Faculty Bibliography

BACKGROUND:, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. METHODS:, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. RESULTS:, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. CONCLUSIONS:Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.

BACKGROUND:The specific research aims of this study included: 1) Conduct an epidemiologic analysis of recreational sports injuries among 1500 children, ages 5-11 in Florida: and 2) Utilize the computerized pediatric concussion tool from ImPACT Applications, Inc. for baseline and follow-up testing to better understand these injuries. This research followed a prospective surveillance design utilizing a large cohort of children, ages, 5-11, who play recreational football, soccer, and baseball/softball in Florida. The study venue was a large athletic facility in Hillsborough County, Florida. The sports observed were soccer (girls' and boys'), baseball, softball, and football. Internal and external advisory boards were consulted throughout the study. METHODS:Certified Athletic Trainers (ATCs) were hired to use High School Reporting Information Online (RIO) for injuries and the Ipad-administered pediatric concussion tool developed by ImPACT Applications, Inc for baseline/follow-up concussion data. RESULTS:Over the course of the project, 26 RIO-reported injuries were reported. Football and soccer produced the greatest rate of injuries. There were 12 concussions which comprised nearly half of all the RIO injuries (46%). We conducted 882 baseline concussion tests and 13 follow-up tests over the 2 years. CONCLUSIONS:To the best of our knowledge, this is the first time data have been collected and reported on sports injuries in the study population. Future studies built on these findings will allow for the development of targeted guidelines and interventions for coaches, players, and parents so sports injury-related morbidity and mortality decrease in our youngest athletes.

RATIONALE: Recent evidence suggests that Obstructive Sleep Apnea (OSA) may be a risk factor for developing Mild Cognitive Impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. OBJECTIVE: To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. METHODS: Data was derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 to 90, were non-depressed and had a consensus clinical diagnosis of cognitively normal. CSF Amyloid beta was measured using ELISA. Subjects received Pittsburgh compound B Positron Emission Tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. MEASUREMENTS AND MAIN RESULTS: We found that severity of OSA indices (lnAHIall [F1,88=4.26, p<.05] and lnAHI4% [F1,87=4.36, p<.05]) were associated with annual rate of change of CSF Abeta42 using linear regression after adjusting for age, sex, BMI and ApoE4 status. LnAHIall and lnAHI4 were not associated with increases in ADPiB-mask most likely due to the small sample size although there was a trend for lnAHIall (F1,28=2.96, p=.09 and F1,28=2.32, n.s. respectively). CONCLUSION: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2 year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.

BACKGROUND:The aim of this study is to determine the clinical characteristics and predictors of survival for patients with multiple metachronous esophageal tumors (MMET) and to compare the survival with patients that have single esophageal tumor (SET). METHOD:We identified all cases of primary esophageal cancer from the Surveillance, Epidemiology and End Results program database from 2000 to 2013. The primary outcome was the development of a second esophageal cancer six months after the diagnosis of the first tumor. A secondary outcome was disease-specific death from esophageal cancer. Chi-square test was used to compare the tumor and demographic characteristics of patients with SET versus the first and second tumor characteristics of patients with MMET. Logistic regression was used to obtain the odds ratios between patients with secondary tumors and those with primary tumors. Accelerated life model was performed for patients with MMET to determine the predictors of survival. RESULTS:Patients with MMET were more likely to have localized stage disease compared to those with SET (P < 0.0001). Distant stage disease for both first tumor (β = -0.402, P = 0.003) and second tumor (β = -0.301, P = 0.033) were predictors of increased mortality. The interval between the first and second tumor affected survival. Intervals of 2-5 years and > 5 years were associated with a reduced hazard with a β = 0.53 and 1.13, P < 0.0001, respectively. CONCLUSION:Early development of a second tumor in MMET is associated with poorer survival. Patients with MMET may benefit from regular follow-up and intervention to prevent the development of a second tumor.

 Obstructive sleep apnea (OSA) and Alzheimer's disease (AD) are highly prevalent conditions with growing impact on our aging society. While the causes of OSA are now better characterized, the mechanisms underlying AD are still largely unknown, challenging the development of effective treatments. Cognitive impairment, especially affecting attention and executive functions, is a recognized clinical consequence of OSA. A deeper contribution of OSA to AD pathogenesis is now gaining support from several lines of research. OSA is intrinsically associated with disruptions of sleep architecture, intermittent hypoxia and oxidative stress, intrathoracic and hemodynamic changes as well as cardiovascular comorbidities. All of these could increase the risk for AD, rendering OSA as a potential modifiable target for AD prevention. Evidence supporting the relevance of each of these mechanisms for AD risk, as well as a possible effect of AD in OSA expression, will be explored in this review.

There is a paucity of data related to sports injuries, concussions, and computerized neurocognitive testing (CNT) among very young athletes playing sports in recreational settings. The purpose of this study was to report baseline CNT results among male and female children, ages 5-11, playing sports in Hillsborough County, Florida using ImPACT Pediatric, which is specifically designed for this population. Data were collected from 2016 to 2017. The results show that 657 baseline tests were conducted and t-tests and linear regression were used to assess mean significant differences in composite scores with sex and age. Results showed that females scored better on visual memory and in general as age increased, baseline scores improved. The results can be used to build further studies on the use of CNT in recreational settings and their role in concussion treatment, management, and interventions.

Burkitt's Lymphoma (BL) has three peaks of occurrence, in children, adults and elderly, at 10, 40 and 70 years respectively. To the best of our knowledge, no study has been conducted to assess predictors of survival in the three age groups. We hypothesized that survival predictors may differ by age group. We, therefore, sought to determine survival predictors for BL in these three groups: children (<15 years of age), adults (40-70 years of age) and elderly (>70 years of age). Using the Surveillance, Epidemiology, and End Results (SEER) database covering the years 2000-2013, we identified 797 children, 1,994 adults and 757 elderly patients newly diagnosed with BL. We used adjusted Cox proportional hazards regression models to determine prognostic factors for survival for each age group. Five-year relative survival in BL for children, adults and elderly were 90.4, 47.8 and 28.9%, respectively. Having at least Stage II disease and multiple primaries were associated with higher mortality in the elderly group. In adults, multiple primaries, Stage III or IV disease, African American race and bone marrow primary were associated with increased mortality whereas Stage IV disease and multiple primaries were associated with worse outcome in children. These findings demonstrate commonalities and differences in predictors of survival that may have implications for management of BL patients.

Study Objectives:Mounting evidence implicates disturbed sleep or lack of sleep as one of the risk factors for Alzheimer's disease (AD), but the extent of the risk is uncertain. We conducted a broad systematic review and meta-analysis to quantify the effect of sleep problems/disorders on cognitive impairment and AD. Methods:Original published literature assessing any association of sleep problems or disorders with cognitive impairment or AD was identified by searching PubMed, Embase, Web of Science, and the Cochrane library. Effect estimates of individual studies were pooled and relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. We also estimated the population attributable risk. Results:Twenty-seven observational studies (n = 69216 participants) that provided 52 RR estimates were included in the meta-analysis. Individuals with sleep problems had a 1.55 (95% CI: 1.25-1.93), 1.65 (95% CI: 1.45-1.86), and 3.78 (95% CI: 2.27-6.30) times higher risk of AD, cognitive impairment, and preclinical AD than individuals without sleep problems, respectively. The overall meta-analysis revealed that individuals with sleep problems had a 1.68 (95% CI: 1.51-1.87) times higher risk for the combined outcome of cognitive impairment and/or AD. Approximately 15% of AD in the population may be attributed to sleep problems. Conclusion:This meta-analysis confirmed the association between sleep and cognitive impairment or AD and, for the first time, consolidated the evidence to provide an "average" magnitude of effect. As sleep problems are of a growing concern in the population, these findings are of interest for potential prevention of AD.