Diabetes and vascular mild cognitive impairment among Chinese ≥50 years: A cross-sectional study with 2020 participants.

BACKGROUND: With the decline of cognitive function in vascular cognitive impairment, the burden on the family and society will increase. Therefore, early identification of vascular mild cognitive impairment (VaMCI) is crucial. The focus of early identification of VaMCI is on the attention of risk factors. Therefore, this study aimed to investigate the relationship between diabetes and VaMCI among the Chinese, hoping to predict the risk of VaMCI by diabetes and to move the identification of vascular cognitive impairment forward. METHODS: We collected data from seven clinical centers and nine communities in China. All participants were over 50 years of age and had cognitive complaints. We collected basic information of the participants, and cognitive function was professionally assessed by the Montreal Cognitive Assessment scale. Finally, logistic regression analysis was used to analyze the correlation between each factor and VaMCI. RESULTS: A total of 2020 participants were included, including 1140 participants with VaMCI and 880 participants with normal cognition. In univariate logistic regression analysis, age, heavy smoking, and diabetes had a positive correlation with VaMCI. At the same time, being married, high education, and light smoking had a negative correlation with VaMCI. After correction, only diabetes (OR = 1.04, 95% CI: 1.01-1.09, p = 0.05) had a positive correlation with VaMCI, and high education (OR = 0.60, 95% CI:.45-.81, p = 0.001) had a negative correlation with VaMCI. CONCLUSION: In our study, we found that diabetes had a positive correlation with VaMCI, and high education had a negative correlation with VaMCI. Therefore, early identification and timely intervention of diabetes may reduce the risk of VaMCI and achieve early prevention of VaMCI.

AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD). In contrast, mice with AGR2 overexpression (Agr2/Tg) exhibited an increased cholesterol level. Mechanistic studies revealed that AGR2 affected cholesterol biogenesis via activation of AKT/sterol regulatory element-binding protein-2 (SREBP2), to some extent, in a PDI motif-dependent manner. Moreover, elevated AGR2 led to a significant decrease in the lipid-lowering efficacy of lovastatin (10 mg· kg-1· d-1, ip, for 2 weeks) in mice with hypercholesterolemia (hyperCho), which was validated by results obtained from clinical samples in statin-treated patients. We showed that lovastatin had limited effect on AGR2 expression, but AGR2 was inducible in Agr2/Tg mice fed a HFD. Further investigations demonstrated that drug-induced liver toxicity and inflammatory reactions were alleviated in hypercholesterolemic Agr2/Tg mice, suggesting the dual functions of AGR2 in lipid management and hyperCho/statin-induced liver injury. Importantly, the AGR2-reduced lipid-lowering efficacy of lovastatin was attenuated, at least partially, by co-administration of a sulfhydryl-reactive compound allicin (20 mg· kg-1· d-1, ip, for 2 weeks). These results demonstrate a novel role of AGR2 in cholesterol metabolism, drug resistance and liver protection, suggesting AGR2 as a potential predictor for selection of lipid-lowering drugs in clinic.

Overexpression of VPS16 correlates with tumor progression and chemoresistance in colorectal cancer.

Vacuolar protein sorting-associated protein 16 homolog (VPS16) is a central member of the VPS core complex (VPS-C) and is reported to function as a tether protein involved in membrane fusion. However, a biological role for VPS16 in tumors remains largely unknown. Herein, we demonstrated that VPS16 was overexpressed in colorectal cancer (CRC) as revealed by qRT-PCR, western blotting, and immunohistochemical analyses. Elevated expression of VPS16 was positively correlated with tumor size and TNM stage, and Kaplan-Meier analysis showed an association between VPS16 and survival in CRC patients. Downregulation of endogenous VPS16 significantly suppressed CRC cell viability both in vitro and vivo; and while our mechanistic analysis showed that VPS16 depletion induced autophagy, but the autophagic flow was deficient as reflected by the inhibition of autolysosomal maturation. Overexpression of VPS16 also mediated oxaliplatin (OX) resistance by promoting the maturation of autolysosomes in CRC. VPS16 may therefore promote cell survival and thus serve as a useful target for cancer therapy in CRC.

Anterior gradient 2 increases long-chain fatty acid uptake via stabilizing FABP1 and facilitates lipid accumulation.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a well-established oncogene. Here, we found that Agr2-/- mice had a decreased fat mass and hepatic and serum lipid levels compared with their wild-type littermates after fasting, and exhibited reduced high-fat diet (HFD)-induced fat accumulation. Transgenic mice overexpressing AGR2 (Agr2/Tg) readily gained fat weight on a HFD but not a normal diet. Proteomic analysis of hepatic samples from Agr2-/- mice revealed that depletion of AGR2 impaired long-chain fatty acid uptake and activation but did not affect de novo hepatic lipogenesis. Further investigations led to the identification of several effector substrates, particularly fatty acid binding protein-1 (FABP1) as essential for the AGR2-mediated effects. AGR2 was coexpressed with FABP1, and knockdown of AGR2 resulted in a reduction in FABP1 stability. Physical interactions of AGR2 and FABP1 depended on the PDI motif in AGR2 and the formation of a disulfide bond between these two proteins. Overexpression of AGR2 but not a mutant AGR2 protein lacking PDI activity suppressed lipid accumulation in cells lacking FABP1. Moreover, AGR2 deficiency significantly reduced fatty acid absorption in the intestine, which might be resulted from decreased fatty acid transporter CD36 in mice. These findings demonstrated a novel role of AGR2 in fatty-acid uptake and activation in both the liver and intestine, which contributed to the AGR2-mediated lipid accumulation, suggesting that AGR2 is an important regulator of whole-body lipid metabolism and down-regulation of AGR2 may antagonize the development of obesity.

The Role of Acupuncture Improving Cognitive Deficits due to Alzheimer's Disease or Vascular Diseases through Regulating Neuroplasticity.

Dementia affects millions of elderly worldwide causing remarkable costs to society, but effective treatment is still lacking. Acupuncture is one of the complementary therapies that has been applied to cognitive deficits such as Alzheimer's disease (AD) and vascular cognitive impairment (VCI), while the underlying mechanisms of its therapeutic efficiency remain elusive. Neuroplasticity is defined as the ability of the nervous system to adapt to internal and external environmental changes, which may support some data to clarify mechanisms how acupuncture improves cognitive impairments. This review summarizes the up-to-date and comprehensive information on the effectiveness of acupuncture treatment on neurogenesis and gliogenesis, synaptic plasticity, related regulatory factors, and signaling pathways, as well as brain network connectivity, to lay ground for fully elucidating the potential mechanism of acupuncture on the regulation of neuroplasticity and promoting its clinical application as a complementary therapy for AD and VCI.

lncARSR sponges miR-34a-5p to promote colorectal cancer invasion and metastasis via hexokinase-1-mediated glycolysis.

Aerobic glycolysis metabolic reprogramming is one of the most important hallmarks of malignant tumors. Increasing evidence indicates that long non-coding RNAs (lncRNAs) are able to regulate glycolysis metabolic reprogramming and promote cancer progression by functioning as competing endogenous RNAs. lncARSR is a newly identified onco-lncRNA in renal cancer, but its potential role in metastatic colorectal cancer (CRC) remains unclear. Here, we analyzed specimens from 89 patients with CRC and demonstrated that lncARSR was highly expressed in CRC tissues and negatively associated with survival. Positron emission tomography-computed tomography imaging with fluoro-2-d-deoxyglucose F18 to evaluate glucose uptake showed that lncARSR expression was positively correlated with maximum standardized uptake values. Functionally, ectopic expression of lncARSR promoted the invasion, metastasis, and glycolysis metabolic reprogramming of CRC cells in vitro and in vivo, while these activities were inhibited by silencing lncARSR expression. Molecularly, lncARSR sponged miR-34a-5p and further mediated hexokinase 1 (HK1)-related aerobic glycolysis in vitro and in vivo. Clinically, high lncARSR and HK1 expression predicted poor survival of patients with CRC, especially when combined with low miR-34a-5p expression. Collectively, we identified lncARSR as an onco-lncRNA in CRC and demonstrated that the combination of lncARSR/miR-34a-5p/HK1 may be a potential prognostic biomarker of CRC.

Inactivation of TFEB and NF-κB by marchantin M alleviates the chemotherapy-driven pro-tumorigenic senescent secretion.

It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-κB (NF-κB) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.

Proteasome inhibition boosts autophagic degradation of ubiquitinated-AGR2 and enhances the antitumor efficiency of bevacizumab.

Anterior gradient 2 (AGR2), a protein belonging to the protein disulfide isomerase (PDI) family, is overexpressed in multiple cancers and promotes angiogenesis to drive cancer progression. The mechanisms controlling AGR2 abundance in cancer remain largely unknown. Here, we observed that AGR2 expression is significantly suppressed by proteasome inhibitor MG132/bortezomib at mRNA and protein levels in lung cancer cells. MG132-mediated repression of AGR2 transcription was independent of ROS generation and ER stress induction, but partially resulted from the downregulated E2F1. Further investigation revealed that MG132 facilitated polyubiquitinated AGR2 degradation through activation of autophagy, as evidenced by predominant restoration of AGR2 level in cells genetic depletion of Atg5 and Atg7, or by autophagy inhibitors. Activation of autophagy by rapamycin noticeably reduced the AGR2 protein in cells and in the mouse tissue samples administrated with bortezomib. We also provided evidence identifying the K48-linked polyubiquitin chains conjugating onto K89 of AGR2 by an E3 ligase UBR5. In addition, an autophagy receptor NBR1 was demonstrated to be important in polyubiquitinated AGR2 clearance in response to MG132 or bortezomib. Importantly, downregulation of AGR2 by proteasome inhibition significantly enhanced antitumor activity of bevacizumab, highlighting the importance of AGR2 as a predictive marker for selection of subgroup patients in chemotherapy.

Targeting the lysosome by an aminomethylated Riccardin D triggers DNA damage through cathepsin B-mediated degradation of BRCA1.

RD-N, an aminomethylated derivative of riccardin D, is a lysosomotropic agent that can trigger lysosomal membrane permeabilization followed by cathepsin B (CTSB)-dependent apoptosis in prostate cancer (PCa) cells, but the underlying mechanisms remain unknown. Here we show that RD-N treatment drives CTSB translocation from the lysosomes to the nucleus where it promotes DNA damage by suppression of the breast cancer 1 protein (BRCA1). Inhibition of CTSB activity with its specific inhibitors, or by CTSB-targeting siRNA or CTSB with enzyme-negative domain attenuated activation of BRCA1 and DNA damage induced by RD-N. Conversely, CTSB overexpression resulted in inhibition of BRCA1 and sensitized PCa cells to RD-N-induced cell death. Furthermore, RD-N-induced cell death was exacerbated in BRCA1-deficient cancer cells. We also demonstrated that CTSB/BRCA1-dependent DNA damage was critical for RD-N, but not for etoposide, reinforcing the importance of CTSB/BRCA1 in RD-N-mediated cell death. In addition, RD-N synergistically increased cell sensitivity to cisplatin, and this effect was more evidenced in BRCA1-deficient cancer cells. This study reveals a novel molecular mechanism that RD-N promotes CTSB-dependent DNA damage by the suppression of BRCA1 in PCa cells, leading to the identification of a potential compound that target lysosomes for cancer treatment.

Terpenoids isolated from Chinese liverworts Lepidozia reptans and their anti-inflammatory activity.

Five new terpenoids (1-5) including two dollabellane-type, one ent-kaurane-type diterpenoids and two sesquiterpenoids were isolated from the Chinese liverwort Lepidozia reptans (L.) Dumort., together with nine known terpenoids (6-14). Their structures were determined on the basis of analysis of MS and NMR spectroscopic data, single-crystal X-ray diffraction and electronic circular dichroism calculations. The selected compounds 1, 2, 6, 7, 9 and 14 were screened for anti-inflammatory activities by the model of LPS-induced nitric oxide (NO) production with macrophage cells, and the mechanism of the active compounds 1 and 2 were further explored.

STAT3 contributes to lysosomal-mediated cell death in a novel derivative of riccardin D-treated breast cancer cells in association with TFEB.

RDD648, a novel derivative of a natural molecule riccardin D, exhibited potent anticancer activity by targeting lysosomes in vitro and in vivo. Mechanistic studies revealed that RDD648 facilitated STAT3 to translocate into the nucleus, and this activity was involved in lysosome-mediated cell death as evidenced by our finding that inhibition of STAT3 alleviated lysosomal membrane permeabilization. Further investigation indicated that nuclear STAT3 directly interacted with transcription factor TFEB, leading to the partial loss of function of TFEB, which is essential for lysosome turnover. The present study first uncovers that STAT3 contributes to lysosomal-mediated cell death in RDD648-treated breast cancer cells though interacting with TFEB, and the findings may be significant in the design of treatments for breast cancers where STAT3 is constitutively expressed.

Downregulation of reticulocalbin-1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells.

Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)-resident Ca2+ -binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase-dependent manner but mainly causes necroptosis in LNCaP cells. An animal-based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.

Hyper-acetylation contributes to the sensitivity of chemo-resistant prostate cancer cells to histone deacetylase inhibitor Trichostatin A.

Therapeutic agents are urgently needed for treating metastatic castration-refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly dependent on enhanced transcription and protein synthesis in an early stage, which subsequently caused ER stress and apoptosis. ChIP analysis indicated that TSA increased H4K16 acetylation, promoting ER stress gene transcription. The changes in Ac-H4K16, ATF3 and ATF4 were also validated in TSA-treated animals. Further study revealed the higher enzyme activity of HDACs and an increase in acetylated proteins in resistant cells. The higher nucleocytoplasmic acetyl-CoA in resistant cells was responsible for elevated acetylation status of protein and a more vigorous growth state. These results strongly support the pre-clinical application of HDAC inhibitors for treating chemotherapy-resistant mCRPC.

Comparison of the Mini-Mental State Examination and Montreal Cognitive Assessment executive subtests in detecting post-stroke cognitive impairment.

AIM: The Montreal Cognitive Assessment (MoCA) has been shown to be more sensitive in detecting executive dysfunction than the Mini-Mental State Examination (MMSE). However, it is still not known whether all the MoCA executive subtests contribute to the superior sensitivity. Thus, the present study aimed to determine how much executive abnormality was detected by the MMSE and MoCA executive subtests in a population-based cohort of Chinese post-stroke patients. METHODS: The MMSE and MoCA were collected from post-stroke patients (within 15 days to 1 month after stroke, including ischemic stroke and hemorrhagic stroke) in 14 hospitals of northern and southern China (including 10 top-graded hospitals and 4 community hospitals) between June 2011 and September 2013. The proportions of patients with incorrect MoCA executive subtests and the proportions of patients with incorrect MMSE executive subtests were compared. RESULTS: A total of 1222 patients (703 men and 519 women, aged 62.06 ± 10.68 and 62.76 ± 9.86 years, respectively) were recruited. The MoCA detected more patients with executive dysfunction than the MMSE (OR 15.399, 95% CI 12.631-18.773; P < 0.001). The likelihood of incorrect MMSE executive tasks increased across decreasing scores of MoCA executive tasks (P < 0.001 for trend). Compared with the MMSE three-step command test (15.5%), the MoCA trail-making (57.8%), abstraction (48.0%) and abstraction (measurement tool; 45.7%) detected more patients with executive dysfunction (P < 0.001), whereas the MoCA digit span forwards (4.3%) and backwards (11.6%) detected fewer patients (P < 0.001 and P = 0.005, respectively). CONCLUSIONS: The MoCA executive tasks are more sensitive in detecting executive dysfunction compared with the MMSE executive tasks. Geriatr Gerontol Int 2017; 17: 2329-2335.

Design, synthesis, biological evaluation and molecular modeling study of novel macrocyclic bisbibenzyl analogues as antitubulin agents.

A series of macrocyclic bisbibenzyls with novel skeletons was designed, synthesized, and evaluated for antiproliferative activity against five anthropic cancer cell lines. Among these novel molecules, compound 47 displayed excellent anticancer activity against HeLa, k562, HCC1428, HT29 and PC-3/Doc cell lines, with IC50 values ranging from of 1.51 µM-5.51 µM, which were more potent than the parent compound, marchantin C. Compounds 44 and 55 with novel bisbibenzyl skeletons also exhibited significantly improved antiproliferative potency. Structure-activity relationship (SAR) analyses of these synthesized compounds were also performed. In addition, compound 47 effectively inhibited tubulin polymerization in HCC1482 cells and induced HCC1482 cell cycle arrest at the G2/M phase in a concentration-dependent manner. The binding mode of compound 47 to tubulin was also investigated utilizing a molecular docking study. In conclusion, the present study discovered several potent antitubulin compounds with novel bisbibenzyl skeletons, and our systematic studies revealed new scaffolds that target tubulin and mitosis and provide progress towards the discovery of novel antitumor drugs discovery.

Riccardin D-N induces lysosomal membrane permeabilization by inhibiting acid sphingomyelinase and interfering with sphingomyelin metabolism in vivo.

Lysosomes are important targets for anticancer drug discovery. Our previous study showed that Riccardin D-N (RD-N), a natural macrocylic bisbibenzyl derivative produced by Mannich reaction, induced cell death by accumulating in lysosomes. Experiments were performed on human lung squamous cell carcinoma tissue from left inferior lobar bronchus of patient xenografts and H460 cells. RD-N was administrated for 25days. The specimens of xenografts in Balb/c athymic (nu+/nu+) male mice were removed for immunohistochemistry, subcellular fractionation, enzyme activities and Western blotting analysis. mRFP-GFP-LC3 reporter was used to examine autophagy in H460 cells. Sphingomyelin assay was evaluated by thin-layer chromatography and assay kit. Lysosomal membrane permeabilization (LMP) caused by acid sphingomyelinase (ASM) inhibition and subsequent changes of sphingomyelin (SM) metabolism selectively destabilized the cancer cell lysosomes in RD-N-treated H460 cells in vitro and tumor xenograft model in vivo. The destabilized lysosomes induced the release of cathepsins from the lysosomes into the cytosol and further triggered cell death. These results explain the underlying mechanism of RD-N induced LMP. It can be concluded that a more lysosomotropic derivative was synthesized by introduction of an amine group, which could have more potential applications in cancer therapy.

Design, synthesis and biological evaluation of novel macrocyclic bisbibenzyl analogues as tubulin polymerization inhibitors.

A series of novel macrocyclic bisbibenzyl analogues was designed, synthesized, and evaluated for their antiproliferative activity in vitro. All of the compounds were tested in five anthropic cancer cell lines, including a multidrug-resistant phenotype. Among these novel molecules, compounds 88, 92 and 94 displayed excellent anticancer activity against Hela, k562, HCC1428, HT29, and PC-3/Doc cell lines, with average IC50 values ranging from 2.23 µM to 3.86 µM, and were more potent than the parental compound marchantin C and much more potent than the positive control Adriamycin. In addition, the mechanism of action of compound 88 was investigated by cell cycle analysis and a tubulin polymerization assay in HCC1482 cells. The binding mode of compound 88 to tubulin was also investigated utilizing a molecular docking study. In conclusion, the present study improves our understanding of the action of bisbibenzyl-based tubulin polymerization inhibitors and provides a new molecular scaffold for the further development of antitumor agents that target tubulin.

Jungermannenone A and B induce ROS- and cell cycle-dependent apoptosis in prostate cancer cells in vitro.

AIM: Jungermannenone A and B (JA, JB) are new ent-kaurane diterpenoids isolated from Chinese liverwort Jungermannia fauriana, which show anti-proliferation activities in cancer cells. In this study we investigated the mechanisms underlying the anticancer action of JA and JB in PC3 human prostate cancer cells in vitro. METHODS: A panel of 9 human cancer cell lines was tested. Cell proliferation was assessed with a real-time cell analyzer and MTT assay. Cell apoptosis, cell cycle distribution and ROS levels were measured using cytometry. Mitochondrial damage was examined by transmission electron microscopy. DNA damage was detected with comet assay. Apoptotic, DNA damage- and cell cycle-related proteins were analyzed using Western blotting. The expression of DNA repair genes was measured with qRT-PCR. RESULTS: Both JA and JB exerted potent anti-proliferative action against the 9 cancer cell lines, and PC3 cells were more sensitive with IC50 values of 1.34±0.09 and 4.93±0.20 µmol/L, respectively. JA (1.5 µmol/L) and JB (5 µmol/L) induced PC3 cell apoptosis, which was attenuated by the caspase inhibitor Z-VAD. Furthermore, both JA and JB caused mitochondrial damage and ROS accumulation in PC3 cells, whereas vitamin C blocked the ROS accumulation and attenuated the cytotoxicity of JA and JB. Moreover, both JA and JB induced DNA damage, accompanied by downregulated DNA repair proteins Ku70/Ku80 and RDA51. JA induced marked cell cycle arrest at the G0/G1 phase, which was related to c-Myc suppression, whereas JB enforced the cell cycle blockade in the G2/M phase, which associated with activation of the JNK signaling. CONCLUSION: Both JA and JB induce prostate cancer apoptosis via ROS accumulation and induction of cell cycle arrest.

Metabolic Syndrome and Cognitive Performance Among Chinese ≥50 Years: A Cross-Sectional Study with 3988 Participants.

BACKGROUND: To date, the relationship between metabolic syndrome (MetS) and cognitive performance has not been well defined. This study aimed to explore the relationship between MetS and cognitive performance among Chinese elderly population. METHODS: A cross-sectional study was performed, with data collected in seven clinical centers from five provinces of Northern China. All recruited participants were ≥50 years of age and complained with cognitive impairment or were reported with cognitive impairment by his/her caregiver(s). MetS was diagnosed according to the criteria issued by Chinese Medical Association Diabetes Association. Cognitive function was scored by Montreal Cognitive Assessment (MoCA). RESULTS: Three thousand nine hundred eighty-eight participants (in an average of 66.4 ± 8.8 years of age, male 53.1%) were included in the analysis. Six hundred seventy-three (16.9%) participants were diagnosed with MetS, and 3013 (75.6%) participants had mild cognitive impairment (MCI) (MoCA score <26). There was no statistically significant difference in the MoCA scores between participants with MetS (21.0 ± 5.4) and without MetS (21.3 ± 5.3). In the logistic regression, after adjusting factors of age, education, marital status, smoking, and physical activity, diabetes and dyslipidemia were associated with MCI, whereas hypertension and overweight or obesity were not. Participants with diabetes had a higher risk of MCI (OR = 1.24, 95% CI: 1.03-1.50). Participants with dyslipidemia had a lower risk of MCI (OR = 0.81, 95% CI: 0.68-0.97). CONCLUSION: In our study, MetS is not associated with cognitive performance in elderly Chinese population. However, elderly Chinese with diabetes would have lower cognition function, and the dyslipidemia might be reversely associated with the cognitive function.