BACKGROUND: We investigated whether carotid intima-media thickness is associated with measures of cerebral blood flow (CBF), white matter hyperintensities, and brain volume in a biracial cohort of middle-aged individuals. METHODS: We performed a cross-sectional cohort study based on data from a multicenter, population-based study Coronary Artery Risk Development in Young Adults. Using linear and logistic regression, we estimated the association of the composite intima-media thickness measured in three segments of carotid arteries (common carotid artery, carotid artery bulb, and internal carotid artery) with volume (cm3) and CBF (mL/100 g/min) in the total brain and gray matter as well as volume of white matter hyperintensities (cm3). RESULTS: In the analysis, 461 participants (54% women, 34% African Americans) were included. Greater intima-media thickness was associated with lower CBF in gray matter (β=-1.36; p = .04) and total brain (β=-1.26; p = .04), adjusting for age, sex, race, education, and total brain volume. The associations became statistically nonsignificant after further controlling for cardiovascular risk factors. Intima-media thickness was not associated with volumes of total brain, gray matter, and white matter hyperintensities. CONCLUSIONS: This study suggests that lower CBF in middle age is associated with markers of atherosclerosis in the carotid arteries. This association may reflect early long-term exposure to traditional cardiovascular risk factors. Early intervention on atherosclerotic risk factors may modulate the trajectory of CBF as people age and develop brain pathology.

3rd Faculty of Medicine Charles University Prague Czech Republic

Center for Alzheimer Research Division of Clinical Geriatrics Department of Neurobiology Care Sciences and Society Karolinska Institutet Huddinge Sweden

Department of Radiology University of Pennsylvania Philadelphia

Division of Cardiovascular Sciences National Heart Lung and Blood Institute Bethesda Maryland

Division of Epidemiology and Community Health University of Minnesota Philadelphia

Laboratory of Epidemiology and Population Sciences National Institute on Aging Bethesda Maryland

National Institute of Mental Health Klecany Czech Republic

Theme Aging Karolinska University Hospital Huddinge Sweden

Zobrazit více v PubMed

Sullivan KJ, Dodge HH, Hughes, et al.Declining incident dementia rates across four population-based birth cohorts. J Gerontol A Biol Sci Med Sci. 2018. doi:10.1093/gerona/gly236. [Epub ahead of print] PubMed DOI PMC

Strand BH, Wills AK, Langballe EM, Rosness TA, Engedal K, Bjertness E. Weight change in midlife and risk of mortality from dementia up to 35 years later. J Gerontol A Biol Sci Med Sci. 2017;72:855–860. doi:10.1093/gerona/glw157 PubMed DOI

Cermakova P, Nelson M, Secnik J, et al. . Living alone with Alzheimer’s disease: data from SveDem, the Swedish dementia registry. J Alzheimers Dis. 2017;58:1265–1272. doi:10.3233/JAD-170102 PubMed DOI PMC

Cermakova P, Szummer K, Johnell K, et al. . Management of acute myocardial infarction in patients with dementia: data from SveDem, the Swedish dementia registry. J Am Med Dir Assoc. 2017;18:19–23. doi:10.1016/j.jamda.2016.07.026 PubMed DOI

Secnik J, Cermakova P, Fereshtehnejad SM, et al. . Diabetes in a large dementia cohort: clinical characteristics and treatment from the Swedish dementia registry. Diabetes Care. 2017;40:1159–1166. doi:10.2337/dc16-2516 PubMed DOI PMC

Jack CR Jr, Bennett DA, Blennow K, et al. ; Contributors NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14:535–562. doi:10.1016/j.jalz.2018.02.018 PubMed DOI PMC

Launer LJ, Lewis CE, Schreiner PJ, et al. . Vascular factors and multiple measures of early brain health: CARDIA brain MRI study. PLoS One. 2015;10:e0122138. doi:10.1371/journal.pone.0122138 PubMed DOI PMC

Elbejjani M, Auer R, Dolui S, Jacobs DR Jr., Haight T, Goff DC Jr., et al. . Cigarette smoking and cerebral blood flow in a cohort of middle-aged adults. J Cereb Blood Flow Metab. 2019;9:78. doi: 10.1038/s41398-019-0401-1 PubMed DOI PMC

Cermakova P, Muller M, Armstrong AC, Religa D, Bryan RN, Lima JAC, et al. . Subclinical cardiac dysfunction and brain health in midlife: CARDIA (Coronary Artery Risk Development in Young Adults) brain magnetic resonance imaging substudy. J Am Heart Assoc. 2017;6. doi:10.1161/JAHA.117.006750 PubMed DOI PMC

Maillard P, Mitchell GF, Himali JJ, et al. . Effects of arterial stiffness on brain integrity in young adults from the Framingham Heart Study. Stroke. 2016;47:1030–1036. doi:10.1161/STROKEAHA.116.012949 PubMed DOI PMC

Moon SW, Kim SY, Jung JY, et al. . Relationship between obstructive lung disease and non-alcoholic fatty liver disease in the Korean population: Korea National Health and Nutrition Examination Survey, 2007–2010. Int J Chron Obstruct Pulmon Dis. 2018;13:2603–2611. doi:10.2147/COPD.S166902 PubMed DOI PMC

Romero JR, Beiser A, Seshadri, et al.Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: the Framingham study. Stroke. 2009;40:1590–1596. doi:10.1161/STROKEAHA.108.535245 PubMed DOI PMC

van Oijen M, de Jong FJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Atherosclerosis and risk for dementia. Ann Neurol. 2007;61:403–410. doi:10.1002/ana.21073 PubMed DOI

de la Torre JC. Cerebral hemodynamics and vascular risk factors: setting the stage for Alzheimer’s disease. J Alzheimer’s dis. 2012;32:553–567. doi:10.3233/JAD-2012–120793 PubMed

Reis JP, Launer LJ, Terry JG, et al. . Subclinical atherosclerotic calcification and cognitive functioning in middle-aged adults: the CARDIA study. Atherosclerosis. 2013;231:72–77. doi:10.1016/j.atherosclerosis.2013.08.038 PubMed DOI PMC

Zeki Al Hazzouri A, Vittinghoff E, Sidney S, Reis JP, Jacobs DR Jr, Yaffe K. Intima-media thickness and cognitive function in stroke-free middle-aged adults: findings from the Coronary Artery Risk Development in Young Adults study. Stroke. 2015;46:2190–2196. doi:10.1161/STROKEAHA.115.008994 PubMed DOI PMC

Kim C, Diez-Roux AV, Nettleton JA, et al. . Sex differences in subclinical atherosclerosis by race/ethnicity in the multi-ethnic study of atherosclerosis. Am J Epidemiol. 2011;174:165–172. doi:10.1093/aje/kwr088 PubMed DOI PMC

Friedman GD, Cutter GR, Donahue RP, et al. . CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41:1105–1116. doi:10.1016/0895-4356(88)90080-7 PubMed DOI

Polak JF, Person SD, Wei GS, et al. . Segment-specific associations of carotid intima-media thickness with cardiovascular risk factors: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Stroke. 2010;41:9–15. doi:10.1161/STROKEAHA.109.566596 PubMed DOI PMC

Green D, Foiles N, Chan C, Schreiner PJ, Liu K. Elevated fibrinogen levels and subsequent subclinical atherosclerosis: the CARDIA Study. Atherosclerosis. 2009;202:623–631. doi:10.1016/j.atherosclerosis.2008.05.039 PubMed DOI PMC

O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999;340:14–22. doi:10.1056/NEJM199901073400103 PubMed DOI

Crouse JR III, Craven TE, Hagaman AP, Bond MG. Association of coronary disease with segment-specific intimal-medial thickening of the extracranial carotid artery. Circulation. 1995;92:1141–1147. doi:10.1161/01.CIR.92.5.1141 PubMed DOI

Wu WC, Lin SC, Wang DJ, Chen KL, Li YD. Measurement of cerebral white matter perfusion using pseudocontinuous arterial spin labeling 3T magnetic resonance imaging—an experimental and theoretical investigation of feasibility. PLoS One. 2013;8:e82679. doi:10.1371/journal.pone.0082679 PubMed DOI PMC

Cermakova P, Formanek T, Kagstrom A, Winkler P. Socioeconomic position in childhood and cognitive aging in Europe. Neurology. 2018;91:e1602–e1610. doi:10.1212/WNL.0000000000006390 PubMed DOI PMC

Yaffe K, Vittinghoff E, Pletcher MJ, et al. . Early adult to midlife cardiovascular risk factors and cognitive function. Circulation. 2014;129:1560–1567. doi:10.1161/CIRCULATIONAHA.113.004798 PubMed DOI PMC

Tai MM. A mathematical model for the determination of total area under glucose tolerance and other metabolic curves. Diabetes care. 1994;17:152–154. doi:10.2337/diacare.17.2.152 PubMed DOI

Vernooij MW, van der Lugt A, Ikram MA, et al. . Total cerebral blood flow and total brain perfusion in the general population: the Rotterdam Scan Study. J Cereb Blood Flow Metab. 2008;28:412–419. doi:10.1038/sj.jcbfm.9600526 PubMed DOI

Sojkova J, Najjar SS, Beason-Held LL, et al. . Intima-media thickness and regional cerebral blood flow in older adults. Stroke. 2010;41:273–279. doi:10.1161/STROKEAHA.109.566810 PubMed DOI PMC

de la Torre JC. Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia. Cardiovasc Psychiatry Neurol. 2012;2012:367516. doi:10.1155/2012/367516 PubMed DOI PMC

Fazekas F, Kleinert R, Offenbacher H, et al. . Pathologic correlates of incidental MRI white matter signal hyperintensities. Neurology. 1993;43:1683–1689. doi:10.1212/WNL.43.9.1683 PubMed DOI

Ruitenberg A, den Heijer T, Bakker SL, et al. . Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol. 2005;57:789–794. doi:10.1002/ana.20493 PubMed DOI

Aanerud J, Borghammer P, Chakravarty MM, et al. . Brain energy metabolism and blood flow differences in healthy aging. J Cereb Blood Flow Metab. 2012;32:1177–1187. doi:10.1038/jcbfm.2012.18 PubMed DOI PMC

Roher AE, Esh C, Kokjohn TA, et al. . Circle of willis atherosclerosis is a risk factor for sporadic Alzheimer’s disease. Arterioscler Thromb Vasc Biol. 2003;23:2055–2062. doi:10.1161/01.ATV.0000095973.42032.44 PubMed DOI

Iadecola C, Yaffe K, Biller J, et al. ; American Heart Association Council on Hypertension; Council on Clinical Cardiology; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Stroke Council Impact of hypertension on cognitive function: a scientific statement from the American heart association. Hypertension. 2016;68:e67–e94. doi:10.1161/HYP.0000000000000053 PubMed DOI PMC

Dorrance AM, Matin N, Pires PW. The effects of obesity on the cerebral vasculature. Curr Vasc Pharmacol. 2014;12:462–472. PubMed PMC

Tchistiakova E, Anderson ND, Greenwood CE, MacIntosh BJ. Combined effects of type 2 diabetes and hypertension associated with cortical thinning and impaired cerebrovascular reactivity relative to hypertension alone in older adults. Neuroimage Clin. 2014;5:36–41. doi:10.1016/j.nicl.2014.05.020 PubMed DOI PMC

Moon JH, Lim S, Han JW, et al. . Carotid intima-media thickness is associated with the progression of cognitive impairment in older adults. Stroke. 2015;46:1024–1030. doi:10.1161/STROKEAHA.114.008170 PubMed DOI

Wolters FJ, Zonneveld HI, Hofman A, et al. ; Heart-Brain Connection Collaborative Research Group Cerebral perfusion and the risk of dementia: a population-based study. Circulation. 2017;136:719–728. doi:10.1161/CIRCULATIONAHA.117.027448 PubMed DOI