Cognitive impairment and cardiovascular diseases in the elderly. A heart–brain continuum hypothesis

Abete, Pasquale; Della-Morte, David; Gargiulo, Gaetano; Basile, Christian; Langellotto, Assunta; Galizia, Gianluigi; Testa, Gianluca; Canonico, V.; Bonaduce, Domenico; Cacciatore, Francesco

doi:10.1016/j.arr.2014.07.003

Cited by 162 publications

(136 citation statements)

References 174 publications

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“…Hypoperfusion, through various mechanisms, has been proposed as a probable candidate for structural and functional brain changes,34, 43, 44 most likely through reduced cardiac output for systolic dysfunction. Further research is required to clarify the causative role of diastolic dysfunction; however, it has recently been associated with the development and progression of white matter lesions, relating to heightened risks of cognitive decline.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Several risk factors for CVD are also risk factors for cognitive impairment 9. Patients with cognitive impairment have the reduced ability to maintain medication adherence and carry out self‐care, thus increasing the risk of CVD 10, 11. However, the association between cognitive impairment and mortality resulting from CVD is less clear.…”

Section: Introductionmentioning

confidence: 99%

Cognitive Impairment and Risk of All‐Cause and Cardiovascular Disease Mortality Over 20‐Year Follow‐up: Results From the BLSA

Tang

et al. 2018

JAHA

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BackgroundCognitive impairment may increase the risk of all‐cause and cardiovascular disease (CVD) mortality. This study examined the association between cognitive function and risk of all‐cause and CVD mortality among the elderly in Beijing, China.Methods and ResultsA total of 1996 participants aged ≥55 years at baseline were enrolled from the BLSA (Beijing Longitudinal Study of Aging). Cognitive function was assessed using the Mini‐Mental State Examination (MMSE), and participants were categorized as: <18, 18 to 23, 24 to 27, and 28 to 30. Cox proportional hazard models were used to estimate the association. Hazard ratio (HR) and 95% confidence interval (CI) were reported. During a 20‐year follow‐up, 1122 (56.21%) participants died, 478 (42.60%) of whom died of CVD. Compared with MMSE scores of 28 to 30, participants with MMSE scores of <18 were independently associated with all‐cause mortality (hazard ratio, 2.14; 95% confidence interval, 1.59–2.87; P<0.001) and CVD mortality (hazard ratio, 4.52; 95% confidence interval, 2.80–7.30, P<0.001). Each 5‐point decrease in MMSE score was associated with a 34% increased risk of all‐cause mortality and a 56% increased risk of CVD mortality. This relationship remained statistically significant after using the competing risk model to consider non‐CVD death as a competing risk event.ConclusionCognitive impairment measured by MMSE score was associated with elevated risk of all‐cause and CVD mortality among the elderly in Beijing, China.

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“…Aging (the main risk factor for sporadic AD [50,185]), vascular conditions [6,[8][9][10][11], and possibly cardiac conditions [7,12,13] cause chronic cerebral hypoperfusion. This in turn reduces oxygen and energy supply to the brain tissue [14], ultimately leading to neuronal damage.…”

Section: Chronic Cerebral Hypoperfusionmentioning

confidence: 99%

“…An imbalance between A production and clearance results in toxic A concentrations, neuronal tau protein hyperphosphorylation and consequent neurofibrillary tangle formation [5]. However, substantial evidence [6][7][8][9][10] suggests that the neurodegenerative process is initiated by chronic cerebral hypoperfusion caused by aging, vascular conditions such as hypertension, atherosclerosis, type II diabetes, hypercholesterolemia [6,[8][9][10][11], and possibly cardiac conditions such as atrial fibrillation and chronic heart failure [7,12,13]. Chronic hypoperfusion causes reduced oxygen, glucose and other nutrient supply to the brain [14], with direct damage not only to parenchymal cells, but also to the blood-brain barrier (BBB), a key mediator of cerebral homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

Marco

Venneri

Farkas

et al. 2015

Neurobiology of Disease

232

185

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Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request.

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Cognitive impairment and cardiovascular diseases in the elderly. A heart–brain continuum hypothesis

Cited by 162 publications

References 174 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

Cognitive Impairment and Risk of All‐Cause and Cardiovascular Disease Mortality Over 20‐Year Follow‐up: Results From the BLSA

Vascular dysfunction in the pathogenesis of Alzheimer's disease — A review of endothelium-mediated mechanisms and ensuing vicious circles

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