A study of suicidal thoughts and behaviour in a sample of adults affected by the 9/11 attacks on New York City's World Trade Center.

Previous research on suicide risk in relation to disasters has yielded varying findings, likely resulting at least in part from inconsistencies in definitions of disaster exposure and assessment of psychiatric disorders. This study examined suicidal thoughts and behaviour in a sample of 379 adults affected by the 9/11 attacks on New York City, using carefully-defined disaster exposure variables and assessing psychopathology with full diagnostic criteria, nearly 3 years after the disaster. Only 7% of the sample reported any postdisaster suicidal thoughts or behaviour, only 1% of which were new (incident) after the disaster, amounting to very little evidence of incident suicidal risk. The occurrence of a postdisaster psychiatric disorder in nearly one-half of the sample (45%) was significantly associated with postdisaster suicide risk (15% vs 1%). Disaster trauma exposure was not associated with postdisaster suicide risk. The findings of this study are not consistent with the disaster experience itself giving rise to suicide risk. Nonetheless, the postdisaster setting provides opportunities for education about and surveillance for suicide risk and other mental health concerns.

Cognitive mediators of adaptive functioning outcomes in survivors of pediatric brain tumors treated with proton radiotherapy.

BACKGROUND: Cranial radiotherapy (RT) is associated with risk for cognitive and adaptive dysfunction. Proton RT (PRT) is a technique hypothesized to spare cognition by reducing exposure to nontarget brain tissue. However, little is known regarding functional outcomes in survivors of pediatric brain tumor (BT) treated with PRT. The present study examined the relationship between cognitive and adaptive outcomes in pediatric BT survivors post-PRT. METHODS: Survivors treated with either focal (n = 33) or craniospinal irradiation (CSI; n = 37) PRT completed neurocognitive evaluations approximately 5 years post-treatment. Results of intelligence testing and ratings of adaptive functioning are reported. Mediation models examined the relationship among radiation field, cognition, and adaptive functioning. RESULTS: The PRT CSI group demonstrated worse cognitive outcomes than the PRT Focal group across each cognitive index (Cohen's d = 0.56-0.70). Parent ratings of adaptive functioning were also worse in the PRT CSI group than the PRT Focal group (Global Adaptive Composite, d = 0.53; conceptual skills, d = 0.67). Cognitive performance fully mediated the relationship between radiation field and adaptive outcomes, while controlling for group differences in tumor histology and RT dose. CONCLUSIONS: Focal PRT survivors demonstrated generally positive outcomes with weaknesses in processing speed and aspects of adaptive functioning. CSI exposure was associated with more consistently poor cognitive and adaptive outcomes. The increased risk for adaptive dysfunction in the PRT CSI group appeared due to the effects of CSI on cognition. Efforts to reduce the volume of tissue exposure to RT remain important.

Neuropsychological functioning following surgery for pediatric low-grade glioma: a prospective longitudinal study.

OBJECTIVE: High survival rates have led to an increased emphasis on the functional outcomes of children diagnosed with low-grade glioma. Most outcomes research has focused on risks associated with radiotherapy, but less is known about neuropsychological risks for patients treated with surgery alone. Here, the authors sought to examine the neuropsychological trajectories of children diagnosed with a low-grade glioma and monitored up to 6 years postsurgery. Secondarily, they explored demographic and clinical predictors of neuropsychological performance. METHODS: The neuropsychological functioning of 32 patients (median age at diagnosis 10.0 years) was prospectively assessed annually for up to 6 years after surgery (median days from surgery at baseline = 72). Tumor location was predominately supratentorial (65.6%). A combination of performance-based and parent-reported measures was used to assess intelligence, memory, executive functioning, and fine motor control in all patients. RESULTS: Binomial tests at the postoperative baseline revealed that the proportion of children falling below the average range (< 16th percentile) was significantly higher than the rate expected among healthy peers on measures of verbal memory, processing speed, executive functioning, and fine motor control (p < 0.05). Even so, linear mixed models indicated that neuropsychological functioning at the postoperative baseline did not significantly change over time for up to 6 years after surgery across all domains. A larger tumor size was associated with a slower reaction time (p < 0.01). A supratentorial tumor location and history of seizures were associated with more parent-reported executive difficulties (p < 0.01). CONCLUSIONS: While radiotherapy is a known risk factor for neuropsychological deficits in pediatric brain tumor patients, findings in this study indicate that children treated for low-grade glioma with surgery alone (without radiotherapy or chemotherapy) remain susceptible to difficulties with memory, executive functioning, and motor functioning that persist over time. Over half of the children in the study sample required school support services to address neuropsychological weaknesses. Although low-grade glioma is often conceptualized as a benign tumor, children treated for this lesion require ongoing monitoring and intervention to address neuropsychological weaknesses resulting from the tumor itself as well as the surgery.

Prospective, longitudinal comparison of neurocognitive change in pediatric brain tumor patients treated with proton radiotherapy versus surgery only.

BACKGROUND: Proton radiotherapy (PRT) reduces the volume of normal tissue receiving radiation dose, which may lead to better neurocognitive outcomes. We examined change in neurocognitive scores over time in pediatric brain tumor patients treated with proton craniospinal irradiation (CSI), proton focal RT, or surgery only. METHODS: Patients received annual neurocognitive evaluations for up to 6 years. We examined Full Scale IQ (FSIQ), Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores. General linear mixed models examined change in scores over time by treatment group, adjusting for significant covariates. RESULTS: Scores from 93 patients treated between 2012 and 2017 (22 proton CSI, 31 proton focal, and 40 surgery only) were examined. Treatment groups were similar on gender (51.6% male), age at treatment (median = 9.7 y), and length of follow-up (median = 2.9 y). The surgery only group had proportionately more gliomas (P < 0.001), and the proton CSI group had more infratentorial tumors (P = 0.001) and higher total RT dose (P = 0.004). The proton focal and surgery only groups exhibited stable neurocognitive scores over time across all indexes (all P > 0.05). In the proton CSI group, WMI, PSI, and FSIQ scores declined significantly (P = 0.036, 0.004, and 0.017, respectively), while VCI and PRI scores were stable (all P > 0.05). CONCLUSIONS: Focal PRT was associated with stable neurocognitive functioning into survivorship. Outcomes were similar whether patients received focal PRT or no radiotherapy, even in neurocognitive domains known to be particularly radiosensitive. Proton CSI emerged as a neurocognitive risk factor, consistent with photon outcomes research.

Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy Mice and in Neurodegenerative Diseases.

It is well-established that inflammation plays an important role in Alzheimer's disease (AD) and frontotemporal lobar dementia (FTLD). Inflammation and synapse loss occur in disease prior to the formation of larger aggregates, but the contribution of tau to inflammation has not yet been thoroughly investigated. Tau pathologically aggregates to form large fibrillar structures known as tangles. However, evidence suggests that smaller soluble aggregates, called oligomers, are the most toxic species and form prior to tangles. Furthermore, tau oligomers can spread to neighboring cells and between anatomically connected brain regions. In addition, recent evidence suggests that inspecting the retina may be a window to brain pathology. We hypothesized that there is a relationship between tau oligomers and inflammation, which are hallmarks of early disease. We conducted immunofluorescence and biochemical analyses on tauopathy mice, FTLD, and AD subjects. We showed that oligomers co-localize with astrocytes, microglia, and HMGB1, a pro-inflammatory cytokine. Additionally, we show that tau oligomers are present in the retina and are associated with inflammatory cells suggesting that the retina may be a valid non-invasive biomarker for brain pathology. These results suggest that there may be a toxic relationship between tau oligomers and inflammation. Therefore, the ability of tau oligomers to spread may initiate a feed-forward cycle in which tau oligomers induce inflammation, leading to neuronal damage, and thus more inflammation. Further mechanistic studies are warranted in order to understand this relationship, which may have critical implications for improving the treatment of tauopathies.