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Background: High Inflammatory content of diet enhances systemic chronic inflammation, a pathway which plays an important role in the development and progression of dementia. We investigated the cross‐sectional relationships between long‐term Dietary Inflammatory Index (DII) scores and beta‐amyloid(Aβ) and tau Positron Emission Tomography(PET) among participants of the community‐based Framingham Heart Study(FHS). Method: 343 adults (mean age 58 years [standard deviation (SD)], 10; 51% women]) completed a validated 126‐item Food Frequency Questionnaire (FFQ). We created a DII score (based on the published method by Shivappa et al. 2014) based on previous studies linking individual dietary factors to six inflammatory markers (i.e. C‐reactive protein, interleukin (IL)‐1β, IL‐4, IL‐6, IL‐10 and tumor necrosis factor‐alpha), consisting of 34 components. A cumulative DII score was calculated by averaging across two FFQs (administered at FHS Generation 2(GEN2) examination cycles 8(2005‐2008) and 9(2011‐2014), and at Generation 3(GEN3) examination cycles 2 (2008‐2011) and 3 (2016‐2019). Cumulative DII scores were examined as a continuous variable and using median‐split(‐1.11). Aβ and tau PET examinations were conducted(2016‐2021) using synthesized 11C‐Pittsburgh compound B(PiB) and/or F‐18‐flortaucipir(FTP) tracers. Examination cycles 9(GEN2) and 3(GEN3) were considered as study baseline. We used linear regression to relate the cumulative DII score to Aβ (Fronto‐lateral‐retrosplenial uptake(FLR) and precuneus) and tau (entorhinal, inferior temporal, rhinal, cortical composite and global composite) PET regions. Result: Higher cumulative DII scores, as compared to DII scores below the median, were associated with higher amyloid precuneus region (β±SE, 0.023±0.011,p = 0.042) after adjustment for age, age‐squared, sex, camera and time between DII exam and PET scan exam. No other relationships were observed between DII and Aβ and tau PET. Interaction analyses showed interactions between DII (median‐split) and age (median‐split 58y) when testing association between median‐split DII and Aβ regions and tau global composite region. Stratified analyses showed relationships between higher DII vs. below median DII and higher amyloid FLR and precuneus region (0.055 ± 0.055,p = 0.037; 0.050±0.022,p = 0.022,respectively) among individuals aged 58y>, but not among individuals <58y (‐0.004±0.006,p = 0.947;0.000±0.000,p = 0.999,respectively). There were no significant interactions by sex and apolipoproteinE4 status in the association between DII and Aβ and tau PET. Conclusion: Higher DII scores were associated with increased Aβ deposition. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Consumption of foods with high flavonoid content may be protective against dementia in older adults, but it is unclear whether this relationship is consistent earlier in life. We investigated the relationship between consumption of flavonoid‐rich fruits in midlife and risk of dementia, including Alzheimer's disease (AD). Method: 1,642 participants from the Framingham Heart Study Offspring cohort who were aged 45‐59 years and did not have prevalent dementia at Exam 5 (1991‐1995), and had a valid food frequency questionnaire data were included. Intake of 12 fruit items with high flavonoid content or are important contributors to overall flavonoid intake at Exam 5 were examined. Total fruit intake was calculated by summing intake of each fruit item. Diagnoses of all‐cause dementia and AD dementia were adjudicated by a multi‐disciplinary consensus committee through 2019. Cox models were used to evaluate the association between higher intake (>30th percentile) versus lower intake (≤30th percentile) of total fruit consumption, as well for each fruit item, and incident dementia, adjusting for demographic, behavior and lifestyle, dietary, genetic, and clinical factors. Result: The sample was, on average, 52 years of age, 53% female, and had 14 years of education, with an average follow up time of 24 years in the study. Higher intake of total fruits was associated with decreased risk of all‐cause dementia (HR = 0.56; 95% CI = 0.32 – 0.98), but not with AD dementia. Decreased risk of all‐cause dementia was associated with higher intake of apples or pears (HR = 0.47; 95% CI = 0.27 – 0.81), and oranges (HR = 0.55; 95% CI = 0.32 – 0.95). Higher intakes of apples or pears (HR = 0.50; 95% CI = 0.25 – 1.00), and oranges (HR = 0.43; 95% CI = 0.22 – 0.85), were also associated with decreased risk of AD dementia. Sex modified the association between total fruit intake in midlife and dementia risk (HRfemale = 0.46; 95% CI = 0.21 – 0.97; HRmale = 0.65; 95% CI = 0.27 – 1.60). Conclusion: Greater consumption of flavonoid‐rich fruits in midlife, particularly apples or pears, as well as oranges, were significantly associated with reduced dementia risk. [ABSTRACT FROM AUTHOR]

Background: Nutritional factors can abet or protect against systemic chronic inflammation, which plays an important role in the development and progression of dementia. We evaluated whether higher (i.e. pro‐inflammatory) Dietary Inflammatory Index(DII) scores were associated with accelerated cognitive decline in the community‐based Offspring Framingham Heart Study(FHS). Method: 889 older adults (mean age 59 years [standard deviation (SD)], 8;58.3% women]) completed validated 126‐item Food Frequency Questionnaires(FFQ), administered at FHS examination cycle 7 (1998‐2001) and examination cycle 5 (1991‐1995) and/or 6 (1995‐1998). We created a DII score (based on the published method by Shivappa et al. 2014); a cumulative DII score was calculated by averaging across a maximum of three FFQs. Cognitive testing was completed at examination cycles 7, 8 (2005‐2008) and 9 (2011‐2014). Exam 7 was considered as study baseline and participants were followed over a mean time of 13.4 years (SD 1.3). We excluded participants with prevalent dementia or stroke at baseline and those with no cognitive testing follow‐up data. We examined associations between the cumulative DII score and cognitive test scores over time using linear mixed models adjusting for age, age‐squared, sex, education, time from exam 7 to neuropsychological exam 7, and time (model1) and additionally for apolipoprotein e4, body mass index, total energy intake, total cholesterol: high‐density lipoprotein ratio, physical activity, smoking and anti‐cholesterol medication (model2). Result: Higher DII scores were significantly associated with accelerated decline in performance on the Trail Making Test B minus A(TMT‐B minus A) (processing speed and executive function), following adjustment for model 1 covariates (β±SE, ‐0.001± 0.0004,p = 0.03). but the association failed to reach significance in Model 2 (‐0.001±0.0003,p = 0.08). We observed no relationship between higher DII scores and other cognitive domains. Stratified analyses showed that higher DII scores were associated with accelerated decline in TMT‐B minus A scores among apolipoprotein e4 carriers (Model 2:‐0.002±0.001,p = 0.047) but not among non‐carriers (Model 2:‐0.0004±0.0004,p = 0.33). Conclusion: Higher DII scores were not associated with cognitive decline. To date, such studies have been very limited, most studies that found a relationship, were cross‐sectional and have used less sensitive testing. Future studies are encouraged to examine whether our findings can be replicated. [ABSTRACT FROM AUTHOR]

Introduction Excess sugar consumption has been linked with Alzheimer's disease (AD) pathology in animal models. Methods We examined the cross-sectional association of sugary beverage consumption with neuropsychological ( N = 4276) and magnetic resonance imaging ( N = 3846) markers of preclinical Alzheimer's disease and vascular brain injury (VBI) in the community-based Framingham Heart Study. Intake of sugary beverages was estimated using a food frequency questionnaire. Results Relative to consuming less than one sugary beverage per day, higher intake of sugary beverages was associated with lower total brain volume (1–2/day, β ± standard error [SE] = −0.55 ± 0.14 mean percent difference, P = .0002; >2/day, β ± SE = −0.68 ± 0.18, P < .0001), and poorer performance on tests of episodic memory (all P < .01). Daily fruit juice intake was associated with lower total brain volume, hippocampal volume, and poorer episodic memory (all P < .05). Sugary beverage intake was not associated with VBI in a consistent manner across outcomes. Discussion Higher intake of sugary beverages was associated cross-sectionally with markers of preclinical AD. [ABSTRACT FROM AUTHOR]

Short self-reported sleep duration is associated with dietary intake and this association may partly mediate the link between short sleep and metabolic abnormalities. Subjective sleep measures, however, may be inaccurate and biased. The objective of this study was to evaluate the associations between actigraphic measures of sleep fragmentation, efficiency and duration and energy and macronutrient intakes. We used data from a subgroup of 439 participants of the population-based cohort, Rotterdam Study. Sleep was assessed using 7-day actigraphy and sleep diaries, and dietary data with a validated food frequency questionnaire. We assessed the associations of actigraphic sleep parameters with dietary intake using multivariable linear regression models. Higher sleep fragmentation was associated with 4.19 g lower carbohydrate intake per standard deviation of fragmentation { β [95% confidence interval ( CI) = −4.19 (−8.0, −0.3)]; P = 0.03}. Each additional percentage increase in sleep efficiency was associated with 11.1 kcal lower energy intake [ β (95% CI) = −11.1 (−20.6, −1.7); P = 0.02]. Furthermore, very short sleep duration (<5.5 h) was associated with 218.1 kcal higher energy intake [ β (95% CI = 218.06 (33.3, 402.8), P = 0.02], relative to the reference group (≥6.5 to <7.5 h). We observed associations between higher sleep fragmentation with lower carbohydrate intake, and both lower sleep efficiency and very short sleep duration (<5 h) with higher energy intake. The association between sleep and higher energy intake could mediate, in part, the link between short sleep or sleep fragmentation index and metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to examine the relationship between usual sugar-sweetened beverage (SSB) consumption and prevalence of abnormal metabolic health across body mass index (BMI) categories. Methods The metabolic health of 6,842 non-diabetic adults was classified using cross-sectional data from the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. Adults were classified as normal weight, overweight or obese and, within these categories, metabolic health was defined based on five criteria-hypertension, elevated fasting glucose, elevated triglycerides, low HDL cholesterol, and insulin resistance. Individuals without metabolic abnormalities were considered metabolically healthy. Logistic regression was used to examine the associations between categories of SSB consumption and risk of metabolic health after stratification by BMI. Results Comparing the highest category of SSB consumers (median of 7 SSB per week) to the lowest category (non-consumers), odds ratios (95% confidence intervals) for metabolically abnormal phenotypes, compared to the metabolically normal, were 1.9 (1.1-3.4) among the obese, 2.0 (1.4-2.9) among the overweight, and 1.9 (1.4-2.6) among the normal weight individuals. Conclusions In this cross-sectional analysis, it is observed that, irrespective of weight status, consumers of SSB were more likely to display metabolic abnormalities compared to non-consumers in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Objectives To investigate the cognitive significance of low to low-normal plasma vitamin B-12 concentrations and to shed light on the role that folate status plays in the association between vitamin B-12 status and cognitive decline. Design Associations between plasma vitamin B-12 and folate and 8-year cognitive decline were evaluated, and the effects of interactions between vitamin B-12 status and folate status and supplemental folate use on cognitive decline were assessed. Setting The Framingham Heart Study - a prospective epidemiological study. Participants Five hundred forty-nine community-dwelling individuals aged 74.8 ± 4.6. Measurements Mini-Mental State Examination ( MMSE), plasma folate, vitamin B-12, methylmalonic acid, homocysteine, demographic factors, and body mass index. Results MMSE scores declined by 0.24 points per year over the 8-year follow-up period. Decline was significantly faster in cohort members in the bottom two plasma vitamin B-12 quintile categories, and no apparent cognitive advantage was associated with plasma vitamin B-12 from 187 to 256.8 pmol/L over less than 186 pmol/L. In cohort members with plasma vitamin B-12 less than 258 pmol/L, having a plasma folate concentration greater than 20.2 nmol/L was associated with an approximate 1-point per year decline, as was use of supplemental folate. Conclusion Plasma vitamin B-12 levels from 187 to 256.8 pmol/L predict cognitive decline. Furthermore, having plasma vitamin B-12 levels in this range or below in conjunction with high plasma folate or supplemental folate use predicts especially rapid cognitive decline. [ABSTRACT FROM AUTHOR]

Vitamin E supplementation has been suggested to improve immune response in the aged in part by altering cytokine production. However, there is not a consensus regarding the effect of supplemental vitamin E on cytokine production in humans. There is evidence that baseline immune health can affect immune response to supplemental vitamin E in the elderly. Thus, the effect of vitamin E on cytokines may depend on their pre-supplementation cytokine response. Using data from a vitamin E intervention in elderly nursing home residents, we examined if the effect of vitamin E on ex vivo cytokine production of IL-1β, IL-6, TNF-α, and IFN-γ depended on baseline cytokine production. We observed that the effect of vitamin E supplementation on cytokine production depended on pre-supplementation production of the respective cytokines. The interactions between vitamin E and baseline cytokine production were not explained by covariates known to impact cytokine production. Our results offer evidence that baseline cytokine production should be considered in studies that examine the effect of supplemental vitamin E on immune and inflammatory responses. Our results could have implications in designing clinical trials to determine the impact of vitamin E on conditions in which cytokines are implicated such as infections and atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prognostic role of the inflammatory cytokine, interleukin 6 (IL-6), and insulin-like growth factor-1 (IGF-1) in predicting 2-year changes in fat-free mass (FFM) while controlling for potential confounders. Design: Population-based cohort, the Framingham Heart Study, examined in 1992–93 and 1994–95. Setting: General community. Participants: Two hundred thirty-two men and 326 women aged 72 to 92. Measurements: IGF-1 was measured using radio-immunoassay and cellular IL-6 production using non-cross-reacting radioimmunoassays. FFM was estimated using population-specific equations for predicting FFM from bioelectrical impedance analysis developed separately for men and women. Results: Higher IGF-1 predicted smaller loss of FFM in men than lower IGF-1 did (P =.002), after adjusting for age, baseline FFM, fat mass, and 2-year weight changes, whereas cellular IL-6 was a significant predictor of sarcopenia in women (P =.02). Weight change was a strong determinant of change in FFM in both sexes (P <.0001). Conclusion: Predictors of sarcopenia include body composition characteristics that are common to men and women and sex-specific metabolic predictors. Sarcopenia appears to reflect a withdrawal of anabolic stimuli, such as growth hormone, in men but an increase in catabolic stimuli, such as cellular IL-6, in women. [ABSTRACT FROM AUTHOR]

Nutritional influences on bone health are well-characterized. Yet, little is known about the correlates and heritability of vitamins K and D, both of which are involved in bone mineralization. The clinical correlates and heritability of measures of vitamin K (plasma phylloquinone and serum % undercarboxylated osteocalcin) and vitamin D status [plasma 25(OH)D] were assessed in 843 men and 919 women (mean age 59 yrs) participating in the Framingham Offspring Study. Associations between biologically plausible clinical factors and measures of vitamins K and D status were determined using stepwise regression. Heritability was determined by SOLAR. Clinical factors accounted for 13.1 (men) and 16.3% (women) of the variability in plasma phylloquinone, with triglycerides and vitamin K intake being the primary correlates; heritability estimates were non-significant. In men 17.1%, and in women 14.6% of the variability in %ucOC was explained by clinical factors in our models; estimated heritability was significant at 23.3% (p = 0.01). Season and vitamin D intake explained 24.7% (men) and 23.8 % (women) of the variability in plasma 25(OH)D, and estimated heritability was 34.8% (p<0.01). In summary, plasma phylloquinone was not significantly heritable, but was associated with triglycerides and vitamin K intake. In contrast, %ucOC, and 25(OH)D were found to be significantly heritable. [ABSTRACT FROM AUTHOR]

Healthy dietary patterns during adulthood may result in reduced hip fracture risk. We examined whether a diet consistent with the 2005 DGA, a government-promulgated healthy dietary pattern to reduce the risk of chronic diseases, was associated with lower risk of incident hip fracture in Framingham Heart Study men and women. We developed a 20-item index (DGAI) to estimate adherence to key DGA dietary recommendations: intake of fruit, legumes, dark green, orange, starchy, and other vegetables, grains, meat, dairy; variety; discretionary calories; % whole grains; % calories as total, saturated, and trans fat; % low fat dairy / lean meat; intake of fiber, cholesterol, sodium, and alcohol. Each DGAI item is scored: 1=meets recommendation, 0.5=partially meets, 0=does not meet. Diet was assessed by food frequency questionnaire at baseline (mean age 76 y). Hip fractures (n=102) were assessed over 14 years (1988 to 2003). Cox-proportional hazards was used to assess risk ratios (95% CI) of hip fracture by DGAI. 386 men and 617 women (67-95 y) had DGAI values between 3.0-16.5 (possible range: 0-20). There was no significant association between DGAI and hip fracture, RR=1.03 (0.95, 1.12), after adjustment for covariates. An overall healthy diet among older individuals does not appear to reduce incident hip fracture risk. Diet earlier in life may be more important in preventing hip fracture than recent dietary intakes. [ABSTRACT FROM AUTHOR]

The traditional Mediterranean diet is associated with a lower risk of cardiovascular diseases (CVD). Improved insulin sensitivity may be one mechanism by which adoption of Mediterranean-style dietary pattern may reduce CVD risk. A diet score was developed to capture a Mediterranean-style dietary pattern in the Framingham Offspring Cohort. We examined the relationship between this diet score and insulin resistance markers (fasting & 2-hr plasma glucose & insulin and the homeostasis model assessment insulin resistance [HOMA-IR]) in 1238 men & 1505 women without diabetes in the cohort. After adjustment for potential confounding factors, a higher diet score, reflecting greater similarity to Mediterranean-style dietary pattern, was associated with lower fasting insulin levels (mean 35 vs 32 µU/mL in the lowest vs highest quartiles of diet score; P trend<0.01), 2-hr insulin (116 vs 98 µU/mL; P trend<0.01), HOMA-IR (8.4 vs 7.7; P trend<0.01) in subjects with abdominal obesity (waist circumference >108 cm in men or >88 cm in women), but not in those with lesser waist circumferences. No significant association was found between the Mediterranean diet score and fasting and 2-hr glucose. In individuals with greater abdominal adiposity, greater consistency with a Mediterranean-style dietary pattern was associated with better insulin sensitivity. [ABSTRACT FROM AUTHOR]

Background The conjoint associations of adherence to the recent physical activity and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood. Methods and Results We evaluated 2379 FHS (Framingham Heart Study) Third Generation participants (mean age, 47 years; 54.4% women) attending examination cycle 2. We examined the cross-sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (binary; moderate-to-vigorous physical activity ≥150 versus <150 min/wk) and 2015 Dietary Guidelines for Americans (binary; 2015 Dietary Guidelines for Americans Adherence Index ≥median versus

Objective: Poor intake of vitamin K is common. Insufficient vitamin K can result in abnormal cartilage and bone mineralization. Furthermore, osteophyte growth, seen in osteoarthritis (OA), may be a vitamin K-dependent process. We undertook this study to determine whether vitamin K deficiency is associated with radiographic features of OA., Methods: We conducted an analysis among 672 participants (mean age 65.6 years, 358 women) in the Framingham Offspring Study, a population-based prospective observational cohort. Levels of plasma phylloquinone (the primary form of vitamin K) had previously been measured in these participants, for whom we also had bilateral hand and knee radiographs. The main outcomes were 1) prevalence ratios (PRs) of OA, osteophytes, and joint space narrowing (JSN) per quartile of plasma phylloquinone level for each joint, adjusting for correlated joints using generalized estimating equations, and 2) adjusted mean number of joints with each feature per quartile of plasma phylloquinone level. Analyses were conducted in hands and knees separately and adjusted for age, sex, body mass index, total energy intake, plasma vitamin D, and femoral neck bone mineral density., Results: The PRs for OA, osteophytes, and JSN and adjusted mean number of joints with all 3 features in the hand decreased significantly with increasing plasma phylloquinone levels (P