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Risk of cognitive decline progression is associated to increased blood-brain-barrier permeability: A longitudinal study in a memory unit clinical cohort.
Puig-Pijoan, A, Jimenez-Balado, J, Fernández-Lebrero, A, García-Escobar, G, Navalpotro-Gómez, I, Contador, J, Manero-Borràs, RM, Puente-Periz, V, Suárez, A, Muñoz, FJ, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024;(1):538-548
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Abstract
INTRODUCTION This study examined the relationship between blood-brain-barrier permeability (BBBp), measured by cerebrospinal fluid/serum albumin ratio (QAlb), and cognitive decline progression in a clinical cohort. METHODS This prospective observational study included 334 participants from the BIODEGMAR cohort. Cognitive decline progression was defined as an increase in Global Deterioration Scale and/or Clinical Dementia Rating scores. Associations between BBBp, demographics, and clinical factors were explored. RESULTS Male sex, diabetes mellitus, and cerebrovascular burden were associated with increased log-QAlb. Vascular cognitive impairment patients had the highest log-QAlb levels. Among the 273 participants with valid follow-up data, 154 (56.4%) showed cognitive decline progression. An 8% increase in the hazard of clinical worsening was observed for each 10% increase in log-QAlb. DISCUSSION These results suggest that increased BBBp in individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis.
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Diet patterns associated with cognitive decline: methods to harmonize data from European and US cohort studies.
Ayala-Garcia, A, Soldevila-Domenech, N, Yi, SY, de la Torre, R, Steffen, LM, ,
Frontiers in nutrition. 2024;:1379531
Abstract
The impact of dietary intake on cognitive outcomes and dementia prevention is a topic of increasing interest. Meta-analyses of observational studies, mostly conducted within US and European populations, have reported benefits of healthy diet patterns on cognitive performance, but results from individual studies have been inconsistent. These inconsistencies are likely due to the diverse methodology used in studies, including different diet and cognitive function assessment instruments, follow-up periods, and analytical methods, which make drawing conclusions relevant to dietary guidance challenging. The objective of this project is to describe a protocol to conduct a retrospective harmonization study on dietary intake and cognitive health using data from European and US studies. The recommendations resulting from the project can be used to support evidence-based synthesis for future iterations of the Dietary Guidelines for Americans or other population-based dietary guidance. Additionally, this study will serve as a harmonization guide for future research on the relationship between diet patterns and cognition. The approach outlined ultimately aims to optimize resources and expedite research efforts for dementia prevention.
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Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays.
Ashton, NJ, Puig-Pijoan, A, Milà-Alomà, M, Fernández-Lebrero, A, García-Escobar, G, González-Ortiz, F, Kac, PR, Brum, WS, Benedet, AL, Lantero-Rodriguez, J, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023;(5):1913-1924
Abstract
INTRODUCTION Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. METHODS In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio. RESULTS All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94). DISCUSSION Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD. HIGHLIGHTS Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.
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Exploring the influence of circulating endocannabinoids and nucleus accumbens functional connectivity on anorexia nervosa severity.
Miranda-Olivos, R, Baenas, I, Steward, T, Granero, R, Pastor, A, Sánchez, I, Juaneda-Seguí, A, Del Pino-Gutiérrez, A, Fernández-Formoso, JA, Vilarrasa, N, et al
Molecular psychiatry. 2023;(11):4793-4800
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Abstract
Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; pFWE < 0.001) and the left supplementary motor area (NAcc-SMA; pFWE < 0.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Although no significant differences in eCBs concentrations were observed between the groups, our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.
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Olive Oil Phenolic Compounds' Activity against Age-Associated Cognitive Decline: Clinical and Experimental Evidence.
Boronat, A, Serreli, G, Rodríguez-Morató, J, Deiana, M, de la Torre, R
Antioxidants (Basel, Switzerland). 2023;(7)
Abstract
Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants could have beneficial effects on brain aging. In this review, we firstly summarize and critically discuss the current preclinical evidence and the potential neuroprotective mechanisms. Existing studies indicate that olive oil phenolic compounds can modulate and counteract oxidative stress and neuroinflammation, two relevant pathways linked to the onset and progression of neurodegenerative processes. Secondly, we summarize the current clinical evidence. In contrast to preclinical studies, there is no direct evidence in humans of the bioactivity of olive oil phenolic compounds. Instead, we have summarized current findings regarding nutritional interventions supplemented with olive oil on cognition. A growing body of research indicates that high consumption of olive oil phenolic compounds is associated with better preservation of cognitive performance, conferring an additional benefit, independent of the dietary pattern. In conclusion, the consumption of olive oil rich in phenolic bioactive compounds has potential neuroprotective effects. Further research is needed to understand the underlying mechanisms and potential clinical applications.
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Anandamide and 2-arachidonoylglycerol baseline plasma concentrations and their clinical correlate in gambling disorder.
Baenas, I, Solé-Morata, N, Granero, R, Fernández-Aranda, F, Pujadas, M, Mora-Maltas, B, Lucas, I, Gómez-Peña, M, Moragas, L, Del Pino-Gutiérrez, A, et al
European psychiatry : the journal of the Association of European Psychiatrists. 2023;(1):e97
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INTRODUCTION Different components of the endocannabinoid (eCB) system such as their most well-known endogenous ligands, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), have been implicated in brain reward pathways. While shared neurobiological substrates have been described among addiction-related disorders, information regarding the role of this system in behavioral addictions such as gambling disorder (GD) is scarce. AIMS Fasting plasma concentrations of AEA and 2-AG were analyzed in individuals with GD at baseline, compared with healthy control subjects (HC). Through structural equation modeling, we evaluated associations between endocannabinoids and GD severity, exploring the potentially mediating role of clinical and neuropsychological variables. METHODS The sample included 166 adult outpatients with GD (95.8% male, mean age 39 years old) and 41 HC. Peripheral blood samples were collected after overnight fasting to assess AEA and 2-AG concentrations (ng/ml). Clinical (i.e., general psychopathology, emotion regulation, impulsivity, personality) and neuropsychological variables were evaluated through a semi-structured clinical interview and psychometric assessments. RESULTS Plasma AEA concentrations were higher in patients with GD compared with HC (p = .002), without differences in 2-AG. AEA and 2-AG concentrations were related to GD severity, with novelty-seeking mediating relationships. CONCLUSIONS This study points to differences in fasting plasma concentrations of endocannabinoids between individuals with GD and HC. In the clinical group, the pathway defined by the association between the concentrations of endocannabinoids and novelty-seeking predicted GD severity. Although exploratory, these results could contribute to the identification of potential endophenotypic features that help optimize personalized approaches to prevent and treat GD.
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Transcriptional response to a Mediterranean diet intervention exerts a modulatory effect on neuroinflammation signaling pathway.
Almanza-Aguilera, E, Hernáez, A, Corella, D, Aguayo, DM, Ros, E, Portolés, O, Valussi, J, Estruch, R, Coltell, O, Subirana, I, et al
Nutritional neuroscience. 2022;(2):256-265
Abstract
Background: The Traditional Mediterranean Diet (TMD) is known to have beneficial effects on several chronic diseases. However, data concerning the whole transcriptome modulation of the TMD are scarce.Objective: We aimed to explore the effects of the TMD on the whole transcriptome of individuals at high cardiovascular risk.Methods: Thirty-four participants at high cardiovascular risk were randomly assigned to a TMD enriched with extra-virgin olive oil (TMD + VOO), mixed nuts (TMD + Nuts), or a control diet based on low-fat diet recommendations. A microarray analysis in circulating peripheral blood mononuclear cells of the participants was conducted before and after 3 months of the intervention. The association of changes in gene expression was modeled into canonical pathways by conducting an untargeted functional analysis with the Ingenuity Pathway Analysis® (IPA). Effects were considered significant when the absolute z-score values were ≥2.0 and the logarithm P (adjusted by the Benjamini-Hochberg procedure [BH]) values were ≥1.30.Results: According to IPA, interventions with TMD + Nuts, TMD + VOO, and control diet downregulated neuroinflammation, triggering receptor expressed on myeloid cells 1 , and cholecystokinin/gastrin-mediated signaling pathways, respectively. The gene expression among these pathways included cytokines, T-cell activation receptors, nuclear factor kappa β/inflammasome components, pro-inflammatory enzymes and cell cycle regulators.Conclusion: The current findings suggest that the TMD enriched with mixed nuts or VOO downregulate transcriptomic pathways, including those related to neuroinflammation, which could influence development of neurodegenerative diseases. Our data should be corroborated in other tissue cells, such as neurons and glial cells. The PREDIMED trial was registered at https://www.controlled-trials.com (ISRCTN35739639).
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Impulsivity is longitudinally associated with healthy and unhealthy dietary patterns in individuals with overweight or obesity and metabolic syndrome within the framework of the PREDIMED-Plus trial.
Gómez-Martínez, C, Babio, N, Júlvez, J, Nishi, SK, Fernández-Aranda, F, Martínez-González, MÁ, Cuenca-Royo, A, Fernández, R, Jiménez-Murcia, S, de la Torre, R, et al
The international journal of behavioral nutrition and physical activity. 2022;(1):101
Abstract
BACKGROUND Few studies have analyzed the associations between impulsivity and dietary patterns. Some of them have shown a cross-sectional inverse relationship between impulsivity and healthy diet scores, whereas others reported a positive association with unhealthy dietary assessments. We aimed to examine longitudinal associations of impulsivity trait with adherence to healthy and unhealthy dietary patterns in older participants at high risk of cardiovascular disease over 3 years of follow-up. METHODS A 3-year prospective cohort analysis within the PREDIMED-Plus-Cognition study conducted in 4 PREDIMED-Plus study centers was performed. The PREDIMED-Plus study aimed to test the beneficial effect of a lifestyle intervention on the primary prevention of cardiovascular disease. The participants with overweight or obesity and metabolic syndrome included in the present study (n = 462; mean age of 65.3 years; 51.5% female) completed both the UPPS-P Impulsive Behavior Scale (range: 0-236 points) and the 143-item Food Frequency Questionnaire at baseline, 1-year and 3-years of follow-up. Ten diet scores assessing healthy and unhealthy dietary patterns were evaluated. Linear mixed models were performed adjusting by several confounders to study the longitudinal associations between impulsivity trait and adherence to dietary pattern scores over 3 years of follow-up (also assessing interactions by sex, age, and intervention group). RESULTS Impulsivity were negatively associated with adherence to the Healthy Plant-Based [β = -0.92 (95%CI -1.67, -0.16)], Mediterranean [β = -0.43 (95%CI -0.79, -0.07)], Energy-Restricted Mediterranean [β = -0.76 (95%CI -1.16, -0.37)], Alternative Healthy Eating Index [β = -0.88 (95%CI -1.52, -0.23)], Portfolio [β = -0.57 (95%CI -0.91, -0.22)], and DASH [β = -0.50 (95%CI -0.79, -0.22)] diet scores over 3 years of follow-up, whereas impulsivity was positively related with adherence to the unhealthy Western diet [β = 1.59 (95%CI 0.59, 2.58)] over time. An interaction by intervention group was found, with those participants in the intervention group with high impulsivity levels having lower adherence to several healthy dietary patterns. CONCLUSIONS Heightened impulsivity was longitudinally associated with lower adherence to healthy dietary patterns and higher adherence to the Western diet over 3 years of follow-up. Furthermore, nutritional intervention programs should consider impulsivity as a relevant factor for the intervention success. TRIAL REGISTRATION Name of registry: Effect of an energy-restricted Mediterranean diet, physical activity and behavioral intervention on the primary prevention of cardiovascular disease. TRIAL REGISTRATION NUMBER ISRCTN 89,898,870. Date of registration: 05/28/2014.
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Effects of Mixing Energy Drinks With Alcohol on Driving-Related Skills.
Pérez-Mañá, C, Mateus, JA, Díaz-Pellicer, P, Díaz-Baggerman, A, Pérez, M, Pujadas, M, Fonseca, F, Papaseit, E, Pujol, J, Langohr, K, et al
The international journal of neuropsychopharmacology. 2022;(1):13-25
Abstract
BACKGROUND Energy drinks (EDs) reduce sleepiness and fatigue and improve driving performance whereas alcohol does just the opposite. Although it is a trendy combination among young people, the effects of alcohol mixed with EDs on driving performance have been poorly studied. The aim was to assess if there is an interaction between the effects of both drinks on driving-related skills as well as perceptions about driving ability. METHODS We conducted a randomized, double-blind, and placebo-controlled 4-way crossover clinical trial. Participants were 16 healthy volunteers. Interventions of 60 g of ethanol and 750 mL of Red Bull (RB) were administered in 2 separated doses. Conditions were alcohol + RB placebo, alcohol + RB, alcohol placebo + RB, and both placebos. Objective performance was assessed using a tracking test and simple reaction time, N-Back, and movement estimation tasks. Additionally, willingness to drive, other subjective effects, and ethanol and caffeine blood concentrations were also measured. RESULTS Alcohol increased the time outside the road in the tracking test and increased simple reaction time, but the addition of RB had no main or interaction effects on performance. Nonetheless, driving-related skills after alcohol + RB were better than after alcohol alone. Willingness to drive increased with the combination of drinks. RB also reduced alcohol-induced sedation whereas drunkenness did not change. These effects were seen even though alcohol + RB increased alcohol (14.8%) and caffeine plasma concentrations (17.6%). CONCLUSIONS Mixing EDs with alcohol predisposes consumers to drive under alcohol influence, perhaps in part because EDs counteract its detrimental effects on driving-related skills. Clinicaltrials.gov: NCT02771587.
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Correction: Impulsivity is longitudinally associated with healthy and unhealthy dietary patterns in individuals with overweight or obesity and metabolic syndrome within the framework of the PREDIMED-Plus trial.
Gómez-Martínez, C, Babio, N, Júlvez, J, Nishi, SK, Fernández-Aranda, F, Martínez-González, MÁ, Cuenca-Royo, A, Fernández, R, Jiménez-Murcia, S, de la Torre, R, et al
The international journal of behavioral nutrition and physical activity. 2022;(1):140