Poorly controlled cholesterol is associated with cognitive impairment in T2DM: a resting-state fMRI study

Debate remains on whether hypercholesterolemia is associated with cognitive impairment. Hence, we investigated whether poorly controlled cholesterol impairs functional connectivity among patients with type 2 diabetes mellitus (T2DM).

Resting-state functional connectivity infers to an interregional cooperation characterized by synchronous and low-frequency (<0.08 Hz) fluctuations on blood oxygen level-dependent functional magnetic resonance imaging (fMRI). We used resting-state fMRI to investigate the functional connectivity of 25 T2DM patients with poorly controlled cholesterol, 22 patients with target cholesterol and 26 healthy controls. Further correlation analysis was conducted between the functional connectivity and clinical data as well as neuropsychological tests.

The three groups did not statistically differ in age, sex, education level, body mass index, blood pressure, fasting C-peptides, and triglyceride. Compared with target cholesterol patients, patients with poorly controlled cholesterol showed significantly increased levels of serum cholesterol, low-density lipoprotein (LDL), and LDL/high-density lipoproteins (HDL) ratio, as well as poor performance in Trail Making Test B (TMT-B) (p<0.05). Disordered functional connectivity of bilateral hippocampus-middle frontal gyrus (MFG) in the poorly controlled group consistently existed when compared with the two other groups. Moreover, the aberrant functional connectivity was associated with the TMT-B scores and the LDL/HDL index in T2DM patients with poorly controlled cholesterol.

T2DM patients with poorly controlled cholesterol showed impaired attention and executive function. The resting-state connectivity disturbance of the hippocampus-MFG may be involved in this process. Decreasing the LDL/HDL ratio can be taken as precaution against cognitive decrements.