Abstract
Objective: Type 2 diabetes mellitus (T2DM) is related to an elevated risk of mild cognitive impairment (MCI). Plasma clusterin is reported associated with the early pathology of Alzheimer's disease (AD) and longitudinal brain atrophy in subjects with MCI. The rs11136000 single nucleotide polymorphism within the clusterin (CLU) gene is also associated with the risk of AD. We aimed to investigate the associations among plasma clusterin, rs11136000 genotype and T2DM-associated MCI.Methods: A total of 231 T2DM patients, including 126 MCI and 105 cognitively healthy controls were enrolled in this study. Demographic parameters were collected and neuropsychological tests were conducted. Plasma clusterin and CLU rs11136000 genotype were examined.Results: Plasma clusterin was significantly higher in MCI patients than in control group (p = 0.007). In subjects with MCI, plasma clusterin level was negatively correlated with Montreal cognitive assessment and auditory verbal learning test_delayed recall scores (p = 0.027 and p = 0.020, respectively). After adjustment for age, educational attainment, and gender, carriers of rs11136000 TT genotype demonstrated reduced risk for MCI compared with the CC genotype carriers (OR = 0.158, χ2 = 4.113, p = 0.043). Multivariable regression model showed that educational attainment, duration of diabetes, high-density lipoprotein cholesterol (HDL-c), and plasma clusterin levels are associated with MCI in T2DM patients.Conclusions: Plasma clusterin was associated with MCI and may reflect a protective response in T2DM patients. TT genotype exhibited a reduced risk of MCI compared to CC genotype. Further investigations should be conducted to determine the role of clusterin in cognitive decline.Trial registration Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536
Highlights
With the development of living condition and the increased number of aging population, type 2 diabetes mellitus (T2DM) is becoming prevalent
In subjects with mild cognitive impairment (MCI), plasma clusterin level was negatively correlated with Montreal cognitive assessment and auditory verbal learning test_delayed recall scores (p = 0.027 and p = 0.020, respectively)
After adjustment for age, educational attainment, and gender, carriers of rs11136000 TT genotype demonstrated reduced risk for MCI compared with the CC genotype carriers (OR = 0.158, χ2 = 4.113, p = 0.043)
Summary
With the development of living condition and the increased number of aging population, type 2 diabetes mellitus (T2DM) is becoming prevalent. According to International Diabetes Federation atlas, the prevalence of T2DM were 8.8 and 10.6% in the world and China by 2015, respectively (Available). Studies have suggested that T2DM patients suffer from mild cognitive impairment (MCI) (Cukierman et al, 2005; Cheng et al, 2012), a transitional stage between normal cognitive aging and dementia (Mariani et al, 2007). A review combined 42 studies showed that the prevalence of MCI was 3–42% and the incidence of MCI was 21.5–71.3 per 1000 person-years, respectively (Ward et al, 2012). The etiology of diabetes-related cognitive impairment is complicated and associated with many factors, such as insulin impairment, high oxidative stress, mitochondrial dysfunction, and dyslipidemia (Ahmad, 2013).
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