Plasma phospholipid very-long-chain SFAs in midlife and 20-year cognitive change in the Atherosclerosis Risk in Communities (ARIC): a cohort study

Abstract Background Very-long-chain SFAs (VLSFAs) have recently gained considerable attention as having beneficial effects on health and aging. Objectives The objective of this study was to assess the associations of plasma phospholipid VLSFAs [arachidic acid (20:0), behenic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0)] with 20-y cognitive decline in the Atherosclerosis Risk in Communities (ARIC) participants. Furthermore, this study compared the associations of plasma phospholipid VLSFAs with 5 common groups of fatty acids [i.e., total SFAs, total MUFAs, total ω-3 (n–3) PUFAs, total marine-derived ω-3 PUFAs, total ω-6 PUFAs]. Methods This study used a cohort study design of 3229 ARIC participants enrolled at the Minnesota field center. Fatty acids were measured at visit 1 (1987–1989); and cognition was assessed at visits 2 (1990–1992), 4 (1996–1998), and 5 (2011–2013) using 3 tests: the Delayed Word Recall Test (DWRT), the Digit-Symbol Substitution Test (DSST), and the Word Fluency Test (WFT). Results Higher proportions of plasma phospholipid total VLSFAs and each individual VLSFA were associated with less decline in WFT, a test of verbal fluency. For example, 1 SD higher in total VLSFAs at baseline was associated with 0.057 SD (95% CI: 0.018, 0.096, P = 0.004) less cognitive decline over 20 y as measured by WFT score. None of the 5 common fatty acid groups were associated with change in WFT, but a higher proportion of plasma phospholipid total MUFAs was associated with greater decline in DWRT; higher total ω-6 PUFAs with less decline in DWRT; and higher total ω-3 and total marine-derived ω-3 PUFAs with less decline in DSST. Conclusions This study suggests that higher proportions of plasma phospholipid VLSFAs in midlife may be associated with less 20-y cognitive decline.

Download Full-text

n–3 Fatty acids, hypertension and risk of cognitive decline among older adults in the Atherosclerosis Risk in Communities (ARIC) study

Public Health Nutrition ◽

10.1017/s1368980007000080 ◽

2008 ◽

Vol 11 (1) ◽

pp. 17-29 ◽

Cited By ~ 35

Author(s):

May A Beydoun ◽

Jay S Kaufman ◽

Philip D Sloane ◽

Gerardo Heiss ◽

Joseph Ibrahim

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Cognitive Decline ◽

Screening Tools ◽

Word Recall ◽

Plasma Fatty Acid ◽

Men And Women ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk ◽

Long Chain

AbstractObjectiveRecent research indicates that n–3 fatty acids can inhibit cognitive decline, perhaps differentially by hypertensive status.DesignWe tested these hypotheses in a prospective cohort study (the Atherosclerosis Risk in Communities). Dietary assessment using a food-frequency questionnaire and plasma fatty acid exposure by gas chromatography were completed in 1987–1989 (visit 1), while cognitive assessment with three screening tools – the Delayed Word Recall Test, the Digit Symbol Substitution Test of the Wechsler Adult Intelligence Scale–Revised and the Word Fluency Test (WFT) – was completed in 1990–1992 (visit 2) and 1996–1998 (visit 4). Regression calibration and simulation extrapolation were used to control for measurement error in dietary exposures.SettingFour US communities – Forsyth County (North Carolina), Jackson (Mississippi), suburbs of Minneapolis (Minnesota) and Washington County (Maryland).SubjectsMen and women aged 50–65 years at visit 1 with complete dietary data (n = 7814); white men and women in same age group in the Minnesota field centre with complete plasma fatty acid data (n = 2251).ResultsFindings indicated that an increase of one standard deviation in dietary long-chain n–3 fatty acids (% of energy intake) and balancing long-chain n−3/n–6 decreased the risk of 6-year cognitive decline in verbal fluency with an odds ratio (95% confidence interval) of 0.79 (0.66–0.95) and 0.81 (0.68–0.96), respectively, among hypertensives. An interaction with hypertensive status was found for dietary long-chain n–3 fatty acids (g day−1) and WFT decline (likelihood ratio test, P = 0.06). This exposure in plasma cholesteryl esters was also protective against WFT decline, particularly among hypertensives (OR = 0.51, P < 0.05).ConclusionOne implication from our study is that diets rich in fatty acids of marine origin should be considered for middle-aged hypertensive subjects. To this end, randomised clinical trials are needed.

Download Full-text

Abstract 061: Long-chain monounsaturated fatty acids and congestive heart failure incidence: the Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.125.suppl_10.a061 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Fumiaki Imamura ◽

Rozenn N Lemaitre ◽

Lyn M Steffen ◽

Aaron R Folsom ◽

David S Siscovick ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Older Adults ◽

Fatty Acids ◽

Congestive Heart Failure ◽

Plasma Phospholipid ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk ◽

Middle Aged Adults ◽

Long Chain

Background: Animal experiments in 1970s demonstrated direct cardiotoxicity of long-chain monounsaturated fatty acid (LCMUFA, 22:1 and 24:1 fatty acids) consumption. We recently found plasma phospholipid 22:1 and 24:1 to be associated with 34% and 75% higher risk (quintiles 5 vs. 1), respectively, of congestive heart failure (CHF) among older adults in the Cardiovascular Health Study. We wished to validate these results in a second independent cohort of middle-aged adults. Methods: We evaluated 3,577 adults free of CHF at baseline (age=54.1±5.8) in the Minnesota subcohort of the Atherosclerosis Risk in Communities Study (ARIC) in whom plasma phospholipid LCMUFA were measured. Incident CHF was ascertained from 1988 to 2008 by annual phone contacts, hospitalization discharge codes, and death certificates. Using multivariate Cox models, we evaluated prospective association of each LCMUFA with incident CHF, and potential mediation via CHF risk factors, including ECG left ventricular hypertrophy, and incident coronary heart disease (CHD). As a negative control, we also evaluated incident stroke, given its many shared risk factors for CHF but no link to potentially direct cardiotoxicity. Results: Mean±SD plasma phospholipid levels (% of total fatty acids) of 22:1 and 24:1 were 0.01±0.03 and 0.58±0.17. Over the 64,438 person-years of follow-up, 330 CHF events occurred. After multivariable adjustment, higher levels of 22:1 and 24:1 were associated with higher risk of CHF (Figure). Hazard ratios (95%CI) for quintiles 5 vs. 1 of 22:1 and 24:1 levels were 1.57 (1.11–2.23) and 1.92 (1.22–3.03) (p trend=0.03 and 0.002), respectively. These associations were only partly attenuated by potential mediators, including incident CHD. Neither LCMUFA was associated with incident stroke (not shown). Conclusions: Higher 22:1 and 24:1 LCMUFA levels were associated with CHF risk in middle-aged adults, consistent with our prior findings in older adults. These findings support the possibility of clinical cardiotoxicity of LCMUFA in humans.

Download Full-text

No Association Found Between Midlife Seropositivity for Infection and Subsequent Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988719856692 ◽

2019 ◽

Vol 33 (1) ◽

pp. 15-21 ◽

Cited By ~ 1

Author(s):

Kristen M. George ◽

Aaron R. Folsom ◽

Faye L. Norby ◽

Pamela L. Lutsey

Keyword(s):

Cognitive Decline ◽

Chlamydia Pneumoniae ◽

Cognitive Change ◽

Word Recall ◽

Linear Regression Models ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk ◽

Z Scores ◽

H Pylori ◽

Hsv 1

Infections of herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), Helicobacter pylori, and Chlamydia pneumoniae may play a role in cognitive decline via systemic inflammation. We hypothesized that Atherosclerosis Risk in Communities study participants who were seropositive in midlife for antibodies to HSV-1, CMV, H pylori, or C pneumoniae would have an accelerated rate of cognitive decline over 20 years. Atherosclerosis Risk in Communities performed a case-cohort study involving a stratified random sample of participants tested for serum immunoglobulin G antibodies to the pathogens of interest. We conducted a longitudinal study using this cohort. Cognitive change was measured using Z scores from the Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF) Tests administered at visits 2 (1990-1992), 4 (1996-1998), and 5 (2011-2013). Linear regression models with generalized estimating equations and inverse probability of attrition weights were used to evaluate associations between infection and cognitive performance. Four hundred twenty-six participants were analyzed, of which 3% were seronegative for all 4 infections, 14% seropositive for one, 33% and 34% seropositive for 2 and 3, respectively, and 16% seropositive for all infections. At baseline, test scores were significantly lower for participants seropositive for H pylori and C pneumoniae. After baseline covariate adjustment, the rate of decline in DWR, DSS, WF, and global Z scores did not differ significantly by infection status for any of the 4 infections. There was also no significant association between the number of infections for which participants were seropositive and cognitive decline. Our study provides no evidence supporting a longitudinal relationship between seropositivity and cognitive decline.

Download Full-text

Abstract WMP115: The Metabolic Syndrome Components and Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

Stroke ◽

10.1161/str.44.suppl_1.awmp115 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

Jennifer L Dearborn ◽

David Knopman ◽

Richey Sharrett ◽

Andrea L Schneider ◽

Clifford Jack ◽

...

Keyword(s):

Metabolic Syndrome ◽

Cognitive Function ◽

Cognitive Decline ◽

Sex Education ◽

Later Life ◽

Cognitive Change ◽

Word Recall ◽

Digit Symbol Substitution Test ◽

The Metabolic Syndrome ◽

Aric Study

Background: Midlife obesity is associated with dementia in later life, but how the metabolic syndrome (MetS) relates to cognitive change is less understood. We hypothesized that MetS would be more predictive of 6-year cognitive decline than its individual components in a large biethnic cohort (the ARIC study) and that combinations of risk factors would further increase likelihood of change. Methods: The MetS was defined in 1987-89 on 10,687 participants with two cognitive assessments at two time points. In subjects aged 44 to 66, obesity measures included body mass index (BMI) and waist-to-hip ratio (WTHR). The main outcome measure was change in 1990-92 to 96-99 of three cognitive tests: Delayed Word Recall (DWR), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Linear and logistic regressions were all adjusted for age, combined race-center, sex, education, smoking, drinking, coronary artery disease and prior stroke. Change was measured as the difference divided by the number of years between visits. Results: At baseline, the prevalence of MetS was 22% (mean age 54 years, 27% black, 55% female, and 28% BMI>30 kg/m2). Subjects with MetS performed in the lowest test quintile (adjusted ORs: DWR 1.3 95% CI 1.1-1.4) in 1996-99, and much of this effect size was explained by an elevated WTHR (DWR OR 1.3 CI 1.1-1.5) and diabetes (DWR OR 1.4 CI 1.2-1.7). MetS was not associated with annual cognitive change, and diabetes was the only significant component associated with change (adjusted beta: DWR 0.03 p=.01, DSST 0.2 p<.001, WFT 0.09 p=.01). Conclusion: MetS at ages 44 to 66 was associated with worse cognitive function at follow-up, but not with annual cognitive decline over several years. Elevated WTHR and diabetes explained most of the association of MetS with cognitive function measures, and diabetes with cognitive decline. Until we have a definition of the MetS more based on pathophysiology, the components of the MetS should be the focus of analysis in future studies.

Download Full-text

Plasma n−3 fatty acids and the risk of cognitive decline in older adults: the Atherosclerosis Risk in Communities Study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/85.4.1103 ◽

2007 ◽

Vol 85 (4) ◽

pp. 1103-1111 ◽

Cited By ~ 156

Author(s):

May A Beydoun ◽

Jay S Kaufman ◽

Jessie A Satia ◽

Wayne Rosamond ◽

Aaron R Folsom

Keyword(s):

Older Adults ◽

Fatty Acids ◽

Cognitive Decline ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk

Download Full-text

Abstract 51: Heart Rate Variability and its Association with Cognitive Decline Over 20 years: The Atherosclerosis Risk in Communities - Neurocognitive Study

Circulation ◽

10.1161/circ.131.suppl_1.51 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Faye L Lopez ◽

Lin Y Chen ◽

Elsayed Z Soliman ◽

Jennifer A Deal ◽

Rebecca F Gottesman ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Cognitive Impairment ◽

Executive Function ◽

Cognitive Function ◽

Cognitive Decline ◽

Word Recall ◽

Atherosclerosis Risk In Communities ◽

Increased Risk ◽

Atherosclerosis Risk

Background: Heart rate variability (HRV) reflects activity of the sympathetic and parasympathetic nervous systems. Low HRV is associated with an increased risk of heart disease and mortality, and risk factors for lower HRV are also linked to cognitive impairment. We assessed whether HRV measures are associated with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) study. Methods: We studied 10,623 individuals (23% African-American, 57% female, mean age 54). HRV measures were obtained from 2-minute electrocardiogram rhythm strips in 1987-89 and include the standard deviation of all normal RR intervals (SDNN), root mean square of successive differences (rMSSD), low frequency (LF) and high frequency (HF) spectral power, and the LF/HF ratio. Cognitive function was measured in 1990-92, 1996-98 and 2011-2013 using 3 neuropsychological tests: Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF). Scores were standardized and their average was used as a test of global cognitive function. HRV measures were log-transformed and we used linear regression models fit with generalized estimating equations to evaluate associations with cognitive performance over time, which was modeled as a linear spline with a knot at year 6 of follow-up. Results: At baseline, lower levels of HRV were significantly associated with reduced scores in all cognitive tests. Lower baseline levels of HRV measures of sympathetic activity (LF and LF/HF ratio) were associated with faster decline in tests evaluating executive function and language (DSST and WF) (table). We did not observe associations between parasympathetic nervous system measures (rMSSD and HF) and cognitive decline. Conclusion: In this large population-based study, markers of cardiac sympathetic dysfunction measured in mid-life were associated with a faster decline in executive function, which is more frequently affected in cognitive impairment of vascular origin. Additional research should explore the mechanism for this association.

Download Full-text

Retinal signs and 20-year cognitive decline in the Atherosclerosis Risk in Communities Study

Neurology ◽

10.1212/wnl.0000000000005205 ◽

2018 ◽

Vol 90 (13) ◽

pp. e1158-e1166 ◽

Cited By ~ 13

Author(s):

Jennifer A. Deal ◽

A. Richey Sharrett ◽

Andreea M. Rawlings ◽

Rebecca F. Gottesman ◽

Karen Bandeen-Roche ◽

...

Keyword(s):

Cognitive Decline ◽

Mixed Models ◽

Neuropsychological Tests ◽

Optical Coherence Tomography Angiography ◽

Cognitive Change ◽

Cognitive Testing ◽

Fundus Photography ◽

Vascular Integrity ◽

Atherosclerosis Risk In Communities ◽

Atherosclerosis Risk

ObjectiveTo test the hypothesis that retinal vascular signs are associated with greater cognitive decline over 20 years in 12,317 men and women 50 to 73 years of age at baseline.MethodsA composite cognitive score was created with 3 neuropsychological tests measured at 3 time points (1990–1992 to 2011–2013). Retinal signs were measured with fundus photography (1993–1995). Differences in cognitive change by retinal signs status were estimated with linear mixed models. Cognitive scores were imputed for living participants with incomplete cognitive testing.ResultsIn multivariable-adjusted analyses that controlled for attrition, loss of vascular integrity (retinopathy and its components) was associated with greater 20-year decline (difference in 20-year cognitive change for moderate/severe vs no retinopathy −0.53 SD, 95% confidence interval −0.74 to −0.33). Estimated differences were similar in participants with and without diabetes mellitus and in white and black participants.ConclusionsRetinopathy was associated with accelerated rates of 20-year cognitive decline. These findings support the exploration of more sensitive measures in the eye such as optical coherence tomography angiography, which may provide surrogate indexes of microvascular lesions relevant to cognitive decline in older adults.

Download Full-text