Dataset Information

Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study.

ABSTRACT: It is unclear how coronary heart disease (CHD) risk across the adult life span affects late-life cognition. We estimated associations of midlife and late-life elevated CHD risk with cognitive trajectories (general cognitive performance, processing speed/executive function, memory) in later life (after age 55 years or age 70 years) among 2,892 Framingham Offspring Study participants who had completed CHD risk assessments approximately every 4 years since 1971 and had undergone neuropsychological testing between 1999 and 2014. We stratified analyses by apolipoprotein E gene (APOE) ?4 allele carrier status. Using linear mixed-effects models, elevated CHD risk in midlife (age 55 years) was associated with lower levels of general cognitive performance (? = -0.560 standard deviation (SD) units, 95% confidence interval (CI): -0.874, -0.246), executive function (? = -0.624 SD units, 95% CI: -0.916, -0.332), and memory (? = -0.560 SD units, 95% CI: -0.907, -0.213) at age 70 years but not with rates of cognitive change. Late-life (age 70 years) elevated CHD risk, however, was associated with somewhat better levels of general cognitive performance and memory. There were associations between duration of elevated CHD risk during midlife and levels (but not trajectories) of later-life cognitive outcomes. Associations were not modified by APOE-?4 status. These findings suggest that midlife elevated CHD risk is associated with lower cognition, independently of APOE-?4 status, suggesting that risk of vascular disease may not contribute a "second hit" to AD risk.

SUBMITTER: Armstrong NM

PROVIDER: S-EPMC7036653 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study.

Armstrong Nicole M NM Bangen Katherine J KJ Au Rhoda R Gross Alden L AL

American journal of epidemiology 20191201 12

It is unclear how coronary heart disease (CHD) risk across the adult life span affects late-life cognition. We estimated associations of midlife and late-life elevated CHD risk with cognitive trajectories (general cognitive performance, processing speed/executive function, memory) in later life (after age 55 years or age 70 years) among 2,892 Framingham Offspring Study participants who had completed CHD risk assessments approximately every 4 years since 1971 and had undergone neuropsychological ...[more]

PMID: 31576397

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Project description:BackgroundRemnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts.Methods and resultsWe analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort.ConclusionRLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation.Clinical trial registrationURL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.

Project description:BACKGROUND:The cell-cycle inhibitor and tumor suppressor cyclin dependent kinase inhibitor, p16ink4a, is one of the two gene products of the ink4a/ARF (cdkn2a) locus on chromosome 9q21. Up-regulation of p16ink4a has been linked to cellular senescence, and findings from studies on different mammalian tissues suggest that p16ink4a may be a biomarker of organismal versus chronological age. OBJECTIVE:The aim of this study was to examine the immunolocalization pattern of p16ink4a in human labial salivary gland (LSG) tissue, and to analyze whether its expression level in LSGs is a peripheral correlate of cognitive decline in late midlife. METHODS:The present study was a part of a study of causes and predictors of cognitive decline in middle-aged men in a Danish birth cohort. It is based on data from 181 male participants from the Danish Metropolit birth cohort, born in 1953, who were examined for age-associated alterations in cognition, dental health, and morphological and autonomic innervation characteristics of the LSGs. The participants were allocated to two groups based on the relative change in cognitive performance from young adulthood to late midlife. LSG biopsies were analyzed by qRT-PCR for the expression level of p16ink4a. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of LSGs. RESULTS:p16ink4a immunoreactivity was observed in LSG ductal, myoepithelial, and stromal cells, but not in acinar cells. The mean relative expression of p16ink4a in LSGs was higher in the group of participants with decline in cognitive performance. A logistic regression analysis revealed that the relative p16 expression was predictive of the participant's group assignment. A negative correlation was found between relative p16ink4a expression and the participant's standardized regression residuals from early adulthood to late midlife cognitive performance scores. CONCLUSIONS:p16ink4a expression in human LSGs may constitute a potential peripheral correlate of cognitive decline. Human labial salivary glands seem suitable for studies on organismal as opposed to chronological age.

Dataset Information

Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study.

Publications

Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study.

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