Diet Quality Scores are Positively Associated with Whole Blood-derived Mitochondrial DNA Copy Number in the Framingham Heart Study

Background Association between diet quality and mitochondrial DNA copy number (mtDNA-CN) remains to be examined. Objectives We aimed to study the relationship between diet quality and mtDNA-CN. Methods We analyzed data from 2,931 Framingham Heart Study (FHS) participants with mean age of 57 years and 55% females. Whole genome sequencing was used to calculate mtDNA-CN from whole blood samples. We examined the cross-sectional associations between three diet quality scores, the Dietary Approaches to Stop Hypertension (DASH) score, the Alternative Healthy Eating Index (AHEI), and the Mediterranean diet-style score (MDS), and mtDNA-CN. Linear mixed models were used to account for maternal lineage. Results We observed that a higher DASH score was positively associated with mtDNA-CN after adjusting for sex, age, energy intake, smoking status, alcohol intake, and physical activity level. One standard deviation (SD) increase in the DASH score was associated with a 0.042 SD greater mtDNA-CN (95% CI: 0.007, 0.077; P = 0.02). Similarly, for each SD increase in AHEI and MDS, mtDNA-CN increased by 0.056 (95% CI: 0.019, 0.092; P = 0.003) and 0.047 (95% CI: 0.01, 0.083; P = 0.01), respectively. Diet quality scores were associated with neutrophil and lymphocyte counts but not platelet counts, e.g., for one SD increase in the DASH, neutrophils decreased by 0.8% (95% CI: 0.5%, 1.1%; P = 4.1 × 10–6), lymphocytes increased by 0.7% (95% CI: 0.4%, 1%, P = 1.2 × 10–5), and there was no significant change in platelet, 0.1 thousands/μL (95% CI: –1.6, 1.9; P = 0.89). Further adjustment for neutrophil, lymphocyte, and platelet counts, the associations between diet quality scores and mtDNA-CN were completely attenuated to nonsignificant (P = 0.95, 0.54, and 0.91, respectively). Conclusions We observed that higher diet quality is associated with a greater whole blood derived mtDNA-CN in middle aged to older adults in FHS participants, and that blood cell composition, particularly neutrophil counts, attenuated the association between diet quality and mtDNA-CN.

Increasing mixed-berry flavonoid intake may reduce depressive symptoms in older adults: Framingham Heart Study

Depression affects more than 250 million people worldwide. Although epidemiological studies have linked higher dietary flavonoids with depression prevention in older women, it is unknown if increasing dietary flavonoids could effectively reduce depression. Mixed berries (blueberry, blackberry, and raspberry) are a rich source of flavonoids, particularly anthocyanin, flavanol, and flavan-3-ol subclasses. Our aim was to determine the association of mixed-berry flavonoid intake with change in depressive symptoms over ~8 years in older adults from the Framingham Heart Study. This community-based prospective longitudinal study included 1,278 adults with assessments on diet (food frequency questionnaire) and depressive symptoms (Center for Epidemiologic Studies Depression, CES-D) at baseline (1998-2001) and follow-up (2005-2008). Absolute change in mixed-berry flavonoid intake (defined as sum of anthocyanin, flavanol, and flavon-3-ols, mg/day) and change in CES-D scores were calculated. Linear regression estimated beta and standard error (SE) for change in CES-D scores per 250 mg/day increase in mixed-berry flavonoids (obtained from ~3/4 cup of mixed berries), adjusting for baseline age, sex, energy-intake, current smoking, body mass index, physical activity, cardiovascular disease, and non-melanoma cancer. Mean age was 59±9 years (range: 33-81), 57% female and mean change in mixed-berry flavonoid intake was 15.0±72.8 mg/day over ~8 years. In adjusted models, each 250 mg/day increase in mixed-berry flavonoid intake was associated with a 1-point reduction in depressive symptoms (beta: -1.06, SE: 0.61, p=0.08) over ~8 years, although this was not statistically significant. These data highlight the need for randomized clinical trials of flavonoid-rich berries to target depressive symptoms in older adults.

The Neutrophil to Lymphocyte Ratio Is Associated With the Risk of Subsequent Dementia in the Framingham Heart Study

Objective: Active neutrophils are important contributors to Alzheimer’s disease (AD) pathology through the formation of capillary stalls that compromise cerebral blood flow (CBF) and through aberrant neutrophil signaling that advances disease progression. The neutrophil to lymphocyte ratio (NLR) is a proxy of neutrophil-mediated inflammation, and higher NLR is found in persons diagnosed with clinical AD. The objective of this study was to investigate whether increased NLR in older adults is independently associated with the risk of subsequent dementia.Methods: We examined associations of baseline NLR with incident dementia risk in the community-based Framingham Heart Study (FHS) longitudinal cohorts. The association between NLR and risk of dementia was evaluated using the cumulative incidence function (CIF) and inverse probability-weighted Cox proportional cause-specific hazards regression models, with adjustment for age, sex, body mass index (BMI), systolic and diastolic blood pressure, diabetes, current smoking status, low-density lipoprotein (LDH), high-density lipoprotein (LDL), total cholesterol, triglycerides, and history of cardiovascular disease (CVD). Random forest survival models were used to evaluate the relative predictive value of the model covariates on dementia risk.Results: The final study sample included 1,648 participants with FHS (average age, 69 years; 56% women). During follow-up (median, 5.9 years), we observed 51 cases of incident dementia, of which 41 were AD cases. Results from weighted models suggested that the NLR was independently associated with incident dementia, and it was preceded in predictive value only by age, history of CVD, and blood pressure at baseline.Conclusion: Our study shows that individuals with higher NLR are at a greater risk of subsequent dementia during a 5.9-year follow-up period. Further evaluating the role of neutrophil-mediated inflammation in AD progression may be warranted.