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BackgroundThe DOC screen was developed to identify Depression, Obstructive sleep apnea, and Cognitive impairment (“DOC” comorbidities) after stroke. Each component has its own score, but additional information may be gained from the time to complete the screen. Cognitive screening completion time is rarely used as an outcome measure. We assessed the added value of using DOC screen completion time as a predictor of impairment on detailed cognitive assessments.MethodsConsecutive English-speaking new referrals to the stroke prevention clinic were consented to participate in detailed neuropsychological testing (n=437). DOC screen scores and times were compared to cognitive test scores using multiple linear regression and receiver operating characteristic (ROC) analysis. All linear regression analyses controlled for age, sex, years of education, and functional outcome as assessed by the modified Rankin score.ResultsAverage completion time for the DOC screen was 3.8 ± 1.3 minutes. After accounting for age, sex and cognitive screen score, completion time was a significant independent predictor, of speed of processing (p = .002, 95% CI: -0.016 to -0.004), verbal fluency (p < .001, CI: -0.012 to -0.006) and executive (p = .004, CI: -0.006 to -0.001), but not memory, function. Completion time above 5.5 minutes (332.5 seconds) was associated with a high likelihood of impairment on gold standard executive (likelihood ratios 3.9-5.2) and speed of processing (likelihood ratio = 5.2) tasks.ConclusionsDOC screen completion time is easy to collect in routine care and is independently associated with speed of processing, language and executive dysfunctions after stroke. People who take more than 5.5 minutes to complete the DOC screen are likely to have deficits in executive functioning and speed of processing. These domains can be challenging to screen for in stroke survivors, and this measure provides a simple, clinically feasible method to screen for these under-appreciated concerns.Clinical Trials Registration Identifier:NCT02363114Clinical Trials URL:https://clinicaltrials.gov/ct2/show/NCT02363114 more...

Oligodendrogliomas are lower-grade, slow-growing gliomas that are ultimately fatal. Although driver mutations are known, the mechanisms underlying their signature slow growth rates are poorly understood. We found evidence for intra-tumoral interactions between neoplastic and non-neoplastic cells in oligodendroglioma tissues. To further study these cell interactions, we used two patient-derived oligodendroglioma cell lines of lower and higher aggressivity. Both oligodendroglioma cell lines released extracellular vesicles that had cytotoxic effects on non-neoplastic and neoplastic cells, but each had distinct vesicular proteomes. Consistent with extracellular vesicles mediating growth inhibitory effects in oligodendrogliomas, higher expression levels of several extracellular vesicle biogenesis genes (SMPD3,TSG101, STAM1) correlates with longer survival in oligodendroglioma patients. Furthermore, SMPD3 overexpression slows oligodendroglioma cell growth in culture. Conversely, SMPD3 knockdown enhances oligodendroglioma proliferation in vitro, in murine xenografts, and in human cerebral organoid co-cultures. Oligodendroglioma-derived extracellular vesicles thus mediate tumor cell microenvironmental interactions that contribute to low aggressivity. more...