In a recent study published within the journal Scientific Reports, researchers examine microstructural brain tissue changes in patients with type 2 diabetes (T2D) using whole-brain diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures that distinguish acute from chronic stages of tissue change. This study hypothesized that patients with T2D will exhibit altered MD values in mood and cognition regulatory areas as in comparison with healthy individuals.

Study: Microstructural brain tissue changes contribute to cognitive and mood deficits in adults with type 2 diabetes mellitus. Image Credit: Elif Bayraktar / Shutterstock.com

Background

T2D, a chronic metabolic disorder, has been shown to change cognition and mood and, because of this, is commonly considered an early risk factor for Alzheimer’s disease (AD) and vascular dementia. In truth, epidemiologic studies have shown that T2D increases the danger of 

cognitive deficits and mood disorders by 1.5- and two-fold, respectively.

Structural magnetic resonance imaging (MRI), attributable to its inadequate sensitivity to tissue changes, cannot detect subtle brain tissue aberrations. Nevertheless, DTI, a non-invasive procedure, shows changes within the brain’s microstructural organization in gray and white matter. DTI also enables measuring MD, which reflects the movement of water molecules, thereby revealing the character of the brain tissue injury and its extent in T2D patients.

So far, researchers haven’t examined direct correlations between tissue changes in brain sites mediating cognition and mood based on MD. Likewise, symptom scores for mood and cognition in T2D patients haven’t been reported.

Concerning the study

In the current study, researchers recruited 68 individuals with T2D who were on medications from the Gonda Diabetes Center of the University of California Los Angeles (UCLA), along with 101 healthy non-diabetic controls. Individuals in each study cohorts were between 40 and 65 years of age.

The Diabetes Complications Severity Index (DCSI) from each patient’s clinical record was determined. Anxiety and depression symptoms were evaluated by Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI-II), respectively. BDI-II or BAI values exceeding nine indicated depression or anxiety, respectively. The Montreal Cognitive Assessment (MoCA) was also administered, with scores of 26 or more indicating no cognitive impairment.

DTI data were collected using a single-shot echo planar imaging technique, generalized auto-calibrating partially parallel acquisition (GRAPPA), with an acceleration factor of two. Next, a visible assessment of all subjects’  T1-, T2-, and PD-weighted images were performed for various pathologies, including cystic lesions, infarcts, or tumors.

MD maps derived from all DTI series were quantified and realigned to remove any variation from head motion-related or other imaging artifacts and averaged. Non-diffusion weighted images were also realigned and averaged. 

Statistical parametric maps showing brain sites with significant MD differences between groups were superimposed onto a mean anatomical image for identification through MRIcroN software. This allowed regions of interest (ROI) values to be obtained on brain regions with significant associations with mood and cognition values between T2D and controls. Whole-brain MD maps were also correlated voxel-by-voxel with mood and cognition scores, including sub-scores for BAI, BDI-II, and MoCA, using partial correlations.

Altered brain structure in diabetics

Widespread microstructural disruptions were observed in brain regions controlling cognitive and mood functions in individuals with T2D as in comparison with controls. Most of those changes were within the chronic stages, with only a number of sites within the acute stage. Patients with T2D also exhibited impairments in visuospatial, language, and a focus cognitive sub-domains, in addition to greater depression and anxiety scores as in comparison with healthy controls.

Cognitive and mood regulatory networks are spread over a big area within the human brain. Thus, extensive microstructural tissue changes in these areas play a singular role in cognitive and mood deficits in T2D patients.

These findings provide vital insights into those changes, in addition to the microstructural neuropathological changes that may contribute to mood and cognitive dysfunctions in patients with T2D mellitus. Notably, all disruptions within the microstructural brain tissue integrity occurred predominantly within the temporal, parietal, temporal cortices, and subcortical regions. 

Just like previous studies, the regions that exhibited chronic tissue changes with increased MD values in T2D patients encompassed brain fibers joining the cerebellum to vermis and anterior crus to cortices, including the frontal, precentral, and superior parietal gyri.

Conclusions

The study findings reveal how MD can facilitate early detection of microstructural brain tissue changes in cognitive and mood regulatory regions in patients with T2D, which cause their altered mood and cognition deficits.