Glycemic control is differentially related to spontaneous cortical activity in patients on the Alzheimer’s disease spectrum

Abstract Diabetes is a major risk factor for developing cognitive impairment and studies have shown that poor glycemic control can increase this risk, but the neural mechanisms are poorly understood. Many studies have linked altered spontaneous cortical activity during the resting-state to Alzheimer’s disease and other neurological conditions associated with cognitive impairment. Herein, we examine whether the strength of spontaneous activity during the resting-state is differentially related to glycemic control in 37 biomarker-positive participants on the Alzheimer’s disease spectrum (ADS) and 43 cognitively normal aging adults. All participants completed resting-state magnetoencephalography (MEG), a blood draw to derive their level of glycemic control (i.e., A1C), and comprehensive neuropsychological assessment. Spontaneous activity was imaged in each of the canonical frequency bands (e.g., alpha) and probed for group differences in the relationship between neural activity and glycemic control. We found significant interactions between A1C and disease status (ADS vs. control) in the delta and alpha bands ( p < 0.001). Specifically, delta power decreased with increasing A1C in the ADS group across a broad area of frontotemporal and inferior parietal cortices, while spontaneous alpha decreased with higher A1C in the control group across inferior frontal and temporal cortex. Importantly, delta activity in the superior frontal cortices mediated the effect of A1C on attention performance in the ADS group. In sum, these data suggest that the impact of glycemic dysregulation on spontaneous cortical activity may differ in those on the ADS compared with cognitively normal controls and that spontaneous delta may be critical for attention function.