Associations of category fluency clustering performance with in vivo brain pathology in autosomal dominant Alzheimer's disease.

OBJECTIVES: Alzheimer's disease (AD) is known to impact semantic access, which is frequently evaluated using the Category Fluency (Animals) test. Recent studies have suggested that in addition to overall category fluency scores (total number of words produced over time), poor clustering could signal AD-related cognitive difficulties. In this study, we examined the association between category fluency clustering performance (i.e., stating words sequentially that are all contained within a subcategory, such as domestic animals) and brain pathology in individuals with autosomal dominant Alzheimer's disease (ADAD). METHODS: A total of 29 non-demented carriers of the Presenilin1 E280A ADAD mutation and 32 noncarrier family members completed the category fluency test (Animals) and the Mini-Mental State Examination (MMSE). The participants also underwent positron emission tomography (PET) scans to evaluate in vivo amyloid-beta in the neocortex and tau in medial temporal lobe regions. Differences between carriers and noncarriers on cognitive tests were assessed with Mann-Whitney tests; associations between cognitive test performance and brain pathology were assessed with Spearman correlations. RESULTS: Animal fluency scores did not differ between carriers and noncarriers. Carriers, however, showed a stronger association between animal fluency clustering and in vivo AD brain pathology (neocortical amyloid and entorhinal tau) relative to noncarriers. CONCLUSION: This study indicates that using category fluency clustering, but not total score, is related to AD pathophysiology in the preclinical and early stages of the disease.

Integrating Lifestyle Factor Science into Neuropsychological Practice: A National Academy of Neuropsychology Education Paper.

OBJECTIVE: The primary aim of this paper is to review evidence and clinical implications related to lifestyle activities associated with promoting brain and cognitive health. Our review targets four key lifestyle factors: physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets. METHOD: We conducted a critical review of the lifestyle factor literature in the four domains listed earlier. We contextualize this literature review by translating findings, when possible, into evidence-based recommendations to consider when providing neuropsychological services. RESULTS: There is significant current evidence supporting the role of physical activity and exercise, social engagement, cognitively stimulating activity, and consuming Mediterranean-style diets on positive brain and cognitive health outcomes. While some null findings are present in all four areas reviewed, the weight of the evidence supports the notion that engaging in these activities may promote brain and cognitive functioning. CONCLUSIONS: Clinical neuropsychologists can have confidence in recommending engagement in physical activity, social activity, and cognitively stimulating activity, and adhering to a Mediterranean-style diet to promote brain and cognitive health. We discuss limitations in existing lifestyle factor research and future directions to enhance the existing evidence base, including additional research with historically underrepresented groups and individuals with neurological conditions.

Plasma p-tau217 predicts in vivo brain pathology and cognition in autosomal dominant Alzheimer's disease.

INTRODUCTION: Plasma-measured tau phosphorylated at threonine 217 (p-tau217) is a potential non-invasive biomarker of Alzheimer's disease (AD). We investigated whether plasma p-tau217 predicts subsequent cognition and positron emission tomography (PET) markers of pathology in autosomal dominant AD. METHODS: We analyzed baseline levels of plasma p-tau217 and its associations with amyloid PET, tau PET, and word list delayed recall measured 7.61 years later in non-demented age- and education-matched presenilin-1 E280A carriers (n = 24) and non-carrier (n = 20) family members. RESULTS: Carriers had higher plasma p-tau217 levels than non-carriers. Baseline plasma p-tau217 was associated with subsequent amyloid and tau PET pathology levels and cognitive function. DISCUSSION: Our findings suggest that plasma p-tau217 predicts subsequent brain pathological burden and memory performance in presenilin-1 E280A carriers. These results provide support for plasma p-tau217 as a minimally invasive diagnostic and prognostic biomarker for AD, with potential utility in clinical practice and trials. HIGHLIGHTS: Non-demented presenilin-1 E280A carriers have higher plasma tau phosphorylated at threonine 217 (p-tau217) than do age-matched non-carriers. Higher baseline p-tau217 is associated with greater future amyloid positron emission tomography (PET) pathology burden. Higher baseline p-tau217 is associated with greater future tau PET pathology burden. Higher baseline p-tau217 is associated with worse future memory performance.

Initial investigation of test-retest reliability of home-to-home teleneuropsychological assessment in healthy, English-speaking adults.

Prior teleneuropsychological research has assessed the reliability between in-person and remote administration of cognitive assessments. Few, if any, studies have examined the test-retest reliability of cognitive assessments conducted in sequential clinic-to-home or home-to-home teleneuropsychological evaluations - a critical issue given the state of clinical practice during the COVID-19 pandemic. This study examined this key psychometric question for several cognitive tests administered over repeated videoconferencing visits 4-6 months apart in a sample of healthy English-speaking adults.A total of 44 participants (ages 18-75) completed baseline and follow-up cognitive testing 4-6 months apart. Testing was conducted in a home-to-home setting over HIPAA-compliant videoconferencing meetings on participants' audio-visual enabled laptop or desktop computers. The following measures were repeated at both virtual visits: the Controlled Oral Word Association Test (FAS), Category Fluency (Animals), and Digit Span Forward and Backward from the Wechsler Adult Intelligence Scale, Fourth Edition. Intraclass correlation coefficients (ICC), Pearson correlations, root mean square difference (RMSD), and concordance correlation coefficients (CCC) were calculated as test-retest reliability metrics, and practice effects were assessed using paired-samples t-tests.Some tests exhibited small practice effects, and test-retest reliability was marginal or worse for all measures except FAS, which had adequate reliability (based on ICC and r). Reliability estimates with RMSD suggested that change within +/- 1 SD on these measures may reflect typical test-retest variability.The included cognitive measures exhibited questionable reliability over repeated home-to-home videoconferencing evaluations. Future teleneuropsychology test-retest reliability research is needed with larger, more diverse samples and in clinical populations.

The role of top-down attentional control and attention-deficit/hyperactivity disorder symptoms in predicting future motor vehicle crash risk.

Objective: Attention-deficit/hyperactivity disorder (ADHD) confers elevated risk for automobile crashes, both as a clinical syndrome and continuously when examining risk as a function of symptom severity. However, the neurocognitive mechanisms and processes underlying this risk remain poorly understood. The current longitudinal study examined whether attention network components reflect neurocognitive pathways linking ADHD symptoms with adverse driving outcomes. Method: Drivers from six U.S. sites participating in the Strategic Highway Research Program Naturalistic Driving Study (N=3,226) were prospectively monitored for objectively identified crashes, near-crashes, and crash/near-crash fault. At study entry, drivers were assessed for ADHD symptoms; completed the Conners' Continuous Performance Test, Second Edition; and were then followed continuously for 1-2 years of routine, on-road driving using technology-enhanced in-car monitoring. Bias-corrected, bootstrapped mediation models examined the extent to which attention network components mediated the association between ADHD symptoms and future driving risk, controlling for known risk factors. Results: As expected, self-reported ADHD symptoms predicted all markers of future driving risk. Higher ADHD symptoms were associated with reduced inhibitory control, lower levels of top-down attentional control (endogenous orienting), and greater arousal decrements (phasic alertness). Controlling for ADHD symptoms, top-down attentional control uniquely predicted future crashes, near-crashes, and culpability for future crashes/near-crashes; only arousal decrements portended future near-crashes. Only top-down attentional control significantly mediated the association between baseline ADHD symptoms and future driving risk. Conclusions: The driving risks associated with ADHD appear to be conveyed in part by impairments in the top-down, voluntary control of attention, rather than by difficulties sustaining attention over time or inhibiting impulses, as is often assumed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Can working memory training work for ADHD? Development of central executive training and comparison with behavioral parent training.

OBJECTIVE: Working memory deficits have been linked experimentally and developmentally with attention-deficit/hyperactivity disorder (ADHD)-related symptoms/impairments. Unfortunately, substantial evidence indicates that extant working memory training programs fail to improve these symptoms/impairments. We hypothesized that this discrepancy may reflect insufficient targeting, such that extant protocols do not adequately engage the specific working memory components linked with the disorder's behavioral/functional impairments. METHOD: The current study describes the development, empirical basis, and initial testing of central executive training (CET) relative to gold-standard behavioral parent training (BPT). Children with ADHD ages 8-13 (M = 10.43, SD = 1.59; 21 girls; 76% Caucasian/non-Hispanic) were treated using BPT (n = 27) or CET (n = 27). Detailed data analytic plans for the pre/post design were preregistered. Primary outcomes included phonological and visuospatial working memory, and secondary outcomes included actigraphy during working memory testing and two distal far-transfer tasks. Multiple feasibility/acceptability measures were included. RESULTS: The BPT and CET samples did not differ on any pretreatment characteristics. CET was rated as highly acceptable by children and was equivalent to BPT in terms of feasibility/acceptability as evidenced by parent-reported high satisfaction, low barriers to participation, and large ADHD symptom reductions. CET was superior to BPT for improving working memory (Group × Time d = 1.06) as hypothesized. CET was also superior to BPT for reducing actigraph-measured hyperactivity during visuospatial working memory testing and both distal far-transfer tasks (Group × Time d = 0.74). CONCLUSIONS: Results provide strong support for continued testing of CET and, if replicated, would support recent hypotheses that next-generation ADHD cognitive training protocols may overcome current limitations via improved targeting. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Social Problems in ADHD: Is it a Skills Acquisition or Performance Problem?

Recent models suggest that social skills training's inefficacy for children with ADHD may be due to target misspecification, such that their social problems reflect inconsistent performance rather than knowledge/skill gaps. No study to date, however, has disentangled social skills acquisition from performance deficits in children with ADHD. Children ages 8-12 with ADHD (n=47) and without ADHD (n=23) were assessed using the well-validated social behavioral analysis framework to quantify cross-informant social skills acquisition deficits, performance deficits, and strengths. Results provided support for the construct and predictive validities of this Social Skills Improvement System (SSIS) alternate scoring method, including expected magnitude and valence relations with BASC-2 social skills and ADHD symptoms based on both parent and teacher report. Acquisition deficits were relatively rare and idiosyncratic for both the ADHD and Non-ADHD groups, whereas children with ADHD demonstrated cross-informant social performance deficits (d=0.82-0.99) on several specific behaviors involving attention to peer directives, emotion regulation, and social reciprocity. Relative to themselves, children with ADHD were perceived by parents and teachers as exhibiting more social strengths than social acquisition deficits; however, they demonstrated significantly fewer social strengths than the Non-ADHD group (d = -0.71 to -0.89). These findings are consistent with recent conceptualizations suggesting that social problems in ADHD primarily reflect inconsistent performance rather than a lack of social knowledge/skills. Implications for refining social skills interventions for ADHD are discussed.

Parent and child neurocognitive functioning predict response to behavioral parent training for youth with ADHD.

Parental cognitive functioning is thought to play a key role in parenting behavior and may inform response to behavioral intervention. This open-label pilot study examined the extent to which parent and child cognition impacted response to behavioral parent training for children with ADHD. Fifty-four participants (27 parent-child dyads; Mages = 10.6 and 45.2 for children and parents, respectively) completed tasks assessing visuospatial and phonological working memory, inhibitory control, and choice-reaction speed at pre-treatment. Drift diffusion modeling decomposed choice-reaction time data into indicators of processing speed (drift rate) and response caution (boundary separation). Parents completed a 10-week manualized behavioral parent training program. Primary outcomes were pre- and post-treatment child ADHD and conduct problem severity, and parent-reported relational frustration and parenting confidence. Bayesian multiple regressions assessed parent and child cognitive processes as predictors of post-treatment outcomes, controlling for pre-treatment behavior. Better child visuospatial and phonological WM and higher parental response caution were associated with greater reductions in inattention. For conduct problems, better parental self-regulation (stronger inhibitory control and greater response caution) predicted fewer post-treatment conduct problems. Higher parental response caution also predicted lower post-treatment relational frustration and higher parental confidence. Bayesian evidence supported no relation between parent and child cognitive functions and treatment-related changes in hyperactivity. This pilot study demonstrates that cognitive processes central to etiologic theories of ADHD and models of parenting behavior can be successfully integrated into treatment outcome research to inform which families are most likely to benefit from behavioral interventions. This study demonstrates the feasibility of bridging the translational research gap between basic and applied clinical science and facilitates research on the role of cognition in psychosocial interventions.

Neurocognitive and behavioral predictors of social problems in ADHD: A Bayesian framework.

OBJECTIVE: Social problems are a key area of functional impairment for children with attention deficit hyperactivity disorder (ADHD), and converging evidence points to executive dysfunction as a potential mechanism underlying ADHD-related social dysfunction. The evidence is mixed, however, with regard to which neurocognitive abilities account for these relations. METHOD: A well-characterized group of 117 children ages 8-13 (M = 10.45, SD = 1.53; 43 girls; 69.5% Caucasian/Non-Hispanic) with ADHD (n = 77) and without ADHD (n = 40) were administered multiple, counterbalanced tests of neurocognitive functioning and assessed for social skills via multi-informant reports. RESULTS: Bayesian linear regressions revealed strong support for working memory and cross-informant interfering behaviors (inattention, hyperactivity/impulsivity) as predictors of parent- and teacher-reported social problems. Working memory was also implicated in social skills acquisition deficits, performance deficits, and strengths based on parent and/or teacher report; inattention and/or hyperactivity showed strong correspondence with cross-informant social problems in all models. There was no evidence for, and in most models strong evidence against, effects of inhibitory control and processing speed. The ADHD group was impaired relative to the non-ADHD group on social skills (d = 0.82-0.88), visuospatial working memory (d = 0.89), and phonological working memory (d = 0.58). In contrast, the Bayesian ANOVAs indicated that the ADHD and non-ADHD groups were equivalent on processing speed, IQ, age, gender, and socioeconomic status (SES). There was no support for or against group differences in inhibition. CONCLUSIONS: These findings confirm that ADHD is associated with impaired social performance, and implicate working memory and core ADHD symptoms in the acquisition and performance of socially skilled behavior. (PsycINFO Database Record

ADHD, depression, and motor vehicle crashes: A prospective cohort study of continuously-monitored, real-world driving.

ADHD is associated with automobile crashes, traffic fatalities, and serious road trauma, but it is unclear whether this risk is (a) driven by ADHD symptoms specifically, and (b) unique to ADHD or transdiagnostic across psychiatric disabilities, such as depression, that also have concentration problems as core symptoms. The current study provides the first prospective, continuously-monitored evaluation of crash risk related to ADHD symptoms, including the first on-road comparison of ADHD with another high-prevalence psychiatric disability (depression). A probability-based sample of 3226 drivers from six U.S. sites, including subsamples with self-reported ADHD (n = 274) and depression (n = 251), consented to have their vehicles outfitted with sophisticated data acquisition technologies to continuously monitor real-world, day-to-day driving from 'engine-on to engine-off' for 1-2 years (Mean = 440 consecutive days/driver, Mean = 9528 miles/driver). Crashes and near-crashes were objectively identified via software-based algorithms and double-coded manual validation (blinded to clinical status). Miles driven, days monitored, age, gender, education, and marital status were controlled. ADHD symptoms portended 5% increased crash risk per increase in symptom severity score (IRR = 1.05). This risk corresponded to approximately 1 biennial crash and 1 annual near-crash per driver with ADHD; crash risk doubled for drivers reporting ADHD symptom severity near the sample's maximum. Analyses based on self-reported clinical status indicated similarly elevated rates for ADHD (IRR = 1.46) and depression (IRR = 1.34) that may be related, in part, to both groups' inattention/concentration symptoms. Risk was not attenuated by ADHD usual treatment, but varied according to antidepressant medication status. Previous studies have significantly underestimated the risk for traffic crashes conveyed by ADHD and depression.

Working memory and organizational skills problems in ADHD.

BACKGROUND: This study tested model-driven predictions regarding working memory's role in the organizational problems associated with ADHD. METHOD: Children aged 8-13 (M = 10.33, SD = 1.42) with and without ADHD (N = 103; 39 girls; 73% Caucasian/Non-Hispanic) were assessed on multiple, counterbalanced working memory tasks. Parents and teachers completed norm-referenced measures of organizational problems (Children's Organizational Skills Scale; COSS). RESULTS: Results confirmed large magnitude working memory deficits (d = 1.24) and organizational problems in ADHD (d = 0.85). Bias-corrected, bootstrapped conditional effects models linked impaired working memory with greater parent- and teacher-reported inattention, hyperactivity/impulsivity, and organizational problems. Working memory predicted organization problems across all parent and teacher COSS subscales (R2  = .19-.23). Approximately 38%-57% of working memory's effect on organization problems was conveyed by working memory's association with inattentive behavior. Unique effects of working memory remained significant for both parent- and teacher-reported task planning, as well as for teacher-reported memory/materials management and overall organization problems. Attention problems uniquely predicted worse organizational skills. Hyperactivity was unrelated to parent-reported organizational skills, but predicted better teacher-reported task planning. CONCLUSIONS: Children with ADHD exhibit multisetting, broad-based organizational impairment. These impaired organizational skills are attributable in part to performance deficits secondary to working memory dysfunction, both directly and indirectly via working memory's role in regulating attention. Impaired working memory in ADHD renders it extraordinarily difficult for these children to consistently anticipate, plan, enact, and maintain goal-directed actions.

The relationship between the Neuro-Quality of Life Depression and Anxiety Measures and the Personality Assessment Inventory in persons with epilepsy.

BACKGROUND: To investigate the associations between the Neuro-Quality of Life (NQOL) Depression and Anxiety measures with an objective emotional inventory (Personality Assessment Inventory; PAI), and demonstrate the clinical utility of the NQOL as screening measures for depression and anxiety in persons with epilepsy (PWE). METHODS: PWE (N=72) were concurrently administered the NQOL Depression and Anxiety measures and the PAI. Pearson product moment correlations were used to determine the relationships between the NQOL measures and the respective PAI scales (i.e., depression, anxiety). One-way ANOVAs were conducted comparing NQOL scores between patients with elevated levels of depression and anxiety (T-score≥65 on the PAI) to profiles that were within normal limits. Using sensitivity and specificity analyses, optimal cut-scores on the NQOL measures were determined. RESULTS: Participants were primarily Caucasian (89%), female (60%), and ~35 years old. The NQOL Depression measure was significantly correlated with the PAI Depression total score (r=.747; p<0.001) and its subscales (p's<0.001). Similarly, the NQOL Anxiety measure was significantly correlated with the PAI Anxiety total score (r=.750; p<0.001) and its subscales (p's<0.001). Compared to profiles that were within normal limits, individuals with elevated depressive symptoms on the PAI had significantly higher NQOL Depression scores (F(1,71)=48.2, p<0.001, d=1.6). Similarly, those who endorsed elevated anxiety on the PAI had significantly higher NQOL Anxiety scores (F(1,71)=32.2, p<0.001, d=1.5). Cut-off scores of 19 on the NQOL Depression and 24 on the NQOL Anxiety measures adequately detected depression (sensitivity=0.67; specificity=0.93; PPV=0.91; NPV=0.74) and anxiety symptoms (sensitivity=0.77; specificity=0.82; PPV=0.81; NPV=0.78) in PWE. CONCLUSIONS: The NQOL Depression and Anxiety measures evidenced strong associations with the PAI Depression and Anxiety scales and may be effective in detecting depressive and anxiety symptoms in PWE using the provided cut-scores.

Motor vehicle driving in high incidence psychiatric disability: comparison of drivers with ADHD, depression, and no known psychopathology.

Although not often discussed in clinical settings, motor vehicle driving is a complex multitasking endeavor during which a momentary attention lapse can have devastating consequences. Previous research suggests that drivers with high incidence psychiatric disabilities such as ADHD contribute disproportionately to collision rates, which in turn portend myriad adverse social, financial, health, mortality, and legal outcomes. However, self-referral bias and the lack of psychiatric comparison groups constrain the generalizability of these findings. The current study addressed these limitations and examined the unique associations among ADHD, Depression, and adverse driving outcomes, independent of self-selection, driving exposure, and referral bias. The Strategic Highway Research Program (SHRP-2) Naturalistic Driving Study comprises U.S. drivers from six sites selected via probability-based sampling. Groups were defined by Barkley ADHD and psychiatric diagnosis questionnaires, and included ADHD (n = 275), Depression (n = 251), and Healthy Control (n = 1828). Primary outcomes included self-reported traffic collisions, moving violations, collision-related injuries, and collision fault (last 3 years). Accounting for demographic differences, ADHD but not Depression portended increased risk for multiple violations (OR = 2.3) and multiple collisions (OR = 2.2). ADHD but not Depression portended increased risk for collision fault (OR = 2.1). Depression but not ADHD predicted increased risk for self-reported injury following collisions (OR = 2.4). ADHD appears uniquely associated with multiple collisions, multiple violations, and collision fault, whereas Depression is uniquely associated with self-reported injury following a collision. Identification of the specific mechanisms underlying this risk will be critical to designing effective interventions to improve long-term functioning for drivers with high incidence psychiatric disability.

Should all patients with pulmonary hypertension undergo HIV serologic testing?

OBJECTIVES: To evaluate the yield of screening patients with pulmonary hypertension (PH) for human immunodeficiency virus (HIV) infection. METHODS: We retrospectively reviewed the records of consecutive patients with PH seen at our institution from July 1992 to November 2008. We assessed HIV risk factors and history of HIV. We estimated the proportion of patients who tested positive for HIV. RESULTS: We identified 445 patients with PH who had serologic testing for HIV antibody. The mean age was 63 years, and 66% were women. Of these patients, 224 (50%) were in World Health Organization diagnostic group I, pulmonary arterial hypertension (PAH). Only 1 patient (0.2%; 95% confidence interval, 0.0%-1.2%) was positive for HIV, and this was the only patient who had a known history of HIV infection. Ten other patients (2.2%) had risk factors for HIV infection but had negative serologic results. The patient who tested positive for HIV had PAH, yielding an estimated prevalence of positive HIV testing in that subgroup of 0.4% (95% confidence interval, 0.0%-2.5%); 6 other patients with PAH (2.7%) had risk factors for HIV but negative serology. CONCLUSIONS: To our knowledge, this is the first study examining the yield of screening patients with PH for HIV using serologic testing. Of the 445 patients tested, only 1 patient was positive for HIV. This patient was known to have risk factors for and exposure to HIV. Patients with PAH should be assessed for risk factors for HIV before testing for HIV in low-risk populations.