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Concept: Framingham, Massachusetts


Because people age differently, age is not a sufficient marker of susceptibility to disabilities, morbidities, and mortality. We measured nineteen blood biomarkers that include constituents of standard hematological measures, lipid biomarkers, and markers of inflammation and frailty in 4704 participants of the Long Life Family Study (LLFS), age range 30-110 years, and used an agglomerative algorithm to group LLFS participants into clusters thus yielding 26 different biomarker signatures. To test whether these signatures were associated with differences in biological aging, we correlated them with longitudinal changes in physiological functions and incident risk of cancer, cardiovascular disease, type 2 diabetes, and mortality using longitudinal data collected in the LLFS. Signature 2 was associated with significantly lower mortality, morbidity, and better physical function relative to the most common biomarker signature in LLFS, while nine other signatures were associated with less successful aging, characterized by higher risks for frailty, morbidity, and mortality. The predictive values of seven signatures were replicated in an independent data set from the Framingham Heart Study with comparable significant effects, and an additional three signatures showed consistent effects. This analysis shows that various biomarker signatures exist, and their significant associations with physical function, morbidity, and mortality suggest that these patterns represent differences in biological aging. The signatures show that dysregulation of a single biomarker can change with patterns of other biomarkers, and age-related changes of individual biomarkers alone do not necessarily indicate disease or functional decline.

Concepts: Sociology, Framingham, Massachusetts, Ageing, Senescence, Epidemiology, Death, Framingham Heart Study, Longitudinal study


Background The prevalence of dementia is expected to soar as the average life expectancy increases, but recent estimates suggest that the age-specific incidence of dementia is declining in high-income countries. Temporal trends are best derived through continuous monitoring of a population over a long period with the use of consistent diagnostic criteria. We describe temporal trends in the incidence of dementia over three decades among participants in the Framingham Heart Study. Methods Participants in the Framingham Heart Study have been under surveillance for incident dementia since 1975. In this analysis, which included 5205 persons 60 years of age or older, we used Cox proportional-hazards models adjusted for age and sex to determine the 5-year incidence of dementia during each of four epochs. We also explored the interactions between epoch and age, sex, apolipoprotein E ε4 status, and educational level, and we examined the effects of these interactions, as well as the effects of vascular risk factors and cardiovascular disease, on temporal trends. Results The 5-year age- and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch (late 1970s and early 1980s), 2.8 per 100 persons during the second epoch (late 1980s and early 1990s), 2.2 per 100 persons during the third epoch (late 1990s and early 2000s), and 2.0 per 100 persons during the fourth epoch (late 2000s and early 2010s). Relative to the incidence during the first epoch, the incidence declined by 22%, 38%, and 44% during the second, third, and fourth epochs, respectively. This risk reduction was observed only among persons who had at least a high school diploma (hazard ratio, 0.77; 95% confidence interval, 0.67 to 0.88). The prevalence of most vascular risk factors (except obesity and diabetes) and the risk of dementia associated with stroke, atrial fibrillation, or heart failure have decreased over time, but none of these trends completely explain the decrease in the incidence of dementia. Conclusions Among participants in the Framingham Heart Study, the incidence of dementia has declined over the course of three decades. The factors contributing to this decline have not been completely identified. (Funded by the National Institutes of Health.).

Concepts: Framingham, Massachusetts, Stroke, Atrial fibrillation, 1990s, Risk, Epidemiology, Medical statistics, Life expectancy


Objective To determine the role of early onset versus late onset hypertension as a risk factor for hypertension in offspring and cardiovascular death.Design Multigenerational, prospective cohort study.Setting Framingham Heart Study.Participants Two generations of community dwelling participants with blood pressure measurements performed at serial examinations spanning six decades: 3614 first generation participants with mortality data and 1635 initially non-hypertensive second generation participants with data available on parental blood pressure.Main outcome measures The main outcome measures were relation of parental early onset hypertension (age <55 years) with incidence of hypertension in offspring, using regression analyses, and relation of age at hypertension onset with cause specific mortality using a case (cardiovascular death) versus control (non-cardiovascular death) design.Results In second generation participants, having one or both parents with late onset hypertension did not increase the risk of hypertension compared with having parents with no hypertension; by contrast, the hazard ratios of hypertension were 2.0 (95% confidence interval 1.2 to 3.5) and 3.5 (1.9 to 6.1) in participants with one and both parents with early onset hypertension, respectively. In first generation decedents, 1151 cardiovascular deaths occurred (including 630 coronary deaths). The odds of cardiovascular death increased linearly with decreasing age of hypertension onset (P<0.001 for trend). Compared with non-hypertensive participants, hypertension onset at age <45 years conferred an odds ratios of 2.2 (1.8 to 2.7) for cardiovascular death and 2.3 (1.8 to 2.9) for coronary death, whereas hypertension onset at age ≥65 years conferred a lower magnitude odds ratios of 1.5 (1.2 to 1.9) for cardiovascular death and 1.4 (0.98 to 1.9) for coronary death (P≤0.002 for differences in odds ratios between hypertension onset at age <45 and age ≥65).Conclusions Early onset and not late onset hypertension in parents was strongly associated with hypertension in offspring. In turn, early onset compared with late onset hypertension was associated with greater odds of cardiovascular, and particularly coronary, death. These findings suggest it may be important to distinguish between early onset and late onset hypertension as a familial trait when assessing an individual's risk for hypertension, and as a specific type of blood pressure trait when estimating risk for cardiovascular outcomes in adults with established hypertension.

Concepts: Parent, Framingham, Massachusetts, Epidemiology, Risk, Blood, Blood pressure, Death, Heart


Soluble ST2 (sST2) is a cardiac biomarker whose concentration rises in response to myocardial strain. Increased sST2 concentrations may predict adverse outcomes in patients with heart failure and myocardial infarction. Because sST2 was largely undetectable with first-generation assays in ambulatory individuals, there are few data regarding its distribution and correlates in community-based populations.

Concepts: Cardiac arrest, Solution, Framingham Heart Study, Circulatory system, Cardiology, Framingham, Massachusetts, Heart, Myocardial infarction


BACKGROUND AND PURPOSE: Parental stroke has been related to an increased risk of stroke in the offspring. This study examines whether parental stroke is also associated with increased vascular brain injury and poorer cognitive performance among offspring free of clinical stroke. METHODS: Multivariable regression analyses were used to relate parental stroke to cross-sectional and change in brain magnetic resonance imaging measures and cognitive function among the offspring, with and without adjustment for vascular risk factors. RESULTS: Stroke- and dementia-free Framingham Offspring (n=1297, age, 61±9 years, 54% women) were studied. Parental stroke by age 65 years was associated with a higher baseline white matter hyperintensity volume (β=0.17±0.08; P=0.027) and with lower visual memory performance (β= -0.80±0.34; P=0.017). During a 6-year follow-up, parental stroke was also associated with increase in white matter hyperintensity volume (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.03-3.38) and decline in executive function (Trails B-A; OR, 1.81; 95% CI, 1.06-3.09). The associations with white matter hyperintensity volume and visual memory attenuated after additional adjustment for concomitant vascular risk factors. CONCLUSIONS: Parental stroke by age 65 years is associated with increased vascular brain injury and lower memory in offspring equivalent to 3 and 7 years of brain aging, respectively. This may be partly attributed to inheritance of vascular risk factors.

Concepts: Framingham Heart Study, Framingham, Massachusetts, Regression analysis, Memory, Cognition, Psychology, Magnetic resonance imaging, Brain


Understanding the social and biological mechanisms that lead to homogamy (similar individuals marrying one another) has been a long-standing issue across many fields of scientific inquiry. Using a nationally representative sample of non-Hispanic white US adults from the Health and Retirement Study and information from 1.7 million single-nucleotide polymorphisms, we compare genetic similarity among married couples to noncoupled pairs in the population. We provide evidence for genetic assortative mating in this population but the strength of this association is substantially smaller than the strength of educational assortative mating in the same sample. Furthermore, genetic similarity explains at most 10% of the assortative mating by education levels. Results are replicated using comparable data from the Framingham Heart Study.

Concepts: Framingham, Massachusetts, Education, DNA, Biology, Marriage, Assortative mating, Demography, Mating


Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS).

Concepts: Longitudinal study, Sleep, Framingham Heart Study, Framingham, Massachusetts


Previous studies have identified effects of age and vascular risk factors on brain injury in elderly individuals. We aimed to establish whether the effects of high blood pressure in the brain are evident as early as the fifth decade of life.

Concepts: Longitudinal study, Framingham, Massachusetts, Vein, Orthostatic hypotension, Blood, Artery, Hypertension, Blood pressure


Previous work from the Framingham Heart Study suggests that brain changes because of arterial aging may begin in young adulthood and that such changes precede cognitive deficits. The objective of this study was to determine the association of arterial stiffness with measures of white matter and gray matter (GM) integrity in young adults.

Concepts: The Association, Adult, Neuroanatomy, Central nervous system, Galen, Hardness, Framingham Heart Study, Framingham, Massachusetts


Research has explored associations between diet, body weight, and the food environment; however, few studies have examined historical trends in food environments.

Concepts: Environment, Framingham Heart Study, Framingham, Massachusetts