Lung Cancer Risks Associated with Occupational Exposure to Pairs of Five Lung Carcinogens: Results from a Pooled Analysis of Case-Control Studies (SYNERGY).

BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.

Respirable crystalline silica and lung cancer in community-based studies: impact of job-exposure matrix specifications on exposure-response relationships.

OBJECTIVES: The quantitative job-exposure matrix SYN-JEM consists of various dimensions: job-specific estimates, region-specific estimates, and prior expert ratings of jobs by the semi-quantitative DOM-JEM. We analyzed the effect of different JEM dimensions on the exposure-response relationships between occupational silica exposure and lung cancer risk to investigate how these variations influence estimates of exposure by a quantitative JEM and associated health endpoints. METHODS: Using SYN-JEM, and alternative SYN-JEM specifications with varying dimensions included, cumulative silica exposure estimates were assigned to 16 901 lung cancer cases and 20 965 controls pooled from 14 international community-based case-control studies. Exposure-response relationships based on SYN-JEM and alternative SYN-JEM specifications were analyzed using regression analyses (by quartiles and log-transformed continuous silica exposure) and generalized additive models (GAM), adjusted for age, sex, study, cigarette pack-years, time since quitting smoking, and ever employment in occupations with established lung cancer risk. RESULTS: SYN-JEM and alternative specifications generated overall elevated and similar lung cancer odds ratios ranging from 1.13 (1st quartile) to 1.50 (4th quartile). In the categorical and log-linear analyses SYN-JEM with all dimensions included yielded the best model fit, and exclusion of job-specific estimates from SYN-JEM yielded the poorest model fit. Additionally, GAM showed the poorest model fit when excluding job-specific estimates. CONCLUSION: The established exposure-response relationship between occupational silica exposure and lung cancer was marginally influenced by varying the dimensions of SYN-JEM. Optimized modelling of exposure-response relationships will be obtained when incorporating all relevant dimensions, namely prior rating, job, time, and region. Quantitative job-specific estimates appeared to be the most prominent dimension for this general population JEM.

Occupational Benzene Exposure and Lung Cancer Risk: A Pooled Analysis of 14 Case-Control Studies.

Rationale: Benzene has been classified as carcinogenic to humans, but there is limited evidence linking benzene exposure to lung cancer. Objectives: We aimed to examine the relationship between occupational benzene exposure and lung cancer. Methods: Subjects from 14 case-control studies across Europe and Canada were pooled. We used a quantitative job-exposure matrix to estimate benzene exposure. Logistic regression models assessed lung cancer risk across different exposure indices. We adjusted for smoking and five main occupational lung carcinogens and stratified analyses by smoking status and lung cancer subtypes. Measurements and Main Results: Analyses included 28,048 subjects (12,329 cases, 15,719 control subjects). Lung cancer odds ratios ranged from 1.12 (95% confidence interval, 1.03-1.22) to 1.32 (95% confidence interval, 1.18-1.48) (Ptrend = 0.002) for groups with the lowest and highest cumulative occupational exposures, respectively, compared with unexposed subjects. We observed an increasing trend of lung cancer with longer duration of exposure (Ptrend < 0.001) and a decreasing trend with longer time since last exposure (Ptrend = 0.02). These effects were seen for all lung cancer subtypes, regardless of smoking status, and were not influenced by specific occupational groups, exposures, or studies. Conclusions: We found consistent and robust associations between different dimensions of occupational benzene exposure and lung cancer after adjusting for smoking and main occupational lung carcinogens. These associations were observed across different subgroups, including nonsmokers. Our findings support the hypothesis that occupational benzene exposure increases the risk of developing lung cancer. Consequently, there is a need to revisit published epidemiological and molecular data on the pulmonary carcinogenicity of benzene.

Cancer Survivors in Saint Lucia Deeply Value Social Support: Considerations for Cancer Control in Under-Resourced Communities.

Understanding the views of cancer survivors on their experience is important for informing community-based interventions. We studied, for the first time, the views of cancer survivors residing in Saint Lucia on their overall care experience. We used interview data from a cohort of adult cancer survivors from Saint Lucia between 2019 and 2020. We performed a thematic analysis to derive themes from codes. Forty-four survivors provided responses to at least one of the three questions. The majority of survivors were black, female and diagnosed with breast cancer. Survivors were interviewed on average five years after diagnosis. Four common themes emerged; "Availability of support groups", "Importance of support from family and friends", "Access to finances" and "Health education and patient navigation". Travel overseas for health services was common among survivors. Survivors expressed emotional distress during travel due to isolation from family and local providers. This is typical among island populations and is distinct from existing patient frameworks. Survivors also suggested that networking amongst providers and interventions assisted families of cancer survivors. Although tertiary care services are limited, we showed that survivors deeply value and depend on their inter-personal relationships during care. Interventions aimed at strengthening the inter-personal environment of survivors are warranted.

Occupational exposure to polycyclic aromatic hydrocarbons and risk of prostate cancer.

BACKGROUND: Several industries entailing exposure to polycyclic aromatic hydrocarbons (PAHs) are known or suspected carcinogens. A handful of studies have assessed the role of PAHs exposure in prostate cancer risk, but none has examined tumor aggressiveness or the influence of screening practices and detection issues. We aimed to examine the association between lifetime occupational exposure to PAHs and prostate cancer risk. METHODS: Detailed work histories were collected from 1,929 prostate cancer cases (436 aggressive) and 1,994 controls from Montreal, Canada (2005-2012). Industrial hygienists applied the hybrid expert approach to assign intensity, frequency and certainty of exposure to benzo[a]pyrene, PAHs from wood, coal, petroleum, other sources, and any source, in each job held. Odds ratios (ORs) for prostate cancer risk associated with lifetime PAHs exposure, adjusted for age, ancestry, education, lifestyle and occupational factors, and 95% confidence intervals (CI), were estimated using unconditional logistic regression. RESULTS: After restriction to probable and definite exposures, and application of a 5-year lag, no clear association emerged for any of the PAHs, although small excesses in risk were apparent with 5-year increments in exposure to PAHs from wood (OR = 1.06, 95%CI 0.95 to 1.18). While analyses by cancer aggressiveness suggested no major differences, some elevated risk of high-grade cancer was observed for exposure to PAHs from wood (OR = 1.37, 95%CI 0.65 to 2.89), frequently occurring among firefighters. CONCLUSION: Findings provide weak support for an association between occupational exposure to PAHs from wood and prostate cancer risk.

Dietary Patterns Are Associated with Risk of Prostate Cancer in a Population-Based Case-Control Study in Montreal, Canada.

This study describes the association between dietary patterns and prostate cancer (PCa) risk in a population-based case-control study conducted in Montreal, Canada (2005-2012). Cases (n = 1919) were histologically confirmed, aged ≤75 years. Concomitantly, controls (n = 1991) were randomly selected from the electoral list and frequency-matched to cases by age (±5 years). During face-to-face interviews, a 63-item food frequency questionnaire focusing on the two years before diagnosis/interview was administered. Three dietary patterns were identified from principal component analysis. Unconditional logistic regression estimated the association between dietary patterns and PCa, adjusting for age, ethnicity, education, family history, and timing of last PCa screening. When comparing scores in the highest vs. lowest quartiles, the Healthy Eating pattern was associated with a decreased risk of overall PCa (Odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61, 0.93); this association was stronger for high-grade cancers (OR = 0.66, 95% CI = 0.48, 0.89). By contrast, the Western Sweet and Beverages pattern was associated with an elevated risk of overall PCa (OR = 1.35, 95% CI = 1.10, 1.66). The Western Salty and Alcohol pattern was not associated with PCa risk. These findings suggest that some dietary patterns influence PCa development.

Welding and the risk of head and neck cancer: the ICARE study.

OBJECTIVE: To investigate the association between occupational exposure to welding and the risk of head and neck cancer in a large French population-based case-control study, the Investigation of occupational and environmental CAuses of REspiratory cancers study. METHODS: Analyses were restricted to men (2703 controls and 1588 cases of squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx). Welding activity and potential confounders were assessed by detailed questionnaires. ORs and CIs (95% CI) were estimated by unconditional logistic regression, adjusted for age, area of residence, tobacco smoking, alcohol consumption and occupational exposure to asbestos. RESULTS: Welding was associated with an increased risk of head and neck cancer overall (OR=1.31, 95% CI 1.03 to 1.67). The association was strongest for laryngeal cancer (OR=1.66, 95% CI 1.15 to 2.38) and the risk increased with the cumulative duration (p-trend <0.01) and the weighted duration (p-trend <0.01) of welding. A cumulative duration and a weighted duration of welding of more than 10 years were also associated with a significantly increased risk of oral cancer (OR=1.82, 95% CI 1.09 to 3.04; OR=2.10, 95% CI 0.99 to 4.45, respectively). A long duration of arc welding was associated with laryngeal cancer, whereas a long duration of spot welding was associated with oral cancer. Welding was not associated with the risk of oropharyngeal and hypopharyngeal cancer. CONCLUSION: Our findings suggest that welding and several welding-related tasks increase the risk of laryngeal cancer and to a lesser extent oral cancer.

Social distribution of tobacco smoking, alcohol drinking and obesity in the French West Indies.

BACKGROUND: Tobacco smoking, alcohol and obesity are important risk factors for a number of non-communicable diseases. The prevalence of these risk factors differ by socioeconomic group in most populations, but this socially stratified distribution may depend on the social and cultural context. Little information on this topic is currently available in the Caribbean. The aim of this study was to describe the distribution of tobacco smoking, alcohol drinking and obesity by several socioeconomic determinants in the French West Indies (FWI). METHODS: We used data from a cross-sectional health survey conducted in Guadeloupe and Martinique in 2014 in a representative sample of the population aged 15-75 years (n = 4054). All analyses were stratified by gender, and encompassed sample weights, calculated to account for the sampling design and correct for non-response. For each risk factor, we calculated weighted prevalence by income, educational level, occupational class and having hot water at home. Poisson regression models were used to estimate age-adjusted prevalence ratios (PR) and 95% confidence intervals (CI). RESULTS: Current smoking and harmful chronic alcohol use were more common in men than in women (PR = 1.80, 95% CI = 1.55-2.09; PR = 4.53, 95% CI = 3.38-6.09 respectively). On the other hand, the prevalence of obesity was higher in women than in men (PR = 0.67, 95% CI = 0.57-0.79). Higher education, higher occupational class and higher income were associated with lower prevalence of harmful alcohol drinking in men (PR = 0.43, 95% CI = 0.25-0.72; PR = 0.73, 95% CI = 0.53-1.01; PR = 0.72, 95% CI = 0.51-1.03 respectively), but not in women. For tobacco smoking, no variation by socioeconomic status was observed in men whereas the prevalence of current smoking was higher among women with higher occupational class (PR = 1.47, 95% CI = 1.13-1.91) and higher income (PR = 1.50, 95% CI = 1.11-2.03). In women, a lower prevalence of obesity was associated with a higher income (PR = 0.43, 95% CI = 0.33-0.56), a higher occupational class (PR = 0.63, 95% CI = 0.50-0.80), a higher educational level (PR = 0.36, 95% CI = 0.26-0.50) and having hot water at home (PR = 0.65, 95% CI = 0.54-0.80). CONCLUSION: Women of high socio-economic status were significantly more likely to be smokers, whereas alcohol drinking in men and obesity in women were inversely associated with socioeconomic status.

Night-Shift Work and Risk of Prostate Cancer: Results From a Canadian Case-Control Study, the Prostate Cancer and Environment Study.

Night-shift work involving disruption of circadian rhythms has been associated with breast cancer risk. A role in prostate cancer is also suspected, but evidence is limited. We investigated the association between night-shift work and prostate cancer incidence in the Prostate Cancer and Environment Study (PROtEuS), a population-based case-control study conducted in 2005-2012 in Montreal, Quebec, Canada. Participants were 1,904 prostate cancer cases (432 high-grade cancers) and 1,965 population controls. Detailed work schedules for each job held for at least 2 years (n = 15,724) were elicited in face-to-face interviews. Night-shift work was defined as having ever worked ≥3 hours between midnight and 5:00 am ≥3 nights/month for ≥1 year. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between night-shift work and prostate cancer, adjusting for age, ancestry, and education. No association was found between overall prostate cancer and night-shift work metrics, including ever exposure, duration, intensity, cumulative exposure, rotating shifts, and early-morning shifts. For none of the exposure indices was there evidence of heterogeneity in odds ratios between low- and high-grade cancers. Sensitivity analyses restricting exposures to ≥7 nights/month or considering screening history yielded similar results. Our findings lend no support for a major role of night-shift work in prostate cancer development.

Head and neck cancer and occupational exposure to leather dust: results from the ICARE study, a French case-control study.

BACKGROUND: Leather dust is an established carcinogen of the sinonasal cavities; however, evidence is lacking regarding its association with other head and neck cancers (HNC). To date, few studies have been conducted on the association between occupational leather dust exposure and the risk of oral, pharyngeal, and laryngeal cancers. The objective of this study was to investigate the association between the risk of HNC and occupational exposure to leather dust. METHODS: Lifestyle habits and occupational history were collected for 2161 patients with squamous cell carcinoma of oral cavity, pharynx, and larynx, and 3555 controls, using a standardized questionnaire. Occupational exposure to leather dust was assessed using a job-exposure matrix. Odds ratios (OR) and 95% confidence intervals (CI) for HNC globally and by subsite were estimated using multivariate unconditional, and polytomous logistic regressions, respectively. RESULTS: Cumulative lifetime exposure to leather dust < 6 mg/m3-years was associated with an increased risk of laryngeal cancer (OR = 2.26, 95% CI: 1.07-4.76); higher levels were not related to elevated risks of HNC. Some tasks performed and the use of some glues were associated with elevated, although non-significant, risks of HNC. No dose-response relationships were observed. CONCLUSION: Our study did not provide enough evidence for an increased risk of HNC related to occupational exposure to leather dust. Further studies are needed to understand the risks of specific tasks in the leather industry.

Occupational exposure to petroleum-based and oxygenated solvents and oral and oropharyngeal cancer risk in men: A population-based case-control study in France.

OBJECTIVE: To examine the association between occupational exposure to petroleum-based and oxygenated solvents and the risk of oral and oropharyngeal cancer. METHODS: The ICARE study is a large population-based case-control study conducted in France between 2001 and 2007. This present analysis was restricted to men and included 350 and 543 cases of squamous cell-carcinoma of the oral cavity and oropharynx, respectively, and 2780 controls. Lifetime tobacco, alcohol consumption and complete occupational history were assessed through detailed questionnaires. Job-exposure matrices allowed us to assess occupational exposure to five petroleum-based solvents (white spirits; diesel/fuel oils/kerosene; gasoline; benzene; special petroleum products) and five oxygenated solvents (diethyl ether; tetrahydrofuran; ketones and esters; alcohols; ethylene glycol). Odds-ratios (ORs), adjusted for age, smoking, alcohol consumption and socioeconomic status, and 95% confidence intervals (CI) were estimated using unconditional logistic models. RESULTS: Associations between oral cancer risk and exposure to white spirits and diesel/fuel oils/kerosene were suggested, but there was no exposure-response trend. Concerning exposure to oxygenated solvents, participants with the highest levels of cumulative exposure to diethyl ether had a significant excess risk of oropharyngeal cancer (OR = 7.78, 95%CI 1.42 to 42.59; p for trend = 0.04). Ever exposure to tetrahydrofuran was associated with a borderline significant increased risk of oral cancer (OR = 1.87, 95%CI 0.97 to 3.61), but no exposure-response trend was observed. Additional adjustments for exposure to other solvents did not substantially change the results. CONCLUSION: Our results do not provide evidence for a major role of petroleum-based and oxygenated solvents in the occurrence of oral and oropharyngeal cancers in men.

Risk factors for salivary gland cancers in France: Results from a case-control study, the ICARE study.

OBJECTIVES: Epidemiological studies on the risk factors for salivary gland cancers (SGC) are rare, concern a small sample size, and show inconsistent results. The aim of the present work was to analyze several risk factors for SGC, using the data from the ICARE study, a multicenter, population-based case-control study. MATERIALS AND METHODS: Data from 73 SGC cases and 3555 controls were collected using a standardized questionnaire on lifestyle habits, personal and family medical history, and lifetime occupational history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regressions. RESULTS: Tobacco use and alcohol consumption were not associated with the risk of SGC. A history of head and neck cancer or that of cervicofacial radiotherapy was associated with a higher risk of SGC (OR = 17.06, 95% CI: 4.34-67.05, and OR = 31.74, 2.48-405.25, respectively). Significantly increased risks were observed for some occupations: waiter (OR = 2.94, 1.11-7.78), charworker (OR = 3.02, 1.38-6.60), electrical and electronic equipment assembler (OR = 7.16, 2.02-25.38), plumber (OR = 3.95, 1.33-11.67), electric arc welder (OR = 6.15, 1.76-21.48), sheet-metal worker (OR = 2.89, 1.01-8.32), building painter (OR = 3.42, 1.01-11.49), and material handling equipment operator (OR = 5.05, 1.71-14.84). Results for industries were consistent with those observed for occupations. CONCLUSION: Our results showed that a history of head and neck cancer, cervicofacial radiotherapy, and several occupations and industries, were associated with an increased risk of SGC. Further studies with larger sample sizes are indicated to confirm our results.

Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France: the ICARE study.

BACKGROUND: To examine associations between occupational exposure to petroleum-based and oxygenated solvents and the risk of hypopharyngeal and laryngeal cancer. METHODS: ICARE is a large, frequency-matched population-based case-control study conducted in France. Lifetime occupational history, tobacco smoking and alcohol consumption were collected. Analyses were restricted to men and included 383 cases of hypopharyngeal cancer, 454 cases of laryngeal cancer, and 2780 controls. Job-exposure matrices were used to assess exposure to five petroleum-based solvents (benzene; gasoline; white spirits; diesel, fuels and kerosene; special petroleum products) and to five oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). Odds ratios (ORs) adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals (CI) were estimated with unconditional logistic models. RESULTS: No significant association was found between hypopharyngeal or laryngeal cancer risk and exposure to the solvents under study. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of white spirits (OR = 1.46; 95% CI: 0.88-2.43) and tetrahydrofuran (OR = 2.63; 95CI%: 0.55-12.65), with some indication of a dose-response relationship (p for trend: 0.09 and 0.07 respectively). CONCLUSION: This study provides weak evidence for an association between hypopharyngeal cancer and exposure to white spirits and tetrahydrofuran, and overall does not suggest a substantial role of exposure to petroleum-based or oxygenated solvents in hypopharyngeal or laryngeal cancer risk.

Occupational exposure to chlorinated solvents and risk of head and neck cancer in men: a population-based case-control study in France.

BACKGROUND: Few epidemiological studies have investigated the link between occupational exposure to solvents and head and neck cancer risk, and available findings are sparse and inconsistent. The objective of this study was to examine the association between occupational exposure to chlorinated solvents and head and neck cancer risk. METHODS: We analyzed data from 4637 men (1857 cases and 2780 controls) included in a population-based case-control study, ICARE (France). Occupational exposure to five chlorinated solvents (perchloroethylene [PCE], trichloroethylene [TCE], methylene chloride [MC], chloroform [CF], and carbon tetrachloride [CT]) was assessed through job-exposure matrices. Odds ratios (ORs) and confidence intervals (95% CI) were estimated by unconditional logistic regression, adjusted for age, tobacco smoking, alcohol consumption, asbestos exposure, and other potential confounders. RESULTS: We observed no association between chlorinated solvent exposure and head and neck cancer risk, despite a non-significant increase in risk among subjects who had the highest cumulative level of exposure to PCE, (OR = 1.81; 95% CI = 0.68 to 4.82). In subsite analysis, the risk of laryngeal cancer increased with cumulative exposure to PCE (p for trend = 0.04). The OR was 3.86 (95% CI = 1.30 to 11.48) for those exposed to the highest levels of PCE. A non-significant elevated risk of hypopharyngeal cancer was also observed in subjects exposed to the highest levels of MC (OR = 2.36; 95% CI = 0.98 to 5.85). CONCLUSION: Our findings provide evidence that high exposure to PCE increases the risk of laryngeal cancer, and suggest an association between exposure to MC and hypopharyngeal cancer. Exposure to other chlorinated solvents was not associated with the risk of head and neck cancer.

Occupational exposure to solvents and risk of head and neck cancer in women: a population-based case-control study in France.

OBJECTIVE: Our objective was to investigate the association between head and neck cancer and occupational exposure to chlorinated, oxygenated and petroleum solvents in women. METHODS: Investigation of occupational and environmental CAuses of REspiratory cancers (ICARE), a French population-based case-control study, included 296 squamous cell carcinomas of the head and neck (HNSCC) in women and 775 female controls. Lifelong occupational history was collected. Job-exposure matrices allowed to assess exposure to 5 chlorinated solvents (carbon tetrachloride; chloroform; methylene chloride; perchloroethylene; trichloroethylene), 5 petroleum solvents (benzene; special petroleum product; gasoline; white spirits and other light aromatic mixtures; diesel, fuels and kerosene) and 5 oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). OR and 95% CIs, adjusted for smoking, alcohol drinking, age and geographical area, were estimated with logistic models. RESULTS: Elevated ORs were observed among women ever exposed to perchloroethylene (OR=2.97, 95% CI 1.05 to 8.45) and trichloroethylene (OR=2.15, 95% CI 1.21 to 3.81). These ORs increased with exposure duration (OR=3.75, 95% CI 0.64 to 21.9 and OR=4.44, 95% CI 1.56 to 12.6 for 10 years or more, respectively). No significantly increased risk of HNSCC was found for occupational exposure to the other chlorinated, petroleum or oxygenated solvents. CONCLUSIONS: These findings suggest that exposure to perchloroethylene or trichloroethylene may increase the risk of HNSCC in women. In our study, there is no clear evidence that the other studied solvents are risk factors for HNSCC.

Mediterranean diet and preserved brain structural connectivity in older subjects.

INTRODUCTION: The Mediterranean diet (MeDi) has been related to a lower risk of Alzheimer's disease; yet, the underlying mechanisms are unknown. We hypothesized that protection against neurodegeneration would translate into higher gray matter volumes, whereas a specific association with preserved white matter microstructure would suggest alternative mechanisms (e.g., vascular pathways). METHODS: We included 146 participants from the Bordeaux Three-City study nondemented when they completed a dietary questionnaire and who underwent a 3-T magnetic resonance imaging at an average of 9 years later, including diffusion tensor imaging. RESULTS: In multivariate voxel-by-voxel analyses, adherence to the MeDi was significantly associated with preserved white matter microstructure in extensive areas, a gain in structural connectivity that was related to strong cognitive benefits. In contrast, we found no relation with gray matter volumes. DISCUSSION: The MeDi appears to benefit brain health through preservation of structural connectivity. Potential mediation by a favorable impact on brain vasculature deserves further research.