The Asia-Pacific Clinical Practice Guidelines for the Management of Frailty

The ability of acute care providers to cope with the influx of frail older patients is increasingly stressed, and changes need to be made to improve care provided to older adults. Our purpose was to conduct a scoping review to map and synthesize the literature addressing frailty in the acute care setting in order to understand how to tackle this challenge. We also aimed to highlight the current gaps in frailty research. This scoping review included original research articles with acutely-ill Emergency Medical Services (EMS) or hospitalized older patients who were identified as frail by the authors. We searched Medline, CINAHL, Embase, PsycINFO, Eric, and Cochrane from January 2000 to September 2015. Our database search initially resulted in 8658 articles and 617 were eligible. In 67% of the articles the authors identified their participants as frail but did not report on how they measured frailty. Among the 204 articles that did measure frailty, the most common disciplines were geriatrics (14%), emergency department (14%), and general medicine (11%). In total, 89 measures were used. This included 13 established tools, used in 51% of the articles, and 35 non-frailty tools, used in 24% of the articles. The most commonly used tools were the Clinical Frailty Scale, the Frailty Index, and the Frailty Phenotype (12% each). Most often (44%) researchers used frailty tools to predict adverse health outcomes. In 74% of the cases frailty predicted the outcome examined, typically mortality and length of stay. Most studies (83%) were conducted in non-geriatric disciplines and two thirds of the articles identified participants as frail without measuring frailty. There was great variability in tools used and more recently published studies were more likely to use established frailty tools. Overall, frailty appears to be a good predictor of adverse health outcomes. For frailty to be implemented in clinical practice frailty tools should help formulate the care plan and improve shared decision making. How this will happen has yet to be determined.

/pdf/what-do-we-know-about-frailty-in-the-acute-care-setting-a-51bpgqg95u.pdf

What do we know about frailty in the acute care setting? A scoping review.

Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer’s disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties. Recently, scientists have put their efforts in establishing metformin’s role in the treatment of neurodegenerative diseases, such as AD, amnestic mild cognitive impairment and Parkinson’s disease. Results of several clinical studies confirm that long term use of metformin in diabetic patients contributes to better cognitive function, compared to participants using other anti-diabetic drugs. The exact mechanism of metformin’s advantageous activity in AD is not fully understood, but scientists claim that activation of AMPK-dependent pathways in human neural stem cells might be responsible for the neuroprotective activity of metformin. Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Aβ (β-amyloid). Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory. In regard to the beneficial effects of metformin, its anti-inflammatory and anti-oxidative properties cannot be omitted. Numerous in vitro and in vivo studies have confirmed that metformin ameliorates oxidative damage.

/pdf/metformin-a-future-therapy-for-neurodegenerative-diseases-2umbv8jxnk.pdf

Metformin – a Future Therapy for Neurodegenerative Diseases

The production of soluble amyloid-β oligomers (AβOs) and the activation of inflammation are two important early steps in the pathogenesis of Alzheimer's disease (AD). The central role of oligomers as responsible for the neuronal dysfunction associated with the clinical features has been extended to the other protein misfolding disorders definable, on this basis, as oligomeropathies. In AD, recent evidence indicates that the mechanism of inflammation as a consequence of neurodegeneration must be assessed in favor of a more direct role of glial activation in the alteration of synaptic function. Our own experimental models demonstrate the efficacy of anti-inflammatory treatments in preventing the cognitive deficits induced acutely by AβOs applied directly in the brain. Moreover, some promising clinical tools are based on immunological activation reducing the presence of cerebral Aβ deposits. However, the strategies based on the control of inflammatory factors as well as the amyloid aggregation show poor or non-therapeutic efficacy. Numerous studies have examined inflammatory factors in biological fluids as possible markers of the neuroinflammation in AD. In some cases, altered levels of cytokines or other inflammatory markers in cerebrospinal fluid correlate with the severity of the disease. Here we propose, according to the precision medicine principles, innovative therapeutic approaches to AD based on the patient's inflammatory profile/state. The earlier intervention and a multifactor approach are two other elements considered essential to improve the chances of effective therapy in AD.

Alzheimer's Disease, Oligomers, and Inflammation.

Sarcopenia is defined as age-associated loss of muscle mass and function, and is frequently accompanied by diabetes mellitus (DM) in older adults. Some of the mechanisms of the development of sarcopenia including insulin resistance, chronic inflammation and mitochondrial dysfunction are also associated with the pathogenesis of DM. Sarcopenia provides the basis for frailty, which is a state that is highly vulnerable to stressors, and can lead to disability, dependency and mortality, and older DM patients are often in a state of frailty. Given the background of an increasing number of older DM patients, the screening and early detection of sarcopenia/frailty and appropriate intervention would be expected to improve the prognosis and quality of life in older patients.

Sarcopenia and frailty in older patients with diabetes mellitus.

Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review

Chinese experts consensus on assessment and intervention for elderly patients with frailty

The present study aimed to examine the changes in DNA methylation of gene promoters associated with type 2 diabetes (T2D). The DNA methylation profile dataset GSE38291 was downloaded from the Gene Expression Omnibus database. A paired t-test was used to analyze differences in the DNA methylation of gene promoters between T2D and normal muscle samples. Gene Ontology (GO) enrichment analysis was performed using online tool, The Database for Annotation, Visualization and Integrated Discovery. Whole-Genome rVISTA was used to analyze the enriched transcription factor (TF) binding sites upstream of the transcription start site in the differentially methylated genes. A total of 38 genes, including Sirtuin 1, N-acetyltransferase 6, phospholipase A2 group XIIB and nuclear factor of activated T cells calcineurin-dependent 1, were identified to be differentially methylated between these two groups. One GO term, DNA geometric change (GO:0032392), was significantly enriched (P<0.05) by the hyper-methylated genes. In addition, the binding sites of one gene, zinc finger E-box binding homeobox 1, and three TFs, methyl CpG binding protein 2, TFEB and TFAP4, were significantly enriched in the hyper- and hypo-methylated genes, respectively. The resulting T2D‑associated genes and potential TFs provided a novel insight into the molecular mechanisms underlying the pathology of T2D. These genes may become promising target genes for the development of treatments for T2D.

/pdf/bioinformatics-analysis-of-abnormal-dna-methylation-in-8gcrral0ku.pdf

Bioinformatics analysis of abnormal DNA methylation in muscle samples from monozygotic twins discordant for type 2 diabetes

Frailty in China.

Background:To estimate the impact of comorbid diabetes on caregiver stress in Alzheimer's disease (AD) patients from the Impact of Cholinergic Treatment Use (ICTUS) study.Methods:Using the Data from the ICTUS study, diabetes mellitus (DM) was recorded at baseline and caregiver burden was assessed twice per year using the Zarit Burden Interview (ZBI) scale. The three-factorial model of ZBI (the effect on the social and personal life of caregivers, the psychological burden and the feelings of guilt) was adopted. Linear mixed models were used to examine the relation between DM and the scores of ZBI.Results:The present analyses were conducted on 1,264 AD subjects. A total of 156 patients (12.3%) had DM with taking antidiabetic medication and/or self-report of a history. At baseline, the caregivers of patients with or without DM had similar ZBI global scores and similar scores of three different factors of ZBI. Unadjusted and adjusted models both indicated that ZBI global score increased over a 24-month follow-up without significant effect of DM. Similarly, unadjusted model showed that DM was not determining any significant difference in the score of any factor. However, adjusted model indicated that in diabetic patients, the scores of the social and personal life of caregivers and the psychological burden increased more slowly than those in non-diabetic patients (p = 0.04 and 0.01, respectively).Conclusions:DM may affect the caregivers’ daily social and personal life and psychological burden in AD patients. It is necessary for further research.

Impact of diabetes on caregiver stress in patients with Alzheimer's disease: data from the ICTUS study

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