Understanding the factors contributing to optimal cognitive function throughout the aging process is essential to better understand successful cognitive aging. Processing speed is an age sensitive cognitive domain that usually declines early in the aging process; however, this cognitive skill is essential for other cognitive tasks and everyday functioning. Evaluating brain network interactions in cognitively healthy older adults can help us understand how brain characteristics variations affect cognitive functioning. Functional connections among groups of brain areas give insight into the brain’s organization, and the cognitive effects of aging may relate to this large-scale organization. To follow-up on our prior work, we sought to replicate our findings regarding network segregation’s relationship with processing speed. In order to address possible influences of node location or network membership we replicated the analysis across 4 different node sets.

Data were acquired as part of a multi-center study of 85+ cognitively normal individuals, the McKnight Brain Aging Registry (MBAR). For this analysis, we included 146 community-dwelling, cognitively unimpaired older adults, ages 85-99, who had undergone structural and BOLD resting state MRI scans and a battery of neuropsychological tests. Exploratory factor analysis identified the processing speed factor of interest. We preprocessed BOLD scans using fmriprep, Ciftify, and XCPEngine algorithms. We used 4 different sets of connectivity-based parcellation: 1)MBAR data used to define nodes and Power (2011) atlas used to determine node network membership, 2) Younger adults data used to define nodes (Chan 2014) and Power (2011) atlas used to determine node network membership, 3) Older adults data from a different study (Han 2018) used to define nodes and Power (2011) atlas used to determine node network membership, and 4) MBAR data used to define nodes and MBAR data based community detection used to determine node network membership.

Segregation (balance of within-network and between-network connections) was measured within the association system and three wellcharacterized networks: Default Mode Network (DMN), Cingulo-Opercular Network (CON), and Fronto-Parietal Network (FPN). Correlation between processing speed and association system and networks was performed for all 4 node sets.

We replicated prior work and found the segregation of both the cortical association system, the segregation of FPN and DMN had a consistent relationship with processing speed across all node sets (association system range of correlations: r=.294 to .342, FPN: r=.254 to .272, DMN: r=.263 to .273). Additionally, compared to parcellations created with older adults, the parcellation created based on younger individuals showed attenuated and less robust findings as those with older adults (association system r=.263, FPN r=.255, DMN r=.263).

This study shows that network segregation of the oldest-old brain is closely linked with processing speed and this relationship is replicable across different node sets created with varied datasets. This work adds to the growing body of knowledge about age-related dedifferentiation by demonstrating replicability and consistency of the finding that as essential cognitive skill, processing speed, is associated with differentiated functional networks even in very old individuals experiencing successful cognitive aging.

Preclinical evidence has identified the trace amine-associated receptor 1 (TAAR1) as a novel regulator of metabolic control. Ulotaront is a TAAR1 and 5-HT1A agonist currently in Phase 3 clinical trials for the treatment of schizophrenia. Here we summarize preclinical results assessing the effects of ulotaront on weight and metabolic parameters.

Effects of ulotaront administration were evaluated on oral glucose tolerance (oGTT), gastric emptying, and in rodent models of weight gain (high-fat diet [HFD]-, corticosterone-, and olanzapine-induced).

Following 15-day oral administration of ulotaront, rats on HFD showed dose-dependent reduction in body weight, food intake, and liver triglyceride content compared to controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in rats switched to ulotaront (vs. vehicle). Consistent with weight-lowering effects in rats, chronic ulotaront treatment normalized corticosterone-induced weight gain in mice. Assessment of oGTT showed a dose-dependent reduction of glucose excursion in response to acute ulotaront administration in naive and diabetic db/db mice. Ulotaront administration also delayed gastric emptying in mice—a likely mechanism driving reductions in glucose excursions during the oGTT. Whole-brain c-fos imaging of ulotaront-treated mice revealed increased neuronal activity in several brain regions associated with regulation of food intake and metabolic signals.

The data indicate that ulotaront not only lacks metabolic liabilities typically associated with antipsychotics but can reduce body weight and improve glucose tolerance in rodent models. The underlying mechanisms may include TAAR1-mediated peripheral effects on glucose homeostasis and/or direct modulation of homeostatic and hedonic neurocircuits regulating energy balance. The beneficial metabolic effects of ulotaront may suggest a substantially improved risk-benefit profile compared to established antipsychotics.

Sunovion Pharmaceuticals Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc.

To estimate the risk of bloodstream infection associated with catheter dwell time in infants.

Retrospective study.

Duke University Medical Center neonatal intensive care unit, an academic, level 3 nursery in Durham, North Carolina.

A case of catheter-associated bloodstream infection was defined as one that occurred in an infant whose culture-positive blood sample was collected more than 24 hours after catheter insertion or within 72 hours after catheter removal. We used multivariable logistic regression to control for the catheter's position and dwell time as well as the infant's sex, gestational age, age at time of catheter insertion, birth weight, and weight at time of catheter insertion.

We identified 135 cases of catheter-associated bloodstream infection. The mean catheter dwell time was 12.2 days (range, 0–113 days), and the mean time to bloodstream infection was 10.8 days (range, 1–57 days). An increase in catheter dwell time was associated with a lower risk of bloodstream infection (odds ratio, 0.975 [95% confidence interval, 0.954–0.996]; P = .02).

increased risk of catheter-associated bloodstream infection was observed with increased catheter dwell time. This may have been due to the infant's improved nutrition, decreased need for other invasive devices, and maturing skin and immune system as catheter dwell time increased.