Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study

Abstract

Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements.The worldwide prevalence of diabetes is increasing rapidly, with the majority of patients having type 2 diabetes (1). Along with cardiovascular risk factors, type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and an increased risk for dementia and Alzheimer disease (2,3). A broad range of cognitive domains are affected in type 2 diabetes, and one of the most commonly affected is processing speed (4,5). However, the underlying pathological mechanism is not yet clear.The progression of normal glucose metabolism to type 2 diabetes is a gradual process in which insulin resistance plays a crucial role. Before the clinical presentation of type 2 diabetes, insulin resistance often is accompanied by other metabolic and vascular abnormalities. The cluster of these cardiovascular risk factors is referred to as the metabolic syndrome and is considered a major risk factor for diabetes (6). Patients with the metabolic syndrome have a high likelihood for diabetes and may display comparable cognitive decrements as seen in patients with type 2 diabetes (5). Furthermore, the cardiovascular risk factors are associated with an increased risk of late-life dementia (7).

Altered brain structural topological properties in type 2 diabetes mellitus patients without complications

“…In T2DM patients, λ was negatively correlated with the ACC of the spatial working memory task, which may reflect that patients with increased λ are worse at dealing with spatial working memory tasks. The changing patterns of clustering coefficients reported in topological network studies on T2DM are not consistent . For example, some studies reported a decreased clustering coefficient in T2DM patients, whereas others reported an increase or no change .…”

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

“…The main feature of T1DM is hyperglycemia and hypoinsulinemia, T2DM is hyperglycemia and insulin resistance. In recent years, there have been ajor reports suggesting that D can affect cognitive function [3-5], and that patients with DM are at a high risk of developing dementia [6] and Alzheimer’s disease (AD) [7, 8]. Adverse changes to the central nervous system (CNS) in diabetes which underlie these pathologies are known as diabetic encephalopathy, which currently has no effective treatment.…”

Cerebral Pathology and Cognition in Diabetes: The Merits of Multiparametric Neuroimaging

“…Interestingly, it was recently shown that participants with type 2 diabetes displayed altered fMRI network measures, characterized by a higher efficiency, compared with control participants (van Bussel et al, 2016c). Also subjects with pre-diabetes were studied, whose network measures fell between those with diabetes and control participants.…”

“…Also subjects with pre-diabetes were studied, whose network measures fell between those with diabetes and control participants. The authors suggested that functional reorganization of the cerebral networks might act as a compensatory mechanism for cognitive decrements (van Bussel et al, 2016c). …”

“…It will also be interesting to investigate cognitive decline in pre-diabetic stages such as the metabolic syndrome or impaired glucose mechanism (Grundy, 2006; van Bussel et al, 2016c). …”