Background
Anxiety and depression are more prevalent in women and caregivers and are associated with increased Alzheimer’s disease (AD) risk. We investigated multimodal predictors of increased ...anxiety/depression during the Covid19‐related confinement in cognitively unimpaired (CU) older adults with an increased risk for AD with a special focus on sex/gender.
Method
We included 921 CU participants from the ALFA study (Table 1). Anxiety and depression (Hospital Depression and Anxiety Scale, HADS), perceived stress (Perceived Stress Scale, PSS) and stress resilience (Brief Resilience Scale, BRS) were measured during Covid19‐related confinement. A subgroup completed the HADS (n=767) and underwent 18Fflutemetamol‐PET imaging and sMRI (n=254) 2.4±0.8 years before confinement. Cross‐sectional anxiety/depression measurements and change in anxiety/depression (delta score) from baseline to confinement were our primary outcomes of interest. We considered amyloid status (+/‐) and cortical thickness (Cth) from the AD signature regions as imaging biomarkers. First, we investigated sex differences in the variables assessed during confinement. Second, we ran regression models to predict (i) cross‐sectional anxiety/depression scores during confinement and (ii) change in anxiety/depression from baseline to confinement. Age, sex, education, APOE‐ε4 status, caregiver status, stress related‐variables and imaging biomarkers were considered as predictors.
Result
Fifteen percent of the participants were caregivers, 69% of which were women. Women showed increased stress perception relative to men (p=<0.001) – notably, when they were caregivers (p=0.01). There were no sex‐differences in stress resilience (p=0.5). In cross‐sectional models, sex (women) and higher stress perception were independent predictors of greater anxiety/depression during confinement (Table 2a). Being a caregiver additionally predicted increase in anxiety/depressive symptomatology from baseline (Table 3a). Finally, in the subsample with biomarkers, amyloid positivity ‐ but not Cth in the AD signature ‐ contributed to predict anxiety/depression both cross‐sectionally (Table 2b) and longitudinally (Table 3b) along with sex (women), caregiver status and stress perception.
Conclusion
Our results showed sex differences in caregiver status and stress perception during the Covid19‐related confinement. Further, women, caregivers and those with higher self‐perceived stress showed an increase in anxiety/depressive symptomatology. Amyloid pathology prior to confinement was associated with greater levels of anxiety/depression suggesting a role of amyloid pathology in anxiety/depressive symptomatology.
Long-term treatment with up to 1.8 mg liraglutide improves cardiovascular and all-cause mortality in patients with type 2 diabetes at high risk for cardiovascular disease (CVD) and is currently under ...investigation in subjects without diabetes. Aim of our study was to investigate whether high dose (3 mg) short-term (5 weeks) treatment with liraglutide in obese patients with no overt type 2 diabetes affects metabolites, lipid and lipoprotein profile and components of activin-follistatin axis in cardiovascular beneficial or detrimental way.
Twenty obese patients participated in a randomized, placebo-controlled, cross-over, double-blind study and were administrated liraglutide 3 mg or placebo for 5 weeks. Metabolites, fatty acids, lipid-lipoprotein profile and concentrations of activins and follistatins (250 parameters) were assessed in serum at start and completion of each treatment.
Concentrations of important cardiovascular markers such as total, free and remnant cholesterol were reduced with liraglutide before and after adjusting for weight loss. Similarly, reductions in number of small and medium size LDL particles and in their total lipid concentration were observed with liraglutide and partially weight-loss related. Tyrosine levels were reduced and behenic acid levels were increased whereas only minor changes were observed in HDL, VLDL and IDL. Concentrations of activin AB and follistatin were significantly reduced in liraglutide-treated group.
Treatment of obese patients without overt type 2 diabetes with high dose of liraglutide for a short period of time induces changes in lipid-lipoprotein and hormonal profile that are suggestive of lower risk of atherosclerosis and CVD. Trial registration ClinicalTrials.gov Identifier: NCT02944500. Study ID Number 2015P000327. Registered November 2016.
To assess the validity and reproducibility of food and nutrient intake estimated with the electronic diet history of ENRICA (DH-E), which collects information on numerous aspects of the Spanish diet.
...The validity of food and nutrient intake was estimated using Pearson correlation coefficients between the DH-E and the mean of seven 24-hour recalls collected every 2 months over the previous year. The reproducibility was estimated using intraclass correlation coefficients between two DH-E made one year apart.
The correlations coefficients between the DH-E and the mean of seven 24-hour recalls for the main food groups were cereals (r = 0.66), meat (r = 0.66), fish (r = 0.42), vegetables (r = 0.62) and fruits (r = 0.44). The mean correlation coefficient for all 15 food groups considered was 0.53. The correlations for macronutrients were: energy (r = 0.76), proteins (r= 0.58), lipids (r = 0.73), saturated fat (r = 0.73), monounsaturated fat (r = 0.59), polyunsaturated fat (r = 0.57), and carbohydrates (r = 0.66). The mean correlation coefficient for all 41 nutrients studied was 0.55. The intraclass correlation coefficient between the two DH-E was greater than 0.40 for most foods and nutrients.
The DH-E shows good validity and reproducibility for estimating usual intake of foods and nutrients.
Abstract INTRODUCTION Brain glucose hypometabolism is a preclinical feature of Alzheimer's disease (AD). Dietary omega‐3 fatty acids promote brain glucose metabolism, but clinical research is ...incipient. Circulating omega‐3s objectively reflect their dietary intake. METHODS This was a cross‐sectional study in 320 cognitively unimpaired participants at increased risk of AD dementia. Using lipidomics, we determined blood docosahexaenoic (DHA) and alpha‐linolenic (ALA) acid levels (omega‐3s from marine and plant origin, respectively). We assessed brain glucose metabolism using 18‐F‐fluorodeoxyglucose (FDG) positron emission tomography (PET). RESULTS Blood ALA directly related to FDG uptake in brain areas known to be affected in AD. Stronger associations were observed in apolipoprotein E ε4 carriers and homozygotes. For DHA, significant direct associations were restricted to amyloid beta–positive tau‐positive participants. DISCUSSION Blood omega‐3 directly relate to preserved glucose metabolism in AD‐vulnerable brain regions in individuals at increased risk of AD dementia. This adds to the benefits of omega‐3 supplementation in the preclinical stage of AD dementia. Highlights Blood omega‐3s were related to brain glucose uptake in participants at risk of Alzheimer's disease (AD) dementia. Complementary associations were observed for omega‐3 from marine and plant sources. Foods rich in omega‐3 might be useful in early features of AD.
Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2D) but also to diabetic vascular complications. It follows that antioxidants might contribute to limiting the diabetes ...burden. In this review we focus on ellagic acid (EA), a compound that can be obtained upon intestinal hydrolysis of dietary ellagitannins, a family of polyphenols naturally found in several fruits and seeds. There is increasing research on cardiometabolic effects of ellagitannins, EA, and urolithins (EA metabolites). We updated research conducted on these compounds and (I) glucose metabolism; (II) inflammation, oxidation, and glycation; and (III) diabetic complications. We included studies testing EA in isolation, extracts or preparations enriched in EA, or EA-rich foods (mostly pomegranate juice). Animal research on the topic, entirely conducted in murine models, mostly reported glucose-lowering, antioxidant, anti-inflammatory, and anti-glycation effects, along with prevention of micro- and macrovascular diabetic complications. Clinical research is incipient and mostly involved non-randomized and low-powered studies, which confirmed the antioxidant and anti-inflammatory properties of EA-rich foods, but without conclusive results on glucose control. Overall, EA-related compounds might be potential agents to limit the diabetes burden, but well-designed human randomized controlled trials are needed to fill the existing gap between experimental and clinical research.
Docosahexaenoic acid (DHA) might help prevent Alzheimer's disease (AD). Red blood cell (RBC) status of DHA is an objective measure of long-term dietary DHA intake. In this prospective observational ...study conducted within the Framingham Offspring Cohort (1490 dementia-free participants aged ≥65 years old), we examined the association of RBC DHA with incident AD, testing for an interaction with
carriership. During the follow-up (median, 7.2 years), 131 cases of AD were documented. In fully adjusted models, risk for incident AD in the highest RBC DHA quintile (Q5) was 49% lower compared with the lowest quintile (Q1) (Hazard ratio HR: 0.51, 95% confidence interval CI: 0.27, 0.96). An increase in RBC DHA from Q1 to Q5 was predicted to provide an estimated 4.7 additional years of life free of AD. We observed an interaction DHA ×
carriership for AD. Borderline statistical significance for a lower risk of AD was observed per standard deviation increase in RBC DHA (HR: 0.71, 95% CI: 0.51, 1.00,
= 0.053) in
carriers, but not in non-carriers (HR: 0.85, 95% CI: 0.65, 1.11,
= 0.240). These findings add to the increasing body of literature suggesting a robust association worth exploring dietary DHA as one strategy to prevent or delay AD.
Cognitive health is a life-long concern affected by modifiable risk factors, including lifestyle choices, such as dietary intake, with serious implications for quality of life, morbidity, and ...mortality worldwide. In addition, nuts are a nutrient-dense food that contain a number of potentially neuroprotective components, including monounsaturated and polyunsaturated fatty acids, fiber, B-vitamins, non-sodium minerals, and highly bioactive polyphenols. However, increased nut consumption relates to a lower cardiovascular risk and a lower burden of cardiovascular risk factors that are shared with neurodegenerative disorders, which is why nuts have been hypothesized to be beneficial for brain health. The present narrative review discusses up-to-date epidemiological, clinical trial, and mechanistic evidence of the effect of exposure to nuts on cognitive performance. While limited and inconclusive, available evidence suggests a possible role for nuts in the maintenance of cognitive health and prevention of cognitive decline in individuals across the lifespan, particularly in older adults and those at higher risk. Walnuts, as a rich source of the plant-based polyunsaturated omega-3 fatty acid alpha-linolenic acid, are the nut type most promising for cognitive health. Given the limited definitive evidence available to date, especially regarding cognitive health biomarkers and hard outcomes, future studies are needed to better elucidate the impact of nuts on the maintenance of cognitive health, as well as the prevention and management of cognitive decline and dementia, including Alzheimer disease.
Metabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological ...mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. Lipid composition was assessed, and lipid related pathways were studied at transcriptional and protein level. Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Lipidomic analysis showed profiles associated with de novo lipogenesis (DNL). BTBR ob/ob mice develop MAFLD profile that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.
Abstract
Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood from humans and mice before and ...after 36 or 24 hours of fasting, respectively, and measure lipid composition of erythrocyte membranes, circulating micro RNAs (miRNAs), and RNA expression at peripheral blood mononuclear cells (PBMCs). Fasting coordinately affects the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane; and reduces the expression of insulin signaling-related genes in PBMCs. When fasted for 24 hours before and 24 hours after administration of oxaliplatin or doxorubicin, mice show a strong protection from toxicity in several tissues. Erythrocyte membrane lipids and PBMC gene expression define two separate groups of individuals that accurately predict a differential protection from chemotherapy toxicity, with important clinical implications. Our results reveal a mechanism of fasting associated with lipid homeostasis, and provide biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.
The omega-3 index, defined as the sum of EPA and DHA in erythrocyte membranes expressed as a percentage of total fatty acids, has been proposed as both a risk marker and risk factor for CHD death. A ...major determinant of the omega-3 index is EPA+DHA intake, but the impact of other dietary fatty acids has not been investigated. In a cross-sectional study on 198 subjects (102 men and 96 women, mean age 66 years) at high cardiovascular risk living in Spain, the country with low rates of cardiac death despite a high prevalence of cardiovascular risk factors, dietary data were acquired from FFQ and blood cell membrane fatty acid composition was measured by GC. The average consumption of EPA+DHA was 0·9 g/d and the mean omega-3 index was 7·1 %. In multivariate models, EPA+DHA intake was the main predictor of the omega-3 index but explained only 12 % of its variability (P < 0·001). No associations with other dietary fatty acids were observed. Although the single most influential determinant of the omega-3 index measured here was the intake of EPA+DHA, it explained little of the former's variability; hence, the effects of other factors (genetic, dietary and lifestyle) remain to be determined. Nevertheless, the high omega-3 index could at least partially explain the paradox of low rates of fatal CHD in Spain despite a high background prevalence of cardiovascular risk factors.
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