The salience network (anterior cingulate cortex (ACC) —insula) plays an important role in regulating attention and memory in the context of decision making and has also been shown to be highly responsive to changes in peripheral glucose levels. Increased age is also associated with changes in glucose homeostasis and the salience network. To investigate these relationships, 40 healthy, cognitively normal, non-diabetic subjects (20 Young (age mean 28±1 years, BMI 28.1 ±1.1 kg/m2, HbA1c 5.3±0.1%) and 20 Old (age mean of 73±2 years, BMI 26.9±0.9 kg/m2, HbA1c 5.5±0.1%)) underwent an OGTT, resting state functional connectivity (FC) MRI brain scanning, and cognitive assessments (Cambridge Neuropsychological Test Automated Battery) . Despite similar BMI, HbA1C, and fasting glucose levels, older individuals had lower disposition index (young: 9±2, old: 3.3±0.4, p=0.005) indicating impaired β-cell function. There were no differences in measures of insulin sensitivity (HOMA-IR (p=0.38) or Matsuda index (p=0.70) . A seed-based analysis using a predefined cubic voxel in the ACC showed differences in FC between the ACC and the left insula (Main Effect by group, P<0.001) with lower connectivity values in Old compared to Young subjects. This connectivity value also correlated with errors on the Paired Associate Learning task, which tests attention and memory (r=-0.5, P=0.001) . Moreover, the connectivity values correlated with the disposition index in older subjects (r=0.49, P=0.03) but not younger subjects (P=0.9) . Thus, in our cohort of healthy, cognitively normal older subjects, impairments in beta-cell function are associated with altered functional connectivity within the salience network. These findings highlight the need for future investigations to determine whether mild age-related changes in glycemic control contribute to neurocognitive changes in older patients.


J.Deajon-jackson: None. C.Lacadie: None. C.Watt: None. D.Scheinost: None. J.J.Hwang: None.


Claude D. Pepper Older Americans Independence Center at Yale School of Medicine (P30AG021342)

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