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Among lifestyle-related factors, low to moderate alcohol drinking has been proposed as a protective factor against the development of age-related changes in cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD) in several longitudinal studies, but contrasting findings also exist. Furthermore, many of these studies were limited by cross-sectional design, restriction by age or sex, or incomplete ascertainment. Different outcomes, beverages, drinking patterns, or follow-up periods, or possible interactions with other lifestyle-related (i.e., smoking) or genetic factors [i.e., apolipoprotein E (APOE) genotyping] may be sources of great variability. Light to moderate alcohol use may be associated with a reduced risk of unspecified incident dementia and AD, while for VaD, cognitive decline, and predementia syndromes, the current evidence is only suggestive of a protective effect. In conclusion, as intervention studies are not feasible in this area, the best evidence comes from an overview of epidemiological studies, suggesting that the protective effects are more likely with wine consumption and the absence of an APOE e4 allele. At present, there is no indication that light to moderate alcohol drinking would be harmful to cognition and dementia, and it is not possible to define a specific beneficial level of alcohol intake.

A possible role of vascular and lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). At present, cumulative evidence suggests that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia, and AD. Among vascular-related factors, metabolic syndrome (MetS) has been associated with the risk of cognitive decline, overall dementia, and VaD, but contrasting findings also existed on the possible role of MetS in AD. If MetS is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals at risk might offer new avenues for disease-course modification. Strategies towards early and effective risk factor management could be of value in reducing risk of metabolic and cognitive decline. Future research is needed to confirm the association between MetS and cognitive impairment and to determine the exact mechanism linking them. Such would provide important insights into the causes and interdependencies of predementia and dementia syndromes, and inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor and MetS management could be employed to delay the onset of dementia syndromes or to prevent the progression of predementia syndromes. In the future, trials could be undertaken to determine whether modifications of these risk factors, including inflammation, could lower risk of developing cognitive decline.

The KEAP1/Nrf2 pathway is a master regulator of several redox-sensitive genes implicated in resistance of tumor cells against chemotherapeutic drugs. Recent data suggest that epigenetic mechanisms may play a pivotal role in the regulation of KEAP1 expression. We performed a comprehensive genetic and epigenetic analysis of the KEAP1 gene in 47 non-small cell lung cancer tissues and normal specimens. Promoter methylation analysis was performed using a quantitative methylation specific PCR assay in real time. Methylation at the KEAP1 promoter region was detected in 22 out of the 47 NSCLCs (47%) and in none of the normal tissues analyzed. Somatic mutations were detected in 7 out of the 47 tumors (15%) and loss of heterozygosity (LOH) in 10 out of the 47 (21%) of the cases. Overall, we found at least one molecular alteration in 57% of the cases. Approximately one third of the tumors had two alterations and this feature was associated with higher risk of disease progression in univariate COX regression analysis (HR = 3.62; 95% CI 1.24-10.65, p = 0.02). This result was confirmed by Kaplan-Meier analysis, which demonstrated an association between worst outcome and KEAP1 double alterations (p = 0.01, Log rank test). Our results further suggest that deregulation of the NRF2/KEAP1 system could play a pivotal role in the cancerogenesis of NSCLC. In addition identifying patients with KEAP1 genetic and epigenetic abnormalities may contribute to disease progression prediction and response to therapy in lung cancer patients.

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The integrated assessment of nutritional status and presence of sarcopenia would help improve clinical outcomes of in-hospital aged patients. We compared three common nutritional screening tools with the new Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria among hospitalized older patients. To this, 152 older patients were assessed consecutively at hospital admission by the Malnutrition Universal Screening Tool (MUST), the Subjective Global Assessment (SGA), and the Nutritional Risk Screening 2002 (NRS-2002). A 46% prevalence of malnutrition was reported according to GLIM. Sensitivity was 64%, 96% and 47%, and specificity was 82%, 15% and 76% with the MUST, SGA, and NRS-2002, respectively. The concordance with GLIM criteria was 89%, 53% and 62% for the MUST, SGA, and NRS-2002, respectively. All the screening tools had a moderate value to diagnose malnutrition. Moreover, patients at high nutritional risk by MUST were more likely to present with sarcopenia than those at low risk (OR 2.5, CI 1.3-3.6). To conclude, MUST is better than SGA and NRS-2002 at detecting malnutrition in hospitalized older patients diagnosed by the new GLIM criteria. Furthermore, hospitalized older patients at high risk of malnutrition according to MUST are at high risk of presenting with sarcopenia. Nutritional status should be determined by MUST in older patients at hospital admission, followed by both GLIM and the European Working Group on Sarcopenia in Older People (EWGSOP2) assessment.