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Background: The effect of marine omega-3 PUFAs on risk of stroke remains unclear., Methods: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome., Results: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P <0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P <0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P =0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P =0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD., Conclusions: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke., Competing Interests: Disclosures Dr O’Keefe reports major ownership interest in Cardiotabs. Dr Harris reports minor ownership interest in Omegaquant Analytics, LLC. Dr Sala-Vila reports travel and grant support from California Walnut Commission. Dr Mora reports compensation for consultant services from Quest Diagnostics. Dr Murphy reports compensation from Pharmavite for consultant services. Dr Bork reports grants from Karen Elise Jensens Fond. Dr Ärnlöv reports compensation from Astellas Pharma for other services; compensation from Boehringer Ingelheim for consultant services; compensation from AstraZeneca for other services; and compensation from Novartis for other services. Dr Geleijnse reports grants from National Institutes of Health to other; grants from Upfield Europe BV to other; and grants from The Dutch Heart Foundation to other. Dr Manson reports grants from National Institutes of Health and compensation from National Institutes of Health for other services. Dr Mora reports compensation from Pfizer for consultant services; employment by Brigham and Women’s Hospital; grants from National Institute of Diabetes and Digestive and Kidney Diseases; and grants from National Heart, Lung, and Blood Institute. Dr Melo van Lent reports grants from National Institutes of Health and grants from Alzheimer’s Association. Dr Mozaffarian reports grants from Rockefeller Foundation; compensation from Beren Therapeutics for other services; stock holdings in HumanCo; compensation from January Inc. for other services; compensation from Filtricine for other services; compensation from Perfect Day for other services; compensation from Tiny Organics for other services; grants from Bill and Melinda Gates Foundation; compensation from Calibrate for other services; grants from Vail Innovative Global Research; grants from Kaiser Permanente Fund at East Bay Community Foundation; compensation from DayTwo for other services; compensation from Instacart health for other services; compensation from Season Health for other services; grants from National Institutes of Health; compensation from Barilla for consultant services; stock holdings in Calibrate; compensation from Kaiser Permanente Fund for other services; compensation from HumanCo for other services

Background and Purpose: Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults., Methods: In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania. NAFLD was assessed through abdominal imaging. Transient hepatic elastography (FibroScan) was used to assess liver fibrosis in FHS and RS. Linear regression models were used to explore the relation of NAFLD and liver fibrosis with brain volumes, including total brain, gray matter, hippocampus, and white matter hyperintensities, adjusting for potential confounders. Results were combined using fixed effects meta-analysis., Results: In total, 5660 and 3022 individuals were included for NAFLD and liver fibrosis analyses, respectively. NAFLD was associated with smaller volumes of total brain (β = -3.5, 95% confidence interval [CI] = -5.4 to -1.7), total gray matter (β = -1.9, 95% CI = -3.4 to -0.3), and total cortical gray matter (β = -1.9, 95% CI = -3.7 to -0.01). In addition, liver fibrosis (defined as liver stiffness measure ≥8.2 kPa) was related to smaller total brain volumes (β = -7.3, 95% CI = -11.1 to -3.5). Heterogeneity between studies was low., Conclusions: NAFLD and liver fibrosis may be directly related to brain aging. Larger and prospective studies are warranted to validate these findings and identify liver-related preventive strategies for neurodegeneration., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Importance: Dementia threatens the well-being of older adults, making efforts toward prevention of great importance., Objective: To evaluate the association of the Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay (MIND) diet with the risk of dementia in 3 prospective studies and a meta-analysis., Design, Setting, and Participants: Cohort analyses included the Whitehall II study (WII), the Health and Retirement Study (HRS), and the Framingham Heart Study Offspring cohort (FOS), and the meta-analysis included 11 cohort studies. Participants were middle-aged and older women and men from WII in 2002 to 2004, HRS in 2013, and FOS in 1998 to 2001 without dementia at the study baseline. Data were analyzed from May 25 to September 1, 2022., Exposures: MIND diet score was measured using food frequency questionnaires, and scores ranged from 0 to 15, with a higher score indicating higher adherence to the MIND diet., Main Outcome and Measures: Incident all-cause dementia, with cohort-specific definitions., Results: Included in this study were 8358 participants (mean [SD] age, 62.2 [6.0] years; 5777 male [69.1%]) from WII, 6758 participants (mean [SD] age, 66.5 [10.4] years; 3965 female [58.7%]) from HRS, and 3020 participants (mean [SD] age, 64.2 [9.1] years; 1648 female [54.6%]) from FOS. The mean (SD) baseline MIND diet score was 8.3 (1.4) in WII, 7.1 (1.9) in HRS, and 8.1 (1.6) in FOS. Over 166 516 person-years, a total of 775 participants (220 in WII, 338 in HRS, and 217 in FOS) developed incident dementia. In the multivariable-adjusted Cox proportional hazard model, higher MIND diet score was associated with lower risk of dementia (pooled hazard ratio [HR] for every 3-point increment, 0.83; 95% CI, 0.72-0.95; P for trend = .01; I2 = 0%). The associations were consistently observed in subgroups defined by sex, age, smoking status, and body mass index. In the meta-analysis of 11 cohort studies with 224 049 participants (5279 incident dementia cases), the highest tertile of MIND diet score was associated with lower risk of dementia compared with the lowest tertile (pooled HR, 0.83; 95% CI, 0.76-0.90; I2 = 35%)., Conclusions and Relevance: Results suggest that adherence to the MIND diet was associated with lower risk of incident dementia in middle-aged and older adults. Further studies are warranted to develop and refine the specific MIND diet for different populations.

Introduction: We investigated cross-sectional associations between the Dietary Inflammatory Index (DII) and measures of brain volume and cerebral small vessel disease among participants of the Framingham Heart Study Offspring cohort., Methods: A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnaires and brain magnetic resonance imaging (MRI)., Results: Higher (pro-inflammatory) DII scores, averaged across a maximum of three time points, were associated with smaller total brain volume (beta ± standard error: -0.16 ± 0.03; P < .0001) after adjustment for demographic, clinical, and lifestyle covariates. In addition, higher DII scores were associated with smaller total gray matter volume (-0.08 ± 0.03; P = .003) and larger lateral ventricular volume (0.04 ± 0.02; P = .03). No associations were observed with other brain MRI measures., Discussion: Our findings showed associations between higher DII scores and global brain MRI measures. As we are one of the first groups to report on the associations between higher DII scores and brain volume, replication is needed to confirm our findings., (© 2022 the Alzheimer's Association.)

Background. Vitamins A, D and E and beta-carotene may have a protective function for cognitive health, due to their antioxidant capacities. Methods. We analyzed data from 1334 non-demented participants (mean age 84 years) from the AgeCoDe study, a prospective multicenter-cohort of elderly general-practitioner patients in Germany, of whom n = 250 developed all-cause dementia and n = 209 developed Alzheimer’s dementia (AD) during 7 years of follow-up. We examined whether concentrations of vitamins A (retinol), D (25-hydroxycholecalciferol) and E (alpha-tocopherol) and beta-carotene, would be associated with incident (AD) dementia. Results. In our sample, 33.7% had optimum vitamin D concentrations (≥50 nmol/L). Higher concentrations of vitamin D were associated with lower incidence of all-cause dementia and AD (HR 0.99 (95%CI 0.98; 0.99); HR0.99 (95%CI 0.98; 0.99), respectively). In particular, subjects with vitamin D deficiency (25.3%, <25 nmol/L) were at increased risk for all-cause dementia and AD (HR1.91 (95%CI 1.30; 2.81); HR2.28 (95%CI 1.47; 3.53), respectively). Vitamins A and E and beta-carotene were unrelated to (AD) dementia. Conclusions. Vitamin D deficiency increased the risk to develop (AD) dementia. Our study supports the advice for monitoring vitamin D status in the elderly and vitamin D supplementation in those with vitamin D deficiency. We observed no relationships between the other vitamins with incident (AD) dementia, which is in line with previous observational studies.

Background and Objectives: Diet may be a key contributor to brain health in midlife. In particular, omega-3 fatty acids have been related to better neurologic outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) omega-3 fatty acid concentrations with MRI and cognitive markers of brain aging in a community-based sample of predominantly middle-aged adults and further explore effect modification by APOE genotype., Methods: We included participants from the Third-Generation and Omni 2 cohorts of the Framingham Heart Study attending their second examination. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentrations were measured from RBC using gas chromatography, and the Omega-3 index was calculated as EPA + DHA. We used linear regression models to relate omega-3 fatty acid concentrations to brain MRI measures (i.e., total brain, total gray matter, hippocampal, and white matter hyperintensity volumes) and cognitive function (i.e., episodic memory, processing speed, executive function, and abstract reasoning) adjusting for potential confounders. We further tested for interactions between omega-3 fatty acid levels and APOE genotype (e4 carrier vs noncarrier) on MRI and cognitive outcomes., Results: We included 2,183 dementia-free and stroke-free participants (mean age of 46 years, 53% women, 22% APOE -e4 carriers). In multivariable models, higher Omega-3 index was associated with larger hippocampal volumes (standard deviation unit beta ±standard error; 0.003 ± 0.001, p = 0.013) and better abstract reasoning (0.17 ± 0.07, p = 0.013). Similar results were obtained for DHA or EPA concentrations individually. Stratification by APOE -e4 status showed associations between higher DHA concentrations or Omega-3 index and larger hippocampal volumes in APOE -e4 noncarriers, whereas higher EPA concentrations were related to better abstract reasoning in APOE -e4 carriers. Finally, higher levels of all omega-3 predictors were related to lower white matter hyperintensity burden but only in APOE -e4 carriers., Discussion: Our results, albeit exploratory, suggest that higher omega-3 fatty acid concentrations are related to better brain structure and cognitive function in a predominantly middle-aged cohort free of clinical dementia. These associations differed by APOE genotype, suggesting potentially different metabolic patterns by APOE status. Additional studies in middle-aged populations are warranted to confirm these findings., (© 2022 American Academy of Neurology.)

Background: Low-grade chronic inflammation associated with unhealthy diets may lead to cognitive aging., Objectives: We evaluated whether higher long-term adherence to an empirical dietary inflammatory pattern (EDIP) was associated with lower cognitive function after age 70 y in the Nurses' Health Study., Methods: A total of 16,058 older (mean ± SD age: 74 ± 2 y) highly educated (≥ bachelor degree) White women completed up to 5 validated 116-item food-frequency questionnaires. An EDIP score, previously derived with the use of reduced rank regression to predict circulating inflammatory markers (i.e., C-reactive protein, TNF-α receptor 2, and IL-6), was computed based on 9 anti-inflammatory and 9 proinflammatory components. A long-term EDIP score was calculated by averaging across 5 exams. The EDIP score was categorized into quintiles, taking the first (anti-inflammatory) quintile as the reference category. Cognitive testing was performed through telephone interviews over 4 follow-up exams (1995-2008). A composite global cognition score, a composite verbal memory score, and the Telephone Interview for Cognitive Status (TICS) were calculated and averaged across the 4 exams (6 y of follow-up). Multivariable linear regressions were used to examine longitudinal relations under study., Results: Higher long-term EDIP scores (i.e., more proinflammatory) were significantly associated with worse performance on global cognitive function (P-trend= 0.018) and TICS (P-trend= 0.004) after adjustment for demographic and lifestyle factors. The associations became nonsignificant after additional adjustments for disease (related) risk factors for dementia. No association was observed between the EDIP score and verbal memory., Conclusions: We observed no relation between long-term EDIP scores and averaged global cognitive function and verbal memory among older women. Our findings suggest no relation between long-term adherence to a proinflammatory diet and cognitive function in a large population of mostly White and generally highly educated older women. Future studies are encouraged to investigate the relation between inflammatory diets and cognitive function in other races/ethnicities and men, and over a longer follow-up period., (Copyright © 2022 American Society for Nutrition.)

The role of nutrition has been investigated for decades under the assumption of one-size-fits-all. Yet there is heterogeneity in metabolic and neurobiological responses to diet. Thus a more personalized approach may better fit biological reality and have increased efficacy to prevent dementia. Personalized nutrition builds on the food exposome, defined as the history of diet-related exposures over the lifetime, and on its interactions with the genome and other biological characteristics (eg, metabolism, the microbiome) to shape health. We review current advances of personalized nutrition in dementia research. We discuss key questions, success milestones, and future roadmap from observational epidemiology to clinical studies through basic science. A personalized nutrition approach based on the best prescription for the most appropriate target population in the most relevant time-window has the potential to strengthen dementia-prevention efforts., (© 2021 the Alzheimer's Association.)

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 incident AD, testing for an interaction with APOE-ε4 carriership. During the follow-up (median, 7.2 years), 131 cases of AD were documented. In fully adjusted models, risk for incident AD in the highest RBC DHA quintile (Q5) was 49% lower compared with the lowest quintile (Q1) (Hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.27, 0.96). An increase in RBC DHA from Q1 to Q5 was predicted to provide an estimated 4.7 additional years of life free of AD. We observed an interaction DHA × APOE-ε4 carriership for AD. Borderline statistical significance for a lower risk of AD was observed per standard deviation increase in RBC DHA (HR: 0.71, 95% CI: 0.51, 1.00, p = 0.053) in APOE-ε4 carriers, but not in non-carriers (HR: 0.85, 95% CI: 0.65, 1.11, p = 0.240). These findings add to the increasing body of literature suggesting a robust association worth exploring dietary DHA as one strategy to prevent or delay AD.

Background: Previous studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent., Objective: To study the cross-sectional associations of pulmonary function with structural brain variables., Methods: Data from six large community-based samples (N = 11,091) were analyzed. Spirometric measurements were standardized with respect to age, sex, height, and ethnicity using reference equations of the Global Lung Function Initiative. Associations of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio FEV1/FVC with brain volume, gray matter volume, hippocampal volume, and volume of white matter hyperintensities were investigated using multivariable linear regressions for each study separately and then combined using random-effect meta-analyses., Results: FEV1 and FVC were positively associated with brain volume, gray matter volume, and hippocampal volume, and negatively associated with white matter hyperintensities volume after multiple testing correction, with little heterogeneity present between the studies. For instance, an increase of FVC by one unit was associated with 3.5 ml higher brain volume (95% CI: [2.2, 4.9]). In contrast, results for FEV1/FVC were more heterogeneous across studies, with significant positive associations with brain volume, gray matter volume, and hippocampal volume, but not white matter hyperintensities volume. Associations of brain variables with both FEV1 and FVC were consistently stronger than with FEV1/FVC, specifically with brain volume and white matter hyperintensities volume., Conclusion: In cross-sectional analyses, worse pulmonary function is associated with smaller brain volumes and higher white matter hyperintensities burden.

Normal cardiac function is directly associated with the maintenance of cerebrovascular health. Whether the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet, designed for the maintenance of neurocognitive health, is associated with cardiac remodelling is unknown. We evaluated 2512 Framingham Offspring Cohort participants who attended the eighth examination cycle and had available dietary and echocardiographic data (mean age 66 years; 55 % women). Using multivariable regression, we related the cumulative MIND diet score (independent variable) to left ventricular (LV) ejection fraction, left atrial emptying fraction, LV mass (LVM), E/e' ratio (dependent variables; primary), global longitudinal strain, global circumferential strain (GCS), mitral annular plane systolic excursion, longitudinal segmental synchrony, LV hypertrophy and aortic root diameter (secondary). Adjusting for age, sex and energy intake, higher cumulative MIND diet scores were associated with lower values of indices of LV diastolic (E/e' ratio: logβ = -0·03) and systolic function (GCS: β = -0·04) and with higher values of LVM (logβ = 0·02), all P ≤ 0·01. We observed effect modification by age in the association between the cumulative MIND diet score and GCS. When we further adjusted for clinical risk factors, the associations of the cumulative MIND diet score with GCS in participants ≥66 years (β = -0·06, P = 0·005) and LVM remained significant. In our community-based sample, relations between the cumulative MIND diet score and cardiac remodelling differ among indices of LV structure and function. Our results suggest that favourable associations between a higher cumulative MIND diet score and indices of LV function may be influenced by cardiometabolic and lifestyle risk factors.

Objective: To determine whether following a Mediterranean-like diet (MeDi) relates to cognitive functions and in vivo biomarkers for Alzheimer disease (AD), we analyzed cross-sectional data from the German DZNE-Longitudinal Cognitive Impairment and Dementia Study. METHOD: The sample (n=512, mean age: 69.5±5.9 years) included 169 cognitively normal participants and subjects at higher AD risk (53 with relatives with AD, 209 with subjective cognitive decline, and 81 with mild cognitive impairment). We defined MeDi adherence based on the Food Frequency Questionnaire. Brain volume outcomes were generated via voxel-based morphometry on T1-MRI and cognitive performance with an extensive neuropsychological battery. AD-related biomarkers (Aβ42/40 ratio, pTau181) in cerebrospinal fluid were assessed in n=226 individuals. We analyzed the associations between MeDi and the outcomes with linear regression models controlling for several covariates. Additionally, we applied hypothesis-driven mediation and moderation analysis., Results: Higher MeDi adherence related to larger mediotemporal gray matter volume (p<0.05 FWE corrected), better memory (β±SE = 0.03 ± 0.02; p=0.038), and less amyloid (Aβ42/40 ratio, β±SE = 0.003 ± 0.001; p=0.008) and pTau181 pathology (β±SE = -1.96±0.68; p=0.004). Mediotemporal volume mediated the association between MeDi and memory (40% indirect mediation). Finally, MeDi favorably moderated the associations between Aβ42/40 ratio, pTau181 and mediotemporal atrophy. Results were consistent correcting for ApoE-ε4 status., Conclusion: Our findings corroborate the view of MeDi as a protective factor against memory decline and mediotemporal atrophy. Importantly, they suggest that these associations might be explained by a decrease of amyloidosis and tau-pathology. Longitudinal and dietary intervention studies should further examine this conjecture and its treatment implications., (© 2021 American Academy of Neurology.)

Background: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) may have different effects on cognitive health due to their anti- or pro-inflammatory properties., Methods: We aimed to prospectively examine the relationships between n-3 and n-6 PUFA contents in serum phospholipids with incident all-cause dementia and Alzheimer's disease dementia (AD). We included 1264 non-demented participants aged 84 ± 3 years from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) multicenter-cohort study. We investigated whether fatty acid concentrations in serum phospholipids, especially eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA), were associated with risk of incident all-cause dementia and AD., Results: During the follow-up window of seven years, 233 participants developed dementia. Higher concentrations of EPA were associated with a lower incidence of AD (hazard ratio (HR) 0.76 (95% CI 0.63; 0.93)). We also observed that higher concentrations of EPA were associated with a decreased risk for all-cause dementia (HR 0.76 (95% CI 0.61; 0.94)) and AD (HR 0.66 (95% CI 0.51; 0.85)) among apolipoprotein E ε4 (APOE ε4) non-carriers but not among APOE ε4 carriers. No other fatty acids were significantly associated with AD or dementia., Conclusions: Higher concentrations of EPA were associated with a lower risk of incident AD. This further supports a beneficial role of n-3 PUFAs for cognitive health in old age.

Background: Adherence to the Mediterranean-DASH for Neurodegenerative Delay (MIND) diet has previously been associated with cognitive decline and dementia. To our knowledge, no prior study has investigated the association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs), or brain atrophy., Objective: We evaluated whether adherence to the MIND diet associated with superior cognitive function, larger brain volumes, fewer SBIs, and less cognitive decline in the community-based Framingham Heart Study., Methods: 2,092 participants (mean±SD, age 61±9) completed Food Frequency Questionnaires, averaged across a maximum of 3-time points (examination cycles 5, 6, and 7), cognitive testing at examination cycle 7 (present study baseline: 1998-2001) and after a mean±SD of 6.6±1.1 years from baseline (n = 1,584). A subset of participants also completed brain magnetic resonance imaging (MRI) at examination cycle 7 (n = 1,904). In addition, participants with dementia, stroke, and other relevant neurological diseases such as significant head trauma, subdural hematoma, or multiple sclerosis were excluded from the analyses., Results: Higher MIND diet scores were associated with better global cognitive function (β±SE,+0.03SD±0.01; p = 0.004), verbal memory, visual memory, processing speed, verbal comprehension/reasoning, and with larger total brain volume (TBV) following adjustments for clinical, lifestyle and demographic covariates, but not with other brain MRI measures (i.e., hippocampal volume, lateral ventricular volume, white matter hyperintensity volume, and SBIs) or cognitive decline., Conclusion: Higher MIND diet scores associated with better cognitive performance and larger TBV at baseline, but not with cognitive decline. Clinical trials are needed to ascertain whether adopting the MIND diet affects trajectories of cognitive decline.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted.

Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background : Evidence whether single &ldquo;cognitive health&rdquo; foods could prevent cognitive decline is limited. We investigated whether dietary intake of red wine, white wine, coffee, green tea, olive oil, fresh fish, fruits and vegetables, red meat and sausages, assessed by a single-food-questionnaire, would be associated with either incident Alzheimer&rsquo;s dementia (AD) or verbal memory decline. Methods: Participants aged 75+ of the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe) cohort were regularly followed over 10 years ( n = 2622; n = 418 incident AD cases). Multivariable-adjusted joint modeling of repeated-measures and survival analysis was used, taking gender and Apolipoprotein E4 ( APOE &epsilon;4) genotype into account as possible effect modifiers. Results : Only higher red wine intake was associated with a lower incidence of AD ( HR = 0.92; P = 0.045). Interestingly, this was true only for men ( HR = 0.82; P < 0.001), while in women higher red wine intake was associated with a higher incidence of AD ( HR = 1.15; P = 0.044), and higher white wine intake with a more pronounced memory decline over time ( HR = &minus;0.13; P = 0.052). Conclusion : We found no evidence for these single foods to be protective against cognitive decline, with the exception of red wine, which reduced the risk for AD only in men. Women could be more susceptible to detrimental effects of alcohol.

Introduction: Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions., Methods: We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined., Results: We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors., Discussion: Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Lutein, a fat-soluble carotenoid with antioxidant properties, may have an effect on respiratory health. However, the evidence is inconsistent. We aimed to cross-sectionally investigate the association between lutein intake and lung function by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC% in adults (aged 45-79 years). We included 4402 participants from the Rotterdam Study, a prospective cohort study in The Netherlands. Lutein intake was assessed using a validated FFQ. Lung function was assessed using spirometry around the same time point as the dietary assessment. No independent association was found between lutein intake and FEV1 (-12·17 (95 % CI -34·21, 9·87) ml per sd increase in lutein) after adjustment for age, sex, height, cohort effect, ethnicity, education, weight, total daily energy intake, smoking status, physical activity, and intakes of fatty acids, dietary fibre, alcohol, β-carotene, β-crypotoxanthin, lycopene and zeaxanthin. There was also no association between lutein and FVC or FEV1/FVC%. However, after stratification by smoking status, lutein intake was significantly associated with lower FEV1/FVC% in current smokers (-1·69 (95 % CI -2·93, -0·45) % per sd increase of lutein) independent of other carotenoids. The present study does not support an independent association between lutein intake and lung function in adults. However, future studies should focus on the potential inverse association between high lutein intake and lung function in specific risk groups such as smokers.

Background: Lutein, a fat-soluble carotenoid present in green leafy vegetables and eggs, has strong antioxidant properties and could therefore be important for respiratory health., Design: We systematically reviewed the literature for articles that evaluated associations of lutein (intake, supplements or blood levels) with respiratory outcomes, published in Medline, Embase, Cochrane Central, PubMed, Web of Science and Google Scholar, up to August 2014., Results: We identified one Randomized Control Trial (RCT), two longitudinal, four prospective and six cross-sectional studies. The individual studies obtained a Quality Score ranging between 3 and 9. Six studies were performed in children, which examined bronchopulmonary dysplasia (BPD), asthma and wheezing. In adults, 7 studies investigated asthma, respiratory function and respiratory mortality. The RCT found a borderline significant effect of lutein/zeaxanthin supplementation in neonates on the risk of BPD (OR 0.43 (95% CI 0.15; 1.17). No association was found between lutein intake or levels and respiratory outcomes in children. A case-control study in adults showed lower lutein levels in asthma cases. Three studies, with a prospective or longitudinal study design, in adults found a small but a significant positive association between lutein intake or levels and respiratory function. No association was found in the other two studies. In relation to respiratory mortality, one longitudinal study showed that higher lutein blood levels were associated with a decreased mortality (HR 0.77 (95% CI 0.60; 0.99), per SD increase in lutein)., Conclusion: The published literature suggests a possible positive association between lutein and respiratory health. However, the literature is scarce and most studies are of observational nature., (Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: The antioxidant lutein is suggested as being beneficial to cardiometabolic health because of its protective effect against oxidative stress, but evidence has not systematically been evaluated., Objective: We aimed to evaluate systematically the effects of lutein (intake or concentrations) on cardiometabolic outcomes in different life stages., Design: This is a systematic review with meta-analysis of literature published in MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar up to August 2014. Included were trials and cohort, case-control, and cross-sectional studies in which the association between lutein concentrations, dietary intake, or supplements and cardiometabolic outcomes was reported. Two independent investigators reviewed the articles., Results: Seventy-one relevant articles were identified that included a total of 387,569 participants. Only 1 article investigated the effects of lutein during pregnancy, and 3 studied lutein in children. Furthermore, 31 longitudinal, 33 cross-sectional, and 3 intervention studies were conducted in adults. Meta-analysis showed a lower risk of coronary heart disease (pooled RR: 0.88; 95% CI: 0.80, 0.98) and stroke (pooled RR: 0.82; 95% CI: 0.72, 0.93) for the highest compared with the lowest tertile of lutein blood concentration or intake. There was no significant association with type 2 diabetes mellitus (pooled RR: 0.97; 95% CI: 0.77, 1.22), but higher lutein was associated with a lower risk of metabolic syndrome (pooled RR: 0.75; 95% CI: 0.60, 0.92) for the highest compared with the lowest tertile. The literature on risk factors for cardiometabolic diseases showed that lutein might be beneficial for atherosclerosis and inflammatory markers, but there were inconsistent associations with blood pressure, adiposity, insulin resistance, and blood lipids., Conclusions: Our findings suggest that higher dietary intake and higher blood concentrations of lutein are generally associated with better cardiometabolic health. However, evidence mainly comes from observational studies in adults, whereas large-scale intervention studies and studies of lutein during pregnancy and childhood are scarce., (© 2016 American Society for Nutrition.)