Glucose instability and neurocognitive outcomes in older adults

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Abstract Older adults are less able to maintain homeostasis or sustain physiological constancy and, although diabetes is common in old age, glucose instability is an underappreciated concern. Diabetes is strongly linked to dementia risk and there is growing evidence that glycemic variability contributes to risk of Alzheimer's disease and related dementias, independent of average glucose or hemoglobin A1c (HbA1c). Wearable continuous glucose monitoring technology is an opportunity to rigorously characterize glucose patterns in older adults across the glycemic spectrum (from no diabetes, to prediabetes, to diabetes) and evaluate associations with neurocognitive outcomes. The proposed project will 1) characterize midlife- and late-life risk factors for specific glucose patterns in old age (glycemic variability, hyperglycemia, and hypoglycemia); 2) evaluate associations of glucose patterns with concurrent symptoms (dizziness, difficulty concentrating, vision disturbances); 3) examine associations of diabetes, glycemic control, and glucose patterns with brain MRI measures and cerebral amyloid beta deposition via florbetapir PET imaging; and 4) evaluate the associations of disordered glucose patterns with progression of cognitive decline and development of mild cognitive impairment or dementia. Completion of these aims will move the field forward in our understanding of the link of diabetes and continuous glucose monitoring-defined glycemic instability with neurocognitive outcomes in older adults.