Cardiac Index Is Associated With Brain Aging

Jefferson, Angela L.; Himali, Jayandra J.; Beiser, Alexa; Au, Rhoda; Massaro, Joseph M.; Seshadri, Sudha; Gona, Philimon; Salton, Carol J; DeCarli, Charles; O’Donnell, Christopher J.; Benjamin, Emelia J.; Wolf, Philip A.; Manning, Warren J.

doi:10.1161/circulationaha.109.905091

Cited by 227 publications

(174 citation statements)

References 45 publications

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“…A 1‐cm/s decrease in Sa was associated with a 1% smaller TBV (14.9±3.2 cm 3 , P <0.0001), which corresponds to the equivalent volume change observed with normal aging over 3.1 years 35. This relationship is consistent with existing literature 8, 36. We expand on previous results by showing an association with Sa, a more sensitive measure of systolic function,37 and by investigating the role of alternative pathways.…”

Section: Discussionsupporting

confidence: 90%

“…We assessed global/overall cognitive function, as well as the domains of verbal memory, visual memory, working memory, fluency, and processing speed, since various cognitive modalities have previously been differentially associated with LV function 2, 4, 8. While we show no significant associations between Sa and cognitive function, we observed strong associations between LV diastolic function and working memory and fluency, and LV global function and visual memory and processing speed.…”

Section: Discussionmentioning

confidence: 68%

“…Yet, results from studies associating cardiac function with cerebral MRI findings are conflicting, with grey matter loss in the hippocampal regions related to LV dysfunction in some studies7 and not others 8, 9…”

Section: Introductionmentioning

confidence: 99%

“…Inconsistencies in associations between LV dysfunction and cognitive status may be explained by selection of study populations, with some samples chosen according to disease or risk status,4 as well as range of measurement of LV and brain indices 2, 4, 8…”

Section: Introductionmentioning

confidence: 99%

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Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study

Park

Williams

Chaturvedi

et al. 2017

JAHA

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BackgroundSubclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross‐sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms.Method and ResultsA total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N‐terminal pro–brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm3; P<0.0001) and hippocampal volumes (0.05±0.02 cm3, P=0.01). Reduced diastolic function was associated with poorer working memory (−0.21±0.07, P=0.004) and fluency scores (−0.18±0.08, P=0.02). Reduced global LV function was associated with smaller hippocampal volume (−0.10±0.03 cm3, P=0.004) and adverse visual memory (−0.076±0.03, P=0.02) and processing speed (0.063±0.02, P=0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory.ConclusionsIn a community‐based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study

Park

Williams

Chaturvedi

et al. 2017

JAHA

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“…In cohorts of older adults without symptoms of heart failure, even subtle cardiac dysfunction is associated with lower brain volume, ischemic lesions, and impaired integrity of the white matter 5, 6, 7, 8, 9. Subclinical cardiac dysfunction frequently occurs in the community and is largely underdiagnosed 10.…”

mentioning

confidence: 99%

Subclinical Cardiac Dysfunction and Brain Health in Midlife: CARDIA (Coronary Artery Risk Development in Young Adults) Brain Magnetic Resonance Imaging Substudy

Čermáková

Muller

Armstrong

et al. 2017

JAHA

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BackgroundWe investigated whether cardiac parameters in young adulthood are associated with indicators of brain health in midlife.Methods and ResultsThis study includes 648 participants from the CARDIA (Coronary Artery Risk Development in Young Adults) study (52% women, 38% black). We studied associations of cardiac parameters assessed by echocardiography (left ventricular ejection fraction, left atrial volume, and left ventricular mass) in young adulthood (mean age: 30 years) with brain measures obtained by magnetic resonance imaging (total brain, gray and white matter volume, white matter integrity, abnormal white matter) in midlife (mean age: 50 years). In 406 individuals with complete measurements, higher left atrial volume was associated with lower white matter fractional anisotropy, independent of traditional cardiovascular risk factors (β=−0.002; P <0.02). The association was strongest in black participants and in men.ConclusionsHigher left atrial volume in early adulthood is associated with impairment of white matter integrity in midlife. Interventions to improve cardiac function in young adults may benefit brain health and should be targeted in particular at black men.

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Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers

et al. 2018

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Importance The association between peripheral inflammatory biomarkers and Alzheimer disease (AD) is not consistent in the literature. It is possible that chronic inflammation, rather than 1 episode of inflammation, interacts with genetic vulnerability to increase the risk for AD. Objective To study the interaction between the apolipoprotein E ( ApoE ) genotype and chronic low-grade inflammation and its association with the incidence of AD. Design, Setting, and Participants In this cohort study, data from 2656 members of the Framingham Heart Study offspring cohort (Generation 2; August 13, 1971-November 27, 2017) were evaluated, including longitudinal measures of serum C-reactive protein (CRP), diagnoses of incident dementia including AD, and brain volume. Chronic low-grade inflammation was defined as having CRP at a high cutoff level at a minimum of 2 time points. Statistical analysis was performed from December 1, 1979, to December 31, 2015. Main Outcomes and Measures Development of AD and brain volumes. Results Of the 3130 eligible participants, 2656 (84.9%; 1227 men and 1429 women; mean [SD] age at last CRP measurement, 61.6 [9.5] years) with both ApoE status and longitudinal CRP measurements were included in this study analysis. Median (interquartile range) CRP levels increased with mean (SD) age (43.3 [9.6] years, 0.95 mg/L [0.40-2.35 mg/L] vs 59.1 [9.6] years, 2.04 mg/L [0.93-4.75 mg/L] vs 61.6 [9.5] years, 2.21 mg/L [1.05-5.12 mg/L]; P < .001), but less so among those with ApoE4 alleles, followed by ApoE3 then ApoE2 genotypes. During the 17 years of follow-up, 194 individuals (7.3%) developed dementia, 152 (78.4%) of whom had AD. ApoE4 coupled with chronic low-grade inflammation, defined as a CRP level of 8 mg/L or higher, was associated with an increased risk of AD, especially in the absence of cardiovascular diseases (hazard ratio, 6.63; 95% CI, 1.80-24.50; P = .005), as well as an increased risk of earlier disease onset compared with ApoE4 carriers without chronic inflammation (hazard ratio, 3.52; 95% CI, 1.27-9.75; P = .009). This phenomenon was not observed among ApoE3 and ApoE2 carriers with chronic low-grade inflammation. Finally, a subset of 1761 individuals (66.3%) underwent brain magnetic resonance imaging, and the interaction between ApoE4 and chronic low-grade inflammation was associated with brain atrophy in the temporal lobe (β = –0.88, SE = 0.22; P < .001) and hippocampus (β = –0.04, SE = 0.01; P = .005), after adjusting for confounders. Conclusions...

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Cardiac Index Is Associated With Brain Aging

Cited by 227 publications

References 45 publications

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study

Subclinical Cardiac Dysfunction and Brain Health in Midlife: CARDIA (Coronary Artery Risk Development in Young Adults) Brain Magnetic Resonance Imaging Substudy

Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers

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