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Healthy lifestyles are promising targets for prevention of cognitive aging, yet the optimal time windows for interventions remain unclear. We selected a case-control sample nested within the Nurses' Health Study (starting year 1976, mean age = 51 years), including 14,956 women aged ≥70 years who were free of both stroke and cognitive impairment at enrollment in a cognitive substudy (1995-2001). Cases (n = 1,496) were women with the 10% worst slopes of cognitive decline, and controls (n = 7,478) were those with slopes better than the median. We compared the trajectories of body mass index (weight (kg)/height (m)2), alternate Mediterranean diet (A-MeDi) score, and physical activity between groups, from midlife through 1 year preceding the cognitive substudy. In midlife, cases had higher body mass index than controls (mean difference (MD) = 0.59 units, 95% confidence interval (CI): 0.39, 0.80), lower physical activity (MD = -1.41 metabolic equivalent of task-hours/week, 95% CI: -2.07, -0.71), and worse A-MeDi scores (MD = -0.16 points, 95% CI: -0.26, -0.06). From midlife through later life, compared with controls, cases had consistently lower A-MeDi scores but a deceleration of weight gain and a faster decrease in physical activity. In conclusion, maintaining a healthy lifestyle since midlife may help reduce cognitive decline in aging. At older ages, both deceleration of weight gain and a decrease in physical activity may reflect early signs of cognitive impairment., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D)., Methods and Findings: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist., Conclusions: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JHYW and RM report research support from Unilever for other projects of the FORCE on other fatty acid biomarkers. RM reports personal fees from the World Bank and Bunge outside the submitted work. IAB reported involvement in a research project partly funded by Unilever. JMG and JdG received funding from Unilever for epidemiological studies of dietary and circulating fatty acids and cardiometabolic disease and for research on assessment of fatty acids. LCdG reported receiving ad hoc consulting fees from the Life Sciences Research Organization. CH reported receiving fees for a conference from Novartis. NGF is an invited member (unpaid) of ILSI-Europe Qualitative Fat Intake Task Force Expert Group on update on health effects of different saturated fats. DM reports research funding from the NIH and the Gates Foundation; personal fees from GOED, DSM, Nutrition Impact, Pollock Communications, Bunge, Indigo Agriculture, Amarin, Acasti Pharma, and America’s Test Kitchen; scientific advisory board, Omada Health, Elysium Health, and DayTwo; and chapter royalties from UpToDate; all outside the submitted work. Patents US8889739 and US9987243 to Tufts University (unlicensed), listing DM as a co-inventor, for use of trans-palmitoleic acid to prevent and treat insulin resistance, type 2 diabetes, and related conditions, as well as reduce metabolic risk factors. SSSM reported receiving an international award and unrestricted grants for meta-analysis work on dairy foods and cardiometabolic diseases from Global and Dutch Dairy Associations. Other authors do not have any conflict of interest to declare. The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Purpose of Review: The effectiveness of the Mediterranean diet in reducing the prevalence of cardiovascular and chronic diseases has been largely evidenced. Although nutrition constitutes an interesting approach in preventing age-related brain disorders, the association between the Mediterranean-style diet and cognitive functions has been very occasionally explored., Recent Findings: Results are provided from only two recent prospective cohorts of older Americans and French individuals (> or =65 years) on the relationship of Mediterranean diet to cognitive functions. A high adherence to the Mediterranean diet has been associated with slower cognitive decline, with reduced risk of mild cognitive impairment conversion to Alzheimer's disease and with reduced risk of Alzheimer's disease., Summary: The possibility that the Mediterranean diet may affect not only the risk for Alzheimer's disease, but also the evolution of cognitive performances a long time before the clinical diagnosis of dementia and subsequent disease course constitutes major promising results. Replication of these results in other populations seems necessary to allow their generalization and to propose the Mediterranean diet as a potential preventive approach against cognitive decline or dementia in addition to its expected benefits against many other unfavorable outcomes in a public health perspective.