Erratum to: Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

[This corrects the article DOI: 10.14283/jarlife.2024.1.].

Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

Background: Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity. Methods: Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aß42, Aß40, Aß42/Aß40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics. Results: In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) . Conclusions: Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes.

Daytime Sleepiness Is Associated with Lower Cognitive Scores: The Look AHEAD Study.

Background: Daytime sleepiness is common in older adults and may result from poor nighttime sleep due to sleep disordered breathing, fragmented sleep, or other sleep disorders. Daytime sleepiness may be associated with cognition in older adults. Objectives: We investigated the association between self-reported daytime sleepiness and cognitive function in the Look AHEAD clinical trial. Design: Observational follow-up of a randomized clinical trial of an intensive lifestyle intervention. Setting: Clinic. Participants: Participants (n=1,778) aged 45-76 years at baseline with type 2 diabetes and overweight or obesity. Interventions: Participants were randomized to an intensive lifestyle intervention for weight loss or a control condition of diabetes support and education. Measurements: Participants provided self-reported levels of daytime sleepiness at baseline and years 12-13. Cognitive function was assessed with a neurocognitive battery at years 12-13 and 18-20. Results: Participants who reported having frequent daytime sleepiness (often or always) performed significantly worse than others on the cognitive composite (-0.35; p-value=0.014) after controlling for covariates. When stratified by intervention arm, participants assigned to the intensive lifestyle intervention who reported often/always having daytime sleepiness performed worse on Digit Symbol Coding (-0.63; p-value=0.05) and Trail Making Part-B (-0.56; p-value=0.02) after controlling for covariates. Statistical interactions revealed associations between daytime sleepiness and the following covariates: race and ethnicity, APOE ε4 carrier status, baseline history of cardiovascular disease, and depression. Conclusions: Daytime sleepiness over ~13 years predicted poorer cognitive performance in older individuals who, by virtue of having diabetes and overweight/obesity, are at high risk for sleep disorders and cognitive impairment.

The relation of preschool child-care quality to children's cognitive and social developmental trajectories through second grade.

The cognitive and socioemotional development of 733 children was examined longitudinally from ages 4 to 8 years as a function of the quality of their preschool experiences in community child-care centers, after adjusting for family selection factors related to child-care quality and development. These results provide evidence that child-care quality has a modest long-term effect on children's patterns of cognitive and socioemotional development at least through kindergarten, and in some cases, through second grade. Differential effects on children's development were found for two aspects of child-care quality. Observed classroom practices were related to children's language and academic skills, whereas the closeness of the teacher-child relationship was related to both cognitive and social skills, with the strongest effects for the latter. Moderating influences of family characteristics were observed for some outcomes, indicating stronger positive effects of child-care quality for children from more at-risk backgrounds. These findings contribute further evidence of the long-term influences of the quality of child-care environments on children's cognitive and social skills through the elementary school years and are consistent with a bioecological model of development that considers the multiple environmental contexts that the child experiences.

Regulation of neurotensin secretion in mammalian C cell lines: potassium and norepinephrine affect the rapid release of the peptide.

Calcitonin (CT) and neurotensin (NT) secreting cell lines (6-23,44-2) were established from a transplantable rat medullary thyroid carcinoma (rMTC). The 44-2 line was used to obtain two colony clones 44-2 B and C secreting 20-30-fold greater NT than CT. These cells were used to study the regulation of Ca2+-modulated NT secretion and to ascertain the role of K+ and NE in the rapid release of NT. Medium NT was measured by a specific RIA with the antiserum N-1-11. Secretion experiments were in replicate 35 mm dishes in Krebs-Ringer-bicarbonate buffer supplemented with 90 mg% glucose (KRBG). Ca2+ (0.5-4.0 mM) stimulated NT release in a dose-dependent manner with an ED50 of 2.0 mM. Ca2+ was required for NT release induced by the Ca2+ ionophore, ionomycin, also K+ (50 mM) and norepinephrine (NE). To determine the mode of NT release in the presence of control (1.0 mM Ca2+) or experimental conditions (Ca2+ 1.0 mM plus 10(-6) NE and/or 50 mM K+), 44-2 cells were incubated in KRBG using an experimental paradigm wherein medium was changed at 10-min intervals, and NT release was quantitated. NE stimulated release of NT by these cells and the amount of NT released with each repetitive pulse of NE remained constant throughout the experiment. K+ (50 mM) elicited a rapid release of NT in the first 0-10 min incubation and the amount of NT released into the buffer was greater than that measured with NE; however, in these experiments, the response to K+ declined progressively and reached basal values at 20-30 min. Our results show neither pulse stimulation nor continuous incubation of cells with NE affected the response of the cells to a subsequent challenge with K+. These results suggest the presence of differentially stimulated, releasable pools of NT in these cells. We conclude that these newly established 44-2 B and C cells provide a useful model to study the regulation of NT release.