Faculty Bibliography

STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) prevalence increases with age, but whether OSA-related sleep disruption could interrupt the processing of previously encoded wake information thought to normally occur during sleep in cognitively normal older adults remains unknown. METHODS:Fifty-two older (age = 66.9 ± 7.7 years, 56 % female), community-dwelling, cognitively normal adults explored a 3D maze environment and then performed 3 timed trials before (evening) and after (morning) sleep recorded with polysomnography (PSG) with a 20-minute morning psychomotor vigilance test (PVT). RESULTS:Twenty-two (22) subjects had untreated OSA (Apnea Hypopnea Index (AHI4%) ≥ 5/hour) where severity was mild on average [median (interquartile range (IQR))] AHI4% = 11.0 (20.7)/hour) and 30 subjects had an AHI4% < 5/hour. No significant differences were observed in overnight percent change in completion time or in the pattern of evening pre-sleep maze performance. However, during the morning post-sleep trials, there was a significant interaction between OSA group and morning trial number such that participants with OSA performed worse on average with each subsequent morning trial, whereas those without OSA showed improvements. There were no significant differences in morning PVT performance suggesting that vigilance is unlikely to account for this difference in morning maze performance. Increasing relative frontal slow wave activity (SWA) was associated with better overnight maze performance improvement in participants with OSA (r= 0.51, p = 0.02) but not in those without OSA, and no differences in slow wave activity were observed between groups. CONCLUSIONS:OSA alters morning performance in spatial navigation independent of a deleterious effect on morning vigilance or evening navigation performance. Relative frontal slow wave activity is associated with overnight performance change in older subjects with OSA, but not those without.

The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACA_VIS neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACA_VIS neurons in anticipation of visual stimuli is crucial for adjusting performance following errors. 30-Hz optogenetic stimulation of ACA_VIS neurons in anesthetized mice recapitulates the increased gamma and reduced theta VIS oscillatory changes that are associated with endogenous post-error performance during behavior and subsequently increased visually evoked spiking, a hallmark feature of visual attention. This frontal sensory neural circuit links error monitoring with implementing adjustments of attention to guide behavioral adaptation, pointing to a circuit-based mechanism for promoting cognitive control.

RATIONALE/BACKGROUND:) may reduce discomfort in those with high nasal resistance and improve adherence in this subgroup. OBJECTIVES/OBJECTIVE:improves adherence over CPAP in subjects with high nasal resistance. METHODS:versus CPAP in World Trade Center dust-exposed subjects with OSA stratified by nasal resistance measured by 4-Phase Rhinomanometry. RESULTS:(mean Δ hours (95% CI)) in subjects with low resistance (0.33h (-0.10, 0.76)) or high nasal resistance (0.26h (-0.14, 0.66)). No significant differences were observed in any of the secondary outcomes between PAP modes. CONCLUSIONS:than to CPAP in subjects with high or low nasal resistance, and, show clinically insignificant better adherence overall with CPAP. Clinical Trial registered with Clinicaltrials.gov (NCT01753999).

BACKGROUND:Decreased cholinergic tone associated with increased proinflammatory cytokines has been observed in several human diseases associated with low-grade inflammation. We examined if this attenuated cholinergic anti-inflammatory pathway (CAP) mechanism contributed to increased neuroinflammation observed in depression. METHODS:We measured cerebrospinal fluid (CSF) cholinergic markers (AChE and BChE activities) in 28 individuals with longstanding late-life major depression (LLMD) and 19 controls and their relationship to central and peripheral levels of pro-inflammatory cytokines (IL-6 and IL-8). Additionally, we examined if these cholinergic indices were related to CSF markers of microglial activation and neuroinflammation (sTREM2 and complement C3). RESULTS:Compared with controls, LLMD patients had a significant reduction in CSF BChE levels. Lower CSF BChE and AChE activities were associated with lower CSF markers of microglial and neuroinflammation (sTREM2 and C3). In addition, in LLMD patients we found an inverse relationship between peripheral marker of inflammation (plasma IL-6) and CSF BChE and AChE levels. CONCLUSIONS:Our results suggest an upregulation of the CAP mechanism in LLMD with an elevation in peripheral markers of inflammation and concomitant reduction in markers of glial activation associated with a higher cholinergic tone. Future studies should confirm these findings in a larger sample including individuals with acute and more severe depressive episodes and across all ages.

We examined the relative contribution of pulmonary diseases (chronic obstructive pulmonary disease, asthma and sleep apnea) to mortality risks associated with Coronavirus Disease (COVID-19) independent of other medical conditions, health risks, and sociodemographic factors. Data were derived from a large US-based case series of patients with COVID-19, captured from a quaternary academic health network covering New York City and Long Island. From March 2 to May 24, 2020, 11,512 patients who were hospitalized were tested for COVID-19, with 4,446 (38.62%) receiving a positive diagnosis for COVID-19. Among those who tested positive, 959 (21.57%) died of COVID-19-related complications at the hospital. Multivariate-adjusted Cox proportional hazards modeling showed mortality risks were strongly associated with greater age (HR = 1.05; 95% CI: 1.04-1.05), ethnic minority (Asians, Non-Hispanic blacks, and Hispanics) (HR = 1.26; 95% CI, 1.10-1.44), low household income (HR = 1.29; 95% CI: 1.11, 1.49), and male sex (HR = 0.85; 95% CI: 0.74, 0.97). Higher mortality risks were also associated with a history of COPD (HR = 1.27; 95% CI: 1.02-1.58), obesity (HR = 1.19; 95% CI: 1.04-1.37), and peripheral artery disease (HR = 1.33; 95% CI: 1.05-1.69). Findings indicate patients with COPD had the highest odds of COVID-19 mortality compared with patients with pre-existing metabolic conditions, such as obesity, diabetes and hypertension. Sociodemographic factors including increased age, male sex, low household income, ethnic minority status were also independently associated with greater mortality risks.

Background: Rodent model and in vitro studies suggest brain temperature has the potential to bidirectionally interact with tau pathology in Alzheimer's Disease (AD): tau phosphorylation is robustly increased by small (<1degreeC) reductions in temperature within the human physiological range, and lower brain thermoregulatory areas may be among those first affected by AD pathology. Here, we evaluated the cross-sectional association between body temperature (Tb), as a proxy for brain temperature, and clinically accessible markers of tau pathology in cognitively normal older adults.
Method(s): Tb was measured continuously over 48 hours with ingestible telemetry combined with a novel pre-processing algorithm. This period included 2 nights of nocturnal polysomnography to facilitate delineation of Tb-tau pathology relationships according to waking vs sleeping time intervals. Tau pathology was assessed with both soluble markers including plasma P-tau (P-tau 181) and cerebrospinal fluid (CSF) P-tau, both sampled the following day, and aggregated tau, namely neurofibrillary tangle (NFT) burden in early (I-III) Braak stage areas imaged with MR-PET using the [18F]MK-6240 radio tracer on average ~ one month later Results: Plasma and CSF P-tau levels were highly correlated with one another and with tau tangle radio tracer uptake (NFT burden), p < 0.05 for all comparisons. Lower Tb (quantified by lower mean Tb and a greater proportion of time Tb was under 37.0degreeC) was associated with increased NFT burden and increased plasma and CSF P-tau levels, p < 0.05 all comparisons. For aggregated tau, lower Tb - tau pathology associations were seen during for Tb recorded during waking, but not during sleeping intervals.
Conclusion(s): Preliminary results suggest that lower body temperature in older adults may be associated with increased aggregated and soluble tau pathology

Objective/UNASSIGNED:Compared to European Americans, research indicates that African Americans have higher white matter hyperintensity (WMH) load; however, the clinical and biological bases underlying this higher burden are poorly understood. We hypothesize that obesity may explain differences in WMH between African and European Americans. Methods/UNASSIGNED:, and WMH load, captured by FLAIR images, as sum of deep and periventricular volumes, scored using the Fazekas scale (0-6), WMH≥4 considered high. Results/UNASSIGNED:=5.3, p=0.02). Conclusion/UNASSIGNED:Results denote that age predicted WMH among European Americans, while obesity predicted WMH among African Americans. Matched sample analyses indicate that obesity increases the odds of WMH, though more pronounced in African Americans. These findings suggest that obesity may explain the differential burden of white matter hyperintensity load, signifying public health and clinical importance.