News in Brief

Abstract

Multimorbidity (having two or more conditions) and concurrent polypharmacy (taking five or more daily medications) are common in older people, increasing the risk of inappropriate prescribing. Nicolas Rodondi (Bern University Hospital, University of Bern, Bern, Switzerland) and colleagues used a cluster-randomised controlled trial (OPERAM) to investigate whether pharmacotherapy optimisation to enhance prescribing quality can lead to a reduction in drug-related hospital admissions. The intervention used a clinical decision-making software (systematic tool to reduce inappropriate prescribing) and also involved shared treatment discussions between the doctor and pharmacist and the patient. This trial had 54 intervention clusters (n=963) and 56 standard care control clusters (n=1045) within four hospitals in Switzerland, the Netherlands, Belgium, and Ireland. Enrolled older adults (median age 79 years) had multimorbidity (median of ten comorbidities) and polypharmacy (median of nine drugs). Inappropriate prescribing was common and in total, a mean of 2·75 (range 0–19) drug recommendations to reduce this effect were made. More than five out of six (789 [86·1%] of 916) patients received at least one drug recommendation, of whom, at 2 months, 491 (62·2%) of 789 had implemented one or more recommendations. The primary outcome of first drug-related hospital admission within 12 months of enrolment was not significantly reduced in the intervention group compared with the control group (211 [21·9%] of 963 vs 234 [22·4%] of 1045; hazard ratio 0·95 [95% CI 0·77–1·17]) and there were no differences in other clinical outcomes, such as death. Systemic inflammation is a key component in the regulation of physiological ageing but knowledge of biomarkers to characterise this state is limited. David Furman (Stanford University School of Medicine, Stanford, CA, USA) and his team have identified a way to track age-related systemic inflammation. They used deep learning on thousands of immune biomarkers to identify predictors of chronic disease from samples collected between 2007 and 2016 in 1001 individuals aged 8–96 years. They developed the inflammatory clock of ageing (iAge), which tracks multimorbidity, frailty, cardiovascular ageing, immunosenescence, and exceptional longevity (≥100 years). One of the most important contributory components to iAge was the cytokine CXCL9, which increased in concentration with age and was involved in cardiovascular ageing, cardiac remodelling, and poor vascular function in healthy adults. CXCL9 controlled inflammation and proliferation in endothelial cells: it impaired vascular function, contributed to arterial stiffness, and led to early senescence in these cells. When CXCL9 was silenced, the effects were reversed. The findings indicate that iAge can help physicians to diagnose patients’ risk for a multitude of chronic diseases and even aid in the detection of signs of early cardiovascular ageing in healthy older adults. Additionally, Furman and his team show the importance of CXCL9 in vascular function and senescence of cells, indicating a potential therapeutic avenue for research in preventing age-related deterioration of the physiological systems. IL-3 is associated with risk and severity of Alzheimer's disease and might have a role to play in neurodegeneration; however, the function of this cytokine is not fully understood. Cameron McAlpine (Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA) and colleagues used a series of in-vitro techniques, such as immunohistochemistry, mouse models and human post-mortem brains, to identify the role of IL-3 in the programming of microglia and the consequential effects on the pathology of Alzheimer's disease. In comparison to wild-type mice, mouse models that were deficient in IL-3 but had five Alzheimer's disease mutations had deterioration in short-term and spatial learning memory, suggesting that IL-3 protects against cognitive function. In terms of signalling, microglia became responsive to IL-3 during Alzheimer's disease by expressing IL-3Rα, concentrations of which were three times higher in the brains of individuals with Alzheimer's disease compared with healthy control donors. IL3RA expression correlated with disease duration and β-amyloid deposits in people with Alzheimer's disease, indicating that IL-3 signalling is relevant in the human brain during disease pathogenesis. To measure the protective effects of this interleukin, IL-3 was deleted, which led to increased β-amyloid burden and a worsening of cognitive function in mice, whereas the reintroduction of IL-3 ameliorated these effects. IL-3 also invoked transcriptional, morphological, and functional programming of the microglia to promote motility and the ability to cluster and clear β-amyloid deposits in mice and humans. The authors identified IL-3 as a key mediator of astrocyte and microglia crosstalk as microglia programming, and therefore, an influence on Alzheimer's disease pathology. Altogether, these findings suggest the potential for use of IL-3 in research as a therapy in people with Alzheimer's disease.