Aleix Sala-Vila

Aleix Sala-Vila
IMIM Hospital del Mar Medical Research Institute | IMIM · Cardiovascular Epidemiology and Genetics Group

Phd

About

158
Publications
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Introduction
I work at the Fundació Institut Hospital del Mar d'Investigacions Mèdiques (IMIM) and I serve as Associate Scientist at the Fatty Acid Research Institute (FARI). With 20 years of experience in lipidomics, my current research mostly focuses on the chromatographic determination of the fatty acid profile in biological samples as objective markers of diet, and their associations with the phenotype of age-related diseases, including cardiovascular disease and Alzheimer’s disease. Twitter: @sala_vila1

Publications

Publications (158)
Article
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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 peri...
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Omega-3 fatty acids are critical for brain function. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. In contrast to the abundant research on the omega-3 docosahexaenoic acid (DHA) in cognition, research on DHA and attention in healthy adolescents is scarce. In addition, the role of alpha-linolenic acid (ALA), t...
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The investigation of resting-state functional connectivity (rsFC) in asymptomatic individuals at genetic risk for Alzheimer’s disease (AD) enables discovering the earliest brain alterations in preclinical stages of the disease. The APOE-ε4 variant is the major genetic risk factor for AD, and previous studies have reported rsFC abnormalities in carr...
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Bempedoic acid (BemA) is an ATP-citrate lyase (ACLY) inhibitor used to treat hypercholesterolemia. We studied the anti-steatotic effect of BemA, and the mechanisms involved, in a model of fatty liver in female rats obtained through the administration of a high-fat diet supplemented with liquid fructose (HFHFr) for three months. In the third month,...
Article
Omega-3 index, the red blood cell (RBC) proportion of the eicosapentaenoic (EPA) + docosahexaenoic (DHA) fatty acids is a clinical marker of age-related disease risk. It is unclear whether regular intake of α-linolenic acid (ALA), a plant-derived n-3 polyunsaturated fatty acid, raises omega-3 index in older adults. Of the 356 participants at the Lo...
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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...
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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 stud...
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Amyloid (Aβ) pathology is the earliest detectable pathophysiological event along the Alzheimer’s continuum, which can be measured both in the cerebrospinal fluid (CSF) and by Positron Emission Tomography (PET). Yet, these biomarkers identify two distinct Aβ pools, reflecting the clearance of soluble Aβ as opposed to the presence of Aβ fibrils in th...
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The mechanisms underlying the lipid-lowering effect of nuts remain elusive. This study explores whether one-year supplementation with walnuts decreases LDL-cholesterol (LDL-C) by affecting the expression of circulating microRNAs (c-miRNA). In this sub-study of the Walnuts and Healthy Aging (WAHA) trial, we obtained fasting serum at baseline and at...
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Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipid...
Article
Red blood cell (RBC) fatty acid (FA) patterns are becoming recognized as long-term biomarkers of tissue FA composition, but different analytical methods have complicated inter-study and international comparisons. Here we report RBC FA data, with a focus on the Omega-3 Index (EPA + DHA in % of total FAs in RBC), from samples of seven countries (USA,...
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Background: Evidence for the role of omega-3 fatty acids in the prevention of atrial fibrillation (AF) remain inconsistent, with some recent RCTs even suggesting possible harm. Whether long-term dietary intake of these fatty acids, as assessed using objective biomarkers, is related to AF is not known. Aims: To prospectively evaluate circulating and...
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Given the evidence of the health benefits of plant-based diets and long-chain n-3 fatty acids, there is keen interest in better understanding the role of alpha-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts a...
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Scope: To delineate the contribution of dietary saturated fatty acids (FA) versus liquid fructose to fatty liver and hypertriglyceridemia. Methods and results: Three groups of female rats were maintained for 3 months in: (1) standard chow (CT); (2) High-fat diet (46.9% of fat-derived calories, rich in palmitic and stearic FA, HFD) and (3) HFD wi...
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Background: Recognizing clinical manifestations heralding the development of Alzheimer's disease (AD)-related cognitive impairment could improve the identification of individuals at higher risk of AD who may benefit from potential prevention strategies targeting preclinical population. We aim to characterize the association of body weight change w...
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PurposeInformation on the association between diet and cardiovascular disease (CVD) in type 1 diabetes (T1D) is scarce. We assessed the association between biomarkers of fatty acid (FA) intake and the presence of carotid plaques (a surrogate marker of future CVD events) in this high-risk population.Methods Cross-sectional study in 167 consecutive T...
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Telomere length (TL) is an objective biomarker of biological aging and it has been proposed to play a crucial role in Alzheimer's disease (AD) progression by impairing cognitive resilience. However, published studies show inconsistent results and a very limited number of studies have evaluated the role of TL in aging and midlife individuals. The ma...
Article
Obesity has been linked to brain atrophy and peripheral inflammation. However, the association between body mass index (BMI) and brain structure can be confounded by Alzheimer’s disease (AD) pathology‐related weight loss, and its association with neuroinflammation remains unknown. We explored associations of BMI with brain structure and biomarkers...
Article
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....
Article
Clinical studies indicate that Alzheimer's disease (AD) disproportionately affects women. Although previous studies reported sex differences in fluid biomarkers, there is a need for a comprehensive analysis across the disease continuum. The aim of this study was to compare AD‐related biomarkers in cerebrospinal fluid (CSF) and plasma between women...
Article
In a sample of cognitively unimpaired (CU) middle‐aged adults with family history (FH) of sporadic Alzheimer’s disease (AD), we (i) classified participants based on similarity patterns of expression in cerebrospinal fluid (CSF) biomarkers of AD, axonal damage, synaptic dysfunction, neuroinflammation, and glial response, and (ii) characterized the p...
Article
Subjective cognitive decline (SCD) is often related to affective symptoms and both predict cognitive decline. We investigated whether SCD status predicted higher anxiety/depression during the Covid19‐related confinement, along with amyloid positivity in cognitively unimpaired older adults. We included 205 participants from the ALFA+ study (Table 1)...
Presentation
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RBC long-chain omega-3 (n–3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction. Our objective was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause...
Article
Background: Cell membrane fatty acid composition has been related to inflammation and cardiovascular risk. Dysregulation of HDL functionis also considered a cardiovascular risk factor. Objective: We aimed to investigate whether the content of cell membrane fatty acids and HDL functionality are linked to each other as well as to inflammation. Me...
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Objective To determine whether CSF synaptic biomarkers are altered in the early preclinical stage of the Alzheimer’s continuum and associated with Alzheimer’s disease (AD) risk factors, primary pathology, and neurodegeneration markers. Methods Cross-sectional study in the ALFA+ cohort, comprising middle-aged cognitively unimpaired participants. CS...
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Background Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer’s disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and t...
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Purpose Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine inta...
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Background Understanding the changes that occur in the transitional stage between absent and overt amyloid-β (Aβ) pathology within the Alzheimer’s continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct...
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The intervention with the Mediterranean diet (MD) pattern has evidenced short-term anti-inflammatory effects, but little is known about its long-term anti-inflammatory properties at molecular level. This study aims to investigate the 3-year effect of MD interventions compared to low-fat diet (LFD) on changes on inflammatory biomarkers related to at...
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Background RBC long-chain omega-3 (n–3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction. Objectives The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease...
Article
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Purpose: Epidemiological studies and clinical trials support the association of nut consumption with a lower risk of prevalent non-communicable diseases, particularly cardiovascular disease. However, the molecular mechanisms underlying nut benefits remain to be fully described. MicroRNAs (miRNAs) are post-transcriptional regulators of gene express...
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Background: Adolescence, when the most complex behaviors are refined to adult sophistication, represents a major window of opportunity and vulnerability for neuropsychological development. To support and protect this complex and active brain growth, different nutritional components considered essential need to be acquired from the diet. For instanc...
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The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42...
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Background The number of APOE-ε4 alleles is a major nonmodifiable risk factor for sporadic Alzheimer disease (AD). There is increasing evidence on the benefits of dietary DHA (22:6n–3) before the onset of AD symptoms, particularly in APOE-ε4 carriers. Brain alterations in the preclinical stage can be detected by structural MRI. Objectives We aimed...
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Neurofilament light chain (NfL) is an axonal protein that when measured in cerebrospinal fluid (CSF) serves as a biomarker of neurodegeneration. We aimed at investigating the association among CSF NfL, presence of Subjective Cognitive Decline (SCD) and hippocampal volume, and how CSF amyloid-β (Aβ) modifies these associations. We included 278 cogni...
Article
Background Fish could play a role in preventing type 2 diabetes (T2D) but there has been little specification about the type of fish and the preventive mechanism involved in its health claim. The sardine is a source of omega-3 and taurine that, in isolation or in synergy, would produce T2D-delaying through different molecular mechanism. Hypothesis...
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Amyloid-β (Aβ) positivity is defined using different biomarkers and different criteria. Criteria used in symptomatic patients may conceal meaningful early Aβ pathology in preclinical Alzheimer. Therefore, the description of sensitive cutoffs to study the pathophysiological changes in early stages of the Alzheimer’s continuum is critical. Here, we c...
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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...
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In Alzheimer’s disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p-tau) in the preclinical stage of the Alzheimer’s continuum. We mea...
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Background and Purpose The red blood cell fatty acid composition objectively reflects the long-term dietary intake of several fatty acids. In patients undergoing carotid endarterectomy, we explored whether red blood cell status of selected fatty acids related to symptomatic carotid artery disease. Methods We included patients with symptomatic (n=2...
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Background: Mounting evidence links poor sleep quality with a higher risk of late-life dementia. However, the structural and cognitive correlates of insomnia are still not well understood. The study aims were to characterize the cognitive performance and brain structural pattern of cognitively unimpaired adults at increased risk for Alzheimer's di...
Article
Telomere length (TL) is a putative biomarker of biological aging and aging‐related outcomes. Observational studies are limited to conclude whether TL is causally associated with AD or a marker of an underlying pathological process. Mendelian randomization (MR) was developed for assessing causality using genetic variants in epidemiological research....
Article
New clinical trials, like the A3, are targeting participants with emerging amyloid pathology (between 20‐40 centiloids (CL). The aim of this study is to describe if there are detectable differences in tau, synaptic, inflammatory, neurodegeneration CSF markers and brain structure in participants with emerging amyloid pathology. CSF Aß42, Aß40, t‐tau...
Article
Neurofilament light chain (NfL) is a biomarker of neurodegeneration. While cerebrospinal (CSF) NfL is increased in individuals with AD dementia as compared to controls and mild cognitive impairment, studies in cognitively unimpaired individuals with subjective cognitive decline (SCD) are scarce. SCD may represent the first clinical symptom of AD. W...
Article
Subjective Cognitive Decline (SCD) is a risk factor for cognitive decline and increases the likelihood of abnormal Alzheimer’s disease (AD) biomarkers. A set of SCD features (SCDplus) has been proposed to be more strongly related with AD pathology, like onset within 5 years. Limited evidence suggest that there is an association between recent SCD o...
Article
The higher prevalence of anxiety‐related disorders in women, as well as the lower opportunities for higher education, may explain differences in brain resilience to AD pathologies. The objectives were to (1) test sex‐differences on brain metabolism and (2) evaluate whether the effects of amyloid, tau, education and anxiety on brain metabolism and s...
Article
Alzheimer’s disease (AD) comprises a preclinical stage characterized by pathophysiological changes that occur decades before symptoms arise. Despite the importance of this stage, the biological pathways involved are not yet well understood. The main aim of this study is to define the pathophysiological processes, as measured by CSF biomarkers chang...
Article
The allele ε4 of the APOLIPOPROTEIN E gene (APOE‐ε4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). However, the underlying mechanisms are not well understood. Our objective was to assess the effect of the APOE‐ε4 allele dose on brain functional connectivity networks in cognitively unimpaired middle‐age individuals, usi...
Article
Increasing evidence suggests that sex influences several aspects of Alzheimer’s disease (AD). Cardiovascular risk factors are associated with AD, and men and women differ in the prevalence of these risk factors. We aimed at determining whether (1) sex and cardiovascular risk factors have an effect on CSF biomarkers; (2) sex modifies the association...
Article
Weight loss is common in Alzheimer’s disease (AD) and may start before cognitive impairment, but little is known about the relationship between weight change and AD biomarkers in the preclinical Alzheimer’s continuum. We aimed to assess the association between weight change and AD biomarkers and cognitive performance in cognitively unimpaired (CU)...
Article
The identification of the earliest biomarker changes and modifiable factors to be targeted in early interventions is crucial for Alzheimer’s disease (AD) prevention. The objective were (1) to evaluate the hypothesis that proximity to parental age at onset (AAO) in sporadic AD is associated with greater AD and neural injury biomarker alterations dur...
Article
Full-text available
In Alzheimer’s disease (AD), tau phosphorylation in the brain and its subsequent release into cerebrospinal fluid (CSF) and blood is a dynamic process that changes during disease evolution. The main aim of our study was to characterize the pattern of changes in phosphorylated tau (p‐tau) in the preclinical stage of the Alzheimer’s continuum. We mea...
Article
Full-text available
Background Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function....
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Non-alcoholic fatty liver disease is a highly prevalent condition without specific pharmacological treatment, characterized in the initial stages by hepatic steatosis. It was suggested that lipid infiltration in the liver might be reduced by caffeine through anti-inflammatory, antioxidative, and fatty acid metabolism-related mechanisms. We investig...
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Based on studies in mice, leptin was expected to decrease body weight in obese individuals. However, the majority of the obese are hyperleptinemic and do not respond to leptin treatment, suggesting the presence of leptin tolerance and questioning the role of leptin as regulator of energy balance in humans. We thus performed detailed novel measureme...
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Objective To evaluate the hypothesis that proximity to parental age at onset (AAO) in sporadic Alzheimer’s disease (AD) is associated with greater AD and neural injury biomarker alterations during midlife and to assess the role of non-modifiable and modifiable factors. Methods This observational study included 290 cognitively unimpaired (CU) parti...
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Diabetic subjects are at increased risk of cardiovascular disease. Atherosclerosis, the common soil of most of the cardiovascular complications, is more prevalent and extensive in this population due not only to hyperglycemia, insulin resistance, and dyslipidemia, but also to inflammation and oxidative stress. Lycopenes are bioactive compounds with...