Previous studies have highlighted links between a high-glycemic-load (GL) diet and Alzheimer’s disease in apolipoprotein E ε4 (APOE4) carriers. However, the impact of high-GL diet on plasma amyloid-β ...(Aβ), an Alzheimer’s disease hallmark that can be detected decades before clinical symptomatology, is unknown. This study examined the association between plasma Aβ peptides (Aβ40, Aβ42 concentration and Aβ42/Aβ40 ratio) and GL. The influence of the GL of four meal types (breakfast, lunch, afternoon snack, and dinner) was also determined. From the prospective Three-City study, 377 participants with plasma Aβ measurements, and who completed the Food Frequency Questionnaire, were selected. The association between plasma Aβ and GL was tested using an adjusted linear regression model. Lunch GL was associated with a lower plasma Aβ42 concentration (β = −2.2 CI = −4.27, −0.12, p = 0.038) and lower Aβ42/Aβ40 ratio (β = −0.009 CI = −0.0172, −0.0007, p = 0.034) in the model adjusted for center, age, sex, education level, APOE4 status, energy intake, serum creatinine, total cholesterol, and Mediterranean-like diet. No significant association was found with the GL of the other meal types. These results suggest that dietary GL may independently modulate the plasma Aβ of the APOE4 status. The mechanism underlying diet, metabolic response, and Aβ peptide regulation must be elucidated.
Statins are a class of widely prescribed drugs used to reduce low-density lipoprotein cholesterol (LDL-C) and important to prevent cardiovascular diseases (CVD). Most statin users are older adults ...with CVD, who are also at high risk of cognitive decline. It has been suggested that statins can alter cognitive performance, although their positive or negative effects are still debated. With more than 200 million people on statin therapy worldwide, it is crucial to understand the reasons behind discrepancies in the results of these studies. Here, we review the effects of statins on cognitive function and their association with different etiologies of dementia, and particularly, Alzheimer’s disease (AD). First, we summarized the main individual and statin-related factors that could modify the cognitive effects of statins. Second, we proposed the underlying mechanisms for the protective and adverse effects of statins on cognitive performance. Finally, we discussed potential causes of discrepancies between studies and suggested approaches to improve future studies assessing the impact of statins on dementia risk and cognitive function.
Recent evidence suggests that a high glycemic load (GL) diet is a risk factor for dementia, especially among apolipoprotein E ε4 allele (
) carriers, while its association with cognitive decline is ...poorly known. Here, we investigated the association of high-GL meals with cognitive decline in older adults during a 12-year follow-up, according to their
carrier status. We used random-effect models and data from 2539 elderly participants from the Three-City study who completed a food frequency questionnaire (FFQ) to longitudinally assess the association of GL with changes in different cognitive domains (verbal fluency, visual memory, attention, visual motor processing speed, episodic memory). In
carriers, afternoon snack with high GL was significantly associated with cognitive decline in visual memory, episodic memory, and global cognition compared with
non-carriers. This study suggests a detrimental association between a high-GL diet and cognitive decline. The promotion of a low GL diet as a target to prevent cognitive decline in high-risk populations deserves more research.
Aim
To test the hypothesis that liver‐expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity.
Methods
Using data from the UK Biobank, we ...identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin‐like growth factor‐1 (IGF‐1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRSLEAP2) using linear and logistic regression models. Sex‐stratified analyses were also conducted.
Results
Five SNPs showed positive associations with obesity‐related traits. rs57880964 was associated with body mass index (BMI) and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF‐1 concentrations in both men and women. GRSLEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF‐1 concentration in both sexes.
Conclusions
These findings reveal sex‐specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF‐1 concentration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Statins are widely used for cardiovascular disease prevention but their effects on cognition remain unclear. Statins reduce cholesterol concentration and have been suggested to provide both ...beneficial and detrimental effects. Our aim was to investigate the cross-sectional and longitudinal association between statin use and cognitive performance, and whether blood low-density lipoprotein, high-density lipoprotein, triglycerides, glucose, C-reactive protein, and vitamin D biomarkers mediated this association. We used participants from the UK biobank aged 40–69 without neurological and psychiatric disorders (n = 147 502 and n = 24 355, respectively). We performed linear regression to evaluate the association between statin use and cognitive performance and, mediation analysis to quantify the total, direct, indirect effects and the proportion meditated by blood biomarkers. Statin use was associated with lower cognitive performance at baseline (β = −0.40 −0.53, −0.28, p = <.0001), and this association was mediated by low-density lipoprotein (proportion mediated = 51.4%, p = .002), C-reactive protein (proportion mediated = −11%, p = .006) and blood glucose (proportion mediated = 2.6%, p = .018) concentrations. However, statin use was not associated with cognitive performance, measured 8 years later (β = −0.003 −0.11, 0.10, p = .96). Our findings suggest that statins are associated with lower short-term cognitive performance by lowering low-density lipoprotein and raising blood glucose concentrations, and better performance by lowering C-reactive protein concentrations. In contrast, statins have no effect on long-term cognition and remain beneficial in reducing cardiovascular risk factors.
Background and Purpose
Statins are competitive inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase (HMGCR), and exert adverse effects on mitochondrial function, although the ...mechanisms underlying these effects remain unclear. We used a tamoxifen‐induced Hmgcr‐knockout (KO) mouse model, a multi‐omics approach and mitochondrial function assessments to investigate whether decreased HMGCR activity impacts key liver energy metabolism pathways.
Experimental Approach
We established a new mouse strain using the Cre/loxP system, which enabled whole‐body deletion of Hmgcr expression. These mice were crossed with Rosa26Cre mice and treated with tamoxifen to delete Hmgcr in all cells. We performed transcriptomic and metabolomic analyses and thus evaluated time‐dependent changes in metabolic functions to identify the pathways leading to cell death in Hmgcr‐KO mice.
Key Results
Lack of Hmgcr expression resulted in lethality, due to acute liver damage caused by rapid disruption of mitochondrial fatty acid β‐oxidation and very high accumulation of long‐chain (LC) acylcarnitines in both male and female mice. Gene expression and KO‐related phenotype changes were not observed in other tissues. The progression to liver failure was driven by diminished peroxisome formation, which resulted in impaired mitochondrial and peroxisomal fatty acid metabolism, enhanced glucose utilization and whole‐body hypoglycaemia.
Conclusion and Implications
Our findings suggest that HMGCR is crucial for maintaining energy metabolism balance, and its activity is necessary for functional mitochondrial β‐oxidation. Moreover, statin‐induced adverse reactions might be rescued by the prevention of LC acylcarnitine accumulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction
In animal models, refined carbohydrates (RF) worsen Alzheimer's disease (AD). However, the long‐term effects of high RF intake on the risk of dementia and AD are poorly described in ...epidemiological studies. Moreover, the interaction between RF and the apolipoprotein E ε4 allele (APOE‐ε4) is unknown. Our study investigated whether RF‐rich diets are associated with the risk of dementia and AD.
Methods
The glycemic load (GL) was quantified in 2777 elderly participants from the French Three‐City Study to estimate RF intake. Then, the associations between GL and risk of dementia and AD, and the interaction with APOE‐ε4 over a 12‐year period were assessed using proportional hazards models.
Results
After adjustment for potential confounders, high afternoon‐snack GL was associated with increased dementia and AD risk in APOE‐ε4 carriers (hazard ratio = 1.27 1.03–1.56).
Discussion
This study highlights that RF‐rich diets are a risk factor for dementia and AD in APOE‐ε4 carriers.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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