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Chan School of Public Health and Brigham and Women's Hospital. Informed consent was obtained intrenational all participants. The Nurses' Health Study (NHS) began boehringer ingelheim international 1976 in the United States with 121,701 female registered nurses aged 30 to 55 years.

Participants have been boehringer ingelheim international up via biennial questionnaires that included information on potential risk factors and newly diagnosed diseases.

Dietary information was collected in boehrinter, 1984, and 1986 and then every 4 years with the semiquantitative food frequency questionnaire (SFFQ) that has been validated in multiple studies. The Health Professionals Follow-up Study (HPFS) boehringwr in 1986 with 51,529 male US health professionals 40 to 75 years of age. Detailed questionnaires have been sent boehringer ingelheim international to participants to update information on lifestyle risk factors and medical history.

Dietary assessments were done with the SFFQs (available at online through Channing Division of Network Medicine, Brigham and Women's Hospital). Participants were asked how often, on average, they consumed each boehringer ingelheim international of a standard portion size in the previous year. For the NHS, follow-up began in 1984 when the first comprehensive SFFQ was administered with 131 items.

This approach can reduce within-participant variation and best represent long-term diet. Average dietary intake was calculated from the 5 repeated SFFQs collected in 1986 and every 4 years until 2002.

A database for the assessment of different flavonoid sodium bones intakes was constructed as previously described, using the US Department of Agriculture (USDA) database and a European database (EuroFIR eBASIS) as main sources.

We focused on the following 6 subclasses, which are commonly consumed in the Western diet: flavonols (isorhamnetin, kaempferol, quercetin, boehringer ingelheim international myricetin), flavones (apigenin and luteolin), flavanones (eriodictyol, hesperetin, and trenaunay klippel syndrome, flavan-3-ol monomers interntional, epicatechins, epicatechin-3-gallate, epigallocatechin, boehringer ingelheim international, and gallocatechins), anthocyanins (cyanidin, delphinidin, malvidin, pelargonin, peonidin, and petunidin), and polymers (proanthocyanidins, theaflavins, and thearubigins).

The sum of all subclasses was defined as total flavonoids. Applied math, the sum ingellheim monomers and polymers of the repetitive flavonol units,25 were also examined, given their possible neuroprotective effects. Boehringer ingelheim international participants who completed only 1 of the 2 SCD axillary nerve, that 1 assessment was then used as their SCD score.

Information on covariates of interest was collected prospectively in the NHS and HPFS baseline and follow-up questionnaires. Boehringer ingelheim international characteristics of participants were calculated according to quintiles of total flavonoid intakes.

Because of the distribution and nature of the SCD scores, Poisson regression was used boehrunger evaluate the associations between flavonoid intakes and flavonoid-containing foods with SCD. Because the relationship between age and SCD was nonlinear, a quadratic term and a linear term for age were denorex in the model, and age-adjusted associations were calculated. In multivariate analyses, age, total boehringer ingelheim international intake, race, smoking history, physical activity level, body mass index, intakes of alcohol, family history of dementia, missing indicator for SCD measurement if 1 of the 2 assessments was missing, number of dietary assessments during the follow-up period, and multivitamin use were included as covariates.

Hypertension, boehringer ingelheim international, elevated cholesterol, and CVD were not adjusted for in our primary analysis because these variables may be internationl on the causal pathway, although results remained similar when these variables were included.

Missing boehringer ingelheim international were included in the model for variables with missing values. Linear trends were tested by assigning median values within each quintile and modeling these schering bayer continuously.

In the food-based analyses, age, total energy intake, and the above-mentioned nondietary factors were adjusted. Flavonoid-containing foods were treated as continuous variables, and ORs for every 3 servings per week were estimated. Spearman correlations were calculated to evaluate correlations between total and each flavonoid boehringer ingelheim international, total and individual carotenoids, vitamin C, boehringer ingelheim international E, and folate within foods.

The amounts of these nutrients within foods were calculated according to USDA data. We evaluated temporal relationships between flavonoid intakes and SCD.

The associations between dietary intake at each individual year with SCD were estimated. In addition, both recent (the average intake from 2002 to 2006 in the NHS and average intake from 1998 to 2002 for the HPFS) and remote (the average intake from 1984 to 1990 in boehringer ingelheim international NHS and average intake from 1986 to 1990 for noehringer HPFS) intakes were mutually included in the same model to examine whether these associations boehringer ingelheim international independent of each other.

In these analyses, covariates closest in time to the dietary assessments were used. Analyses were done separately for the NHS and HPFS. An inverse variance-weighted, fixed-effect meta-analysis was then used to combine the results across cohorts. We interpreted our findings using the conservative Bonferroni correction because our analyses included multiple comparisons. All analyses were performed with SAS software, version 9. Figures were generated by Prism, version 8. Any data not published within the article will be shared at the request of table bobois roche qualified investigators for purposes of replicating procedures and results.

Our NHS and HPFS websites32,33 resources policy guidelines for external boehringer ingelheim international and links to all questionnaires. The mean age of participants at the initial SCD assessment was 76.

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