RESUMO
BACKGROUND: Oxylipins are products derived from polyunsaturated fatty acids (PUFAs) that play a role in cardiovascular disease and aging. Fish oil-derived n-3 PUFAs promote the formation of anti-inflammatory and vasodilatory oxylipins; however, there are little data on oxylipins derived from α-linolenic acid (C18:3n-3), the primary plant-derived n-3 PUFA. Walnuts are a source of C18:3n-3. OBJECTIVES: To investigate the effect on serum oxylipins of a diet enriched with walnuts at 15% energy (30-60 g/d; 2.6-5.2 g C18:3n-3/d) for 2 y compared to a control diet (abstention from walnuts) in healthy older males and females (63-79 y). METHODS: The red blood cell proportion of α-linolenic acid was determined by gas chromatography as a measure of compliance. Ultra-performance liquid chromatography-tandem mass spectrometry was used to measure serum concentrations of 53 oxylipins in participants randomly assigned to receive the walnut diet (n = 64) or the control diet (n = 51). Two-year concentration changes (final minus baseline) were log-transformed (base log-10) and standardized (mean-centered and divided by the standard deviation of each variable). Volcano plots were then generated (fold change ≥1.5; false discovery rate ≤0.1). For each oxylipin delta surviving multiple testing, we further assessed between-intervention group differences by analysis of covariance adjusting for age, sex, BMI, and the baseline concentration of the oxylipin. RESULTS: The 2-y change in red blood cell C18:3n-3 in the walnut group was significantly higher than that in the control group (P < 0.001). Compared to the control diet, the walnut diet resulted in statistically significantly greater increases in 3 C18:3n-3-derived oxylipins (9-HOTrE, 13-HOTrE, and 12,13-EpODE) and in the C20:5n-3 derived 14,15-diHETE, and greater reductions of the C20:4n-6-derived 5-HETE, 19-HETE, and 5,6-diHETrE. CONCLUSIONS: Long-term walnut consumption changes the serum oxylipin profile in healthy older persons. Our results add novel mechanistic evidence on the cardioprotective effects of walnuts. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01634841.
Assuntos
Ácidos Graxos Ômega-3 , Juglans , Masculino , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Oxilipinas , Ácido alfa-Linolênico , Dieta , Ácidos Graxos Insaturados , Ácidos Graxos Ômega-3/farmacologiaRESUMO
The combination of transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) can provide original data to investigate age-related brain changes. We examined neural activity modulations induced by two multifocal tDCS procedures based on two distinct montages fitting two N-back task-based fMRI patterns ("compensatory" and "maintenance") related to high working memory (WM) in a previous publication (Fernández-Cabello et al. Neurobiol Aging (2016);48:23-33). We included 24 participants classified as stable or decliners according to their 4-year WM trajectories following a retrospective longitudinal approach. Then, we studied longitudinal fMRI differences between groups (stable and decliners) and across multifocal tDCS montages ("compensatory" and "maintenance") applied using a single-blind sham-controlled cross-over design. Decliners evidenced over-activation of non-related WM areas after 4 years of follow-up. Focusing on tDCS effects, among the decliner group, the "compensatory"-tDCS montage reduced the activity over the posterior regions where these subjects showed longitudinal hyperactivation. These results reinforce the notion that tDCS effects are characterized by an activity reduction and might be more noticeable in compromised systems. Importantly, the data provide novel evidence that cognitive trajectories predict tDCS effects in older adults.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/terapia , Imageamento por Ressonância Magnética/tendências , Estimulação Transcraniana por Corrente Contínua/tendências , Idoso , Disfunção Cognitiva/fisiopatologia , Estudos Cross-Over , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Método Simples-Cego , Estimulação Transcraniana por Corrente Contínua/métodosRESUMO
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 expression and play a pivotal role in health and disease. Exosomes are extracellular vesicles released from cells and mediate intercellular communication. Whether nut consumption modulates circulating miRNAs (c-miRNAs) transported in exosomes is poorly described. METHODS: Cognitively healthy elderly subjects were randomized to either control (n = 110, abstaining from walnuts) or daily supplementation with walnuts (15% of their total energy, ≈30-60 g/day, n = 101) for 1-year. C-miRNAs were screened in exosomes isolated from 10 samples, before and after supplementation, and identified c-miRNA candidates were validated in the whole cohort. In addition, nanoparticle tracking analysis and lipidomics were assessed in pooled exosomes from the whole cohort. RESULTS: Exosomal hsa-miR-32-5p and hsa-miR-29b-3p were consistently induced by walnut consumption. No major changes in exosomal lipids, nanoparticle concentration or size were found. CONCLUSION: Our results provide novel evidence that certain c-miRNAs transported in exosomes are modulated by walnut consumption. The extent to which this finding contributes to the benefits of walnuts deserves further research.
Assuntos
Exossomos , Juglans , MicroRNAs , Suplementos Nutricionais , NozesRESUMO
Neuroimaging investigations have revealed interindividual variations in anatomy, metabolism, activity, and connectivity of specific cortical association areas through which years of education (YoE), as a common proxy of cognitive reserve, may operate in the face of age- or pathology-associated brain changes. However, the associated molecular properties of YoE-related brain regions and the biological pathways involved remain poorly understood. In the present study we first identified brain areas that showed an association between cortical thickness and YoE among 122 cognitively healthy older human individuals (87 female). We subsequently characterized molecular properties of these regions by studying brain-wide microarray measurements of regional gene expression. In accordance with previous studies, we observed that YoE were associated with higher cortical thickness in medial prefrontal, anterior cingulate, and orbitofrontal areas. Compared with the rest of the cortex, these regions exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in ionotropic and metabotropic neurotransmission as well as activation of immune response. Our genome-wide expression profile analysis of YoE-related brain regions points to distinct molecular pathways that may underlie a higher capacity for plastic changes in response to lifetime intellectual enrichment and potentially also a higher resilience to age-related pathologic brain changes.SIGNIFICANCE STATEMENT We combined a neuroimaging-based analysis with a transcriptome-wide gene expression approach to investigate the molecular-functional properties of cortical regions associated with educational attainment, as a commonly used proxy for cognitive reserve, in older individuals. The strongest association with education was observed in specific areas of the medial prefrontal cortex, and these areas exhibited a distinct gene expression profile characterized by relative upregulation of gene sets implicated in neurotransmission and immune responses. These findings complement previous neuroimaging studies in the field and point to novel biological pathways that may mediate the beneficial effects of high educational attainment on adaptability to cope with, or prevent, age-related brain changes. The identified genes and pathways now warrant further exploration in mechanistic studies.
Assuntos
Reserva Cognitiva/fisiologia , Escolaridade , Perfilação da Expressão Gênica , Giro do Cíngulo/metabolismo , Neuroimagem , Córtex Pré-Frontal/metabolismo , Idoso , Feminino , Estudo de Associação Genômica Ampla , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/imunologia , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/imunologiaAssuntos
Juglans/química , Lipoproteínas/efeitos dos fármacos , Idoso , Feminino , Humanos , MasculinoRESUMO
In the past few years, there has been an increasing awareness of the regional vulnerability of the hippocampus to age-related processes. However, to date, no studies have assessed the effects of age on different structural magnetic resonance parameters in the specific hippocampal subfields. In this study, we measured volume, mean diffusivity (MD) and fractional anisotropy (FA) in the presubiculum, subiculum, fimbria, cornu ammonis (CA) 1,2-3,4-DG and the whole hippocampus in fifty cognitively intact elder adults between 50 and 75 years of age (20 men, 30 women). Segmentation of hippocampal subfields was performed using FreeSurfer. Individual MD and FA images were coregistered to T1-weighted volumes using FLIRT of FSL. Linear regression analyses were performed to assess the effects of age on the anatomical measures of each subfield. In addition, multiple regression analyses were also carried out to assess which of the anatomical measures that showed a correlation with age in the previous analyses, were the best age predictors in the hippocampus. In agreement with previous studies, our results showed a significant association between age and volume (P < 0.001) as well as MD (P < 0.001) in the whole hippocampus. Regarding the specific hippocampal subfields, we found that age had a significant negative effect on volume in CA2-3 (P < 0.001) and CA4-DG (P < 0.001). Importantly, we found a positive effect of age on MD in CA2-3 (P < 0.001) and fimbria (P < 0.001) as well as a negative age effect on FA in the subiculum (P < 0.001). Multiple regression analyses revealed that the best overall predictors of age in the hippocampus were MD in the fimbria and volume of CA2-3, which explained 73.8% of the age variance. These results indicate that age has an effect both on volume and diffusion tensor imaging measures in different subfields, suggesting they provide complementary information on age-related processes in the hippocampus.
Assuntos
Envelhecimento/patologia , Hipocampo/patologia , Idoso , Anisotropia , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
BACKGROUND: Nutritional strategies to maintain bone health in aging individuals are of great interest. Given the beneficial nutrient composition of walnuts, rich in alpha-linolenic (the vegetable n-3 fatty acid) and polyphenols, their regular consumption might be a dietary option to reduce age-related bone loss. We determined whether daily walnut consumption improves bone mineral density (BMD) and circulating biomarkers of bone turnover. METHODS: The Walnuts and Healthy Aging study (WAHA) is a two-center, parallel, randomized controlled trial evaluating the effect of a diet enriched with walnuts at ≈15% energy compared with a control diet for 2 years on age-related health outcomes in healthy men and women aged 63-79 years. Changes in BMD were a prespecified secondary outcome only at the Barcelona node of the trial, where 352 participants were randomized. Retention rate was 92.6%. Primary endpoints were 2-year changes in BMD at the spine and the nondominant femoral neck, determined by dual-energy X-ray absorptiometry (DXA). Secondary endpoints were 2-year changes in bone turnover biomarkers (adrenocorticotropic hormone, Dickkopf WNT signaling pathway inhibitor-1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, parathyroid hormone, and fibroblast growth factor-23), which were quantified in 211 randomly selected participants. RESULTS: The walnut diet versus the control diet had no effect on 2-year changes in BMD at the spine (0.15% vs. 0.35%, p = 0.632) and femoral neck (-0.90% vs. -0.70%, p = 0.653), or on bone turnover biomarkers. Results were similar in participants treated or not with bone resorption inhibitors or those with or without osteoporosis/osteopenia at inclusion. CONCLUSIONS: Compared with the usual diet, a diet enriched with walnuts at 15% of energy for 2 years failed to improve BMD or circulating markers of bone metabolism in healthy older people.
Assuntos
Biomarcadores , Densidade Óssea , Juglans , Humanos , Masculino , Feminino , Idoso , Densidade Óssea/efeitos dos fármacos , Pessoa de Meia-Idade , Biomarcadores/sangue , Envelhecimento Saudável , Absorciometria de Fóton , Nozes , Remodelação Óssea/fisiologia , Remodelação Óssea/efeitos dos fármacos , Osteoporose/prevenção & controle , Dieta/métodosRESUMO
OBJECTIVE: Previous observational studies reported beneficial effects of the Mediterranean diet (MedDiet) on cognitive function, but results were inconsistent. We assessed the effect on cognition of a nutritional intervention using MedDiets in comparison with a low-fat control diet. METHODS: We assessed 522 participants at high vascular risk (44.6% men, age 74.6 ± 5.7 years at cognitive evaluation) enrolled in a multicentre, randomised, primary prevention trial (PREDIMED), after a nutritional intervention comparing two MedDiets (supplemented with either extra-virgin olive oil (EVOO) or mixed nuts) versus a low-fat control diet. Global cognitive performance was examined by Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) after 6.5 years of nutritional intervention. Researchers who assessed the outcome were blinded to group assignment. We used general linear models to control for potential confounding. RESULTS: After adjustment for sex, age, education, Apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, participants allocated to the MedDiet+EVOO showed higher mean MMSE and CDT scores with significant differences versus control (adjusted differences: +0.62 95% CI +0.18 to +1.05, p=0.005 for MMSE, and +0.51 95% CI +0.20 to +0.82, p=0.001 for CDT). The adjusted means of MMSE and CDT scores were also higher for participants allocated to the MedDiet+Nuts versus control (adjusted differences: +0.57 (95% CI +0.11 to +1.03), p=0.015 for MMSE and +0.33 (95% CI +0.003 to +0.67), p=0.048 for CDT). These results did not differ after controlling for incident depression. CONCLUSIONS: An intervention with MedDiets enhanced with either EVOO or nuts appears to improve cognition compared with a low-fat diet. ISRCTN:35739639.
Assuntos
Cognição , Disfunção Cognitiva/epidemiologia , Dieta com Restrição de Gorduras/psicologia , Dieta Mediterrânea/psicologia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/prevenção & controle , Disfunção Cognitiva/dietoterapia , Demência/dietoterapia , Demência/epidemiologia , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Nozes , Azeite de Oliva , Óleos de Plantas/uso terapêutico , Prevenção Primária/métodos , Espanha/epidemiologiaRESUMO
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 1 year from 330 free-living participants (63-79 year, 68% women), allocated into a control group (CG, abstinence from walnuts, n = 164) and a walnut group (WG, 15% of daily energy as walnuts, ~30-60 g/d, n = 166). Participants in the WG showed a 1 year decrease in LDL-C (-9.07, (95% confidence interval: -12.87; -5.73) mg/dL; p = 0.010 versus changes in the CG). We conducted a miRNA array in eight randomly selected participants in the WG who decreased in LDL-C. This yielded 53 c-miRNAs with statistically significant changes, 27 of which survived the correction for multiple testing. When validating them in the full population, statistical significance lasted for hsa-miR-551a, being upregulated in the WG. In mediation analysis, the change in hsa-miR-551a was unrelated to LDL-C decrease. Long-term supplementation with walnuts decreased LDL-C independently of the changes in c-miRNA. The hsa-miR-551a upregulation, which has been linked to a reduced cell migration and invasion in several carcinomas, suggests a novel mechanism of walnuts in cancer risk.
Assuntos
LDL-Colesterol , MicroRNA Circulante , Juglans , Idoso , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-IdadeRESUMO
Despite the well-described deleterious effects of aging on cognition, some individuals are able to show stability. Here, we aimed to describe the functional and structural brain characteristics of older individuals, particularly focusing on those with stable working memory (WM) performance, as measured with a verbal N-back task across a 2-year follow-up interval. Forty-seven subjects were categorized as stables or decliners based on their WM change. Stables were further subdivided into high performers (SHP) and low performers (SLP), based on their baseline scores. At both time points, magnetic resonance imaging (MRI) data were acquired, including task-based functional MRI (fMRI) and structural T1-MRI. Although there was no significant interaction between overall stables and decliners as regards fMRI patterns, decliners exhibited over-activation in the right superior parietal lobule at follow-up as compared to baseline, while SHP showed reduced the activity in this region. Further, at follow-up, decliners exhibited more activity than SHP but in left temporo-parietal cortex and posterior cingulate (i.e., non-task-related areas). Also, at the cross-sectional level, SLP showed lower activity than SHP at both time points and less activity than decliners at follow-up. Concerning brain structure, a generalized significant cortical thinning over time was identified for the whole sample. Notwithstanding, the decliners evidenced a greater rate of atrophy comprising the posterior middle and inferior temporal gyrus as compared to the stable group. Overall, fMRI data suggest unsuccessful compensation in the case of decliners, shown as increases in functional recruitment during the task in the context of a loss in WM performance and brain atrophy. On the other hand, among older individuals with WM cognitive stability, differences in baseline performance might determine dissimilar fMRI trajectories. In this vein, the findings in the SHP subgroup support the brain maintenance hypothesis, suggesting that stable and high WM performance in aging is sustained by functional efficiency and maintained brain structure rather than compensatory changes.
Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Memória de Curto Prazo/fisiologia , Idoso , Mapeamento Encefálico , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tamanho do ÓrgãoRESUMO
BACKGROUND: Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. OBJECTIVES: The Walnuts And Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut intervention in cognitively healthy elders. METHODS: We randomly allocated 708 free-living elders (63-79 y, 68% women) to a diet enriched with walnuts at â¼15% energy (30-60 g/d) or a control diet (abstention from walnuts). We administered a comprehensive neurocognitive test battery at baseline and 2 y. Change in the global cognition composite was the primary outcome. We performed repeated structural and functional brain MRI in 108 Barcelona participants. RESULTS: A total of 636 participants completed the intervention. Besides differences in nutrient intake, participants from Barcelona smoked more, were less educated, and had lower baseline neuropsychological test scores than those from Loma Linda. Walnuts were well tolerated and compliance was good. Modified intention-to-treat analyses (n = 657) uncovered no between-group differences in the global cognitive composite, with mean changes of -0.072 (95% CI: -0.100, -0.043) in the walnut diet group and -0.086 (95% CI: -0.115, -0.057) in the control diet group (P = 0.491). Post hoc analyses revealed significant differences in the Barcelona cohort, with unadjusted changes of -0.037 (95% CI: -0.077, 0.002) in the walnut group and -0.097 (95% CI: -0.137, -0.057) in controls (P = 0.040). Results of brain fMRI in a subset of Barcelona participants indicated greater functional network recruitment in a working memory task in controls. CONCLUSIONS: Walnut supplementation for 2 y had no effect on cognition in healthy elders. However, brain fMRI and post hoc analyses by site suggest that walnuts might delay cognitive decline in subgroups at higher risk. These encouraging but inconclusive results warrant further investigation, particularly targeting disadvantaged populations, in whom greatest benefit could be expected.This trial was registered at clinicaltrials.gov as NCT01634841.
Assuntos
Disfunção Cognitiva/dietoterapia , Juglans/metabolismo , Nozes/metabolismo , Idoso , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/psicologia , Feminino , Envelhecimento Saudável , Humanos , Imageamento por Ressonância Magnética , Masculino , Memória , Pessoa de Meia-Idade , EspanhaRESUMO
Nut consumption lowers blood cholesterol and is associated with reduced cardiovascular disease, but effects on blood pressure (BP) are inconsistent. We assessed the 2-year effects of a walnut diet versus a control diet on office BP and 24-hours ambulatory BP in free-living elders participating in the Walnuts and Healthy Aging study, a randomized trial testing the effects of walnuts at ≈15% energy on age-related disorders. In a prespecified analysis, we enrolled 305 participants, of whom 236 (75%) completed the study (65% women; age, 69 years; 60% with mild hypertension). Walnuts were well tolerated, and compliance was >98%. Mean baseline office BP was 128/79 mm Hg. Adjusted changes from baseline in mean office systolic BP were -4.61 mm Hg (95% CI, -7.43 to -1.79 mm Hg) in the walnut group and -0.59 mm Hg (-3.38 to 2.21 mm Hg) in controls ( P=0.051). Respective changes in mean systolic 24-hour ambulatory BP were -3.86 mm Hg (CI, -5.45 to -2.26 mm Hg) and -2.00 mm Hg (CI, -3.58 to -0.42 mm Hg; P=0.111). No changes in diastolic BP were observed. In participants in the upper tertile of baseline 24-hour ambulatory systolic BP (>125 mm Hg), mean 2-year systolic 24-hour BP was -8.5 mm Hg (CI, -12 to -5.0 mm Hg) in the walnut group and -2.5 mm Hg (CI, -6.3 to 1.3 mm Hg) in controls ( P=0.034). During the trial, participants in the walnut group required less uptitration of antihypertensive medication and had better overall BP regulation than controls. Walnut consumption reduces systolic BP in elderly subjects, particularly in those with mild hypertension. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01634841 .
Assuntos
Envelhecimento/fisiologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Dieta/métodos , Hipertensão/prevenção & controle , Juglans , Idoso , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: Shortening of leukocyte telomere length (LTL) is a biomarker of aging. Epidemiologic studies of LTL in relation to dietary fatty acids have reported conflicting results. The red blood cell (RBC) fatty acid status is a valid objective biomarker of long-term dietary intake of C18:2n-6, C18:3n-3 and long-chain n-3 polyunsaturated fatty acids (C20:5n-3 and C22:6n-3). In healthy older individuals, we investigated whether LTL relates to the RBC proportions of the main dietary polyunsaturated fatty acids (PUFA), and to the RBC proportion of arachidonic acid (C20:4n-6), a fatty acid that can generate pro-inflammatory lipid mediators once released from cell membranes. DESIGN: Cross-sectional study in 344 subjects (mean age 68.8 y, 68.6% women) who participated in a randomized controlled trial testing whether a diet enriched in walnuts can delay the onset of age-related diseases (https://clinicaltrials.gov/ct2/show/NCT01634841). At baseline, we assessed LTL by high-throughput quantitative fluorescence and determined fatty acids in RBCs by gas chromatography. RESULTS: In multivariate models adjusted for age and gender, the RBC proportions of dietary PUFA were unrelated to LTL. In contrast, the RBC proportion of arachidonic acid inversely related to LTL (regression coefficient [95% confidence interval], -0.10 (-0.19 to -0.01), P = 0.023). CONCLUSION: An increasing proportion of C20:4n-6 in RBCs is associated with shorter telomeres. Further research is needed to investigate the role of this fatty acid and its derived lipid mediators in the aging process.
Assuntos
Envelhecimento/fisiologia , Ácido Araquidônico/sangue , Eritrócitos/química , Leucócitos/química , Telômero/química , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologiaRESUMO
Randomized controlled trials on diet and shortening of leukocyte telomere length (LTL) mostly focus on marine-derived n-3 polyunsaturated fatty acids (PUFA). Walnuts are a sustainable source of n-3 PUFA. We investigated whether inclusion of walnuts (15% of energy) in the diet for 2 years would maintain LTL in cognitively healthy elders (63â»79 years old) compared to a control group (habitual diet, abstaining from walnuts). This opportunistic sub-study was conducted within the Walnuts and Healthy Aging study, a dual-centre (Barcelona, Spain and Loma Linda University, California) parallel trial. A sub-set of the Barcelona site participants were randomly assigned to the walnut (n = 80) or control group (n = 69). We assessed LTL at baseline and at 2 years and we conducted repeated-measures ANCOVA with 2 factors: time (baseline, 2 years) and group (control, walnut) and their interaction. Adjusted means (95% confidence interval) of LTL (in kb) in controls were 7.360 (7.084,7.636) at baseline and 7.061 (6.835,7.288) after 2 years; corresponding values in the walnut group were 7.064 (6.807,7.320) and 7.074 (6.864,7.284). The time × intervention interaction was nearly significant (p = 0.079), suggestive of a trend of walnut consumption in preserving LTL. This exploratory research finding should be confirmed in trials with adequate statistical power.
Assuntos
Dieta , Juglans , Leucócitos/química , Telômero/genética , Idoso , Envelhecimento/fisiologia , Biomarcadores/sangue , California , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espanha , Ácido alfa-Linolênico/sangueRESUMO
High education, as a proxy of cognitive reserve (CR), has been associated with cognitive advantage amongst old adults and may operate through neuroprotective and/or compensation mechanisms. In neuromaging studies, indirect evidences of neuroprotection can be inferred from positive relationships between CR and brain integrity measures. In contrast, compensation allows high CR elders to sustain greater brain damage. We included 100 cognitively normal old-adults and investigated the associations and interactions between education, speed of processing (SP), memory and two brain integrity measures: cortical thickness (CTh) of gray matter (GM) and fractional anisotropy (FA) in the white matter (WM). High education was associated with better cognitive performance, enlarged CTh in frontal lobe areas and reduced measures of FA in several areas. Better SP performance in higher educated subjects was related to more preserved GM and WM, while memory status amongst high educated elders was better explained by a putative compensatory mechanism and independently from cerebrovascular risk indicators. Moreover, we analyzed the direct effect of age on measures of brain integrity and found a stronger negative effect on WM than in CTh, which was accentuated amongst the high CR sample. Our study suggests that the cognitive advantage associated to high education among healthy aging is related to the coexistence of both neuroprotective and compensatory mechanisms. In particular, high educated elders seem to have greater capacity to counteract a more abrupt age impact on WM integrity.
Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Córtex Cerebral/fisiologia , Cognição/fisiologia , Escolaridade , Substância Cinzenta/anatomia & histologia , Substância Branca/anatomia & histologia , Idoso , Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Feminino , Substância Cinzenta/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valores de Referência , Substância Branca/fisiologiaRESUMO
Cognitive reserve (CR) models posit that lifestyle factors such as education modulate the relationship between brain damage and cognition. However, the functional correlates of CR in healthy aging are still under investigation. White matter hyperintensities (WMHs) are a common age-associated finding that impacts cognition. In this study, we used functional magnetic resonance imaging to characterize the patterns of brain activation during a working memory task in older participants with high and low levels of education (as a proxy of CR) and high and low WMH volumes. Ninety older volunteers (aged 63-76 years) and 16 young adults (aged 21-27) completed the study. We found that older adults with higher education had better working memory performance than their less educated peers. Among the highly educated participants, those with WMH over-recruited areas engaged by young volunteers and showed activation in additional cortical and subcortical structures. However, those with low WMH differed little with respect to their younger counterparts. Our findings demonstrate that the functional mechanisms subtending the effects of education, as a proxy of CR, are modulated according to the WMH burden.
Assuntos
Envelhecimento/patologia , Envelhecimento/psicologia , Cognição/fisiologia , Reserva Cognitiva/fisiologia , Imageamento por Ressonância Magnética , Memória/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Idoso , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
IMPORTANCE: Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain ω-3 polyunsaturated fatty acids (LCω3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LCω3PUFA protection against DR, but clinical data are lacking. OBJECTIVE: To determine whether LCω3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years. DESIGN, SETTING, AND PARTICIPANTS: In late 2015, we conceived a prospective study within the randomized clinical trial Prevención con Dieta Mediterránea (PREDIMED), testing Mediterranean diets supplemented with extra virgin olive oil or nuts vs a control diet for primary cardiovascular prevention. The trial was conducted in primary health care centers in Spain. From 2003 to 2009, 3614 individuals aged 55 to 80 years with a previous diagnosis of type 2 diabetes were recruited. Full data were available for 3482 participants (48% men; mean age 67 years). EXPOSURES: Meeting the dietary LCω3PUFA recommendation of at least 500 mg/d for primary cardiovascular prevention, as assessed by a validated food-frequency questionnaire. MAIN OUTCOMES AND MEASURES: The main outcome was incident DR requiring laser photocoagulation, vitrectomy, and/or antiangiogenic therapy confirmed by an external adjudication committee. RESULTS: Of the 3482 participants, 48% were men and the mean age was 67 years. A total of 2611 participants (75%) met target LCω3PUFA recommendation. During a median follow-up of 6 years, we documented 69 new events. After adjusting for age, sex, intervention group, and lifestyle and clinical variables, participants meeting the LCω3PUFA recommendation at baseline (≥500 mg/d) compared with those not fulfilling this recommendation (<500 mg/d) showed a 48% relatively reduced risk of incident sight-threatening DR, with a hazard ratio of 0.52 (95% CI, 0.31-0.88; P = .001). This association was slightly stronger for yearly updated LCω3PUFA intake (relative risk, 0.48; 95% CI, 0.28-0.82; P = .007). CONCLUSIONS AND RELEVANCE: In middle-aged and older individuals with type 2 diabetes, intake of at least 500 mg/d of dietary LCω3PUFA, easily achievable with 2 weekly servings of oily fish, is associated with a decreased risk of sight-threatening DR. Our results concur with findings from experimental models and the current model of DR pathogenesis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: http://www.controlled-trials.com/ISRCTN35739639.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Medição de Risco/métodos , Alimentos Marinhos , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/dietoterapia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Introduction: An unwanted consequence of population aging is the growing number of elderly at risk of neurodegenerative disorders, including dementia and macular degeneration. As nutritional and behavioral changes can delay disease progression, we designed the Walnuts and Healthy Aging (WAHA) study, a two-center, randomized, 2-year clinical trial conducted in free-living, cognitively healthy elderly men and women. Our interest in exploring the role of walnuts in maintaining cognitive and retinal health is based on extensive evidence supporting their cardio-protective and vascular health effects, which are linked to bioactive components, such as n-3 fatty acids and polyphenols. Methods: The primary aim of WAHA is to examine the effects of ingesting walnuts daily for 2 years on cognitive function and retinal health, assessed with a battery of neuropsychological tests and optical coherence tomography, respectively. All participants followed their habitual diet, adding walnuts at 15% of energy (≈30-60 g/day) (walnut group) or abstaining from walnuts (control group). Secondary outcomes include changes in adiposity, blood pressure, and serum and urinary biomarkers in all participants and brain magnetic resonance imaging in a subset. Results: From May 2012 to May 2014, 708 participants (mean age 69 years, 68% women) were randomized. The study ended in May 2016 with a 90% retention rate. Discussion: The results of WAHA might provide high-level evidence of the benefit of regular walnut consumption in delaying the onset of age-related cognitive impairment and retinal pathology. The findings should translate into public health policy and sound recommendations to the general population (ClinicalTrials.gov identifier NCT01634841).