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Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.
Older adults with treatment-resistant depression (TRD) benefit more from treatment augmentation than switching. It is useful to identify moderators that influence these treatment strategies for personalised medicine.
Aims
Our objective was to test whether age, executive dysfunction, comorbid medical burden, comorbid anxiety or the number of previous adequate antidepressant trials could moderate the superiority of augmentation over switching. A significant moderator would influence the differential effect of augmentation versus switching on treatment outcomes.
Method
We performed a preplanned moderation analysis of data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) randomised controlled trial (N = 742). Participants were 60 years old or older with TRD. Participants were either (a) randomised to antidepressant augmentation with aripiprazole (2.5–15 mg), bupropion (150–450 mg) or lithium (target serum drug level 0.6 mmol/L) or (b) switched to bupropion (150–450 mg) or nortriptyline (target serum drug level 80–120 ng/mL). Treatment duration was 10 weeks. The two main outcomes of this analysis were (a) symptom improvement, defined as change in Montgomery–Asberg Depression Rating Scale (MADRS) scores from baseline to week 10 and (b) remission, defined as MADRS score of 10 or less at week 10.
Results
Of the 742 participants, 480 were randomised to augmentation and 262 to switching. The number of adequate previous antidepressant trials was a significant moderator of depression symptom improvement (b = −1.6, t = −2.1, P = 0.033, 95% CI [−3.0, −0.1], where b is the coefficient of the relationship (i.e. effect size), and t is the t-statistic for that coefficient associated with the P-value). The effect was similar across all augmentation strategies. No other putative moderators were significant.
Conclusions
Augmenting was superior to switching antidepressants only in older patients with fewer than three previous antidepressant trials. This suggests that other intervention strategies should be considered following three or more trials.
This manuscript introduces a new Bayesian finite mixture methodology for the joint clustering of row and column stimuli/objects associated with two-mode asymmetric proximity, dominance, or profile data. That is, common clusters are derived which partition both the row and column stimuli/objects simultaneously into the same derived set of clusters. In this manner, interrelationships between both sets of entities (rows and columns) are easily ascertained. We describe the technical details of the proposed two-mode clustering methodology including its Bayesian mixture formulation and a Bayes factor heuristic for model selection. We present a modest Monte Carlo analysis to investigate the performance of the proposed Bayesian two-mode clustering procedure with respect to synthetically created data whose structure and parameters are known. Next, a consumer psychology application is provided examining physician pharmaceutical prescription behavior for various brands of prescription drugs in the neuroscience health market. We conclude by discussing several fertile areas for future research.
Existing test statistics for assessing whether incomplete data represent a missing completely at random sample from a single population are based on a normal likelihood rationale and effectively test for homogeneity of means and covariances across missing data patterns. The likelihood approach cannot be implemented adequately if a pattern of missing data contains very few subjects. A generalized least squares rationale is used to develop parallel tests that are expected to be more stable in small samples. Three factors were varied for a simulation: number of variables, percent missing completely at random, and sample size. One thousand data sets were simulated for each condition. The generalized least squares test of homogeneity of means performed close to an ideal Type I error rate for most of the conditions. The generalized least squares test of homogeneity of covariance matrices and a combined test performed quite well also.
Objectives: Studies in PD have traditionally focused on motor features, however, interest in non-motor manifestations has increased resulting in improved knowledge regarding the prognosis of the disease. Although several studies have explored the incidence of dementia in PD cohorts, these studies have been conducted mainly in reference centers in high-income countries (HIC). In this study we aimed to analyze the prevalence of cognitive impairment in people with parkinsonism and PD and its association with incident dementia in a population- based study, of elderly from six Latin American countries.
Methods: This report consists of the analysis of data from a follow-up of 12,865 elderly people aged 65 years or older, carried out by 10/66 Dementia Research Group. Residents of urban and rural areas, from six low and middle- income countries (Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico and Peru). Exposures include parkinsonism and PD defined according to the UK Parkinson’s Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main exposure and dementia was measured through the dementia diagnosis algorithm from 10/66 DRG.
Results: At baseline, the overall prevalence of cognitive impairment was 14% (n = 1,581), in people with parkinsonism and PD, it was of 30.0% and 26.2%, respectively. Parkinsonism and PD were individually associated with prevalent and incident dementia after controlling for age, sex, and education. The pooled odds ratios from a fixed-effects meta-analysis were 2.2 (95% CI: 1.9 – 2.6) for parkinsonism and 1.9 (95% CI: 1.4 – 2.4) for PD. Regarding incident dementia, the pooled sub-Hazard ratio estimated using a competing risk model was 1.5 (95% CI: 1.2 –1.9) for parkinsonism and 1.5 (95% CI: 1.0 – 2.2) forPD.
Conclusions: Parkinsonism and PD were associated cross-sectionally with the presence of cognitive impairment, and prospectively with incident dementia in elderly people in the community population of Latin America studied. Systematic screening for cognitive impairment and dementia with valid tools in PD patients may help with earlier detection of those at highest risk for adverse outcomes. Identifying modifiable risk factors could potentially lead to efficient interventions even in advanced stages of PD.
Background: Limited knowledge exists about the association between Parkinsonism or Parkinson’s disease (PD) and cognitive impairment and dementia in Latin America.
Objectives: The study aimed to determine the cross-sectional and prospective associations between Parkinsonism and PD with cognitive impairment and dementia in a large multi-country cohort in Latin America.
Methods: The 10/66 is a prospective, observational cohort study. This population-based cohort study was based in six Latin American countries: Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico, and Peru. The study includes 12,865 participants from six countries, including residents aged 65 years and living in urban and rural catchment areas. Exposures included diagnosed Parkinsonism and PD defined according to the United Kingdom Parkinson’s Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main outcome measure for cross-sectional analysis and dementia was used to measure the prospective association with the exposures. Logistic regression models were used to explore the association between Parkinsonism/PD with cognitive impairment at baseline. Competing risk models were used to assess the prospective association between Parkinsonism/PD with incident dementia accounting for competing risk of mortality. Individual country analyses were combined via fixed-effect meta-analysis.
Results: At baseline, the prevalence of cognitive impairment in people with Parkinsonism and PD was 30% and 26.2%, respectively. Parkinsonism (OR 2.2 (95%CI 1.9 – 2.6)) and PD (1.9 (95%CI 1.4 – 2.4)) were individually associated with baseline and incident cognitive impairment after accounting for age, sex, and education, after pooling. In competing risk models, the pooled sub- hazard ratios for dementia in the fixed effect metanalysis were 1.5 (95%CI 1.2 – 1.9) for parkinsonism and 1.5 (95%CI 1.0 – 2.2) for PD.
Conclusions: Parkinsonism and PD were cross-sectionally associated with cognitive impairment and prospectively associated with incident dementia in Latin America. Routine screening for cognitive impairment and dementia with validated tools in PD patients may aid earlier detection of those at greater risk ofadverseoutcomes.
From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.
People with mental illness often experience a concealable stigmatized identity that may be invisible to others. As a result, they are often faced with the dilemmas of whether to disclosure or conceal their diagnosis and their experience. However, in order to overcome the social stigma and self-stigma that hinder their recovery, they must establish a network and social support through identity disclosure.
Objectives
This study investigates the effect of clinical characteristics (symptom and social function level), self-stigma and social support on the disclosure of people with mental illness.
Methods
The research was conducted with 236 respondents who are currently using community mental health services. (Male: 51.9%, Female: 48.1%; Mean age = 47.97±13.24; SPR: 66.8%, other diagnosis: 33.2%).
Results
Most respondents disclosed their mental illness to health service providers and family, but they are least open about their identity toward neighbors and co-workers. A regression analysis of predictors of disclosure revealed that only social functioning level and social support had significant predictive power. It was discovered that individuals with better level of social function and social support disclosure more about their mental illness.
Conclusions
A program that increases social functions and support network can be recommended to improve disclosure efficacy.
The Korean Basketball League(KBL) holds an annual draft to allow teams to select new players, mostly graduates from the elite college basketball teams even though some are from high school teams. In sports games, many factors might influence the success of an athlete. In addition to possessing excellent physical and technical factors, success in a sports game is also influenced by remarkable psychological factors. Several studies reported that elite sports players can control their anxiety during competition, which may lead to better performance. In particular, the temperament and characteristics of players have been regarded as crucial determinants of the player’s performance and goal. In this regard, numerous studies suggest that personality is considered to be an important predictor of long-term success in professional sports
Objectives
Based on previous reports and studies, we hypothesized that physical status, temperament and characteristics, and neurocognitive functions of basketball players could predict the result of KBL draft selection. Especially, temperament and characteristics were associated with the result of KBL selection. The basketball performances including average scores and average rebound were associated with emotional perception and mental rotation.
Methods
We recruited the number of 44 college elite basketball players(KBL selection, n=17; Non-KBL selection, n=27), and the number of 35 age-matched healthy comparison subjects who major in sports education in college. All participants were assessed with the Temperament and Character Inventory(TCI), Sports Anxiety Scales(SAS), Beck Depression Inventory(BDI), Perceived Stress Scale (PSS-10), Trail Making Test(TMT), and Computerized Neuro-cognitive Test(CNT) for Emotional Perception and Mental Rotation.
Results
Current results showed that physical status, temperament and characteristics, and Neurocognitive functions of college basketball players could predict the KBL draft selection. Among temperament and characteristics, novelty seeking and reward dependence were associated with KBL draft selection. The basketball performances including average scores and average rebound were associated with emotional perception and mental rotation.
Conclusions
In order to be a good basketball player for a long time, it was confirmed that temperamental factors and Neurocognitive factors were very closely related. Furthermore, it is also judged that these results can be used as basic data to predict potential professional basketball players.
Mental healthcare services that address a variety of primary complaints which are highly related to maladaptive personality traits among the general population are important to prevent developing psychiatric disorders.
Objectives
This study aimed to examine the effectiveness of a digital mental health service (named “Mindling”) that focuses on maladaptive personality traits in the general population.
Methods
Participants were recruited through a South Korean community website and screened for adults between the ages of 18 and 60 in terms of personality traits such as perfectionism, low self-esteem, social isolation, or anxiety. Participants were allocated to four intervention programs (Riggy, Pleaser, Shelly, and Jumpy) based on their screening results and were randomly assigned to digital treatment and waitlist groups. Each intervention program was conducted online for 10 weeks. The primary outcomes were all measured by self-report questionnaires; in addition to stress levels, each program included measures of perfectionism (Riggy), low self-esteem (Pleaser), loneliness (Shelly), and anxiety (Jumpy). The secondary outcomes included self-efficacy, depression, and other psychological states. All participants completed pre-treatment (baseline), intervention (week 5), and post-treatment (week 10) assessments, and the treatment group completed a separate follow-up assessment (week 14).
Results
In the treatment group, 70.05% of the participants completed the full course of the digital intervention. The mean scores for each primary outcome measure and some secondary outcome measures were significantly different between baseline and post-treatment in the treatment group for the Total, Riggy, Pleaser, Shelly, and Jumpy programs, but these differences were not observed in the waitlist group. In addition, mean differences between the treatment and waitlist groups at post-treatment assessment were significant for all primary outcome measures and some secondary outcome measures. Specifically, the levels of stress (Total program), perfectionism (Riggy), loneliness (Shelly), and anxiety (Jumpy) were significantly lower in the treatment group, while self-esteem (Pleaser) was higher. In addition, the mean differences between post-treatment and follow-up assessment data were not statistically significant for all primary outcome measures and nearly all secondary outcome measures.
Conclusions
This study validated the effectiveness of the digital intervention program targeting maladaptive personality traits and suggested its sustainable effects.
Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.
Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.
While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches.
Methods
Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation.
Results
A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3–2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83–7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2–10.5%; RR: 1.56, 95% CI: 1.38–1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2–11.3%; RR: 1.60, 95% CI: 1.42–1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses.
Conclusions
Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.
Faecal examinations for helminth eggs were performed on 1869 people from two riverside localities, Vientiane Municipality and Saravane Province, along the Mekong River, Laos. To obtain adult flukes, 42 people positive for small trematode eggs (Opisthorchis viverrini, heterophyid, or lecithodendriid eggs) were treated with a 20–30 mg kg−1 single dose of praziquantel and purged. Diarrhoeic stools were then collected from 36 people (18 in each area) and searched for helminth parasites using stereomicroscopes. Faecal examinations revealed positive rates for small trematode eggs of 53.3% and 70.8% (average 65.2%) in Vientiane and Saravane Province, respectively. Infections with O. viverrini and six species of intestinal flukes were found, namely, Haplorchistaichui, H. pumilio, H. yokogawai, Centrocestus caninus,Prosthodendrium molenkampi, and Phaneropsolus bonnei. The total number of flukes collected and the proportion of fluke species recovered were markedly different in the two localities; in Vientiane, 1041 O. viverrini (57.8 per person) and 615 others (34.2 per person), whereas in Saravane, 395 O. viverrini (21.9 per person) and 155207 others (8622.6 per person). Five people from Saravane harboured no O. viverrini but numerous heterophyid and/or lecithodendriid flukes. The results indicate that O. viverrini and several species of heterophyid and lecithodendriid flukes are endemic in these two riverside localities, and suggest that the intensity of infection and the relative proportion of fluke species vary by locality along the Mekong River basin.
Good social connections are proposed to positively influence the course of cognitive decline by stimulating cognitive reserve and buffering harmful stress-related health effects. Prior meta-analytic research has uncovered links between social connections and the risk of poor health outcomes such as mild cognitive impairment, dementia, and mortality. These studies have primarily used aggregate data from North America and Europe with limited markers of social connections. Further research is required to explore these associations longitudinally across a wider range of social connection markers in a global setting.
Research Objective:
We examined the associations between social connection structure, function, and quality and the risk of our primary outcomes (mild cognitive impairment, dementia, and mortality).
Method:
Individual participant-level data were obtained from 13 longitudinal studies of ageing from across the globe. We conducted survival analysis using Cox regression models and combined estimates from each study using two-stage meta-analysis. We examined three social constructs: connection structure (living situation, relationship status, interactions with friends/family, community group engagement), function (social support, having a confidante) and quality (relationship satisfaction, loneliness) in relation to the risks of three primary outcomes (mild cognitive impairment, dementia, and mortality). In our partially adjusted models, we included age, sex, and education and in fully adjusted models used these variables as well as diabetes, hypertension, smoking, cardiovascular risk, and depression.
Preliminary results of the ongoing study:
In our fully adjusted models we observed: a lower risk of mild cognitive impairment was associated with being married/in a relationship (vs. being single), weekly community group engagement (vs. no engagement), weekly family/friend interactions (vs. not interacting), and never feeling lonely (vs. often feeling lonely); a lower risk of dementia was associated with monthly/weekly family/friend interactions and having a confidante (vs. no confidante); a lower risk of mortality was associated with living with others (vs. living alone), yearly/monthly/weekly community group engagement, and having a confidante.
Conclusion:
Good social connection structure, function, and quality are associated with reduced risk of incident MCI, dementia, and mortality. Our results provide actionable evidence that social connections are required for healthy ageing.
Our study goal was to characterize the relative frequencies of molecular and phenotypic traits of tuberous sclerosis complex (TSC) in a Canadian adult population. Previous studies have sought to identify TSC-related genotypic and phenotypic trends in pediatric cohorts, but little is known about clinical manifestations and severity when it presents in adults.
Methods:
We conducted a retrospective chart review of adult patients seen at the TSC clinic at the University Health Network genetics clinics (Toronto, Ontario) to compare trends in the relative frequency of TSC manifestations with genotype.
Results:
Fifty-one patients were eligible for this study. Eight patients had a pathogenic/likely pathogenic variant in the tuberous sclerosis complex 1 (TSC1) gene, 18 had a tuberous sclerosis complex 2 (TSC2) pathogenic/likely pathogenic variant, 6 patients had multiple variants identified in TSC1/TSC2 or TSC2/PKD1, 11 had no mutation identified (NMI) and 8 had no genetic testing done. Patients with a pathogenic/likely pathogenic variant in TSC2 presented with an increased involvement of multiple systems and a higher frequency of TSC-related manifestations relative to the other mutation groups.
Conclusion:
Previous studies comparing the wide phenotypic variability with TSC genotype have mainly comprised pediatric cohorts. With a focus on adults, we found trends to be similar across previous literature. An informed multidisciplinary approach should be taken to ensure proper surveillance and management of adults with TSC until a correlation between genotype and phenotype, especially past infancy, is better understood.
The COVID-19 pandemic significantly disrupted schools and learning formats. Children with epilepsy are at-risk for generalized academic difficulties. We investigated the potential impact of COVID-19 on learning in those with epilepsy by comparing achievement on well-established academic measures among school-age children with epilepsy referred prior to the COVID-19 pandemic and those referred during the COVID-19 pandemic.
Participants and Methods:
This study included 466 children [52% male, predominately White (76%), MAge=10.75 years] enrolled in the Pediatric Epilepsy Research Consortium Epilepsy (PERC) Surgery database project who were referred for surgery and seen for neuropsychological testing. Patients were divided into two groups based on a proxy measure of pandemic timing completed by PERC research staff at each site (i.e., “were there any changes to typical in-person administration [of the evaluation] due to COVID?”). 31% of the sample (N = 144) were identified as having testing during the pandemic (i.e., “yes” response), while 69% were identified as having testing done pre-pandemic (i.e., “no” response). Of the 31% who answered yes, 99% of administration changes pertained to in-person testing or other changes, with 1% indicating remote testing. Academic achievement was assessed by performance measures (i.e., word reading, reading comprehension, spelling, math calculations, and math word problems) across several different tests. T-tests compared the two groups on each academic domain. Subsequent analyses examined potential differences in academic achievement among age cohorts that approximately matched grade level [i.e., grade school (ages 5-10), middle school (ages 11-14), and high school (ages 15-18)].
Results:
No significant differences were found between children who underwent an evaluation before the pandemic compared to those assessed during the pandemic based on age norms across academic achievement subtests (all p’s > .34). Similarly, there were no significant differences among age cohorts. The average performance for each age cohort generally fell in the low average range across academic skills. Performance inconsistently varied between age cohorts. The youngest cohort (ages 5-10) scored lower than the other cohorts for sight-word reading, whereas this cohort scored higher than the middle cohort (ages 11-14) for math word problems and reading comprehension. There were no significant differences between the two pandemic groups on demographic variables, intellectual functioning, or epilepsy variables (i.e., age of onset, number of seizure medications, seizure frequency).
Conclusions:
Academic functioning was generally equivalent between children with epilepsy who underwent academic testing as part of a pre-surgical evaluation prior to the pandemic compared to those who received testing during the pandemic. Additionally, academic functioning did not significantly differ between age cohorts. Children with epilepsy may have entered the pandemic with effective academic supports and/or were accustomed to school disruptions given their seizure history. Replication is needed as findings are based on a proxy measure of pandemic timing and the extent to which children experienced in-person, remote, and hybrid learning is unknown. Children tested a year into the pandemic, after receiving instruction through varying educational methods, may score differently than those tested earlier. Future research can address these gaps. Although it is encouraging that academic functioning was not disproportionately impacted during the pandemic in this sample, children with epilepsy are at-risk for generalized academic difficulties and continued monitoring of academic functioning is necessary.
White matter hyperintensities (WMH) are a radiological marker of small vessel cerebrovascular disease that are related to cognition and memory decline in aging and Alzheimer’s disease (AD). However, the mechanisms that link WMH to memory impairment and whether they interact with or act independently of AD pathophysiology are unclear. The transentorhinal cortex (BA35) is among the earliest anatomical regions to show tau deposition and subsequent atrophy, and baseline posterior WMH is related to longitudinal cortical thinning of the entorhinal cortex. However, it is unclear whether regional WMH are related to BA35 volume specifically, and whether this relationship is influenced by amyloid-β (Aβ) burden. We hypothesized that WMH in the vascular territory of the posterior cerebral artery (PCA), which perfuses both posterior and medial temporal lobe regions, would be associated with reduced BA35 volume and with lower memory in older adults independently of Aβ.
Participants and Methods:
114 older adults without dementia, aged 60 to 98 years (mean (SD) = 78.31 (11.02), 71 (62.8%) women), were included. Regional WMH volumes were derived from T2-FLAIR images using ANTs, a vascular territory atlas and manual editing. Global Aβ was assessed with 18F-florbetapir PET, using SUVR of a cortical composite region (FBP mean SUVR) with a cerebellar reference region. Total transentorhinal (BA35) volume was derived using T1 and T2-weighted images using ASHS. To assess hippocampal pattern separation ability, an index of episodic memory, participants completed both object (MDT-O) and spatial (MDT-S) versions of a mnemonic discrimination task, with the lure discrimination index as the outcome. Using linear regressions, we first tested for associations among PCA-defined WMH, Aβ, BA35 volume, and MDT-S and MDT-O scores. We then tested whether the relationship between PCA-defined WMH and MDT-O performance was mediated by BA35 volume and whether this mediation was moderated by Aβ. All models adjusted for age, sex, and education.
Results:
PCA-defined WMH were related to higher FBP mean SUVR (b=0.287, p=0.042) and lower BA35 volume (b=-0.222, p=0.038). PCA-defined WMH were also negatively related to MDT-O performance (b=-0.229, p=0.044), but not to MDT-S (b=-0.171, p=0.118). FBP mean SUVR was not related to BA35 volume (b=-0.131, p=0.344) or MDT performance (MDT-S: b=-0.138, p=0.348; MDT-O: b=0.059, p=0.690). Furthermore, FBP mean SUVR did not interact with PCA-defined WMH to predict memory performance (interaction b=-0.039, p=0.973), nor BA35 volume (interaction b=-0.140, p=0.894). The association of PCA-defined WMH to MDT-O was fully mediated by BA35 volume (indirect effect b=-0.0005, 95% CI (-0.0014, -0.0003)). This mediation was not moderated by FBP mean SUVR (indirect effect b=-0.00001, 95% CI (-0.001, 0.001)).
Conclusions:
We found that PCA-defined WMH were related to memory performance in older adults, and this association is fully mediated by transentorhinal volume. While PCA-defined WMH are related to higher global Aβ burden, there is no interaction between PCA-defined WMH and Aβ on BA35 volume. These findings point to an amyloid-independent vascular pathway towards memory decline in aging and AD. Future work should examine whether the pathway linking PCA-defined WMH to transentorhinal cortex atrophy and subsequent memory decline is mediated by regional tau pathology.
The Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database Project is a multisite collaborative that includes neuropsychological evaluations of children presenting for epilepsy surgery. There is some evidence for specific neuropsychological phenotypes within epilepsy (Hermann et al, 2016); however, this is less clear in pediatric patients. As a first step, we applied an empirically-based subtyping approach to determine if there were specific profiles using indices from the Wechsler scales [Verbal IQ (VIQ), Nonverbal IQ (NVIQ), Processing Speed Index (PSI), Working Memory Index (WMI)]. We hypothesized that there would be at least four profiles that are distinguished by slow processing speed and poor working memory as well as profiles with significant differences between verbal and nonverbal reasoning abilities.
Participants and Methods:
Our study included 372 children (M=12.1 years SD=4.1; 77.4% White; 48% male) who completed an age-appropriate Wechsler measure, enough to render at least two index scores. Epilepsy characteristics included 84.4% with focal epilepsy (evenly distributed between left and right focus) and 13.5% with generalized or mixed seizure types; mean age of onset = 6.7 years, SD = 4.5; seizure frequency ranged from daily to less than monthly; 53% had structural etiology; 71% had an abnormal MRI; and mean number of antiseizure medications was two. Latent profile analysis was used to identify discrete underlying cognitive profiles based on intellectual functioning. Demographic and epilepsy characteristics were compared among profiles.
Results:
Based on class enumeration procedures, a 3-cluster solution provided the best fit for the data, with profiles characterized by generally Average, Low Average, or Below Average functioning. 32.8% were in the Average profile with mean index scores ranging from 91.7-103.2; 47.6% were in the Low Average profile with mean index ranging from 80.7 to 84.5; and 19.6% were in the Below Average profile with mean index scores ranging from 55.0-63.1. Across all profiles, the lowest mean score was the PSI, followed by WMI. VIQ and NVIQ represented relatively higher scores for all three profiles. Mean discrepancy between indices within a profile was as large as 11.5 IQ points. No demographics or epilepsy characteristics were significantly different across cognitive phenotypes.
Conclusions:
Latent cognitive phenotypes in a pediatric presurgical cohort were differentiated by general level of functioning; however, across profiles, processing speed was consistently the lowest index followed by working memory. These findings across phenotypes suggest a common relative weakness which may result from a global effect of antiseizure medications and/or the widespread impact of seizures on neural networks even in a largely focal epilepsy cohort; similar to adult studies with temporal lobe epilepsy (Hermann et al, 2007). Future work will use latent profile analysis to examine phenotypes across other domains relevant to pediatric epilepsy including attention, naming, motor, and memory functioning. These findings are in line with collaborative efforts towards cognitive phenotyping which is the aim of our PERC Epilepsy Surgery Database Project that has already established one of the largest pediatric epilepsy surgery cohorts.