Citations

Trial RegistrationClinicalTrials.gov Identifier: NCT03501992

AbstractA robust and heterogenous secretory phenotype is a core feature of most senescent cells. In addition to mediators of age‐related pathology, components of the senescence associated secretory phenotype (SASP) have been studied as biomarkers of senescent cell burden and, in turn, biological age. Therefore, we hypothesized that circulating concentrations of candidate senescence biomarkers, including chemokines, cytokines, matrix remodeling proteins, and growth factors, could predict mortality in older adults. We assessed associations between plasma levels of 28 SASP proteins and risk of mortality over a median follow‐up of 6.3 years in 1923 patients 65 years of age or older with zero or one chronic condition at baseline. Overall, the five senescence biomarkers most strongly associated with an increased risk of death were GDF15, RAGE, VEGFA, PARC, and MMP2, after adjusting for age, sex, race, and the presence of one chronic condition. The combination of biomarkers and clinical and demographic covariates exhibited a significantly higher c‐statistic for risk of death (0.79, 95% confidence interval (CI): 0.76–0.82) than the covariates alone (0.70, CI: 0.67–0.74) (p < 0.001). Collectively, these findings lend further support to biomarkers of cellular senescence as informative predictors of clinically important health outcomes in older adults, including death.

Background: Multiple algorithms with variable performance have been developed to identify dementia using combinations of billing codes and medication data that are widely available from electronic health records (EHR). If the characteristics of misclassified patients are clearly identified, modifying existing algorithms to improve performance may be possible. Objective: To examine the performance of a code-based algorithm to identify dementia cases in the population-based Mayo Clinic Study of Aging (MCSA) where dementia diagnosis (i.e., reference standard) is actively assessed through routine follow-up and describe the characteristics of persons incorrectly categorized. Methods: There were 5,316 participants (age at baseline (mean (SD)): 73.3 (9.68) years; 50.7% male) without dementia at baseline and available EHR data. ICD-9/10 codes and prescription medications for dementia were extracted between baseline and one year after an MCSA dementia diagnosis or last follow-up. Fisher’s exact or Kruskal-Wallis tests were used to compare characteristics between groups. Results: Algorithm sensitivity and specificity were 0.70 (95% CI: 0.67, 0.74) and 0.95 (95% CI: 0.95, 0.96). False positives (i.e., participants falsely diagnosed with dementia by the algorithm) were older, with higher Charlson comorbidity index, more likely to have mild cognitive impairment (MCI), and longer follow-up (versus true negatives). False negatives (versus true positives) were older, more likely to have MCI, or have more functional limitations. Conclusions: We observed a moderate-high performance of the code-based diagnosis method against the population-based MCSA reference standard dementia diagnosis. Older participants and those with MCI at baseline were more likely to be misclassified.

Abstract Background: Adherence to recommended colorectal cancer (CRC) screening among US adults is below the public health target of 80%. The multi-target stool DNA assay (mt-sDNA) is a self-administered CRC screening test that may remove barriers to adherence. To improve understanding of long-term outcomes and the real-world impact of mt-sDNA screening, Mayo Clinic and Exact Sciences Laboratories are collaborating on a prospective cohort study of CRC incidence and mortality outcomes in individuals screened with mt-sDNA. We conducted an embedded experiment to identify the optimal incentive protocol for maximizing participation while managing study costs. Methods: A subset of the opt-in cohort was randomized to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year one of recruitment, as well as the incentive experiment, are reported. Results: During year 1 of the Voyage trial, a total of 600,258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26,429 (4.4%) opted in, 14,365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2,333 were randomized to the pre-incentive arm while 2,342 were randomized to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs. 52.0% for the post-consent incentive arm (1217/2432), p<0.001). A cost reduction was observed for the pre-consent incentive group. Higher response rates were seen among older vs. younger individuals, reflecting a common pattern in healthcare-related survey research participation. Age adjusted incidence rates for CRC have been shown to vary regionally; thus, adjustment for differential response by region will be important to ensure representativeness. Conclusions: CRC incidence and mortality vary with age; thus, adjusting for differential participation by age will be important in analyses of Voyage data. Pre-consent incentive option was associated with a higher participation rate and lower costs, and will be used for the remainder of the study recruitment. Trial Registration: NCT04124406; October 11th, 2019

Objective Ceramides have been associated with several ageing-related conditions but have not been studied as a general biomarker of multimorbidity (MM). Therefore, we determined whether ceramide levels are associated with the rapid development of MM. Design Retrospective cohort study. Setting Mayo Clinic Biobank. Participants 1809 persons in the Mayo Clinic Biobank ≥65 years without MM at the time of enrolment, and with ceramide levels assayed from stored plasma. Primary outcome measure Persons were followed for a median of 5.7 years through their medical records to identify new diagnoses of 20 chronic conditions. The number of new conditions was divided by the person-years of follow-up to calculate the rate of accumulation of new chronic conditions. Results Higher levels of C18:0 and C20:0 were associated with a more rapid rate of accumulation of chronic conditions (C18:0 z score RR: 1.30, 95% CI: 1.10 to 1.53; C20:0 z score RR: 1.26, 95% CI: 1.07 to 1.49). Higher C18:0 and C20:0 levels were also associated with an increased risk of hypertension and coronary artery disease. Conclusions C18:0 and C20:0 were associated with an increased risk of cardiometabolic conditions. When combined with biomarkers specific to other diseases of ageing, these ceramides may be a useful component of a biomarker panel for predicting accelerated ageing.

Background: The Rochester Epidemiology Project (REP) medical records-linkage system offers a unique opportunity to integrate medical and residency data with existing environmental data, to estimate individual-level exposures. Our primary aim was to provide an archetype of this integration. Our secondary aim was to explore the association between groundwater inorganic nitrogen concentration and adverse child and adolescent health outcomes. Methods: We conducted a nested case-control study in children, aged seven to eighteen, from six counties of southeastern Minnesota. Groundwater inorganic nitrogen concentration data were interpolated, to estimate exposure across our study region. Residency data were then overlaid, to estimate individual-level exposure for our entire study population (n = 29,270). Clinical classification software sets of diagnostic codes were used to determine the presence of 21 clinical conditions. Regression models were adjusted for age, sex, race, and rurality. Results: The analyses support further investigation of associations between nitrogen concentration and chronic obstructive pulmonary disease and bronchiectasis (OR: 2.38, CI: 1.64–3.46) among boys and girls, thyroid disorders (OR: 1.44, CI: 1.05–1.99) and suicide and intentional self-inflicted injury (OR: 1.37, CI: >1.00–1.87) among girls, and attention deficit conduct and disruptive behavior disorders (OR: 1.34, CI: 1.24–1.46) among boys. Conclusions: Investigators with environmental health research questions should leverage the well-enumerated population and residency data in the REP.