Abstract Body (Do not enter title and authors here): Background: Dysglycemia is a well-established risk factor for cognitive decline. The association of long-term glucose control with early neuroimaging markers of dementia remains largely unexplored.
Hypothesis: Higher visit-to-visit variability in glucose and HbA1c, indicating worse glucose control, are associated with lower total and regional gray matter volume (GMV) and higher white matter hyperintensity (WMH) volume.
Methods: Fasting glucose (FG) was measured in MESA participants at Exam 1 (2000–02) and each of 5 follow-up exams through Exam 6 (2016-18), and HbA1c was measured at Exam 2 (2002–04), Exam 5 (2010–12), and Exam 6. We calculated intraindividual variability in FG and HbA1c as the SD (SD_FG; SD_A1c), average real variability (ARV_FG; ARV_A1c), and variability independent of the mean (VIM_FG; VIM_A1c) through Exam 6. Total and regional GMV and WMH volume were assessed by 3T brain MRI (2017-22). We report the SD difference in GMV and log-unit difference in WMH volume per two-fold increment in glucose or HbA1c variability with 95% CI from multivariable linear regression models adjusted for total intracranial volume, study site, age, sex, race/ethnicity, education, vascular risk factors, and APOE ε4 allele status.
Results: A total of 1,424 Exam 6 participants (mean (SD) age 72 (8) yrs; 46% men; 28% with diabetes at Exam 6) had ≥3 FG measurements (mean: 5.9 measurements) and MRI data. Two-fold increments of SD_FG, ARV_FG, and VIM_FG were associated with –0.08 (–0.11, –0.06), –0.09 (–0.12, –0.06), and –0.10 (–0.14, –0.06) SD differences in total GMV and 0.13 (0.06, 0.19), 0.13 (0.06, 0.20), and 0.16 (0.05, 0.26) log-unit differences in WMH volumes, respectively (Table 1). Associations appeared strongest with frontal lobe GMV. Further adjustment for mean FG through Exam 6 only modestly attenuated results. In 839 participants with 3 HbA1c measurements, two-fold increments of SD_A1c, ARV_A1c, and VIM_A1c were associated with –0.20 (–0.30, –0.10), –0.77 (–1.20, –0.38), and –0.26 (–0.39, –0.12) SD differences in total GMV and 0.3 (0.04, 0.55), 1.40 (0.38, 2.3), and 0.36 (0.02, 0.70) log-unit differences in WMH volumes, respectively (Table 2). Neither glucose nor HbA1c variability were associated with temporal lobe or hippocampal volumes. Associations did not differ by diabetes status.
Conclusion: Higher variability of glucose and HbA1c over 16–18 years were associated with lower GMV and higher WMH volumes in a diverse, community dwelling sample of older adults.