This is the first study in a Western population showing that risk of malnutrition and overt malnutrition, as assessed using the MNA-SF, are independent predictors of postoperative delirium. Accordingly, nutritional status should be assessed in individuals with hip fracture before surgery to determine risk of developing delirium.

The intestinal microbiota actively converts dietary flavanols into phenolic acids, some of which are bioavailable in vivo and may promote resilience to select neurological disorders by interfering with key pathologic mechanisms. Since every person harbors a unique set of gut bacteria, we investigated the influence of the gut microbiota's interpersonal heterogeneity on the production and bioavailability of flavonoid metabolites that may interfere with the misfolding of alpha (α)synuclein, a process that plays a central role in Parkinson's disease and other α-synucleinopathies. We generated two experimental groups of humanized gnotobiotic mice with compositionally diverse gut bacteria and orally treated the mice with a flavanol-rich preparation (FRP). The two gnotobiotic mouse groups exhibited distinct differences in the generation and bioavailability of FRP-derived microbial phenolic acid metabolites that have bioactivity towards interfering with αsynuclein misfolding or inflammation. We also demonstrated that these bioactive phenolic acids are effective in modulating the development and progression of motor dysfunction in a Drosophila model of α-synucleinopathy. Lastly, through in vitro bacterial fermentation studies, we identified select bacteria that are capable of supporting the generation of these bioavailable and bioactive phenolic acids. Outcomes from our studies provide a better understanding of how interpersonal heterogeneity in the gut microbiota differentially modulates the efficacy of dietary flavanols to protect against select pathologic mechanisms. Collectively, our findings provide the basis for future developments of probiotic, prebiotic, or synbiotic approaches for modulating the onset and/or progression of α-synucleinopathies and other neurological disorders involving protein misfolding and/or inflammation. Keywordsmicrobiome; humanized gnotobiotic mice; polyphenol metabolism; phenolic acids; αsynucleinopathy; Drosophila MATERIALS AND METHODS Chemicals, solvents, peptides and proteinsChemicals were obtained from Sigma-Aldrich (St Louis, MO, USA) and, unless otherwise stated, were of the highest purity available. Solvents were high-performance liquid chromatography (HPLC) grade and were obtained from Fisher Scientific. Water was doubledistilled and deionized using a Milli-Q system (Millipore Corp., Bedford, MA). Monomeric α-synuclein peptide was purchased from rPeptide (Watkinsville, GA). Glutathione Stransferase (GST) was purchased from Sigma-Aldrich.

Delirium is an acute neuropsychiatric syndrome and one of the most common presenting symptoms of acute medical illnesses in older people. Delirium can be triggered by a single cause, but in most cases, it is multifactorial as it depends on the interaction between predisposing and precipitating factors. Delirium is highly prevalent in older patients across various settings of care and correlates with an increased risk of adverse clinical outcomes. Several pathophysiological mechanisms may contribute to its onset, including neurotransmitter imbalance, neuroinflammation, altered brain metabolism, and impaired neuronal network connectivity. Several screening and diagnostic tools for delirium exist, but they are unfortunately underutilized. Additionally, the diagnosis of delirium superimposed on dementia poses a formidable challenge – especially if dementia is severe. Non-pharmacological approaches for the prevention and multidomain interventions for the treatment of delirium are recommended, given that there is currently no robust evidence of drugs that can prevent or resolve delirium. This article aims to review the current understanding about delirium in older people. To achieve this goal, we will describe the epidemiology and outcomes of the syndrome, the pathophysiological mechanisms that are supposed to be involved, the most commonly used tools for screening and diagnosis, and prevention strategies and treatments recommended. This review is intended as a brief guide for clinicians in hospital wards to improve their knowledge and practice. At the end of the article, we propose an approach to improve the quality of care provided to older patients throughout a systematic detection of delirium.

Neurodegenerative disorders constitute a group of multifaceted conditions characterized by the progressive loss of neurons and synaptic connections consequent to a combination of specific genetic predispositions and stochastic stressors. The neuropathologies observed in both Alzheimer’s and Parkinson’s disease are in part attributed to compounding intrinsic and extrinsic environmental stressors, which we propose may be limited by the administration of specific grape derived phytochemicals and their metabolized derivatives, specifically polyphenols isolated from grape botanicals. Current therapies for neurodegenerative disorders are limited as they solely target the final disease pathologies including behavioral changes, cognitive deficits, proteinopathies and neuronal loss; however, this strategy is not a sustainable approach toward managing disease onset or progression. This review discusses the application of grape derived polyphenols as an adjunctive treatment paradigm for the prevention of neuropathologies associated with Alzheimer’s disease, Parkinson’s disease and Chronic Traumatic Encephalopathy by simultaneously ameliorating two stochastic stressors that facilitate their disease pathologies: inflammation and oxidative stress. The biophysical attributes of grape-derived polyphenols buffer against redox potential dependent peripheral and neuroinflammation and down regulate the activation of inflammasomes in microglia and astrocytes, which could provide a novel mechanism through which grape-derived polyphenols simultaneously suppress risk factors across pathologically distinct neurodegenerative conditions. This approach therefore offers a prophylactic mode, not feasible through current pharmacological agents, to target activity dependent risk factors for neurodegenerative disorders that manifest over an individual’s lifetime.

Previous evidence has suggested that dietary supplementation with a bioactive dietary polyphenol preparation (BDPP) rescues impairment of hippocampus-dependent memory in a mouse model of sleep deprivation (SD). In the current study, we extend our previous evidence and demonstrate that a mechanism by which dietary BDPP protects against SD-mediated cognitive impairment is via mechanisms that involve phosphorylation of the mammalian target of rapamycin complex 1 and its direct downstream targets, including the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) and the ribosomal protein S6 kinase β-1 (p70S6K). In additional mechanistic studies in vitro, we identified the brain bioavailable phenolic metabolites derived from the metabolism of dietary BDPP that are responsible for the attenuation of SD-mediated memory impairments. On the basis of high-throughput bioavailability studies of brain bioavailable metabolites after dietary BDPP treatment, we found that select polyphenol metabolites [ e.g., cyanidin-3'- O-glucoside and 3-(3'-hydroxyphenyl) propionic acid] were able to rescue mTOR and p70S6K phosphorylation in primary cortico-hippocampal neuronal cultures, as well as rescue 4E-BP1 phosphorylation in response to treatment with 4EGI-1, a specific inhibitor of eIF4E-eIF4G interaction. Our findings reveal a previously unknown role for dietary polyphenols in the rescue of SD-mediated memory impairments via mechanisms involving the promotion of protein translation.-Frolinger, T., Smith, C., Cobo, C. F., Sims, S., Brathwaite, J., de Boer, S., Huang, J., Pasinetti, G. M. Dietary polyphenols promote resilience against sleep deprivation-induced cognitive impairment by activating protein translation.