Faculty Bibliography

The Electrophysiology Professional Interest Area (EPIA) and Global Brain Consortium endorsed recommendations on candidate electroencephalography (EEG) measures for Alzheimer's disease (AD) clinical trials. The Panel reviewed the field literature. As most consistent findings, AD patients with mild cognitive impairment and dementia showed abnormalities in peak frequency, power, and "interrelatedness" at posterior alpha (8-12 Hz) and widespread delta (< 4 Hz) and theta (4-8 Hz) rhythms in relation to disease progression and interventions. The following consensus statements were subscribed: (1) Standardization of instructions to patients, resting state EEG (rsEEG) recording methods, and selection of artifact-free rsEEG periods are needed; (2) power density and "interrelatedness" rsEEG measures (e.g., directed transfer function, phase lag index, linear lagged connectivity, etc.) at delta, theta, and alpha frequency bands may be use for stratification of AD patients and monitoring of disease progression and intervention; and (3) international multisectoral initiatives are mandatory for regulatory purposes.

Sleep disorders, despite being very frequent in adults with Down syndrome (DS), are often overlooked due to a lack of awareness by families and physicians and the absence of specific clinical sleep guidelines. Untreated sleep disorders have a negative impact on physical and mental health, behavior, and cognitive performance. Growing evidence suggests that sleep disruption may also accelerate the progression to symptomatic Alzheimer's disease (AD) in this population. It is therefore imperative to have a better understanding of the sleep disorders associated with DS in order to treat them, and in doing so, improve cognition and quality of life, and prevent related comorbidities. This paper reviews the current knowledge of the main sleep disorders in adults with DS, including evaluation and management. It highlights the existing gaps in knowledge and discusses future directions to achieve earlier diagnosis and better treatment of sleep disorders most frequently found in this population.

BACKGROUND:Inflammatory mechanisms are believed to contribute to the manifestation of major depressive disorder (MDD). Central cholinergic activity may moderate this effect. Here, we tested if volume of the cholinergic basal forebrain is associated with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglial activation in people with late life MDD. METHODS:Basal forebrain volume was determined from structural MRI scans and levels of CSF sTREM2 with immunoassay in 29 people with late-life MDD and 20 healthy older controls at baseline and 3 years follow-up. Associations were determined using Bayesian analysis of covariance. RESULTS:and total tau. Evidence was in favor of absence of an effect for baseline levels of CSF sTREM2 in MDD cases and for baseline and follow up data in controls. LIMITATIONS/CONCLUSIONS:The sample size of repeated CSF examinations was relatively small. Therefore, we used Bayesian sequential analysis to assess if effects were affected by sample size. Still, the number of cases was too small to stratify effects for different antidepressive treatments. CONCLUSIONS:Our data agree with the assumption that central cholinergic system integrity may contribute to regulation of microglia activity in late-life MDD.

BACKGROUND AND OBJECTIVES/UNASSIGNED:The effect of the ambient environment, sound, light, and movement, on the nighttime rest-activity of patients hospitalized with moderate-severe traumatic brain injury (TBI) is poorly understood. The purpose of this study was to examine how sound, light, and movement in these patients' hospital rooms may contribute to nighttime awakenings. METHODS/UNASSIGNED:An observational design was used with 18 adult participants on a neuroscience step-down unit diagnosed with moderate-severe TBI. For up to five consecutive nights, actigraphy was used to capture nighttime awakenings while a custom-made multisensory device captured sound, light, and movement exposures in the participant's room. RESULTS/UNASSIGNED:< .05), but reductions in light did not. CONCLUSION/UNASSIGNED:The ambient environment seems to impede restful sleep in immediate post-injury phase of patients with moderate-severe TBI.

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.

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.

Efforts to control the current coronavirus disease 2019 (COVID-19) pandemic have led to national lockdowns around the world. Reactions to the rapidly evolving outbreak were shared on social media platforms. We conducted a mixed-methods analysis of tweets collected from May 10 to May 24, 2020, using MAXQDA software in conjunction with Twitters search API using the keywords: "COVID-19," "coronavirus pandemic," "Covid19," "face masks," and included terms such as "Queens," "Bronx," "New York." A total of 7, 301 COVID-19-related tweets across the globe were analyzed. We used SAS Text Miner V.15.1 for descriptive text mining to uncover the primary topics in unstructured textual data. Content analysis of tweets revealed six themes: surveillance, prevention, treatments, testing and cure, symptoms and transmission, fear, and financial loss. Our study also demonstrates the feasibility of using Twitter to capture real-time data to assess the public's concerns and public health needs during the COVID-19 pandemic.

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.

Objective/UNASSIGNED:The study objective was to examine predictors of sleep disturbance and strain among caregivers of persons living with dementia (PLWD). Methods/UNASSIGNED:This cross-sectional study utilized a sample of community-dwelling older adults and their family caregivers drawn from the 2017 National Health and Aging Trends Study and National Study of Caregiving. Multivariable logistic regression was used to assess the association between caregiver and PLWD characteristics and a composite measure of caregiving strain. High caregiving strain was defined as a total score of ≥ 5 on the 6 caregiving strain items (e.g., emotional difficulty, no time for self). We used multivariable proportional odds models to examine predictors of caregiver sleep-related outcomes (trouble falling back to sleep and interrupted sleep), after adjusting for other caregiver and PLWD factors. Results/UNASSIGNED:Of the 1,142 family caregivers, 65.2% were female, 15% were Black, and 14% were Hispanic. Average age was 60 years old. Female caregivers were more likely to report high level of strain compared to male caregivers (OR: 2.61, 95% CI = 1.56, 4.39). Compared to non-Hispanic Whites, non-Hispanic Black and Hispanic caregivers had reduced odds of reporting greater trouble falling back asleep [OR = 0.55, CI (0.36, 0.82) and OR = 0.56, CI (0.34, 0.91), respectively]. The odds of reporting greater trouble falling back asleep was significantly greater among caregivers with high blood pressure vs. caregivers without high blood pressure [OR = 1.62, CI (1.12, 2.33)]. Conclusion/UNASSIGNED:In this cross-sectional study, caregivers with greater sleep difficulty (trouble falling back asleep) were more likely to report having high blood pressure. We found no racial/ethnic differences in interrupted sleep among caregivers to PLWD. These results suggest that interventions to improve sleep among caregivers to PLWD may decrease poor cardiovascular outcomes in this group.