To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
1) Evaluate the association of self- and study-partner report of subjective cognitive decline (SCD) to objective cognitive performance across ethnoracial groups. 2) Evaluate the concordance of self- and study partner report of SCD across ethnoracial groups.
Participants and Methods:
Participants were 5241 non-Hispanic White (NHW), 267 non-Hispanic Black (NHB), 225 Hispanic, and 228 Asian participants screened for the A4 study (N=5961). Participants completed the Preclinical Alzheimer Cognitive Composite (PACC), and self- and study partner-report of SCD using the Cognitive Function Index (CFI). Analysis of variance was used to assess difference in key variables by ethnoracial group. Regression analyses were conducted to evaluate the association of SCD and objective performance by ethnoracial group, and the association between self-and study partner report of SCD by ethnoracial group.
Results:
Asian participants reported the highest mean CFI relative to all other groups, while NHW reported the lowest (F(3,5957)=41.93, p <.001). Asian and NHW participants had higher PACC scores relative to NHB and Hispanic participants (F(3,5957)=41.93, p <.001). Regression analyses revealed higher CFI was associated with lower PACC score across groups, and this association was strongest in the Asian sample relative to other groups (F(10, 5897)=40.49, p<.001,R2=.06). Evaluation of study partner characteristics suggested NBH participants had the highest proportion on non-spousal study partners relative to other groups. Regression analyses revealed no differences in the association of self- and study partner report of SCD across ethnoracial groups (F(10, 5859)=132.9, p<.001, R2=0.18).
Conclusions:
Results suggest that that SCD is associated with objective cognitive performance across racial groups, although the strength of this association appears to vary in this sample. There is also consistent concordance between self- and study partner report of SCD across groups, despite differences in study partner relationships. SCD may be considered a valid predictor of subtle cognitive change across groups in the A4 sample. Limitations include small group sizes relative to the large NHW sample. Future work with larger, more representative samples are needed to further validate these findings.
Individuals with Spina Bifida (SB) are at increased risk for difficulties with various aspects of adaptive functioning. Poorer adaptive functioning could delay or prevent an individual from successfully living independently and managing their own condition. Despite the importance of understanding adaptive functioning in SB, currently the literature on predictors of and associated neurocognitive skills with adaptive functioning is sparse. Thus, this retrospective chart review study aimed to explore the extent to which intellectual functioning, predicts adaptive functioning in a clinical sample of children with SB.
Participants and Methods:
A retrospective chart review of children with SB was conducted at a Midwestern academic medical center. Children were seen in the context of routine neuropsychological evaluations to identify neuropsychological diagnoses and provide treatment recommendations. All measures were administered based on the age of the child and in accordance with administration guidelines. Only children with complete data were included in analyses. The sample included 42 participants (Mage=10.89, SDage=3.15; 18 male, 24 female). Intellectual functioning was evaluated using either the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) or Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV). Adaptive functioning was evaluated using primary caregiver-report scores from the Adaptive Behavior Assessment System - Third Edition (ABAS-3). Hierarchical regressions were conducted to investigate the extent to which intellectual functioning predicts parent-reported adaptive functioning. The unique contribution of each predictor variable was also considered.
Results:
Model predictors included participant sex, verbal comprehension, working memory, processing speed, and full scale IQ to predict 4 different indices on the ABAS-3. Results showed a significant contribution of participant sex in all models, with males having been rated as having poorer adaptive skills. Intellectual functioning did not significantly contribute to the models. Semipartial correlations revealed that processing speed and working memory often each accounted for a fair amount of variability when controlling for all of the remaining variables in the models. In particular, when accounting for all of the remaining variables, processing speed accounted for 6.3% of variability in global adaptive functioning, 6.1% in Conceptual Skills, and 10.11% in Social Skills. Furthermore, after controlling for all of the other variables, working memory accounted for 4.5% of the variability in global adaptive functioning.
Conclusions:
The present results suggest that males with SB are at increased risk for poorer adaptive functioning, and there may be some preliminary evidence of processing speed and working memory playing contributory roles as well. This may suggest at least in childhood, the verbal and global cognitive capacities of individuals with SB are not as contributory to adaptive functioning as more basic cognitive skills, such as processing speed and working memory. It is recommended that males with SB in particular should be closely monitored with regard to their development of adaptive skills, as they may be at risk of poorer adaptive abilities. Additionally, our findings provide preliminary evidence of processing speed and working memory impacting adaptive functioning. Thus, interventions and accommodations targeting both of these domains may be appropriate to implement to help with poorer adaptive skills in this population.
Those at genetic risk for Alzheimer's Disease (AD) because of the ApoE ε4 allele show differences in activation during olfactory information processing and memory in areas such as MTL structures, entorhinal cortex, posterior cingulate, precuneus, and inferior parietal lobule, suggesting preclinical AD neuropathology and olfactory impairment as a biomarker for predicting later AD onset (Murphy, 2019). The effects of smoking on AD have varied, with early studies suggesting either no effect or protective effects, and recent studies suggesting smoking as a risk factor for AD but with the need for further investigation in preclinical stages. Therefore, this study focused on olfaction and smoking as risk factors for preclinical AD neuropathology by studying differences in fMRI BOLD signal changes in smokers and nonsmokers during olfactory tasks.
Participants and Methods:
Archival data from 25 non-demented older adults recruited from the UCSD Alzheimer's Disease Research Center who completed an Assessment Scale-Cognitive Subscale (ADAS-Cog) and functional MRI scans at 3T, acquired during performance of an odor identification task. Odor Identification (OI) measured correct (hits) or incorrect (misses) identification of odors presented by an olfactometer to deliver the odor stimuli in short, controlled durations during fMRI scanning.
Results:
fMRI data were preprocessed using fMRIprep, smoothed at 4mm, scaled, and first level analyses were conducted using 3dDeconvolve in AFNI with time points corresponding to hits and misses as regressors. Differences between smokers and nonsmokers revealed smokers show a larger difference in BOLD signal change from hits minus misses at five significant clusters (p = 0.01 with the minimum cluster size [voxels] at 42). Peak areas of significant clusters included the right precuneus, right calcarine gyrus, left inferior parietal lobule, left superior parietal lobule, and left middle occipital gyrus. Analyses suggested a greater difference in activity between hits and misses in smokers compared to nonsmokers, with more activity during hits.
Conclusions:
Differences in activation between smokers and nonsmokers during an olfactory identification task, with greater activity in smokers during hits, suggests greater effort to correctly identify an odor. These findings of hyperactivation in areas (such as the precuneus and inferior parietal lobule) are similar to findings of hyperactivation during odor memory observed in studies of ε4 carriers during preclinical stages. Results provide further insight into smoking as a risk factor for AD. Moreover, results suggest the risk of smoking could potentially be reflected in altered activity in olfactory information processing networks in preclinical stages of AD. The study highlights the need for research to further understand the role smoking plays in the development of AD and the use of olfaction as a biomarker to aid in disease detection, prevention, and stage-associated treatments.
Assessment of performance validity during neuropsychology evaluation is essential to reliably interpret cognitive test scores. Studies (Webber et al., 2018; Wisdom, et al., 2012) have validated the use of abbreviated measures, such as Trial 1 (T1) of the Test of Memory Malingering (TOMM), to detect invalid performance. Only one study (Bauer et al., 2007) known to these authors has examined the utility of Green’s Word Memory Test (WMT) immediate recall (IR) as a screening tool for invalid performance. This study explores WMT IR as an independent indicator of performance validity in a mild TBI (mTBI) veteran population.
Participants and Methods:
Participants included 211 (Mage = 32.1, SD = 7.4; Medu = 13.1, SD = 1.64; 94.8% male; 67.8% White) OEF/OIF/OND veterans with a history of mTBI who participated in a comprehensive neuropsychological evaluation at one of five participating VA Medical Centers. Performance validity was assessed using validated cut scores from the following measures: WMT IR and delayed recall (DR); TOMM T1; WAIS-IV reliable digit span; CVLT-II forced choice raw score; Wisconsin Card Sorting Test failure to maintain set; and the Rey Memory for Fifteen Items test, combo score. Sensitivity and specificity were calculated for each IR score compared with failure on DR. In addition, sensitivity and specificity were calculated for each WMT IR score compared to failure of at least one additional performance validity measure (excluding DR), two or more measures, and three or more measures, respectively.
Results:
Results indicated that 46.8% participants failed to meet cut offs for adequate performance validity based on the standard WMT IR cut score (i.e., 82.5%; M = 81.8%, SD = 17.7%); however, 50.2% participants failed to meet criteria based on the standard WMT DR cut score (M = 79.8% SD = 18.6%). A cut score of 82.5% or below on WMT IR correctly identified 82.4% (i.e., sensitivity) of subjects who performed below cut score on DR, with a specificity of 94.2%. Examination of IR cutoffs compared to failure of one or more other PVTs revealed that the standardized cut score of 82.5% or below had a sensitivity of 78.2% and a specificity of 72.4%; whereas, a cut score of 65% or below had a sensitivity of 41% and a specificity of 91.3%. Similarly, examination of IR cutoffs compared to failure of two or more additional PVTs revealed that the cut score of 60% or below had a sensitivity of 45.7% and specificity of 93.1% ; whereas, a cut score of 57.5% or below had a sensitivity of 57.9% and specificity of 90.9% when using failure of three or more PVTs as the criterion.
Conclusions:
Results indicated that a cut score of 82.5% or below on WMT IR may be sufficient to detect invalid performance when considering WMT DR as criterion. Furthermore, WMT IR alone, with adjustments to cut scores, appears to be a reasonable way to assess symptom validity compared to other PVTs. Sensitivity and specificity of WMT IR scores may have been adversely impacted by lower sensitivity of other PVTs to independently identify invalid performance.
Modern perspectives of rehabilitation after traumatic brain injury (TBI) emphasize the importance of individualized holistic approaches (i.e., physical and psychological adjustment) and collaboration toward goals (e.g., among the survivor, rehabilitation professionals, family/friends, etc.). Recent research has sought to employ a holistic, value-based approach (via the Valued Living Questionnaire) to measuring goals and whether those with TBI are acting in accordance with them, and quality of life outcomes. However, no research has examined whether rehabilitation practices are consistent with survivor values using this framework. The aim of the current study was to investigate the impact of value-consistent rehabilitation practices on quality of life and psychological adjustment outcomes in those with TBI.
Participants and Methods:
The current study included a sample of 73 adults with a history of TBI (M years since injury = 7.6, SD = 9.7) between the ages of 18 and 72 (Mage = 44.0 years, SD = 13.1; 73% female, 90.4% white) who had participated in outpatient rehabilitation. Individuals were recruited from brain injury support groups on Facebook and completed a series of surveys measuring TBI severity [Ohio State University Traumatic Brain Injury Identification Method-Short Form (OSU-TBI-ID)], value-consistent rehabilitation practices [modified Valued Living Questionnaire (VLQ)], life satisfaction [Life Satisfaction Questionnaire-9 (LiSat-9)], and psychological flexibility [Acceptance & Action Questionnaire - Acquired Brain Injury (AAQ-ABI)]. Discrepancy scores were calculated to compare perceived importance of and how helpful rehabilitation was for each VLQ domain. Bivariate Pearson correlations were conducted to investigate the relationships between value-consistent rehabilitation, life satisfaction, and psychological flexibility.
Results:
The VLQ domains with the greatest discrepancies were spirituality (-2.26), marriage/intimate relations (-2.06), and family relations (-2.02) such that rehabilitation helped less in these domains despite their importance. Greater levels of value-consistent rehabilitation were related to higher levels of life satisfaction overall (r = 0.40, p < 0.001) and lower levels of reactive avoidance of emotions related to one’s brain injury (r = -0.26, p = 0.03). In terms of specific domains of life satisfaction, greater value-consistent rehabilitation was related to higher levels of vocational (r= 0.44, p < .001), physical self-care (r = 0.28, p = 0.018), and friendship satisfaction (r= 0.41, p < .001).
Conclusions:
Our findings suggest rehabilitation practices may not be acting proportionately with TBI survivor values. Moreover, our results suggest value-consistent rehabilitation is important for long term quality of life and psychological adjustment outcomes. Future work should seek to identify factors that optimize opportunity for individualized treatment.
Caregiver burden tends to worsen as severity of dementia increases, and elevated burden can lead to negative consequences for dementia caregivers. In contrast, positive aspects of caregiving, such as feelings of being useful, needed, or appreciated as a caregiver, are associated with better outcomes. Caregivers reporting fewer positive experiences robustly demonstrate greater burden, suggesting that a lack of positive aspects of caregiving could be a key component of the relationship between dementia severity and burden. This study investigated whether an indirect effect of positive aspects of caregiving would be observed on the association between dementia severity and burden.
Participants and Methods:
Data were extracted from the medical records of 724 patients enrolled for services at an outpatient memory clinic. Caregiver-care recipient dyads were included based on a clinically supported patient diagnosis on the dementia spectrum following a comprehensive geriatric evaluation and having fully completed assessments from an informal caregiver. Caregivers completed the Zarit Burden Interview (ZBI) and the Positive Aspects of Caregiving (PAC) measures. The Montreal Cognitive Assessment and Mini-Mental State Exam were used to estimate dementia severity, standardized to create a single variable. Multiple potential covariates (e.g., age, gender, education, nature of dyadic relationship) were considered for inclusion in the model. A cross-sectional mediation analysis using the Hayes PROCESS macro explored presence of an indirect effect of PAC on the relationship between dementia severity and ZBI using 5000 bootstrap samples.
Results:
Of the proposed covariates, only caregiver age was correlated with any of the primary variables; this variable was controlled in subsequent analyses. Significant relationships emerged between dementia severity and ZBI (r=-.12, p<.001), between PAC and ZBI (r=-.23, p<.001), and between dementia severity and PAC (r=-.07, p<.05). An indirect effect of positive aspects of caregiving on the relationship between dementia severity and ZBI was statistically significant (B= .0092, BC 95% CI [.0008, .0185]), accounting for 14.4% of the variance in the model.
Conclusions:
A small but significant indirect effect of positive aspects of caregiving was observed on the association between dementia severity and burden. Results suggest that as dementia severity worsens, a caregiver who experiences greater positive aspects of caregiving will sustain less burden. Longitudinal examination of these relationships is needed to fully understand causality. Findings may help healthcare providers tailor treatment to alleviate caregiver burden.
Remote assessment for cognitive screening and monitoring in the elderly has many potential advantages, including improved convenience/access and ease of repeat testing. As remote testing becomes more feasible and common, it is important to examine what factors might influence performance and adherence with these new methods. Personal beliefs about one’s ability to remember effectively have been shown to impact memory performance, especially in older adults (Lineweaver & Hertzog, 1998). The perception of a low level of personal control over memory may impact a person’s use of memory strategies which might otherwise enhance performance, as well as their beliefs about the efficacy of those strategies (Lineweaver et al., 2021). The present study examined the relationship between perceived memory self-efficacy and performance and adherence on self-administered, smartphonebased remote cognitive assessments.
Participants and Methods:
Participants were 123 cognitively unimpaired adults (ages 55-80, 68.3% female, 87% White, M= 16.5 years of education) recruited from the Butler Hospital Alzheimer’s Prevention Registry as part of an ongoing study evaluating novel cognitive assessment methods. A cutoff of score of ≥34 on the modified Telephone Interview for Cognitive Status (TICSm) was required for enrollment. Perceived memory self-efficacy was assessed using two subscales of the Personal Beliefs about Memory Instrument (PBMI; Lineweaver et al., 1998): “prospective control”, the perception of control one currently has to influence future memory functioning, and “future control”, the perception of the amount of control over memory function one will have in the future. Participants completed three brief self-administered cognitive testing sessions per day for 8 consecutive days using a mobile app-based platform developed as part of the National Institute of Aging’s Mobile Toolbox initiative. Cognitive tasks assessed visual working memory (WM), processing speed (PS), and episodic memory (EM)(see Thompson et al., 2022).
Results:
Statistical analyses were conducted using univariate ANOVA tests to look for main effects of each PBMI subscale score on remote assessment adherence and average performance on each task over 8 days. After adjusting for aging, we found a higher rate of false alarms (proportion of misidentified stimuli) on the WM task was associated with higher levels of both self-reported prospective control (F(2, 86) = 4.188, p = .018) and future control (F(2, 96) = 5.003, p = .009). Increased response time on the PS task was also associated with higher levels of future control when adjusted for aging (F(2, 96) = 6.075, p = .003). There was no main effect of memory self-efficacy ratings on EM. We found no main effects of memory self-efficacy ratings on assessment adherence.
Conclusions:
These findings suggest perceptions of high prospective and future control are associated with positive response bias on a forced-choice WM task, and high perceptions of future control are also associated with slower response times on PS tasks. Future research should examine whether this is due to increased deliberation, cautiousness, or other factors. Limitations include the potentially limited generalizability of this largely White, highly educated, and motivated sample self-selected for AD research. Next steps for this research include comparing these results with the effects of perceived self-efficacy on in-person cognitive assessments.
The Cordoba Naming Test (CNT) is a 30-item confrontation naming test developed in Argentina. A common confrontation naming task used in the United States is the Boston Naming Test (BNT). Research shows that age affects BNT performance in the 60-item long form. In fact, studies show that scores on confrontation naming tasks increase in childhood and continue to improve until approximately 40 years of age. However, after this period, scores start to subsequently decline, and especially so after 70 years of age. On the other hand, some studies have reported that older adults maintain high BNT performance despite advancing age. To our knowledge, no study has investigated the aging effects of the CNT across various age groups. We expected CNT scores to increase significantly from young adulthood to mid-adulthood and then significantly decline with advancing age.
Participants and Methods:
The present study sample consisted of 272 neurologically and psychologically healthy participants with a mean age of 27.06 (SD = 12.21) with 14.29 years of education completed (SD = 2.46). Participants were divided into six different age groups: 18-19-year-old group, 20-29-year-old group, 30-39-year-old group, 40-49-year-old group, 50-59-year-old group, and 60-69-year-old group. All participants consented to voluntary participation and completed the CNT and a comprehensive background questionnaire in English. The CNT consisted of 30 black and white line drawings, ranging from easy to hard difficulty. An ANCOVA, controlling for gender, was used to evaluate CNT performance between the six age groups. We used a threshold of p < .05 for statistical significance.
Results:
Results revealed significant group differences between the six age groups on the CNT, p = .000, ηp2 = .14. A post-hoc test revealed that the 30-39-year-old group outperformed the 18-19-year-old, 20-29-yearold, and 60-69-year-old groups on the CNT. Finally, the 40-49-year-old group outperformed the 18-19-year-old and 60-69-year-old groups on the CNT.
Conclusions:
As we predicted, participants demonstrated steady improvement in the CNT until the age of 40. However, we found that until the age of 60, CNT performance started to decline significantly. Our data suggests that CNT performance declines significantly at the age of 60 compared to previous research using the BNT. Research shows other demographic variables (e.g., gender, linguistic factors) influence BNT performance. Future investigations on the CNT using a healthy sample should use a multivariate statistical analysis method to help explain influencing factors across aging. This research can have the potential to improve public health to better support and understand individuals from diverse backgrounds.
Several studies have noted associations of higher white matter hyperintensities (WMHs) with cognitive slowing and elevated depressive symptoms in older adults. Depression is also directly associated with cognitive slowing in later life. However, the influence of WMHs on the relationship between depressive symptoms and processing speed is unclear. This interrelationship between depression, processing speed, and WMH may differ between racial groups given the well-documented evidence of racial disparities in vascular disease, WMHs, and cognitive performance, however the literature is sparse. The goal of this current study, therefore, was to investigate whether WMHs mediate the relationship between depressive symptoms and processing speed, and if this relationship differs between Black and White older adults.
Participants and Methods:
A total of 171 non-Hispanic White and 111 non-Hispanic Black older adults (total sample mean age = 82.71 ± 2.74; 42.91% male) from the Healthy Brain Project (a substudy of the Health, Aging, and Body Composition Study) underwent MRI as well as a neuropsychological evaluation. Total WMH volume was quantified for each participant using an automated procedure and normalized to total brain volume. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Digit Symbol Substitution Test (DSST) served as a measure of processing speed. Causal mediation analyses were performed between CES-D and DSST scores across the total sample as well as within racial groups (Black and White), with total WMH volume as the mediator.
Results:
The direct effect of the CES-D on DSST was significant (p = 0.012) for the total sample, reflecting slower processing speed at higher levels of depressive symptoms, but the indirect effect was not (p = 0.207). When analyses were stratified by racial group, the indirect effect was significant for Black (p = 0.054; 37.17% mediated) but not White participants (p = 0.207): For Black participants, the inverse relationship between depressive symptoms and processing speed was mediated by a positive relationship between depressive symptoms and WMHs.
Conclusions:
While these data support previous findings relating depressive symptoms to slower processing speed across racial groups, our findings also demonstrate a greater impact of WMHs on this relationship in Black older adults compared to their White counterparts. This suggests that WMHs may serve as an important risk factor for cognitive slowing in older Black adults with higher depressive symptoms. Future studies are needed to further investigate the role of WMHs on depression-related deficits in processing speed and other cognitive domains in racially diverse groups.
Determine how characteristics of deployment mild traumatic brain injury (TBI) and blast exposure influence the relationship between the functional brain connectome with cognitive outcomes and symptom severity.
Participants and Methods:
N = 181 Iraq and Afghanistan combat veterans completed structured clinical interviews, cognitive testing, self-report questionnaires, and magnetoencephalography (MEG). MEG data were acquired in the resting-state with eyes open. MEG data were beamformed to identify brain regions active at rest. Functional brain connectomes representing the unique network present for a given individual were created using active brain regions identified for each participant. Network metrics describing these connectomes were calculated at the participant level. Cognitive tests included the WAIS-IV, Trail Making Test Parts A&B, and the Controlled Oral Word Association test. Due to differences in normative data across tests, raw scores were used in analyses. Symptom measures included the PTSD Checklist - 5 (PCL-5), Patient Health Questionnaire (PHQ-9), Neurobehavioral Symptoms Inventory (NSI), Quality of Life After Brain Injury (QOLIBRI), Pittsburgh Sleep Quality Index (PsQi), the Distress Tolerance Scale (DTS), and the PROMIS Pain Interference Scale (PROMIS-PI).
Results:
Hierarchical linear regression analyses revealed that several network metrics were significantly related to both cognitive outcomes and symptom severity after adjusting for demographic covariates and clinical characteristics.
The relationship between Global Efficiency (GE) and cognitive outcomes was moderated by deployment TBI on the WAIS-IV Full Scale Index (FSI), Perceptual Reasoning Index (PRI), and General Ability Index (GAI). In all cases, when deployment TBI was absent, greater GE was associated with poorer cognitive scores. The relationship between GE and symptom severity was moderated by the severity of blast exposure. Greater GE was associated with lower symptom severity at lower blast severities for the PHQ-9 and QOLIBRI A (thinking) and E (negative emotions). Moderation effects were also observed for the PSQI. In the absence of deployment TBI, greater GE was associated with better sleep quality; however, in the presence of deployment TBI, greater GE was associated with poorer sleep quality. Other connectome-outcome relationships were not consistently moderated by Deployment TBI or blast history
Conclusions:
Results demonstrated relationships between several aspects the functional connectome of the brain with both cognitive outcomes and symptom severity beyond effects of common demographic and clinical variables. Moderation analyses revealed that the relationship between GE of the connectome and outcomes is frequently disrupted by deployment TBI and blast. GE is a measure of the ease of information transfer through the network. These results identified consistent relationships between GE and outcomes in the absence of deployment TBI or blast, but these relationships disappear when deployment TBI or blast are present. Participants in this study were on average 11 years post-TBI or blast exposure, suggesting these are chronic rather than acute effects. GE was significantly correlated with most symptom severity measures as well as the WAIS-IV PRI, GAI, VCI, and FSI. Future efforts to normalize the relationship between GE and outcomes following TBI may improve rehabilitation outcomes and directly affect areas of concern commonly reported by service members following TBI or blast exposure.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary form of cerebral small vessel disease leading to early cerebrovascular changes. These changes result from mutations in the NOTCH3 gene that cause progressive accumulations of granular osmiophilic material (GOM) deposits, thickening arterial walls and reducing or restricting blood flow in the brain. The clinical presentation of CADASIL is characterized by migraines with aura, early and recurrent strokes, progressive cognitive impairment, and psychiatric disturbances. CADASIL is rare but frequently underrecognized or misdiagnosed. A genetic condition with a 50% risk of inheritance from an affected parent, the gold standard for diagnosis is genetic testing to determine the presence of mutations in the NOTCH3 gene. This presentation aims to familiarize neuropsychologists with the condition of CADASIL through a unique case study highlighting important psychological, social, and ethical considerations raised by genetic testing.
Participants and Methods:
This case study presents a 67-year-old, right-handed, married female diagnosed with CADASIL who was referred for neuropsychological evaluation of cognitive function and low mood concerns following multiple ischemic events.
Results:
Results revealed severe cognitive deficits in domains of attention, learning, and memory. Her superior verbal abilities and executive function remained largely intact. Assessment of mood revealed elevations in symptoms of depression and anxiety. The patient was aware of CADASIL in her father, paternal aunt, and younger brother, but elected to forego any genetic testing to confirm whether she had the condition until she experienced a stroke at age 61. She has two adult children who have also elected to forego testing and currently remain asymptomatic. Cognitive profile, mood disturbances, and patient perspectives on refraining from pre-symptomatic genetic testing for CADASIL diagnosis will be discussed.
Conclusions:
Aspects of this case are consistent with a small body of literature evidencing distinct psychological, emotional, and social challenges among families carrying genetic risk of CADASIL. While providing an example of an often underrecognized neurological disorder with which neuropsychologists should be familiar, this case uniquely raises ethical questions relevant to care providers and current treatment guidelines regarding genetic testing among families carrying highly heritable neurological conditions. In particular, personal ethical challenges around deciding to pursue or forego pre-symptomatic testing, and implications for family planning, highlight the importance of genetic counseling for affected families.
HSCT is increasingly used for curative therapy for patients with high risk hematologic diseases. Existing research regarding the neurocognitive impact of HSCT on pediatric patients is notably variable. One area of identified risk is attention/working memory (WM) [Perkins et al., 2007]. The current study examines the degree to which difficulties in attention/WM are present prior to HSCT, as assessed using parent-report of working memory and cognitive tests of attention span and working memory.
Participants and Methods:
Participants were 19 children and adolescents ages 6-17 years (M= 9.63, SD= 3.22) who were enrolled in a prospective longitudinal study monitoring neurocognitive outcomes in children undergoing HSCT. Participants were eligible for this study if they were 2-18 years old at the time of transplant and had a diagnosis that qualified for an allogenic HSCT. Participants were ineligible if they had a pre-HSCT developmental delay, were non-English speaking, and had a prior HSCT or prior CAR T-cell therapy. Participants were 53% female and 95% Caucasian. Diagnoses in the current study sample included acute lymphoblastic leukemia (n=10), acute myeloid leukemia (n=8), and myelodysplastic syndrome (n=1).
Measures included were the Working Memory Index score from the Behavior Rating Inventory of Executive Function (BRIEF; Gioia et al., 2000) and the Digit Span subtest from the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV; Wechsler, 2003) and the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV; Wechsler, 2008).
Results:
Mean scores on parent-reported WM scores and cognitive measures of attention/WM fell within normal limits, including the Digit Span Total score (M = 48.42, SD= 6.33), Digit Span Forward score (M = 47.28, SD = 9.9.83), and Digit Span Backward score (M = 48.94, SD = 6.31). However, further analyses suggested that between 11-32% of patients had scores falling at least one standard deviation below the mean on these measures, with more than half of the sample (52.6%) identified with at least one measured weakness in attention and WM. The most commonly identified weakness (33.3% of patients) was Digit Span Forward. Correlations between parent-reported WM issues and cognitive measures of attention and WM were generally strong, with parent report of WM significantly correlated with the Digit Span Total score (r(18)= -0.52, p=.02) and the Digit Span Forward score (r(18) = -0.51, p=.03). No correlations were found between Digit Span Backward and other measures of attention and WM.
There were no significant differences in WM scores between patients with ALL and AML. Additional analyses will examine potential contribution of medical factors (e.g., pre-HSCT treatment) to pre-HSCT performance on measures of attention and WM.
Conclusions:
These results suggest that, prior to undergoing HSCT, pediatric patients present with attention and WM issues. This finding has implications for research related to neurocognitive outcomes in HSCT, indicating the need to obtain pre-HSCT cognitive data in this area in order to fully understand potential change after HSCT. In addition, providers may need to consider adapting communication methods with patients during their transplant stay, given potential attention and WM issues within this population.
Evidence suggests that the most consistent cognitive impairment found in individuals experiencing posttraumatic stress disorder symptomology is verbal memory impairment (Johnsen & Asbjornsen, 2008). More specifically, research has shown that patients with PTSD perform poorer on verbal memory tasks relating to logical (story) memory than on word memory tasks, such as CVLT-III (Barrera-Valencia et al., 2017). While recent literature accounts for memory impairments related to PTSD, less is known about this relationship for individuals with mere trauma exposure compared to individuals without trauma exposure. The present research aims to determine if there is a significant impact on WMS-LM when compared to CVLT-III for individuals in a community sample that have been exposed to a traumatic event in their lifetime.
Participants and Methods:
One hundred nineteen patients presented to a community-based practice for neuropsychological evaluation. Patients were screened for trauma exposure during a clinical interview. Immediate and long delay trials of Wechsler Memory Scale IV Logical Memory (WMS-LM) were used to examine structured learning and memory and the California Verbal Learning Test (CVLT-II) immediate and long delay recalls were used to examine unstructured learning and memory. Out of the 119 patients, 36 patients reported trauma exposure. Twenty-five were diagnosed as “normal,” 62 were diagnosed with mild cognitive impairment, and 32 were diagnosed with dementia. A one-way MANOVA was conducted to examine the relationship across the multiple dependent variables.
Results:
There was a statistically significant difference in immediate recall in memory based on exposure to trauma, F (2, 116) = 3.28, p < .05; Wilk’s A = 0.947, partial n2 = .53, such that individuals with trauma exposure performed better. For long delay recall performance, there was a similar trend though it did not reach statistical significance F (2, 114) = 3.03, p = .052; Wilk’s A = 0.949, partial n2 = .51.
Conclusions:
Data showed that patients who reported trauma exposure scored significantly higher on immediate recall performance on CVLT and WMS-LM than those who did not report trauma exposure. Although research suggests that patients who were exposed to trauma often experience cognitive deficits on verbal memory tasks, evidence also shows that trauma exposure can lead to higher immediate recall performance in memory related to attentional allocation modeling (Hayes et al., 2012).
Pediatric traumatic brain injury (TBI) is the leading cause of disability in children under the age of 15, often resulting in executive function deficits and poor behavioral outcomes. Damage to white matter tracts may be a driving force behind these difficulties. We examined if whether 1) greater TBI severity was associated with worse neurobehavioral outcome, 2) greater TBI severity was associated with tract-based white matter microstructure, and 3) worse neurobehavioral outcome was associated with white matter microstructure.
Participants and Methods:
Twelve children with complicated-mild TBI (cmTBI; Mage=12.59, nmale=9), 17 with moderate-to-severe TBI (msTBI; Mage =11.50, nmale=11), and 21 with orthopedic injury (OI; Mage =11.60, nmale=16), 3.94 years post injury on average, were recruited from a large midwestern children’s hospital with a Level 1 Trauma Center. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Child Behavior Checklist (CBCL) while children completed 64-direction diffusion tensor imaging in a Siemens 3T scanner. White matter microstructure was quantified with FMRIB’s Diffusion Toolbox (FSLv6.0.4). Tract-Based Spatial Statistics computed fractional anisotropy (FA) and mean diffusivity (MD) for the cingulum bundle (CB), inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and uncinate fasciculus (UF), bilaterally.
Results:
Group differences were assessed using one-way ANOVA. Children with msTBI were rated as having worse Sluggish Cognitive Tempo on the CBCL than children with cmTBI and OI (p=.02, eta2=.143); no other parent-rated differences reached significance. Group differences were found in left SLF FA (p=.031; msTBI<cmTBI=OI) and approached significance in left UF FA (p=.062, eta2=.114; msTBI<OI). Group differences were also found in right IFOF MD (p=.048; msTBI>OI) and left SLF MD (p=.013; msTBI>cmTBI=OI). Bivariate correlations assessed cross-domain associations. Higher left IFOF FA was associated with better BRIEF Metacognitive Skills (r=-.301, p=.030) and CBCL School Competence (r=.280; p=.049). Higher left SLF FA was associated with better BRIEF Behavioral Regulation and Metacognitive Skills (r=-.331, p=.017 and r=-.291, p=.036, respectively), and CBCL School Competence and Attention Problems (r=.398, p=.004 and r=-.435, p=.001, respectively). Similarly, higher right UF FA was broadly associated with better neurobehavioral outcomes, including Behavioral Regulation and Metacognitive Skills (r=-.324, p=.019 and r=-.359, p=.009, respectively), and School Competence, Attention Problems, and Sluggish Cognitive Tempo (r=.328, p=.020, r=-.398, p=.003, and r=-.356, p=.010, respectively). Higher right CB MD was associated with worse Behavioral Regulation (r=.327, p=.018) and more Attention Problems (r=.278, p=.046); higher left and right SLF MD was associated with Sluggish Cognitive Tempo (r=.363, p=.008, r=.408, p=.003, respectively).
Conclusions:
Children with TBI, particularly msTBI, were rated as having cognitive slowing; while other anticipated group differences in neurobehavioral outcomes were not found, this appears driven by milder difficulties in cmTBI and OI groups. In fact, across CBCL and BRIEF subscales, children with msTBI were rated as approaching or exceeding a full standard deviation deficit based on normative data. TBI severity was also associated with white matter microstructure and cross-domain associations linked microstructure with observable neurobehavioral morbidities, suggesting a possible mechanism post-injury. Future longitudinal studies would be useful to examine the temporal evolution of deficits.
Psychosocial factors show a significant relationship between child behavior problems, family functioning, and cognitive performance in children with Sickle Cell Disease, marking those as important targets for intervention among this population. The purpose of this research is to address the effects of psychosocial factors impact on specific cognitive domains.
Participants and Methods:
Archival data from the National Institutes of Health’s Cooperative Study of Sickle Cell Disease was used. Data was restricted to individuals aged 14 or younger (N= 2,408), with 47.8% (n = 1,152) identified as female and 52.2% (n = 1,256) as male. Black or African American (96.9%, n = 2,334) children made up the majority of the sample, with the remainder coded as “other” (2.8%, n = 68). The measures utilized included the Wechsler Intelligence Scale for Children-Revised (WISC-R), Wechsler Intelligence Scale for Children-Third Edition (WISC-III), Peabody Picture Vocabulary Test (PPVT), Achenbach Child Behavior Checklist, and Family Environment Scale (FES).
Results:
Bivariate correlations were completed with significant correlations found between FES and performance on the WISC-R/III and PPVT. Supportiveness subscale on the FES demonstrated several statistically significant correlations with WAIS FSIQ (r = .21, p = .000) as well as the Information (r = .22, p = .000), Similarities (r = .17, p = .001), Arithmetic (r = .13, p = .021), Block Design (r = .11, p = .036), Vocabulary (r = .22, p = .000), Object Assembly (r = .12, p = .033), Comprehension (r = .19, p = .000), and Digit Span (r = .13, p = .014) subscales. A statistically significant correlation was observed between the PPVT and the Supportiveness subscale (r = .34, p = .000).
Conclusions:
Various areas of cognitive functioning are affected by family dynamics. Improvement in family functioning would benefit the cognitive functioning of children with SCD. To increase aspects of family functioning including supportiveness, early identification of children with SCD, targeted interventions, and family and/or individual therapy for caregivers are suggested.
Multiple sclerosis (MS), an inflammatory autoimmune disease of the central nervous system, is characterized by damage to white matter via myelin degeneration with resulting sclerotic plaques and lesions. Upwards of 70% of people with MS show cognitive changes in multiple domains including verbal memory. Advances in disease-modifying therapies have increased the expected lifespan of people with MS, making aging with MS a critical emerging area of study. Memory declines during normal aging, yet the specific impact of MS on verbal memory in aging is inconclusive and understudied. To address this gap in knowledge, we examined whether MS was associated with verbal learning slope, total learning, delayed recall, and recognition performance in older adults. We further explored whether MS disease severity influenced these memory operations.
Participants and Methods:
Participants included two cohorts: older adults with MS recruited from MS centers and patient registries, and healthy controls recruited from the community. A total of 164 adults age 60 and older without dementia were included in the current study, 79 in the MS group (mean age = 65.05 + 4.72; %female = 62) and 85 in the control group (mean age = 69.53 + 6.65; %female = 65.9). All participants were administered a neuropsychological battery including the Hopkins Verbal Learning Test-Revised (HVLT-R). The Patient Determined Disease Steps (PDDS), a patient-rated score of disability severity in MS comprised of eight steps related to walking ability, was used to operationalize MS severity. Using a median split, the PDDS was dichotomized into low (PDDS = 0-2) versus high (PDDS = 3-5) MS severity groups. Linear regression models were run to examine the effect of group (MS vs. control) and disease severity (PDDS) on four operations from the HVLT-R: learning slope, total learning, delayed recall, and recognition. Statistical analyses adjusted for age, years of education, and sex.
Results:
Linear regression models revealed that older adults with MS showed lower total learning compared to healthy controls (β = -.18, p = .03). Learning slope, delayed recall, and recognition did not differ by group (p > .05). Compared to healthy controls, older adults with high MS severity performed worse on total learning (β = -.21; p = .01) and delayed recall (β = -.18; p = .03). Group differences on learning slope and recognition were not significant (p > .05).
Conclusions:
The presence of MS was associated with worse total learning. Moreover, high severity of MS was associated with worse total learning and delayed recall in older adults. These results delineate the influence of MS on specific memory operations and emphasize the potential utility of disease severity on cognitive performance in aging.
Health disparities among African Americans (AAs) in the United States are evident, especially among older adults and people living with HIV (PLWH). These health disparities include worse cognitive functioning among AAs than White counterparts. Though disparities in health literacy among AAs impact health outcomes across clinical populations, less is known on the mechanistic role health literacy may play in explaining racial differences in cognitive functioning among older PLWH. The current study investigated the association between health literacy and global cognitive functioning among middle-aged and older AA and White adults with and without HIV in the Deep South.
Participants and Methods:
Two hundred and seventy-three people (170 PLWH: 146 AA, 24 White; 103 HIV-negative: 67 AA, 36 White) were enrolled in an observational study and completed measures of sociodemographic characteristics, as well as the reading subtest of the Wide Range Achievement Test-3rd Edition to assess verbal IQ. A composite score of socioeconomic status (SES) was created using total years of education and annual household income. Neurocognitive functioning was assessed using a comprehensive cognitive battery (i.e., verbal, attention/working memory, executive function, learning, recall, speed of processing, and motor), from which a sample-based global Z-score composite was created. Health literacy was measured using a sample-based composite Z-score derived from the Rapid Estimate of Adult Literacy in Medicine, Test of Functional Health Literacy in Adults Reading Comprehension, Newest Vital Sign, and Expanded Numeracy Scale. First, multivariable linear regression analyses were performed within both PLWH and HIV-negative samples examining the association between race, SES, verbal IQ, and health literacy with cognitive functioning. These results informed two bootstrap confidence interval mediation analyses to determine whether health literacy mediated the association between race and global cognitive functioning.
Results:
In both PLWH and HIV-negative individuals, linear regressions showed that Whites had better global cognitive functioning, health literacy, and verbal IQ than AAs. Linear regressions showed that health literacy had an independent association with cognitive function when accounting for verbal IQ and SES. Mediations showed that health literacy significantly mediated the association between race and global cognitive functioning in both samples, independent of verbal IQ (PLWH: b = .07, 95% CI [0.0096, 0.2149]; HIV-negative: b = .15, 95% CI [0.0518, 0.2877]), indicating that Whites were expected to obtain higher global cognitive Z-scores than AAs in both PLWH and HIV-negative samples, through the mediating effect of better health literacy.
Conclusions:
Health literacy significantly mediated the association between race and global cognitive functioning among middle-aged and older adults with and without HIV, underscoring the importance of health literacy in explaining racial disparities in cognitive outcomes among AAs in the Deep South. Findings have implications for guiding clinicians and healthcare providers in developing interventions that promote health literacy in these underserved populations, which may have downstream impacts on cognitive functioning. Future work is needed to examine mechanisms whereby health literacy impacts neurocognition among AA PLWH.
Community reintegration and participation have been shown to be significantly correlated to improved Quality of Life (QoL) following moderate to severe traumatic brain injury (msTBI), yet these models often come with significant levels of unaccounted variability (Pierce and Hanks, 2006). Measures for community participation frequently employ objective measures of participation, such as number of outings in a week or current employment status (Migliorini et al., 2016), which may not adequately account for lifestyle differences, especially in aging populations. Less often integrated are subjective measures of an individual’s own belongingness and autonomy within the community (Heineman et al., 2011), also referred to as their participation enfranchisement (PE). The present study examines three questions pertinent to the potential clinical value of PE. First, do measures of objective participation significantly predict an individual’s PE ratings? Second, are both types of measures equally successful predictors of QoL for aging individuals with chronic-stage msTBI. Finally, would controlling for either objective or subjective integration ratings enable neurocognitive assessments to better predict QoL post injury?
Participants and Methods:
41 older-adults (M= 65.32; SD= 7.51) with a history of msTBI were included (M= 12.59 years post-injury;SD= 8.29) for analysis. Subjective community integration was measured through the Participation Enfranchisement Survey. The Participation Assessment with Recombined Tools-Objective (PART-O) provided the objective measurement of participation. Quality of life was assessed through the Quality of Life after Brain Injury (QOLIBRI). An estimate of neurocognitive performance was created through the Brief Test of Adult Cognition by Telephone (BTACT), which includes six domains including: verbal-learning and memory (immediate and delayed recall), working memory (digit-span backwards), reasoning (number sequencing), semantic fluency (category fluency), and processing speed (backwards counting). Performance on the BTACT, PE ratings, and PART-O scores were included as the dependent variables in stepwise, linear regression models predicting QoL ratings to assess the differential contribution of the dependent variables and potential interaction effects.
Results:
While both the PART-O (f(1,39)=5.52;p=.024,n2=.124) and the PE survey (f(1,39)=14.31 ;p<.001,n2=.268) significantly predicted QoL, the addition of PE in the PART-O model resulted in significant (20.9%) reduction in unaccounted variance. Further in the model controlling for PE, PART-O no longer provides a significant (p=.15) contribution to the model estimating QoL (f(2,38)=8.41; p=.001). Performance on the BTACT correlated with PART-O (p<.0001), but not PE (p=.13) ratings. Finally, across two models controlling for BTACT performance, PE (p=.002,partial n2=.23), but not PART-O (p=.28,partial n2=.031) contributed significantly to QoL predictions. No significant interactions between PART-O, PE, and/or BTACT were observed when added to any model.
Conclusions:
MsTBI impacts nearly every facet of an individual’s life, and as such, improving QoL post-injury requires a broad, yet well-considered approach. The objective ratings of participation, subjective PE, BTACT performance, all independently predicted quality of life in this sample. However, after controlling for neurocognitive assessment performance, PE was shown to independently contribute to quality of life, while the PART-O ratings no longer provided significant contribution. While community integration is a vital factor to consider for long-term rehabilitation, tailoring what “integration” means to the patient may hold significant potential to improve long-term quality of life.
To examine the relationships between baseline gray matter volumes, diagnostic status, and executive function performance at 24-month follow-up, and the relative importance of predictors of executive function in a cohort of non-demented older adults.
Participants and Methods:
The study sample included 147 participants from the Alzheimer’s Disease Neuroimaging Initiative (mean age = 70.6, SD = 6.4; mean education = 17 years, SD = 2.4). At baseline, 49 participants were diagnosed as cognitively normal (CN), 60 as early mild cognitive impairment (EMCI), and 38 as late mild cognitive impairment (LMCI). Magnetic resonance imaging (MRI) data were collected at baseline. A composite score of executive function and FreeSurfer-derived gray matter regions-of-interest (ROI; whole brain, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, superior parietal lobule, inferior parietal lobule, hippocampus) were examined. Hierarchical linear regression models were employed to assess whether brain volume predicted executive function at 24-month follow-up and interaction effects between baseline ROI volume and diagnostic status. Age, gender, education, Mini-Mental State Examination scores, and APOE-e4 allele status were included as control variables in each model. Relative importance metrics, which quantifies an individual regressor’s contribution to a multiple regression model, were computed using the Lindemen, Merenda, and Gold (lmg) method to assess the relative contribution of each variable in predicting executive function performance.
Results:
Across all participants, baseline gray matter ROI volume accounted for a significant amount of variance in executive function at 24-months after accounting for control variables. Specifically, anterior cingulate cortex and superior parietal lobule accounted for an additional 7% and 6% of variance in executive function at 24-months. Significant brain region X diagnostic status interaction effects were observed in executive function performance at 24-months. Relative importance metrics within each group indicated that age is the most important predictor of executive function at 24-months for CN, anterior cingulate cortex is most important for EMCI, and Mini-Mental Examination score is most important for LMCI.
Conclusions:
Our findings implicate frontoparietal gray matter regions as significant predictors of executive function performance at 24-months, and that this relationship is moderated by diagnostic status. Our results indicate that the value of specific variables to predict executive function performance varies based on diagnostic status. Specifically, anterior cingulate cortex was a significant predictor of executive function performance across all participants and was the most important variable in predicting performance in the earliest stage of mild cognitive impairment. These results support previous studies examining gray matter correlates of executive function and extend the literature by exploring predictors of executive function in early and late stages of mild cognitive impairment.