Elena H Martinez-Lapiscina

Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial

IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. DESIGN, SETTING, AND PARTICIPANTS Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. INTERVENTIONS Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. RESULTS Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (-0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (-0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and -0.17 (-0.32 to -0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (-0.25 to 0.31), and -0.33 (-0.57 to -0.09). Changes from baseline of the global cognition composite were 0.05 (-0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, -0.05 (-0.27 to 0.18) for the Mediterranean diet plus nuts, and -0.38 (-0.57 to -0.18) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls. CONCLUSIONS AND RELEVANCE In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN35739639.

Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial

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

Mediterranean diet and the incidence of cardiovascular disease: A Spanish cohort

BACKGROUND AND AIM The Mediterranean diet is considered a model for healthy eating. However, prospective evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce. The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area. METHODS AND RESULTS We followed-up 13,609 participants (60 percent women, mean age: 38 years) initially free of cardiovascular disease (CVD) during 4.9 years. Participants were part of a prospective cohort study of university graduates from all regions of Spain. Baseline diet was assessed using a validated 136-item food-frequency questionnaire. A 9-point score was used to appraise adherence to the Mediterranean diet. Incident clinical events were confirmed by a review of medical records. We observed 100 incident cases of CVD. In multivariate analyses, participants with the highest adherence to the Mediterranean diet (score>6) exhibited a lower cardiovascular risk (hazard ratio=0.41, 95% confidence interval [CI]: 0.18-0.95) compared to those with the lowest score (<3). For each 2-point increment in the score, the adjusted hazard ratios were 0.80 (95% CI: 0.62-1.02) for total CVD and 0.74 (0.55-0.99) for coronary heart disease. CONCLUSIONS There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults.

Virgin olive oil supplementation and long-term cognition: the Predimed-Navarra randomized, trial

ObjectiveXXXto assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet).DesignXXXrandomized trial after 6.5 years of nutritional intervention.SettingEight primary care centers affiliated to the University of Navarra.ParticipantsA random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1± 5.7 years at cognitive evaluation).InterventionsNutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter.MeasurementsXXXcognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention.ResultsBetter post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. 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, this group also showed lower MCI (OR=0.34 95% CI: 0.12–0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls.ConclusionA long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.

Trans-Synaptic Axonal Degeneration in the Visual Pathway in Multiple Sclerosis

To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans‐synaptic degeneration in multiple sclerosis (MS).

Nut consumption and incidence of hypertension: The SUN prospective cohort *

BACKGROUND AND AIMS The consumption of tree nuts could reduce the risk of hypertension, but scarce research has been done to evaluate this potential association. We assessed the association between nut consumption and the incidence of hypertension among 9919 Spanish university graduates followed-up biennially for a median of 4.3 years. METHODS AND RESULTS Food habits were assessed with a validated 136-item food-frequency questionnaire. Nut consumption was classified into four categories: rarely/never, 1-3/month, 1/week, and 2+/week. A participant was classified as an incident case of hypertension when, being free of hypertension at baseline, he/she subsequently reported a physician-made diagnosis of hypertension in at least one of the follow-up questionnaires. The incidence of hypertension was 12.4 per 1000 person-years. We found no association between nut consumption and incidence of hypertension after adjusting for sex, age and other dietary and non-dietary potential confounders (hazard ratio [HR] for those in the highest vs. lowest nut consumption category=0.77 [IC 95%: 0.46-1.30] p=0.795). Results were not modified when we stratified them analyses according to sex or to body mass index. CONCLUSION Our data do not provide evidence for an inverse association between nut consumption and incident hypertension in our cohort. Further results from cohorts and trials with a higher baseline risk of hypertension should be obtained to test this relationship.

Colour vision impairment is associated with disease severity in multiple sclerosis

Background: Colour vision assessment correlates with damage of the visual pathway and might be informative of overall brain damage in multiple sclerosis (MS). Objective: The objective of this paper is to investigate the association between impaired colour vision and disease severity. Methods: We performed neurological and ophthalmic examinations, as well as magnetic resonance imaging (MRI) and optical coherence tomography (OCT) analyses, on 108 MS patients, both at baseline and after a follow-up of one year. Colour vision was evaluated by Hardy, Rand and Rittler plates. Dyschromatopsia was defined if colour vision was impaired in either eye, except for participants with optic neuritis (ON), for whom only the unaffected eye was considered. We used general linear models adjusted for sex, age, disease duration and MS treatment for comparing presence of dyschromatopsia and disease severity. Results: Impaired colour vision in non-ON eyes was detected in 21 out of 108 patients at baseline. At baseline, patients with dyschromatopsia had lower Multiple Sclerosis Functional Composite (MSFC) scores and Brief Repeatable Battery-Neuropsychology executive function scores than those participants with normal colour vision. In addition, these patients had thinner retinal nerve fiber layer (RNFL), and smaller macular volume, normalized brain volume and normalized gray matter volume (NGMV) at baseline. Moreover, participants with incident dyschromatopsia after one-year follow-up had a greater disability measured by the Expanded Disability Status Scale and MSFC-20 and a greater decrease in NGMV than participants with normal colour vision. Conclusions: Colour vision impairment is associated with greater MS severity.

The multiple sclerosis visual pathway cohort: understanding neurodegeneration in MS

BackgroundMultiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations.FindingsThe MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway.DiscussionThe analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.

Dynamic molecular monitoring of retina inflammation by in vivo Raman spectroscopy coupled with multivariate analysis.

Retinal tissue is damaged during inflammation in Multiple Sclerosis. We assessed molecular changes in inflamed murine retinal cultures by Raman spectroscopy. Partial Least Squares-Discriminant analysis (PLS-DA) was able to classify retina cultures as inflamed with high accuracy. Using Multivariate Curve Resolution (MCR) analysis, we deconvolved 6 molecular components suffering dynamic changes along inflammatory process. Those include the increase of immune mediators (Lipoxygenase, iNOS and TNFα), changes in molecules involved in energy production (Cytochrome C, phenylalanine and NADH/NAD+) and decrease of Phosphatidylcholine. Raman spectroscopy combined with multivariate analysis allows monitoring the evolution of retina inflammation.

Retrograde retinal damage after acute optic tract lesion in MS

The anterior visual pathway is frequently affected in multiple sclerosis (MS), but how axonal damage extends from the site of the lesion to neuronal bodies in the retina or lateral geniculate nucleus is poorly understood. Thanks to optical coherence tomography (OCT), it is possible to map and quantify the retrograde diffusion of axonal damage to the retina.1 Lesions in the anterior optic pathway promote significant atrophy of retinal nerve fibre layer (RNFL), which develops in the first 3 months after damage and remains stable after 3 months. Moreover, it has been recently demonstrated that retinal damage in MS is complex and may distinctly affect retinal layers, combining either layer thinning (suggesting the presence of synapse loss and neuronal loss) or layer thickening (suggesting the presence of oedema and inflammation). In fact, the analysis of the ganglion cell/inner plexiform layer (ganglion cell layer (GCL)+inner plexiform layer complex (IPL)) and inner nuclear layer (INL) better correlates with functional disability and prognosis than with RNFL atrophy.2 Acute focal lesions of the optic tracts are infrequently recognised in MS, and they constitute an excellent opportunity to study retrograde axonal degeneration. Previous studies with OCT have shown the homonymous hemimacular atrophy ipsilateral to the optic tract lesion as a specific pattern of retinal atrophy in optic tract lesions,3 with a preferential impact on the GCL.4 A patient with relapsing–remitting MS presented with non-painful, new onset, acute bilateral visual deficit. Automated visual field tests demonstrated non-congruent bilateral homonymous right hemianopsia (figure 1A). Visual acuity (Snellen chart) and colour …