Research

INTRODUCTION: The present study examined the dimensional structure of the neuropsychological test batteries from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) versions 2.0 and 3.0 and measurement equivalence across UDS versions and race/ethnicity groups.

METHODS: There were 49,895 participants included in the present study. The best-fitting model was developed and tested in separate samples. Multiple group confirmatory factor analysis (CFA) evaluated measurement equivalence across UDS versions and race/ethnicity groups.

RESULTS: Results identified a best-fitting four-factor model with residual structure. Multiple group CFA supported partial scalar invariance by UDS version and race/ethnicity group. Regarding race/ethnicity groups, the Language and Attention domains had more non-invariant intercepts, which most affected the White group.

DISCUSSION: A four-factor model effectively summarizes the UDS neuropsychological test batteries across UDS versions and race/ethnicity groups. Crucial differences in measurement parameters must be accounted for in studies using these neuropsychological tests as outcomes.

HIGHLIGHTS: A four-factor model summarizes cognition across Uniform Data Set (UDS) versions and race/ethnicity groups. Measurement invariance exists across race/ethnicity groups. Model fit differs between cognitively impaired and unimpaired samples. Accounting for differences in measurement parameters across groups is essential. Tailored normative data are crucial for certain UDS tests, including category fluency.

We investigated the associations of pregnancy levels of heavy metals and trace elements with the risk of gestational diabetes mellitus (GDM). Participating pregnant women were from the Boston Birth Cohort. We measured levels of mercury, lead, cadmium, selenium, and manganese in maternal red blood cells collected after delivery. We verified the GDM diagnosis using ICD codes, medication history, and plasma glucose profile abstracted from medical records. We used modified Poisson regression and Bayesian kernel machine regression models to examine associations of metals and elements, individually and as a mixture, with GDM. We stratified the analyses by race and ethnicity. Among 1256 pregnant women, 58% were non-Hispanic Black and 22% were Hispanic. Overall, each doubling of mercury and manganese levels was associated with 1.14 (95% CI: 1.01-1.28) and 0.65 (95% CI: 0.50-0.84) times the risk of GDM, respectively. In the race- and ethnicity-stratified analyses, the mercury-GDM association was stronger among Black women, and higher selenium levels were associated with higher GDM risk only among Hispanic women (Pinteraction = 0.01). In conclusion, women with higher mercury or lower manganese levels during pregnancy were more likely to develop GDM. An increased GDM risk associated with higher selenium levels was observed only in Hispanic women.

STUDY OBJECTIVES: Circulating non-esterified fatty acids (NEFAs) have been associated with impaired glucose metabolism but their modifiable determinants remain uncertain. We sought to determine the association between objectively-measured sleep disordered breathing (SDB), which is also associated with dysglycemia, and NEFA levels among community-dwelling older adults.

METHODS: We analyzed 787 older adults who had total fasting and post-load NEFAs measured in 1996-1997 in the Cardiovascular Health Study and underwent polysomnography between 1995 and 1997 in the Sleep Heart Health Study. We used multivariable linear regression to model NEFAs as a function of four SDB parameters: apnea-hypopnea index, arousal index, hypoxemia, and slow-wave sleep, and tested formal mediating effects by insulin sensitivity estimated with the Gutt index.

RESULTS: The mean age of study participants was 77.5 ± 4.3 years. The proportion of females and non-Hispanic whites was 58.7 per cent and 84.2 per cent, respectively. We did not find statistically significant associations between any of the SDB parameters and fasting NEFAs, but higher amounts of slow-wave sleep were significantly associated in a linear fashion with lower total post-load NEFAs in unadjusted and adjusted models [adjusted: β = -0.004, SE = 0.001, p = .02]. In mediation analyzes, 10 per cent of the slow wave sleep-NEFA association was mediated by Gutt-estimated insulin sensitivity (p = .45 for the indirect effect).

CONCLUSIONS: Among the SDB measures studied, only higher levels of objectively measured slow-wave sleep were significantly associated with lower levels of post-load NEFAs, although the underlying mechanism is uncertain. Establishing a causal link would make SDB interventions a promising target for NEFA regulation.

BACKGROUND: Heart rate variability (HRV) is a measure of autonomic function that has been associated with worse lung function and worse respiratory health. Using data from a community-based cohort, we aimed to test if HRV is associated with lung function and self-reported chronic lung disease (CLD).

METHODS: The Atherosclerosis Risk in Communities (ARIC) study is a community-based cohort that collected HRV measurements from 14-day continuous ECG patches and self-reported CLD at visit 6 (2016-2017). Pulmonary function testing was performed a prior visit (visit 5; 2011-2013). We used multivariate linear regression to test cross-sectional associations between HRV and lung function, and logistic regression to test associations between HRV and self-reported CLD. All analyses were adjusted for important confounders including smoking, demographics, and medications.

RESULTS: HRV and lung function measurements were available for 1456 participants. Included participants had a mean ± standard deviation (SD) age of 78.7 ± 4.5 years, 59.6 % were female, and 30.1 % were African American. Higher HRV reflective of overall HRV (standard deviation of normal RR intervals) and sympathetic activity [low frequency (LF) to high frequency (HF) ratio (LF/HF)] were associated with better lung function and lower odds of self-reported CLD. Higher HRV reflective of parasympathetic function (HF) was associated with worse lung function and higher odds of self-reported CLD.

CONCLUSIONS: We confirmed associations between HRV and respiratory health outcomes. Our data from a community-based cohort demonstrate the importance of utilizing several HRV measurements to capture multiple components of autonomic function when analyzing respiratory health outcomes.

BACKGROUND: Advanced glycation end-products result from chemical modification of proteins under conditions of hyperglycemia or oxidative stress common with advancing age. Advanced glycation end-product (AGE) formation alters vascular and cardiac structure and function, yet the prospective associations of circulating AGEs with heart failure (HF) and atrial fibrillation (AF) have not been studied.

METHODS: We evaluated the associations of serum Nε-carboxymethyl-lysine (CML), a major AGE in tissue proteins, and incident HF and AF in the CHS (Cardiovascular Health Study), a population-based cohort of older adults. HF subtypes were examined secondarily, as were prevalent echocardiographic phenotypes. CML was measured by immunoassay.

RESULTS: Among 2685 eligible participants (age 77±5; 63% women; 17% with diabetes), 832 HF and 1016 AF events occurred over a median follow-up of 9 years. After adjustment for potential confounders, serum CML was associated with a higher risk of incident HF and AF (hazard ratio per SD, 1.10 and 1.09 [95% CI, 1.02-1.17 and 1.02-1.16], respectively). The association with AF was attenuated and nonsignificant after adjusting for estimated glomerular filtration rate and urine albumin-creatinine ratio. The CML-HF relation was similarly attenuated after adjusting for time-updated myocardial infarction. Both associations were nonsignificant after adjusting for natriuretic peptides or excluding those with elevated levels at baseline. Secondary analyses of incident HF subtypes or baseline cardiac mechanics showed no significant associations.

CONCLUSIONS: In older adults, serum CML was prospectively associated with higher risk of HF and AF independent of potential confounders, with evidence of attenuation by certain putative mediators. AGEs and AGE-countering therapies merit additional evaluation in this high-risk population.