Faculty Bibliography

BACKGROUND:This study examined the relationships between resilience and sleep disturbance in a diverse sample of older women with a history of hypertension and whether this relationship is moderated by individuals' race/ethnicity. METHODS:Sample includes 700 females from a community-based study in Brooklyn, New York with a mean age of 60.7 years (SD=6.52). Of the participants, 28.1% were born in the U.S.; 71% were African-descent, 17.4% were European and 11.6% were Hispanics descents. Data were gathered on demographics and sleep disturbance using the Comprehensive Assessment and Referral Evaluation (CARE) and the Stress Index Scale (SIS). Resilience Factors were assessed with both the Index of Self-Regulation of Emotion (ISE) and religious health beliefs. Chi-Square, Anova, Student t-tests, and multilinear regression analysis were conducted to explore associations between resilience factors and sleep disturbance. Associations between resilience factors and sleep disturbance were examined using stratified multilinear regression analysis in three models by race/ethnicity. Regression models was conducted examining the interaction between resilience factors and stress RESULTS: Resilience factor, ISE emerged as the strongest independent predictor of sleep disturbance [B(SE) = -0.368(0.008); p < .001] for African descents. ISE was not a significant predictor of sleep disturbance among Hispanic participants [B(SE) = -0.218(0.022);p = .052], however interaction effect analysis revealed that stress level moderates significantly the relationship between ISE, and their sleep disturbance [B(SE) = 0.243(0.001);p = .036]. CONCLUSIONS:Results of our study suggest that resilience factors might be a more important protective factor for sleep disturbance among diverse older females.

Increasing evidence links cognitive-decline and Alzheimer's disease (AD) to various sleep disorders, including obstructive sleep apnea (OSA). With increasing age, there are substantial differences in OSA's prevalence, associated comorbidities and phenotypic presentation. An important question for sleep and AD researchers is whether OSA's heterogeneity results in varying cognitive-outcomes in older-adults compared to middle-aged adults. In this review, we systematically integrated research examining OSA and cognition, mild cognitive-impairment (MCI) and AD/AD biomarkers; including the effects of continuous positive airway pressure (CPAP) treatment, particularly focusing on characterizing the heterogeneity of OSA and its cognitive-outcomes. Broadly, in middle-aged adults, OSA is often associated with mild impairment in attention, memory and executive function. In older-adults, OSA is not associated with any particular pattern of cognitive-impairment at cross-section; however, OSA is associated with the development of MCI or AD with symptomatic patients who have a higher likelihood of associated disturbed sleep/cognitive-impairment driving these findings. CPAP treatment may be effective in improving cognition in OSA patients with AD. Recent trends demonstrate links between OSA and AD-biomarkers of neurodegeneration across all age-groups. These distinct patterns provide the foundation for envisioning better characterization of OSA and the need for more sensitive/novel sleep-dependent cognitive assessments to assess OSA-related cognitive-impairment.

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.

Introduction: We determined whether Obstructive Sleep Apnea (OSA) and beta-Amyloid Burden (Abeta) act additively or synergistically to promote conversion from cognitive normal (CN) to mild cognitive impairment (MCI) and from MCI to AD.
Method(s): In this longitudinal observational study, we examined CN (n=298) and MCI (n=418) older adults from the ADNI database (adni.loni.usc.edu). OSA was self-reported during a clinical interview. Brain Abeta was assessed using Florbetapir-PET imaging. The primary outcome of the analysis was conversion from CN to MCI (CN participants) and from MCI to AD (MCI participants). Participants were required to have a baseline and at least one follow-up clinical visit that identified their cognitive status. Logistic mixed-effects models with random intercept and slope were used to assess associations between OSA, Abeta, and risk of conversion from CN to MCI, and MCI to AD. All models included age at baseline, sex, APOE4 status, years of education, and their interactions with time.
Result(s): Of the 716 participants, 329 (46%) were women. The overall mean (SD) age was 74.7 (5.0) years, and the overall mean (SD) follow-up time was 5.5 (1.7) years (Range: 2.7 - 10.9 years). In CN participants at baseline, conversion to MCI was associated with both OSA (beta = 0.418; 95% CI, 0.133 to 0.703; P < .001) and higher Abeta-burden (beta = 0.554; 95% CI, 0.215 to 0.892; P < .001). The interaction of OSA and Abeta burden with time was significant (beta = 1.169, 95% CI, 0.776 to 1.562; P < .001), suggesting a synergistic effect. In MCI participants at baseline, conversion to AD was associated with both OSA (beta = 0.637; 95% CI, 0.291 to 0.982; P < .001) and higher Abeta-burden (beta = 1.061; 95% CI, 0.625 to 1.497; P < .001). The interaction of OSA and Abeta burden with time was significant (beta = 1.312, 95% CI, 0.952 to 1.671; P < .001), suggesting a synergistic effect.
Conclusion(s): In both CN and MCI elderly, Abeta modified the risk of progression to AD in OSA participants. OSA patients maybe more physiologically susceptible as Abeta load becomes increasingly abnormal

Introduction: We determined whether the co-occurrence of OSA and hypertension interact synergistically to promote beta-Amyloid burden and cognitive decline in clinically normal older adults Methods: Prospective longitudinal study utilizing NYU cohort of community-dwelling cognitively-normal elderly, with baseline and at least one follow-up of CSF-Abeta42 (measured using ELISA), and neuropsychological visits. OSA was defined using AHI4%. Hypertension diagnosis was according to AHA-guidelines. Cognitive variables assessed included Logic-2, Animal-Fluency [AF], Vegetable-Fluency [VF]), Boston-Naming-Test [BNT], Digit-Symbol-Substitution-Test [DSST], Trails Making Test-A and B [TMT-A and B]). Linear mixed-effects models with random intercept and slope were used to assess associations between OSA, hypertension, and longitudinal changes in CSF-Abeta and cognition, controlling for age-at-baseline, sex, APOE4-status, years-of-education, and their interactions with time.
Result(s): Of the 98 participants, 63 (64.3%) were women. The mean (SD) age was 69.6 (7.3) years and follow-up time was 2.46 (0.64) years. OSA and hypertension were each associated with faster rate-of-change in CSF-Abeta42 (beta = -3.11; 95%CI, -3.71, -2.51; and beta= -2.82, 95% CI -3.29, -2.35, P < .01 for both respectively). The interaction of OSA and hypertension with time was significant (beta= -1.28, 95% CI -1.78 to -0.78, P < .01) suggesting a synergistic effect. No significant associations were seen between annual-changes in CSF-Abeta42 and cognitive-decline. However, faster decline in VF, and DSST were associated with OSA (beta = -0.054; 95%CI, -0.094, -0.013; P = .02; beta = -0.058; 95%CI, -0.084, -0.033; P < .05 for both respectively), and with hypertension (beta = -0.048; 95%CI, -0.079, -0.017; P = .04; beta = -0.078; 95%CI, -0.098, -0.057; P = .002; respectively). The interaction of OSA and hypertension with time was significant for both VF and DSST (beta = -0.033, 95%CI, -0.048, -0.018; P < .001 and beta = -0.040, 95%CI, -0.064, -0.016; P < .001, respectively), suggesting a synergistic effect.
Conclusion(s): In cognitive-normal elderly OSA individuals, vascular risk may complement AD-biomarkers in assessing risk of prospective cognitive-decline in preclinical AD

STUDY OBJECTIVES/OBJECTIVE:To determine the effect of self-reported clinical diagnosis of Obstructive Sleep Apnea (OSA) on longitudinal changes in brain amyloid-PET and CSF-biomarkers (Aβ42, T-tau and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI) and Alzheimer's Disease (AD) elderly. METHODS:Longitudinal study with mean follow-up time of 2.52±0.51 years. Data was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI and 325 AD elderly. Main Outcomes were annual rate-of-change in brain amyloid-burden (i.e. longitudinal increases in florbetapir-PET uptake or decreases in CSF-Aβ42 levels); and tau-protein aggregation (i.e. longitudinal increases in CSF total-tau (T-tau) and phosphorylated-tau (P-tau)). Adjusted multi-level mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate-of-biomarker-change differed between participants with and without OSA. RESULTS:In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B=.06, 95% CI .02, .11 and B=.08, 95% CI .05, .12 respectively) and decrease in CSF-Aβ42 levels (B=-2.71, 95% CI -3.11, -2.35 and B=-2.62, 95% CI -3.23, -2.03, respectively); as well as increases in CSF T-tau (B=3.68, 95% CI 3.31, 4.07 and B=2.21, 95% CI 1.58, 2.86, respectively) and P-tau (B=1.221, 95% CI, 1.02, 1.42 and, B=1.74, 95% CI 1.22, 2.27, respectively); compared to OSA- participants. No significant variations in the biomarker changes over time were seen in the AD group. CONCLUSIONS:In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.

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 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.