Mielke, Michelle M.

Objectives To determine the association between multiple chronic conditions and risk of incident mild cognitive impairment ( MCI ) and dementia. Design Prospective cohort study. Setting Olmsted County, Minnesota. Participants Cognitively normal individuals (N = 2,176) enrolled in the Mayo Clinic Study of Aging ( MCSA ). Measurements Participants were randomly selected from the community, evaluated by a physician, and underwent neuropsychometric testing at baseline and at 15‐month intervals to assess diagnoses of MCI and dementia. Information on International Classification of Diseases, Ninth Revision codes for chronic conditions in the 5 years before enrollment was electronically captured using the Rochester Epidemiology Project medical records linkage system. Multimorbidity was defined as having two or more chronic conditions, and the association between multimorbidity and MCI and dementia was examined using Cox proportional hazards models. Results Of 2,176 cognitively normal participants (mean age ± standard deviation 78.5 ± 5.2; 50.6% male), 1,884 (86.6%) had multimorbidity. The risk of MCI or dementia was higher in persons with multimorbidity (hazard ratio ( HR ) = 1.38, 95% confidence interval ( CI ) = 1.05–1.82) than in those with one or no chronic condition. The HR was of greater magnitude in persons with four or more conditions ( HR = 1.61, 95% CI = 1.21–2.13) than in those with two or three conditions ( HR = 1.03, 95% CI = 0.76–1.39) and for men with multimorbidity( HR = 1.53, 95% CI = 1.01–2.31) than for women with multimorbidity ( HR = 1.20, 95% CI = 0.83–1.74), compared to those with one or no chronic condition. Conclusion In older adults, having multiple chronic conditions is associated with greater risk of MCI and dementia. This is consistent with the hypothesis that multiple etiologies may contribute to MCI and late‐life dementia. Preventing chronic diseases may be beneficial in delaying or preventing MCI and dementia.

SummaryIt has been increasingly recognized at the basic science level that perturbations in ceramide metabolism are associated with the development and progression of many age‐related diseases. However, the translation of this work to the clinic has lagged behind. Understanding the factors longitudinally associated with plasma ceramides and dihydroceramides (DHCer) at the population level and how these lipid levels change with age, and by sex, is important for the clinical development of future therapeutics and biomarkers focused on ceramide metabolism. We, therefore, examined factors cross‐sectionally and longitudinally associated with plasma concentrations of ceramides and DHCer among Baltimore Longitudinal Study of Aging participants (n = 992; 3960 total samples), aged 55 years and older, with plasma at a mean of 4.1 visits (range 2–6). Quantitative analyses were performed on a high‐performance liquid chromatography‐coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess the relationships between plasma ceramide and DHCer species and demographics, diseases, medications, and lifestyle factors. Women had higher plasma concentrations of most ceramide and DHCer species and showed steeper trajectories of age‐related increases compared to men. Ceramides and DHCer were more associated with waist–hip ratio than body mass index. Plasma cholesterol and triglycerides, prediabetes, and diabetes were associated with ceramides and DHCer, but the relationship showed specificity to the acyl chain length and saturation. These results demonstrate the importance of examining the individual species of ceramides and DHCer, and of establishing whether intra‐individual age‐ and sex‐specific changes occur in synchrony to disease onset and progression.

AbstractIntroductionThe feasibility and validity of brief computerized cognitive batteries at the population‐level are unknown.MethodsNondemented participants (n = 1660, age 50–97 years) in the Mayo Clinic Study on Aging completed the computerized CogState battery and standard neuropsychological battery. The correlation between tests was examined and comparisons between CogState performance on the personal computer (PC) and iPad (n = 331), and in the clinic vs. at home (n = 194), were assessed.ResultsWe obtained valid data on greater than 97% of participants on each test. Correlations between the CogState and neuropsychological tests ranged from −0.462 to 0.531. Although absolute differences between the PC and iPad were small and participants preferred the iPad, performance on the PC was faster. Participants performed faster on Detection, One Card Learning, and One Back at home compared with the clinic.DiscussionThe computerized CogState battery, especially the iPad, was feasible, acceptable, and valid in the population.