Relationship between antihypertensive medications and cognitive impairment: Part I. review of human studies and clinical trials

Purpose of review: There is an established association between hypertension and increased risk of poor cognitive performance and dementia including Alzheimer’s disease; however, associations between antihypertensive medications (AHMs) and dementia risk are less consistent. An increased interest in AHM has resulted in expanding publications; however, none of the recent reviews are comprehensive. Our extensive review includes 15 observational and randomized controlled trials (RCTs) published over the last 5 years, assessing the relationship between AHM and cognitive impairment. Recent findings: All classes of AHM showed similar result patterns in human studies with the majority of study results reporting point estimates below one and only a small number of studies (N = 15) reporting statistically significant results in favor of a specific class. Summary: Only a small number of studies reported statistically significant results in favor of a specific class of AHM. Methodological limitations of the studies prevent definitive conclusions. Further work is now needed to evaluate the class of AHM and cognitive outcomes in future RCTs, with a particular focus on the drugs with the promising results in both animals and human observational studies

The importance of coat colour and coat type for productive performance of beef cattle under subtropical conditions

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Chemical Composition, in situ Degradability and in vitro Gas Production of Tagasaste (Chamaecytisus palmensis) Forage Harvested at Different Stages

The leguminous tree tagasaste is highly productive in the Ethiopian highlands. However, its nutritional value, as affected by the different agronomic practices is not fully understood under the tropical highland conditions. This study investigated the quality profile of tagasaste forage harvested at different re-growth stages by measuring the chemical composition, in situ degradability and in vitro gas production. Tagasaste re-growths after one year of establishment was harvested and the re-growths starting from the main rainy season (July) was harvested at 4, 6, 8 and 10 months. The harvested forages were fractionated into leaves and edible branches. Chemical composition, in situ degradability using rumen fistulated steers and in vitro gas production using rumen fluid from rumen fistulated dry cows were evaluated. The average crude protein (CP) content of tagasaste in the leaves ranged between 189 and 242 g kg-1 dry matter (DM) was not significantly affected by harvesting stage regrowth. The neutral detergent fibre, acid detergent fibre, acid detergent lignin and ether extract contents of tagasaste increased with length of re-growth. The amino acid profile of tagasaste protein showed high contents of the essential amino acids leucine and lysine but lower contents of methionine and histidine. Tagasaste grown under Ethiopian highland conditions was found deficient in phosphorus, sulphur, and sodium, but had adequate amounts of calcium, potassium, zinc and iron. The average in situ potential and effective degradability of leaves were 795 and 518 g kg-1 DM respectively and was lowest at the 10 months harvesting stage. The in vitro gas production declined with length of re-growth. Gas production was higher for leaves followed by branches with mean value of 43.7 and 39.1 ml 200-1 mg DM at 24 h respectively. The high CP content, degradability and in vitro gas production of tagasaste forage reveals its high potential to be used as a protein supplement for ruminants. The studied quality parameters should be further verified using animal performance

A piece of the puzzle: analyses of recent strandings and historical records reveal new genetic and ecological insights on New Zealand sperm whales

Cetacean strandings provide important opportunities to extend current knowledge on species or populations, particularly for species that are notoriously difficult to study, such as sperm whales Physeter macrocephalus (parāoa). Between 25 May and 9 June 2018, 13 male sperm whales stranded in Taranaki, New Zealand (NZ), with an additional male stranding 1 mo later in Clifford Bay, Marlborough. We profiled these 14 males for mitochondrial DNA (mtDNA) and carbon and nitrogen stable isotopes to examine their similarity to sperm whales from other geographic areas. Analyses of mtDNA revealed 7 haplotypes, including 1 not previously described (‘New’), and an additional haplotype (‘M’) new to NZ that had been previously reported in sperm whales of the Pacific region. Analysis of rare haplotypes found in NZ males suggested genetic links within NZ and the Southwest Pacific. Differences in stable isotope ratios indicated that, despite the close temporal proximity of these stranding events, individuals originated from at least 2 separate groups, with the whale stranded in Clifford Bay identified as being a regular visitor to Kaikōura, South Island. The analysis of stranding records in NZ dating back to 1873 indicated an increase in recorded single strandings since 1970, and a peak in single strandings in the austral summer months, but no seasonality for mass strandings. Sex predicted latitudinal location for single strandings, with 95.1% of female strandings occurring north of 42° S, fitting the general global distribution of female sperm whales limited to lower latitudes. This study provides the first temporal and spatial assessment of sperm whale strandings in NZ and highlights the need for future research on movements and genetic exchange between NZ sperm whales and sperm whales in the wider Pacific region.Publishe

Frequency of coexistent eye diseases and cognitive impairment or dementia: a systematic review and meta-analysis

Objective: We aim to quantify the co-existence of age-related macular degeneration (AMD), glaucoma, or diabetic retinopathy (DR) and cognitive impairment or dementia. Method: MEDLINE, EMBASE, PsycINFO and CINAHL were searched (to June 2020). Observational studies reporting incidence or prevalence of AMD, glaucoma, or DR in people with cognitive impairment or dementia, and of cognitive impairment or dementia among people with AMD, glaucoma, or DR were included. Results: Fifty-six studies (57 reports) were included but marked by heterogeneities in the diagnostic criteria or definitions of the diseases, study design, and case mix. Few studies reported on the incidence. Evidence was sparse but consistent in individuals with mild cognitive impairment where 7.7% glaucoma prevalence was observed. Prevalence of AMD and DR among people with cognitive impairment ranged from 3.9% to 9.4% and from 11.4% to 70.1%, respectively. Prevalence of AMD and glaucoma among people with dementia ranged from 1.4 to 53% and from 0.2% to 25.9%, respectively. Prevalence of DR among people with dementia was 11%. Prevalence of cognitive impairment in people with AMD, glaucoma, and DR ranged from 8.4% to 52.4%, 12.3% to 90.2%, and 3.9% to 77.8%, respectively, and prevalence of dementia in people with AMD, glaucoma and DR ranged from 9.9% to 62.6%, 2.5% to 3.3% and was 12.5%, respectively. Conclusions: Frequency of comorbid eye disease and cognitive impairment or dementia varied considerably. While more population-based estimations of the co-existence are needed, interdisciplinary collaboration might be helpful in the management of these conditions to meet healthcare needs of an ageing population. Trial registration: PROSPERO registration: CRD42020189484

Parameter selection for peak alignment in chromatographic sample profiling: objective quality indicators and use of control samples

In chromatographic profiling applications, peak alignment is often essential as most chromatographic systems exhibit small peak shifts over time. When using currently available alignment algorithms, there are several parameters that determine the outcome of the alignment process. Selecting the optimum set of parameters, however, is not straightforward, and the quality of an alignment result is at least partly determined by subjective decisions. Here, we demonstrate a new strategy to objectively determine the quality of an alignment result. This strategy makes use of a set of control samples that are analysed both spiked and non-spiked. With this set, not only the system and the method can be checked but also the quality of the peak alignment can be evaluated. The developed strategy was tested on a representative metabolomics data set using three software packages, namely Markerlynx™, MZmine and MetAlign. The results indicate that the method was able to assess and define the quality of an alignment process without any subjective interference of the analyst, making the method a valuable contribution to the data handling process of chromatography-based metabolomics data

High dietary fat consumption impairs axonal mitochondrial function in vivo

Peripheral neuropathy (PN) is the most common complication of prediabetes and diabetes. PN causes severe morbidity for Type 2 diabetes (T2D) and prediabetes patients, including limb pain followed by numbness resulting from peripheral nerve damage. PN in T2D and prediabetes is associated with dyslipidemia and elevated circulating lipids; however, the molecular mechanisms underlying PN development in prediabetes and T2D are unknown. Peripheral nerve sensory neurons rely on axonal mitochondria to provide energy for nerve impulse conduction under homeostatic conditions. Models of dyslipidemia in vitro demonstrate mitochondrial dysfunction in sensory neurons exposed to elevated levels of exogenous fatty acids. Herein, we evaluated the effect of dyslipidemia on mitochondrial function and dynamics in sensory axons of the saphenous nerve of a male high-fat diet (HFD)-fed murine model of prediabetes to identify mitochondrial alterations that correlate with PN pathogenesis in vivo. We found that the HFD decreased mitochondrial membrane potential (MMP) in axonal mitochondria and reduced the ability of sensory neurons to conduct at physiological frequencies. Unlike mitochondria in control axons, which dissipated their MMP in response to increased impulse frequency (from 1 to 50 Hz), HFD mitochondria dissipated less MMP in response to axonal energy demand, suggesting a lack of reserve capacity. The HFD also decreased sensory axonal Ca^{2+} levels and increased mitochondrial lengthening and expression of PGC1α, a master regulator of mitochondrial biogenesis. Together, these results suggest that mitochondrial dysfunction underlies an imbalance of axonal energy and Ca^{2+} levels and impairs impulse conduction within the saphenous nerve in prediabetic PN

Study protocol for development and validation of a single tool to assess risks of stroke, diabetes mellitus, myocardial infarction and dementia: DemNCD-Risk

Introduction Current efforts to reduce dementia focus on prevention and risk reduction by targeting modifiable risk factors. As dementia and cardiometabolic non-communicable diseases (NCDs) share risk factors, a single risk-estimating tool for dementia and multiple NCDs could be cost-effective and facilitate concurrent assessments as compared with a conventional single approach. The aim of this study is to develop and validate a new risk tool that estimates an individual's risk of developing dementia and other NCDs including diabetes mellitus, stroke and myocardial infarction. Once validated, it could be used by the public and general practitioners. Methods and analysis Ten high-quality cohort studies from multiple countries were identified, which met eligibility criteria, including large representative samples, long-term follow-up, data on clinical diagnoses of dementia and NCDs, recognised modifiable risk factors for the four NCDs and mortality data. Pooled harmonised data from the cohorts will be used, with 65% randomly allocated for development of the predictive model and 35% for testing. Predictors include sociodemographic characteristics, general health risk factors and lifestyle/behavioural risk factors. A subdistribution hazard model will assess the risk factors' contribution to the outcome, adjusting for competing mortality risks. Point-based scoring algorithms will be built using predictor weights, internally validated and the discriminative ability and calibration of the model will be assessed for the outcomes. Sensitivity analyses will include recalculating risk scores using logistic regression. Ethics and dissemination Ethics approval is provided by the University of New South Wales Human Research Ethics Committee (UNSW HREC; protocol numbers HC200515, HC3413). All data are deidentified and securely stored on servers at Neuroscience Research Australia. Study findings will be presented at conferences and published in peer-reviewed journals. The tool will be accessible as a public health resource. Knowledge translation and implementation work will explore strategies to apply the tool in clinical practice

Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations

Background: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research. Objectives: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer’s disease (AD) using cohort studies. Design, Setting, Participants and Measurements: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model. Results: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project. Conclusions: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings

Are food allergic consumers ready for informative precautionary allergen labelling?

Abstract Precautionary allergen labelling (PAL) has resulted in consumer confusion. Previous research has shown that interpretive labels (using graphics, symbols, or colours) are better understood than the traditional forms of labels. In this study, we aimed to understand if consumers would use interpretive labels (symbol, mobile phone application and a toll-free number) with or without medical advice that was advocated by the food industry rather than the normal PAL. This is relevant information for industry and clinicians as it provides an insight into the food allergic perception regarding PAL