Neurovascular coupling in patients with type 2 diabetes mellitus

Abstract

Functional and metabolic neural changes in Type 2 diabetes mellitus (T2DM) can be associated with poor cognitive performances. Here we analyzed the functional-metabolic neurovascular coupling (NVC) in the brain of T2DM patients. Thirty-three patients (70 ± 6 years, 15 males) with recent T2DM diagnosis and 18 healthy control (HC) subjects (65 ± 9 years, 9 males) were enrolled in a brain MRI study to identify the potential effects of T2DM on NVC. T2DM patients were either drug-naive (n = 19) or under treatment with metformin (n = 14) since less than 6 months. Arterial spin labeling and blood oxygen level dependent resting-state functional MRI (RS-fMRI) images were combined to derive NVC measures in brain regions and large-scale networks in a standard brain parcelation. Altered NVC values in T2DM patients were correlated with cognitive performances spanning several neurological domains using Spearman correlation coefficients. Compared to HC, T2DM patients had reduced NVC in the default mode network (DMN) and increased NVC in three regions of the dorsal (DAN) and salience-ventral (SVAN) attention networks. NVC abnormalities in DAN and SVAN were associated with reduced visuo-spatial cognitive performances. A spatial pattern of NVC reduction in the DMN, accompanied by isolated regional NVC increases in DAN and SVAN, could reflect the emergence of (defective) compensatory processes in T2DM patients in response to altered neurovascular conditions. Overall, this pattern is reminiscent of neural abnormalities previously observed in Alzheimer’s disease, suggesting that similar neurobiological mechanisms, secondary to insulin resistance and manifesting as NVC alterations, might be developing in T2DM pathology.

The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

“…Furthermore, a longitudinal study by Zhang Y. et al (2021) over 5 years indicated that T2DM may accelerate NVC damage in specific brain regions (left insula), leading to memory decline ( Zhang Y. et al, 2021 ). Canna et al (2022) identified spatial patterns of decreased NVC in the default mode network of T2DM patients, accompanied by isolated increases in NVC in the dorsal attention network (DAN) and ventral attention network (VAN), with DAN and VAN NVC abnormalities associated with declines in visual-spatial cognitive abilities ( Canna et al, 2022 ). This may reflect the emergence of compensatory processes in response to changes in neurovascular status in T2DM patients.…”

Common neurodegenerative pathways in brain aging, cognitive decline, type 2 diabetes & metabolic syndrome

“…Metabolic alterations contributing to normal neuronal function and decreased glucose metabolism occur in AD brains 39 . A recent brain MRI study revealed the presence of AD-like functional-metabolic neurovascular coupling (NVC) in the brain of T2DM patients 40 . T2DM represents one of the key components of the Metabolic syndrome (MetS) including obesity, hypertension, and cardiovascular diseases.…”

Perspective: Disentangling the effects of tES on neurovascular unit

“…The therapeutic effects of tES on brain metabolism are relevant in dementia (61) since the early stage of Alzheimer's disease (AD) shares molecular and cellular features, including insulin resistance and mitochondrial dysfunctions (85), where AD has been called "type 3 diabetes" (86)(87)(88). Elevated glucose levels during long-standing diabetes have been shown to induce structural and functional changes in different proteins in the body, including albumin, globulins, fibrinogen, and collagens (89).…”