Abstract
BackgroundLow-density lipoprotein cholesterol (LDL-C) metabolic disorder is common in individuals with diabetes. The role of LDL-C in mild cognitive impairment (MCI) remains to be explored. We aim to investigate the associations between LDL-C at different levels and details of cognition decline in patients with type 2 diabetes mellitus (T2DM).MethodsPatients with T2DM (n = 497) were recruited. Clinical parameters and neuropsychological tests were compared between patients with MCI and controls. Goodness of fit was assessed to determine the linear or U-shaped relationship between LDL-C and cognitive function. The cut-off point of LDL-C was calculated. Correlation and regression were carried out to explore the relationship between cognitive dysfunction and LDL-C levels above and below the cut-off point.ResultsAlthough no significant difference in LDL-C levels was detected in 235 patients with MCI, compared with 262 patients without MCI, inverted-U-shaped association was determined between LDL-C and Montreal Cognitive Assessment (MoCA). The cut-off point of LDL-C is 2.686 mmol/l. LDL-C (>2.686 mmol/l) is positively related to Trail Making Test B (TMTB) indicating executive function. LDL-C (<2.686 mmol/l) is positively associated with Clock Drawing Test (CDT) reflecting visual space function in patients with T2DM.ConclusionInverted U-shaped correlation was found between serum LDL-C and cognitive function in patients with T2DM. Despite that the mechanisms of different LDL-C levels involved in special cognitive dysfunctions remain incompletely clarified, excessive LDL-C damages executive function, while the deficient LDL-C impairs visual space function.Trial registrationChiCTR-OCC-15006060.
Highlights
Low-density lipoprotein cholesterol (LDL-C) metabolic disorder is common in individuals with diabetes
Increase in age could significantly reduce the synthesis of cholesterol in astrocytes, which may lead to the loss of synapses [3]
Baseline data of patients with type 2 diabetes mellitus (T2DM) in mild cognitive impairment (MCI) or non-MCI group increased cholesterol is a common risk factor of Alzheimer’s disease (AD) and our previous study showed that poorly controlled LDL-C is related to executive function in diabetic patients [13], no significant difference in total cholesterol (TC) and LDL-C levels were found among T2DM patients with or without MCI (P = 0.196 and 0.475 respectively)
Summary
Low-density lipoprotein cholesterol (LDL-C) metabolic disorder is common in individuals with diabetes. The role of LDL-C in mild cognitive impairment (MCI) remains to be explored. We aim to investigate the associations between LDL-C at different levels and details of cognition decline in patients with type 2 diabetes mellitus (T2DM). Increase in age could significantly reduce the synthesis of cholesterol in astrocytes, which may lead to the loss of synapses [3]. In patients with Alzheimer’s disease (AD), the levels of enzymes associated with cholesterol synthesis in the brain decreased significantly, and the process of cholesterol synthesis changed [4]. Insulindeficient diabetic mice exhibited reduction in brain cholesterol synthesis and cognitive decline. Hypercholesterolemia is a common risk factor of AD [11, 12] and MCI [13], a stage between normal cognitive function and AD dementia [14]
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