Obesity-induced Cognitive Impairment in Older Adults: a Microvascular Perspective

Overview

Journal Am J Physiol Heart Circ Physiol

Publisher American Physiological Society

Specialties Cardiology & Vascular Diseases
Physiology

Date 2020 Dec 18

PMID 33337961

Citations 45

Authors

Priya Balasubramanian

Tamas Kiss

Stefano Tarantini

Adam Nyul-Toth

Chetan Ahire

Andriy Yabluchanskiy

Tamas Csipo

Agnes Lipecz

Adam Tabak

Adam Institoris

Anna Csiszar

Zoltan Ungvari

Affiliations

Soon will be listed here.

Abstract

Over two-thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling responses, microvascular rarefaction, and blood-brain barrier disruption in the genesis of cognitive impairment in geriatric obesity are considered. The potential contribution of adipose-derived factors and fundamental cellular and molecular mechanisms of senescence to exacerbated obesity-induced cerebromicrovascular impairment and cognitive decline in aging are discussed.

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References

Zhang P, Yu Y, Qin Y, Zhou Y, Tang R, Wang Q . Alterations to the microbiota-colon-brain axis in high-fat-diet-induced obese mice compared to diet-resistant mice. J Nutr Biochem. 2019; 65:54-65. DOI: 10.1016/j.jnutbio.2018.08.016. View

Tarantini S, Valcarcel-Ares M, Yabluchanskiy A, Tucsek Z, Hertelendy P, Kiss T . Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype. J Gerontol A Biol Sci Med Sci. 2018; 73(7):853-863. PMC: 6001893. DOI: 10.1093/gerona/glx177. View

Ding Q, Ash C, Mracek T, Merry B, Bing C . Caloric restriction increases adiponectin expression by adipose tissue and prevents the inhibitory effect of insulin on circulating adiponectin in rats. J Nutr Biochem. 2011; 23(8):867-74. DOI: 10.1016/j.jnutbio.2011.04.011. View

Di Marco L, Venneri A, Farkas E, Evans P, Marzo A, Frangi A . Vascular dysfunction in the pathogenesis of Alzheimer's disease--A review of endothelium-mediated mechanisms and ensuing vicious circles. Neurobiol Dis. 2015; 82:593-606. DOI: 10.1016/j.nbd.2015.08.014. View

Elias M, Elias P, Sullivan L, Wolf P, DAgostino R . Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study. Int J Obes Relat Metab Disord. 2003; 27(2):260-8. DOI: 10.1038/sj.ijo.802225. View

Childs B, Baker D, Wijshake T, Conover C, Campisi J, van Deursen J . Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016; 354(6311):472-477. PMC: 5112585. DOI: 10.1126/science.aaf6659. View

Willeumier K, Taylor D, Amen D . Elevated BMI is associated with decreased blood flow in the prefrontal cortex using SPECT imaging in healthy adults. Obesity (Silver Spring). 2011; 19(5):1095-7. PMC: 3125099. DOI: 10.1038/oby.2011.16. View

Gorelick P, Scuteri A, Black S, DeCarli C, Greenberg S, Iadecola C . Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011; 42(9):2672-713. PMC: 3778669. DOI: 10.1161/STR.0b013e3182299496. View

Birdsill A, Carlsson C, Willette A, Okonkwo O, Johnson S, Xu G . Low cerebral blood flow is associated with lower memory function in metabolic syndrome. Obesity (Silver Spring). 2013; 21(7):1313-20. PMC: 3742665. DOI: 10.1002/oby.20170. View

10.

Shinmura K, Tamaki K, Saito K, Nakano Y, Tobe T, Bolli R . Cardioprotective effects of short-term caloric restriction are mediated by adiponectin via activation of AMP-activated protein kinase. Circulation. 2007; 116(24):2809-17. DOI: 10.1161/CIRCULATIONAHA.107.725697. View

11.

Chantler P, Shrader C, Tabone L, dAudiffret A, Huseynova K, Brooks S . Cerebral Cortical Microvascular Rarefaction in Metabolic Syndrome is Dependent on Insulin Resistance and Loss of Nitric Oxide Bioavailability. Microcirculation. 2015; 22(6):435-45. PMC: 4551443. DOI: 10.1111/micc.12209. View

12.

Guadagni V, Drogos L, Tyndall A, Davenport M, Anderson T, Eskes G . Aerobic exercise improves cognition and cerebrovascular regulation in older adults. Neurology. 2020; 94(21):e2245-e2257. PMC: 7357295. DOI: 10.1212/WNL.0000000000009478. View

13.

Bruce-Keller A, Salbaum J, Luo M, Blanchard 4th E, Taylor C, Welsh D . Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2014; 77(7):607-15. PMC: 4297748. DOI: 10.1016/j.biopsych.2014.07.012. View

14.

Lynch C, Kinzenbaw D, Chen X, Zhan S, Mezzetti E, Filosa J . Nox2-derived superoxide contributes to cerebral vascular dysfunction in diet-induced obesity. Stroke. 2013; 44(11):3195-201. PMC: 4011083. DOI: 10.1161/STROKEAHA.113.001366. View

15.

Prickett C, Stolwyk R, OBrien P, Brennan L . Neuropsychological Functioning in Mid-life Treatment-Seeking Adults with Obesity: a Cross-sectional Study. Obes Surg. 2017; 28(2):532-540. DOI: 10.1007/s11695-017-2894-0. View

16.

Motoshima H, Wu X, Mahadev K, Goldstein B . Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun. 2004; 315(2):264-71. DOI: 10.1016/j.bbrc.2004.01.049. View

17.

Montagne A, Barnes S, Sweeney M, Halliday M, Sagare A, Zhao Z . Blood-brain barrier breakdown in the aging human hippocampus. Neuron. 2015; 85(2):296-302. PMC: 4350773. DOI: 10.1016/j.neuron.2014.12.032. View

18.

Huby A, Antonova G, Groenendyk J, Gomez-Sanchez C, Bollag W, Filosa J . Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis. Circulation. 2015; 132(22):2134-45. DOI: 10.1161/CIRCULATIONAHA.115.018226. View

19.

Csipo T, Mukli P, Lipecz A, Tarantini S, Bahadli D, Abdulhussein O . Assessment of age-related decline of neurovascular coupling responses by functional near-infrared spectroscopy (fNIRS) in humans. Geroscience. 2019; 41(5):495-509. PMC: 6885078. DOI: 10.1007/s11357-019-00122-x. View

20.

Ouyang S, Hsuchou H, Kastin A, Wang Y, Yu C, Pan W . Diet-induced obesity suppresses expression of many proteins at the blood-brain barrier. J Cereb Blood Flow Metab. 2013; 34(1):43-51. PMC: 3887347. DOI: 10.1038/jcbfm.2013.166. View