Faculty Bibliography

 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.

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.

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.

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.

Introduction: Sleep may play a role in AD pathogenesis, but the timing, role, and extent to which sleep disturbances in late-life are associated with increasing burden of AD neuropathology remains unclear. Sleep spindles have been implicated in sleep quality. Wakefulness is mediated by an arousal system beginning in the brainstem and continuing on to the diencephalon and innervating the thalamus, the region where sleep spindle oscillations are generated. In AD pathology, hyperphosphorylated tau (P-Tau) protein accumulates in the brainstem, from where it spreads to the entorhinal cortices, hippocampi and other brain regions. These tau aggregates may interfere with the sleep-wake cycle resulting in down-regulation of sleep spindles and associated sleep disruption. Increased CSF P-tau and T-tau levels are likely related to the formation of neurofibrillary tangles in the brainstem and limbic system (Braak stages I-IV). Methods: 49 cognitively normal (CDR=0) elderly (66.95 +/- 7.76 years) subjects completed a structural MRI, lumbar puncture (LP) and nocturnal polysomnography (NPSG) within 4.65 +/- 6.81 months of the LP. From the NPSG, spindle frequency and density were analyzed for stages NREM1, NREM2 and NREM3, using an automated optimization algorithm which decomposes the EEG as a sum of transient and oscillatory components. This was used to detect the spindles and a Fourier analysis was performed to evaluate the spindle frequency in Hz. Results: Spindle frequency and density in NREM2 sleep were inversely associated with CSF P-tau (r= -0.355, p<0.05; r=-0.476, p<0.05) and CSF T-tau (r=-0.405, p<.05; r=-0.542, p<.05) using partial correlation controlling for age and ApoE4 allele. There were no associations between spindle frequency or density and CSF P-tau or CSF T-tau in stages NREM1, NREM3. Conclusion: The association of spindle frequency and density in NREM2 to CSF P-tau and CSF T-tau in cognitively normal elderly suggest either that tau pathology may produce an early downstream effect on sleep spindles, or that changes in sleep spindles can identify a process relating to tau pathology. Whether the association of tau to spindles is a non-specific effect of tau on increasing sleep fragmentation in general remains an area of active investigation

BACKGROUND:Primary cesarean deliveries are a major contributor to the large increase in cesarean delivery rates in the United States over the past 2 decades and are an essential focus for the reduction of related morbidity and costs. Studies have shown that primary cesarean delivery rates among low-risk women in the United States vary 3-fold across hospitals and are not explained by differences in patient case-mix. However, the extent to which maternal vs hospital characteristics contribute to this variation remains poorly understood because previous studies were limited in scope and did not assess the influence of factors such as maternal ethnicity subgroups or prepregnancy obesity. OBJECTIVE:We assessed the contribution of individual- and hospital-level risk factors to the hospital variation in primary cesarean delivery rates among low-risk women in Florida. STUDY DESIGN/METHODS:Our population-based retrospective cohort study used Florida's linked birth certificate and hospital discharge records for the period of 2004-2011. The study population was comprised of 412,192 nulliparous, singleton, vertex, live births with labor at 37-40 weeks gestation in 122 nonmilitary delivery hospitals. Data were analyzed with logistic mixed-effects regression with cesarean delivery as the outcome. This approach provided adjusted risk estimates at an individual and hospital level and the estimated percent of hospital variation statewide that was explained by these factors. RESULTS:The primary cesarean delivery rate in the study population was 23.9%, with hospital-specific estimates that ranged from 12.8-47.3%. Leading risk factors for cesarean delivery were maternal age ≥35 years (adjusted relative risk, 2.22), prepregnancy obesity (body mass index, ≥30 kg/m(2); adjusted relative risk, 1.73), medical risk conditions (adjusted relative risk, 1.72), labor induction (adjusted relative risk, 1.52), and delivery in hospitals located in Miami-Dade County (adjusted relative risk, 1.73). Hospital geographic location was a significant effect modifier for prepregnancy obesity, medical conditions, and labor induction (P < .05), with a tendency towards lower adjusted relative risks for these factors in Miami-Dade County relative to other Florida regions. Conversely, Miami-Dade County had an increased prevalence of higher-risk ethnic subgroups, such as Cuban or Puerto Rican mothers, and also substantially higher adjusted relative risks that were associated with practice-related factors, such as delivery during weekday hours. Whereas hospital geographic location contributed to 39.6% of the observed variation statewide, the estimated contribution of maternal ethnicity ranged from 1.6-15.7% among Florida regions. CONCLUSIONS:Hospital geographic location contributes to hospital variation in primary cesarean delivery rates among low-risk women in Florida. In contrast to previous studies, our findings suggest that individual level risk factors such as maternal ethnicity also contribute to some of this variation, with differing extent by region. These individual factors likely interact with practice factors and add to the variation. This study was limited by not including maternal Bishop score before induction or obstetrics provider in the analysis. These were not available on the dataset but likely contribute to the variation. Our findings suggest potential issues to consider in quality improvement efforts, such as the need for future qualitative research that focuses on mothers in higher-risk ethnic subgroups and providers in high-rate hospitals, particularly those in Miami-Dade County. These studies may help to identify potential cultural differences in maternal beliefs and expectations for delivery and maternal reasons for differences in obstetrics practices.