Association between nutrition and cognition in a multi-ethnic cohort from Singapore.

BACKGROUND: Nutrition, a modifiable risk factor, presents a low-cost prevention strategy to reduce the burden of cognitive impairment and dementia. However, studies examining the effects of dietary patterns on cognition are lacking in multi-ethnic Asian populations. We investigate the association between diet quality, measured with the Alternative Healthy Eating Index (AHEI)-2010, and cognitive impairment in middle-aged and older adults of different ethnicities (Chinese, Malay, Indian) in Singapore. METHODS: This cross-sectional study (n = 3138; mean age: 50.4 ± 9.8, 58.4% women) was based on data from the Singapore Multi-Ethnic Cohort. Dietary intake collected with a validated semi-quantitative Food Frequency Questionnaire was converted into AHEI-2010 scores. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analysed as a continuous or binary outcome (cognitively impaired or not, using cut-offs of ≥ 24, 26 or 28 for no education, primary school education and secondary school education and above). Multivariable linear and logistic regression models were used to examine associations between AHEI-2010 and cognition, adjusting for covariates. RESULTS: A total of 988 (31.5%) participants had cognitive impairment. Higher AHEI-2010 scores were significantly associated with higher MMSE scores [ß = 0.44; 95% confidence interval (CI) 0.22-0.67 highest vs. lowest quartile; p-trend < 0.001] and lower odds of cognitive impairment [OR 0.69; 95% CI 0.54-0.88; p-trend = 0.01] after adjusting for all the covariates. No significant associations were observed for individual dietary components of the AHEI-2010 with MMSE or cognitive impairment. CONCLUSION: Healthier dietary patterns were associated with better cognitive function in middle-aged and older Singaporeans. These findings could inform better support to promote healthier dietary patterns in Asian populations.

Histone-lysine N-methyltransferase EHMT2 (G9a) inhibition mitigates tumorigenicity in Myc-driven liver cancer.

Hepatocellular carcinoma (HCC) is the third deadliest and sixth most common cancer in the world. Histone-lysine N-methyltransferase EHMT2 (also known as G9a) is a histone methyltransferase frequently overexpressed in many cancer types, including HCC. We showed that Myc-driven liver tumours have a unique H3K9 methylation pattern with corresponding G9a overexpression. This phenomenon of increased G9a was further observed in our c-Myc-positive HCC patient-derived xenografts. More importantly, we showed that HCC patients with higher c-Myc and G9a expression levels portend a poorer survival with lower median survival months. We demonstrated that c-Myc interacts with G9a in HCC and cooperates to regulate c-Myc-dependent gene repression. In addition, G9a stabilises c-Myc to promote cancer development, contributing to the growth and invasive capacity in HCC. Furthermore, combination therapy between G9a and synthetic-lethal target of c-Myc, CDK9, demonstrates strong efficacy in patient-derived avatars of Myc-driven HCC. Our work suggests that targeting G9a could prove to be a potential therapeutic avenue for Myc-driven liver cancer. This will increase our understanding of the underlying epigenetic mechanisms of aggressive tumour initiation and lead to improved therapeutic and diagnostic options for Myc-driven hepatic tumours.