PMID- 34054500
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220423
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 13
DP  - 2021
TI  - Increased Plasma Level of 24S-Hydroxycholesterol and Polymorphism of CYP46A1 SNP 
      (rs754203) Are Associated With Mild Cognitive Impairment in Patients With Type 2 
      Diabetes.
PG  - 619916
LID - 10.3389/fnagi.2021.619916 [doi]
LID - 619916
AB  - BACKGROUND: Abnormal cholesterol metabolism is common in type 2 diabetes mellitus 
      (T2DM) and causes dementia. Cholesterol 24S-hydroxylase (CYP46A1) converts 
      cholesterol into 24S-hydroxycholesterol (24-OHC) and maintains cholesterol 
      homeostasis in the brain. OBJECTIVE: This study aimed to investigate the roles of 
      24-OHC and the CYP46A1 (rs754203) polymorphism in patients with T2DM and mild 
      cognitive impairment (MCI). METHODS: A total of 193 Chinese patients with T2DM 
      were recruited into two groups according to the Montreal Cognitive Assessment 
      (MoCA). Demographic and clinical data were collected, and neuropsychological 
      tests were conducted. Enzyme-linked immunosorbent assay (ELISA) and Seqnome 
      method were used to detect the concentration of plasma 24-OHC and the CYP46A1 
      rs754203 genotype, respectively. RESULTS: Compared with 118 healthy cognition 
      participants, patients with MCI (n = 75) displayed a higher plasma level of 
      24-OHC and total cholesterol concentration (all p = 0.031), while no correlation 
      was found between them. In the overall diabetes population, the plasma level of 
      24-OHC was negatively correlated with MoCA (r = -0.150, p = 0.039), and it was 
      further proved to be an independent risk factor of diabetic MCI (OR = 1.848, p = 
      0.001). Additionally, patients with MCI and the CC genotype of CYP46A1 rs754203 
      showed the highest plasma level of 24-OHC even though the difference was not 
      statistically significant, and they obtained low scores in both the verbal 
      fluency test and Stroop color and word test A (p = 0.008 and p = 0.029, 
      respectively). CONCLUSION: In patients with T2DM, high plasma level of 24-OHC and 
      the CC genotype carrier of CYP46A1 rs754203 may portend a high risk of developing 
      early cognitive impairment, including attention and executive deficits.
CI  - Copyright (c) 2021 Shi, Jia, Tian, Zhang, An, Zhu, Cao, Yuan and Wang.
FAU - Shi, Jijing
AU  - Shi J
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Jia, Jianhong
AU  - Jia J
AD  - Department of Endocrinology, Siyang Hospital of Traditional Chinese Medicine, 
      Suqian, China.
FAU - Tian, Sai
AU  - Tian S
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Zhang, Haoqiang
AU  - Zhang H
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - An, Ke
AU  - An K
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Zhu, Wenwen
AU  - Zhu W
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Cao, Wuyou
AU  - Cao W
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
AD  - School of Medicine, Southeast University, Nanjing, China.
FAU - Yuan, Yang
AU  - Yuan Y
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
FAU - Wang, Shaohua
AU  - Wang S
AD  - Department of Endocrinology, Affiliated Zhongda Hospital of Southeast University, 
      Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20210513
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC8155290
OTO - NOTNLM
OT  - 24S-hydroxycholesterol
OT  - attention function
OT  - executive function
OT  - mild cognitive impairment
OT  - type 2 diabetes mellitus
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/01 06:00
MHDA- 2021/06/01 06:01
PMCR- 2021/01/01
CRDT- 2021/05/31 06:07
PHST- 2020/10/21 00:00 [received]
PHST- 2021/03/29 00:00 [accepted]
PHST- 2021/05/31 06:07 [entrez]
PHST- 2021/06/01 06:00 [pubmed]
PHST- 2021/06/01 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2021.619916 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2021 May 13;13:619916. doi: 10.3389/fnagi.2021.619916. 
      eCollection 2021.