processing speed and cognitive flexibility were assessed with the Stroop Color and Word Test (SCWT).
Results:
The results showed significant differences in phonemic fluency between the groups during the online assessment in Spanish (F= 5.31, p = 0.026), and in the offline assessments in Spanish (F=6.44, p = 0.015) and English (F=10.80, p = 0.002), with participants in the active condition performing better. While no differences were observed in the performance of the groups in verbal fluency in Basque, neither in the online (F=1.06, p = 0.31), nor in the offline assessment (F=2.62, p = 0.11). Furthermore, no significant differences were observed between groups in semantic verbal fluency tasks in any of the languages, neither during stimulation nor offline. However, there were no differences between conditions in the online (Spanish, F=0.86, p = 0.35; English, F=2.95, p = 0.09; and Basque, F=0.01 p = 0.94) and offline (Spanish, F=2.53, p = 0.11; English, F=0.74, p = 0.39; and Basque, F=1.39, p = 0.24) semantic tasks. In creativity, significant differences were observed between groups on the RAT (F=9.58, p = 0.003), while no differences were observed in the performance of any of the three dimensions of the UU (Originality, F=0.44, p = 0.51; Flexibility, F=0.42, p = 0.51; Fluency, F=0.69, p = 0.41). In the SCWT, statistically significant differences were only observed in the colour-word part (F=7.60, p = 0.008) during the online assessment, showing a better performance of the participants under the tRNS condition compare to the sham condition.
Conclusions:
The results obtained in this study suggest that the excitatory effects of tRNS over the L-DLPFC L-IFG could contribute to the improvement of phonemic verbal fluency and verbal convergent thinking, in healthy individuals.
Late life depression (LLD) refers to a diagnosis of major depressive disorder in people older than 60, and has been linked to significant cognitive impairment and increased risk of Alzheimer's disease. Although anxiety and depression are highly comorbid, the impact of anxiety on cognition in LLD is far less researched. This is important given that over 20% of middle aged and older adults endorse clinically significant chronic worry. Generalized anxiety disorder in older adults with major depression is associated with poorer cognition and worse treatment outcomes compared with those without anxiety. Therefore, the purpose of the study is to examine the role of anxiety on memory in LLD. We hypothesized that presence of anxiety among older depressed adults would be associated with worse cognitive performance over time.
Participants and Methods:
Participants included 124 individuals (69.4% female, 90.3% Caucasian) aged 60 or above (M = 71.5, SD = 7.4) who met criteria for major depression, single episode or recurrent. They completed the State Trait Anxiety Inventory, Montgomery Asberg Depression Rating Scale, and a measure of verbal episodic memory (WMS-IV Logical Memory) as part of a larger neuropsychological battery. Data were collected from baseline to three years as part of a larger NIMH-supported longitudinal study. Two-level linear mixed-effect models were fitted to predict memory. State and trait anxiety were used as time-varying predictors. The between-person (level 2) and within-person (level 1) effects of anxiety on memory were assessed controlling for the time trend, age, education, gender, race, and change in depression over time.
Results:
Plot trajectories across variables revealed a negative correlation such that as anxiety decreased, memory improved over time. Hierarchical linear mixed-effect models revealed that average state anxiety was a marginally significant between-person (level2) predictor for memory [B=-0.041, t(128)=-1.8, p=0.083]. Individuals with greater average state anxiety were more likely to experience memory decline compared to those with lower average state anxiety. In addition, the within-person effect (level 1) of state anxiety was significant [B=-0.096, t(253)=-2.7, p=0.007]. As an individual's anxiety increased over time, their memory declined. Trait anxiety showed a significant within-person effect on memory [B=-0.087, t(254)=-2.0, p=0.048], but a non-significant between-person effect [B=-0.005, t(124)=-0.06, p=0.95].
Conclusions:
Anxiety appears to increase the risk of memory decline in older adults with major depression, a cohort who are already at risk of cognitive decline. Changes in anxiety increased risk of memory decline even when accounting for changes in depression over time. Although the causal link between anxiety and cognitive impairment remains unclear, it is possible that anxiety and worry may compete for cognitive resources necessary for demanding tasks and situations, detracting from abilities, such as attention and working memory. Older adults with depression may also have difficulty coping adaptively with anxiety, which may negatively affect cognition. Finally, presence of anxiety may represent a form of mild behavioral impairment, a prodrome of cognitive decline leading to dementia. Overall, the present study highlights the negative impact of anxiety on memory performance, indicating that treatment interventions targeting anxiety in older adults are essential to help prevent cognitive decline.
Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease of the central nervous system. Apathy is significantly higher in adults with MS compared to healthy populations. Apathy is a lack of motivation that can cause dysfunctions in each step of goal-directed behaviors. Apathy is associated with diminished ability to perform activities of daily living, tasks requiring normal executive function, and quality of life. Across various neurodegenerative disorders, apathy has been regarded as a predictor of poor cognition and functional outcomes. However, the severity of apathy and its association with cognitive function in older adults with MS have not been reported. This study's objective was to address this gap of knowledge. Hence, we evaluated: 1) the severity of apathy symptoms in older adults with MS compared to healthy older adults and, 2) the association of apathy symptoms and global cognitive functioning in older adults with MS compared to controls.
Participants and Methods:
Participants were community-residing older adults (age >60ys) enrolled in a cohort study, “Brain Predictors of Mobility and Falls in Older Adults with Multiple Sclerosis.” Healthy controls (n=59; mean age=66.25± 3.37; %female=47.5) and persons with MS (n=69; mean age=64.58± 3.88; %female=62.3) were included in the analysis. Using McDonald criteria, MS diagnosis was physician-confirmed by medical record review, apathy symptoms were assessed through 4 apathy symptom questions on the 30-item Geriatric Depression Scale (GDS), and global cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Covariates included age, gender, years of education, global health score (GHS), and depression (GDS w/out apathy questions). For the first objective, a linear regression model was used with a bi-level group status variable (MS vs controls) serving as a predictor of apathy symptoms. For the second objective, two linear regression models stratified by group status were run with apathy symptoms as a predictor of global cognitive functioning.
Results:
The presence of MS was significantly associated with worse apathy (β=.34, p < .001) and it remained significant after adjusting for covariates (β=.19, p=.03). Additionally, apathy was negatively associated with global cognition in persons with MS (β=-.32, p =.01) and this association remained significant after adjusting for covariates (β=-.33, p =.01) except depression (β=-.27, p =.08). The association of apathy and global cognitive functioning was not significant in healthy controls (β=.01, p=.95).
Conclusions:
This study is the first to report worse apathy symptoms in older persons with MS compared to healthy controls. Additionally, worse apathy symptoms were associated lower global cognitive functioning in older adults with MS but not in healthy controls.
Caregivers to persons with dementia (PWD) consistently report lower sleep quality than non-caregiving controls. Low sleep quality, in addition to being unhealthy for the caregiver, may also impact the quality of care provided to the PWD. One factor that may contribute to poor sleep among caregivers is neurobehavioral symptoms (NBS) of the PWD. NBS, such as mood changes, lack of motivation, and disinhibition, are consistently rated as some of the most distressing symptoms by caregivers. Furthermore, they can include some symptoms related to sleep, such as nighttime wandering and REM sleep behaviors. Prior correlational research indicates a very strong association between NBS of the PWD and sleep quality of the caregiver. However, there are third variables, particularly demographics of the caregiver, which may better explain this relationship. When these variables are controlled in research, findings on the association between PWD NBS and caregiver sleep quality are mixed. Thus, we sought to investigate the relation between PWD NBS and caregiver sleep quality while controlling for caregiver demographics.
Participants and Methods:
Fifty caregivers to PWD completed a survey containing the Mild Behavioral Impairment Checklist as a measure of PWD NBS, the Pittsburgh Sleep Quality Index as a measure of caregiver sleep quality, and caregiver demographics. The relationship between PWD NBS and caregiver sleep quality was assessed using hierarchical linear regression. First, we examined the relationship between caregiver demographics (age, gender, income) and caregiver sleep quality. Second, we added NBS to the model to assess for incremental predictive utility by examining change in R2.
Results:
A significant correlation was found between PWD NBS and caregiver sleep quality, with higher PWD NBS associated with worse caregiver sleep quality (r(48) = .34, p = .014). A hierarchal regression found that caregiver demographics explained a non-significant proportion of variance in reported caregiver sleep quality (F(3, 44) = 1.05, p = .382, R2 = .07). When PWD NBS was added in model two, there was a significant change in variance explained in the overall model (F(1,43) = 2.65, p = .046, AR2 = .13, R2 = .20). Across both models, PWD NBS was the only variable significantly associated with caregiver sleep quality (B = .08, p = .011).
Conclusions:
In line with previous studies, these results indicate a moderate relationship between PWD NBS and caregiver sleep quality. Furthermore, findings suggested that PWD NBS is a risk factor for poor caregiver sleep quality, above and beyond caregiver demographic characteristics. Individuals designing interventions aimed at improving caregiver sleep quality should consider including PWD NBS as an intervention target. Future research should replicate these findings in a longitudinal sample to further evaluate causality.
We introduce a geometric analysis of turbulent mixing in density-stratified flows based on the alignment of the density gradient in two orthogonal bases that are locally constructed from the velocity gradient tensor. The first basis connects diapycnal mixing to rotation and shearing motions, building on the recent ‘rortex–shear decomposition’ in stratified shear layers (Jiang et al., J. Fluid Mech., vol. 947, 2022, A30), while the second basis connects mixing to the principal axes of the viscous dissipation tensor. Applying this framework to datasets taken in the stratified inclined duct laboratory experiment reveals that density gradients in locations of high shear tend to align preferentially (i) along the direction of minimum dissipation and (ii) normal to the plane spanned by the rortex and shear vectors. The analysis of the local alignment across increasingly turbulent flows offers new insights into the intricate relationship between the density gradient and dissipation, and thus diapycnal mixing.
High-grade gliomas are aggressive and infiltrate surrounding brain parenchyma, making gross total resection difficult, and despite aggressive treatment, its recurrence is inevitable (Zhou et al., 2016). Repeated tumor resections have been shown to increase survival (Chaichana et al., 2013) but the cost of doing so on quality of life (QoL) and functioning is not known. To address this gap, we compared changes in QoL using the Functional Assessment of Cancer Therapy-Brain questionnaire (FACT-Br; Weitzner et al., 1995) in high-grade glioma patients undergoing first versus repeat surgical resection.
Participants and Methods:
Thirty-three patients with high-grade gliomas (mean age=52, 54.5% female) that underwent tumor resection and completed comprehensive neuropsychological evaluations that included FACT-Br pre-operative and at 2-week follow up were included in this study. FACT-Br assesses four QoL domains: physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), and functional well-being (FWB). A subscale total score was computed for each domain, and these subscale scores were summed to compute a total score for overall QoL. Difference scores were computed for each subscale score and total score by subtracting patients’ pre-operative rating from post-operative rating. More positive scores indicate lesser perceived changes of QoL post-operatively. One-way MANOVA analysis was run to compare the difference scores between patients that underwent first resection and those that underwent repeated resection.
Results:
There was no significant difference in perceived changes of overall QoL between the two groups of patients. However, patients with previous resection reported larger decline in perceived physical well-being compared to patients without previous resection (F(1,30)=99.93, p<.05,partial n2=.16). There were no significant differences in other QoL domains between the two groups.
Conclusions:
We showed no differences in perceived changes across most QoL domains in patients undergoing repeat versus first surgical resection for treatment of high-grade glioma, suggesting that repeated resections may be a viable strategy in managing tumor recurrences. Specifically, there were no group differences in social, emotional, and functional well-being pre-to postoperatively. However, patients with previous resection reported significantly larger decline in their perceived physical well-being than those without any previous resection. A possible explanation is that patients with previous resection underwent adjuvant therapies (e.g., radiation therapy, chemotherapy) and experienced tumor progression necessitating reoperation, which could have made them more vulnerable to the physical impacts of surgery. Our findings are encouraging and may provide useful insight to guide treatment strategies and patient’s decision making to optimize both surgical and functional outcomes.
Individuals who have experienced a mild traumatic brain injury, or concussion, often experience a variety of cognitive and emotional sequelae. Specifically, concussions can place individuals at increased risk for experiencing symptoms of depression. It is important to understand if loss of consciousness (LOC) is related to higher rates of depression in order to improve care and cognitive functioning by appropriately monitoring for mood-related symptoms post-concussion. The current study sought to examine the relationship between depressive symptoms (measured using the PHQ-9), working memory (WM; measured using RBANS Digit Span subtest), and presence of LOC in individuals who have sustained a head injury. The relationships between presence of LOC, depressive symptoms, and WM performance were examined, as it was expected LOC would result in greater depressive symptoms and negatively impact WM performance. Finally, the relationship between depressive symptoms and WM performance, while controlling for LOC, was also assessed.
Participants and Methods:
Data was drawn from archival medical records of 40 patients who underwent brief neuropsychological screening in an outpatient, community clinic after being referred following a head injury. Patients ranged in ages from14 to 75, with a mean age of 39.1. The average years of education amongst patients was 14.62. Twenty-five (62%) of the patients were women. Ten individuals endorsed LOC secondary to their head injury.
Results:
The average PHQ-9 score was 9.68 (SD=7.69). LOC did not impact reported depressive symptoms (p >.05). The correlation between LOC and WM performance was also nonsignificant (p >.05). While it was predicted there would be an inverse relationship between PHQ-9 scores and WM performance, there was no statistical significance (p >.05). Similarly, there was no significant relationship between PHQ-9 and WM performance when controlling for LOC (p >.05).
Conclusions:
While the relationships between LOC, depressive symptoms, and WM performance were found to be nonsignificant, understanding the course and best supports of cognitive and emotional sequelae of head injuries is of paramount importance. Future research exploring these relationships with larger, diverse populations would likely prove beneficial.
Cognitive difficulties in Multiple Sclerosis (MS) are important contributors to impairment in instrumental activities of daily living. A non-randomised controlled trial was conducted to explore the effects of a cognitive rehabilitation protocol on MS patients' daily life functionality.
Participants and Methods:
Seventy-five relapsing-and-remitting MS patients were recruited. Intervention Group (IG, n=31) underwent 16 individual rehabilitation sessions (1hx2/week; weeks 2-10), which included paper and pencil cognitive stimulation exercises and training memory strategies and external memory aids; and a booster session (week 37). Control Group (CG, n=44) received care as usual. These primary outcome measures were applied at baseline and at weeks 11, 36, and 62: Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ), Mental Slowness Questionnaire (MSQ), Mental Slowness Observation Test (MSOT), and Sydney Psychosocial Reintegration Scale-2 (SPRS-2). Score differences from baseline were calculated for all measures and follow-up time points except for SPRS-2, which was only applied twice (baseline and week 62). Linear regressions fitted with generalized estimating equations (GEE) were performed to verify the effects of time and group on the outcome measures. Baseline scores were included in the model as covariates for all outcome measure except SPRS-2. Chi-square and Mann-Whitney tests were applied to compare demographic and clinical characteristics of the groups.
Results:
Groups had similar demographic (i.e., sex, age, and education) and clinical (i.e., age at disease onset, disease duration, disease modifying treatments, and Expanded Disability Status Scale score) characteristics. IG's MSQ score progressively improved, whereas CG's score did not change from baseline (group x time effect: p<0.001) throughout follow-up. IG's MSNQ score improved from baseline at weeks 11 and 36, but not at week 62. CG's MSNQ score did not change from baseline throughout follow-up (group x time effect: p=0.025). Both IG's and CG's performance on the MSOT improved (time effects). Though, the IG showed greater improvement at follow-up (group effects) on MSOT score and time (both p<0.001). IG's SPRS-2 improved, whereas CG's score declined (group x time effect: p<0.001).
Conclusions:
Combining restorative techniques with strategy-based compensatory techniques may produce significant and persistent effects on MS patients' self-reported everyday functioning and on their objective performance of instrumental tasks.
Inequity in Alzheimer’s disease and related dementias (ADRD) clinical research is severely hindering our progress towards a cure for all, while inflating national costs. ADRD alone is currently costing United States 321 billion dollars in 2022, projected to increase to 1 trillion by 2050. Alzheimer’s disease disproportionately impacts Black, Hispanic, Asian or Native Americans. Yet, ADRD clinical research to date has not included equitable number of participants from communities of color to be representative of the U.S. population. Hispanic/Latinos currently represent 1% of ADRD clinical trials’ samples despite representing 18% of the US population.
Participants and Methods:
In our previous outreach and recruitment study with the Human Connectome Project - Aging, we attained a 11.35% recruitment success rate of Hispanics/Latinos living in Los Angeles County Districts. We implemented a comprehensive Spanish-English bilingual, multi-method, multi-setting community-academic engagement, outreach, and recruitment protocol with a focus on brain health literary and ADRD biomarker research literacy.
Results:
Whereas community educational engagement and outreach was the most efficient and highest interest turn-out recruitment strategy, 61% of engaged and interested Hispanic/Latinos (50 years old and older) were automatically excluded during the telephone screening due to English-language proficiency/fluency. Highest enrollment success rate was from UCLA mailing list, clinical registries, and referrals. Hispanics/Latinos successfully recruited were bilingual or multilingual, 83% identified white as their racial background, 85% attained higher education, and 70% resided in middle-to-high income levels areas.
Conclusions:
Our results captured institutional barriers leading to a recruitment bias towards affluent Hispanics/Latinos with access to healthcare systems. Our applied science of recruitment and retention requires significant improvements in study design and methodology, tailored and targeted to communities’ socio-ecological context. It also requires the extrapolation of generalizable theoretically informed mechanisms of successful engagement, recruitment, and retention strategies for replication and/or modification in other settings/locations, and countries.
Imitation has pervasive associations with social and communicative development. However, few methods have been developed to measure this construct in typically developing infants, and even less is available for at-risk populations, such as infants born preterm. Autism spectrum disorder (ASD), a particular risk of premature birth, is associated with atypical imitation and social communication. Although imitation emerges in infancy, most current screening and diagnostic tools for ASD cannot be utilized prior to 12 months. The present study aimed to develop and validate a caregiver-report measure of infant imitation, characterize imitation profiles at 4, 6, and 9 months in term and preterm infants, and explore the relationship between imitation and scores on an ASD screening questionnaire at 18 months.
Participants and Methods:
Participants (N = 571) were recruited from a larger multi-site study of PediaTrac™ v3.0, a web-based tool for monitoring and tracking infant development, and were surveyed longitudinally at birth, 2, 4, 6, 9, 12, 15, and 18 months. Participants completed the online PediaTrac™ survey and several reliable and validated questionnaires via pen-and-paper format. For the purposes of this study, only the Ages and Stages Questionnaire (3rd ed.; ASQ-3), Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP), Brief Infant Sleep Questionnaire (BISQ), and the Modified Checklist for Autism in Toddlers - Revised with Follow-Up (M-CHAT-R/F) were examined. The following hypotheses were tested: (1) proposed imitation items will represent a unitary latent construct, for which convergent and discriminant validity will be demonstrated, (2) there will be measurement invariance between term status groups at each assessment period, (3) preterm infants will obtain lower caregiver-reported imitation scores compared to term infants, and (4) imitation abilities at the assessment period with the most robust imitation factor will predict M-CHAT-R/F scores at 18 months.
Results:
Distinct imitation factors at 4, 6, and 9 months were modeled with confirmatory and exploratory factor analyses. Relationships between the factors and established measures of infant communication (CSBS; ASQ) and sleep (BISQ) revealed convergent and discriminant validity, respectively. Strict measurement invariance was demonstrated for the 4- and 9-month factors, and metric invariance for the 6-month measure. Full term infants scored higher on imitation at 9 months, though variance in this outcome was related to term status differences in sensorimotor skills. Lastly, the 9-month imitation factor, coupled with 6-month sensorimotor skills, predicted 18-month ASD risk over and above gestational age.
Conclusions:
This study provides support for the assessment of infant imitation, utilizing imitation to detect risk in preterm infants, and extending the age of identification for ASD risk into the first year. PediaTrac™ imitation, in combination with the PediaTrac™ sensorimotor domain, may be useful in detecting developmental risk, and specifically risk for ASD, within the first year, leading to earlier initiation of intervention. Further, with its minimal completion time and ease of dissemination through digital platforms, this measure can expand access to care and improve long-term outcomes for children and families.
Type 2 diabetes (T2D) is a risk factor for cognitive impairment/dementia and has been shown to modify the impact of Alzheimer’s disease (AD) biomarkers on cognition and everyday functioning. Studies examining amyloid-ß (Aß), one of the hallmark AD pathologies, have shown mixed results regarding associations of Aß biomarkers with cross-sectional cognition as well as T2D, though Aß is generally associated with future cognitive declines. The purpose of the present study is to examine whether T2D impacts the associations between amyloid positron emission tomography (PET) and cognition in older Veterans.
Participants and Methods:
The current study included 202 mostly male Vietnam-Era Veterans from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DOD ADNI) study (age M=69.38 years, SD=4.37; 40% with self-reported T2D) who completed neuropsychological testing and florbetapir PET imaging. The Aß PET standardized uptake variable ratio (SUVR) was measured using a previously-validated summary SUVR calculated by dividing the mean uptake across 4 AD-vulnerable cortical regions by whole cerebellar uptake. General linear models examined whether T2D moderated the relationship of Aß PET with memory, attention/executive functioning, and language composite scores. Models adjusted for age, education, apolipoprotein E e4 carrier status, vascular risk burden, depressive symptoms, post-traumatic stress disorder (PTSD) symptom severity, and history of traumatic brain injury (TBI).
Results:
There was no main effect of diabetes on memory, attention/executive functioning, or language performance, and higher Aß PET SUVR was only associated with worse attention/executive functioning performance (ß=-.146, 95% CI [-.261, -.031], p=.013). The Aß PET x T2D interaction was significant for attention/executive functioning such that higher Aß PET SUVR was associated with lower attention/executive functioning scores, but only in those with T2D (ß=-.116, [-.225, -.006], p=.038). This interaction was not significant for language or memory.
Conclusions:
The results show that Aß may negatively impact attention/executive functioning, but this effect was only found in Veterans with T2D. Prior work has suggested that T2D may be more associated with tau biomarkers than markers of Aß, so it is possible that the current results are due to a compounding effect of Aß pathology plus microvascular and/or tau pathology. Notably, the sample was relatively young, a relatively large proportion had elevated PTSD symptoms and/or a TBI history (which have both been shown to relate to attention/executive function), and the measures that made up the attention/executive composite (Trail Making Test A and B) have been shown to be particularly sensitive - all of which may have contributed to the domain-specific effects. Future research is needed to investigate the role that tau and vascular pathology may play in cognition among individuals with T2D. Longitudinal studies are also needed to better understand the timing and progression of these relationships.
Hypertension is a common disorder that has been inconsistently associated with worse cognition in older adults. Antihypertensive medications offer treatment for high blood pressure but previous studies on the association between blood pressure, antihypertensive use, and cognitive performance in older adults have yielded inconsistent findings. Individuals without high blood pressure may also take antihypertensive medications for other medical conditions, including migraines. It is unclear whether antihypertensive medications have any effect on cognitive performance in older adults, and whether the differences, if any, are similar in hypertensives and normotensives.
Participants and Methods:
4,969 participants from the National Alzheimer Coordinating Center (NACC) database were included in this study (Mage=72.4 years, SD=7.3 years). Cognitive assessment included Letter Fluency, Category Fluency (animals and vegetables), Trail Making Test A & B, Digit Ordering (forward and backward), and MoCA total score. Participants were included if they had a clinician diagnosis of hypertension or normotension and recorded history of whether they take any antihypertensive medication. Participants with a history of stroke were excluded. Cognitive differences between medication groups were investigated in hypertensive participants and normotensive participants using Bayesian Mann-Whitney tests.
Results:
Bayesian Mann-Whitney tests in hypertensive individuals showed no cognitive differences between those taking antihypertensive medications and those not taking antihypertensives (all BF10s < 3). Bayesian Mann-Whitney tests in normotensive individuals showed individuals taking antihypertensive medications performed worse on Trail Making Test B compared to individuals not taking antihypertensives (123.6 seconds vs 108.8 seconds; BF10 = 35.1), with a small effect size (d=-.156).
Conclusions:
These results suggest that antihypertensive use in older adults with normal blood pressure may be associated with worse executive functioning. Antihypertensive use in normotensive older adults may lower blood pressure and reduce cerebral perfusion, resulting in worse cognitive functioning. Future studies should investigate long-term antihypertensive use and associated cognitive changes in both hypertensive and normotensive individuals.
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:
This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:
Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:
The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.