We examined the relative associations of aortic and carotid artery stiffness with cerebrovascular disease (CeVD), cognition, and dementia subtypes in a memory clinic cohort of 272 participants (mean age = 75.4, SD = 6.8). We hypothesized that carotid artery stiffness would have greater effects on outcomes, given its proximate relationship to the brain. Aortic and carotid artery stiffness were assessed with applanation tonometry and carotid ultrasonography, respectively. CeVD markers included white matter hyperintensities (WMH), lacunes, cerebral microbleeds, cortical infarcts, and intracranial stenosis. Cognition was assessed by the Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a neuropsychological battery. Multivariable linear regression was conducted to determine associations of arterial stiffness with WMH and cognition, while logistic regression analysed associations with CeVD markers and dementia subtypes. Carotid artery stiffness z-score was associated with WMH, cortical infarcts, vascular cognitive impairment, and MMSE, independent of age, sex, education, vascular risk factors, and aortic stiffness z-score. Although aortic stiffness z-score was independently associated with cortical infarcts, this became non-significant after further adjusting for carotid artery stiffness z-score. We found that carotid artery stiffness had greater effects on CeVD, cognitive function and impairment in memory clinic patients compared to aortic stiffness.
ZiemanSJMelenovskyVKassDA.Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol2005;
25: 932–943.
2.
SchellingerINMatternKRaazU.The hardest part: arterial stiffness in the context of healthy aging. Arterioscler Thromb Vasc Biol2019;
39: 1301–1306.
3.
SingerJTrollorJNBauneBT, et al.
Arterial stiffness, the brain and cognition: a systematic review. Ageing Res Rev2014;
15: 16–27.
4.
van SlotenTTProtogerouADHenryRM, et al.
Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: a systematic review and meta-analysis. Neurosci Biobehav Rev2015;
53: 121–130.
5.
LaurentSKatsahianSFassotC, et al.
Aortic stiffness is an independent predictor of fatal stroke in essential hypertension. Stroke2003;
34: 1203–1206.
6.
Mattace-RasoFUvan der CammenTJHofmanA, et al.
Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam study. Circulation2006;
113: 657–663.
7.
Alvarez-BuenoCCunhaPGMartinez-VizcainoV, et al.
Arterial stiffness and cognition among adults: a systematic review and meta-analysis of observational and longitudinal studies. J Am Heart Assoc2020;
9: e01462120200228.
8.
WardlawJMSmithEEBiesselsGJ, et al.
Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol2013;
12: 822–838.
9.
DueringMBiesselsGJBrodtmannA, et al.
Neuroimaging standards for research into small vessel disease-advances since 2013. Lancet Neurol2023;
22: 602–618.
10.
ParkJHOvbiageleB.Post-stroke diastolic blood pressure and risk of recurrent vascular events. Eur J Neurol2017;
24: 1416–1423.
11.
JiangCLiSWangY, et al.
Diastolic blood pressure and intensive blood pressure control on cognitive outcomes: insights from the SPRINT MIND Trial. Hypertension2023;
80: 580–589.
12.
SpenceJD.Blood pressure gradients in the brain: their importance to understanding pathogenesis of cerebral small vessel disease. Brain Sci2019;
9: 21.
13.
RudilossoSLaredoCMancosuM, et al.
Cerebral perfusion and compensatory blood supply in patients with recent small subcortical infarcts. J Cereb Blood Flow Metab2019;
39: 1326–1335.
14.
van DintherMHooghiemstraAMBronEE, et al.
Lower cerebral blood flow predicts cognitive decline in patients with vascular cognitive impairment. Alzheimers Dement2024;
20: 136–144.
15.
JeffersonALCambroneroFELiuD, et al.
Higher aortic stiffness is related to lower cerebral blood flow and preserved cerebrovascular reactivity in older adults. Circulation2018;
138: 1951–1962.
16.
ChuangSYChengHMBaiCH, et al.
Blood pressure, carotid flow pulsatility, and the risk of stroke: a community-based study. Stroke2016;
47: 2262–2268.
17.
Van SlotenTTSedaghatSLaurentS, et al.
Carotid stiffness is associated with incident stroke a systematic review and individual participant data Meta-Analysis. J Am Coll Cardiol2015;
66: 2116–2125.
18.
AribisalaBSMorrisZEadieE, et al.
Blood pressure, internal carotid artery flow parameters, and age-related white matter hyperintensities. Hypertension2014;
63: 1011–1018.
19.
RobertCLingLHTanESJ, et al.
Effects of carotid artery stiffness on cerebral small-vessel disease and cognition. J Am Heart Assoc2022;
11: e027295.
20.
van SlotenTTStehouwerCD.Carotid stiffness: a novel cerebrovascular disease risk factor. Pulse (Basel)2016;
4: 24–27.
21.
BaradaranHGuptaA.Carotid artery stiffness: imaging techniques and impact on cerebrovascular disease. Front Cardiovasc Med2022;
9: 852173–20220315.
22.
MitchellGF.Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol (1985)2008;
105: 1652–1660.
23.
RensmaSPvan SlotenTTLaunerLJ, et al.
Cerebral small vessel disease and risk of incident stroke, dementia and depression, and all-cause mortality: a systematic review and meta-analysis. Neurosci Biobehav Rev2018;
90: 164–173.
24.
LiuYBraidyNPoljakA, et al.
Cerebral small vessel disease and the risk of Alzheimer’s disease: a systematic review. Ageing Res Rev2018;
47: 41–48.
25.
MitchellGFvan BuchemMASigurdssonS, et al.
Arterial stiffness, pressure and flow pulsatility and brain structure and function: the age, gene/environment susceptibility – Reykjavik study. Brain2011;
134: 3398–3407.
26.
HaidarMAvan BuchemMASigurdssonS, et al.
Wave reflection at the origin of a first-generation branch artery and target organ protection: the AGES-Reykjavik study. Hypertension2021;
77: 1169–1177.
27.
Van BortelLMLaurentSBoutouyrieP, et al.
Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens2012;
30: 445–448.
28.
PaucaALO’RourkeMFKonND.Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform. Hypertension2001;
38: 932–937.
29.
MurgoJPWesterhofNGiolmaJP, et al.
Aortic input impedance in normal man: relationship to pressure wave forms. Circulation1980;
62: 105–116.
30.
CarerjSNipoteCZimbalattiC, et al.
Normal vascular aging evaluated by a new tool: e-tracking. European Journal of Echocardiography2006;
7: S49.
31.
VrizODriussiCLa CarrubbaS, et al.
Comparison of sequentially measured aloka echo-tracking one-point pulse wave velocity with SphygmoCor carotid-femoral pulse wave velocity. SAGE Open Med2013;
1: 2050312113507563.
32.
LimSLGaoQNyuntMS, et al.
Vascular health indices and cognitive domain function: Singapore longitudinal ageing studies. J Alzheimers Dis2016;
50: 27–40.
33.
WahlundLOBarkhofFFazekasF, et al.
A new rating scale for Age-Related white matter changes applicable to MRI and CT. Stroke2001;
32: 1318–1322.
34.
CordonnierCPotterGMJacksonCA, et al.
Improving interrater agreement about brain microbleeds. Stroke2009;
40: 94–99.
35.
HilalSSainiMTanCS, et al.
Ankle-brachial index, cognitive impairment and cerebrovascular disease in a Chinese population. Neuroepidemiology2014;
42: 131–138.
36.
FolsteinMFFolsteinSEMchughPR, et al. “
Mini-Mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res1975;
12: 189–198.
37.
NasreddineZSPhillipsNABédirianV, et al.
The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc2005;
53: 695–699.
38.
XuXLin ChanQHilalS, et al.
The diagnostic utility of the NINDS-CSN neuropsychological battery in memory clinics. Dement Geriatr Cogn Dis Extra2016;
6: 276–282.
39.
YeoDGabrielCChenC, et al.
Pilot validation of a customized neuropsychological battery in elderly Singaporeans. Neurol J South East Asia1997;
2: 123.
40.
WechslerD. Wechsler Memory Scale. 3rd Edition. The Psychological Corporation: San Antonio, TX, 1997.
41.
RennickR.Manual for the repeatable cognitive perceptual-motor battery.
Axon:
Clinton Township, MI, 1979.
42.
DuboisBSlachevskyALitvanI, et al.
The FAB: a frontal assessment battery at bedside. Neurology2000;
55: 1621–1626.
43.
PorteusSD. The Maze Test and Clinical Psychology. Pacific Books: Palo Alto, CA, 1959.
44.
MackWJFreedDMWilliamsBW, et al.
Boston naming test: shortened versions for use in Alzheimer’s disease. J Gerontol1992;
47: P154–158.
45.
IsaacsBKennieAT.The set test as an aid to the detection of dementia in old people. Br J Psychiatry1973;
123: 467–470.
46.
SmithA. Symbol Digit Modalities Test. Western Psychological Services: Los Angeles, CA, 1973.
47.
DillerLBen-YishayYGerstmanLJ, et al. Studies in cognition and rehabilitation in hemiplegia. Rehabilitation Monograph No. 50.
University Medical Center:
New York, 1974.
48.
SunderlandTHillJLMellowAM, et al.
Clock drawing in Alzheimer’s disease. J Am Geriatr Soc1989;
37: 725–729.
49.
WechslerDDe LemosMM.Wechsler adult intelligence scale-revised.
New York:
Psychological Corporation, 1981.
50.
SahadevanSTanNJLTanT, et al.
Cognitive testing of elderly Chinese people in Singapore: influence of education and age on normative scores. Age Ageing1997;
26: 481–486.
51.
McKhann DrachmanDFolsteinMKatzmanR, et al.
Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology1984;
34: 939–944.
52.
RománGCTatemichiTKErkinjunttiT, et al.
Vascular dementia. Neurology1993;
43: 250–250.
53.
de HavenonAWongKHElkhetaliA, et al.
Carotid artery stiffness accurately predicts white matter hyperintensity volume 20 years later: a secondary analysis of the atherosclerosis risk in the community study. AJNR Am J Neuroradiol2019;
40: 1369–1373.
54.
LiXLyuPRenY, et al.
Arterial stiffness and cognitive impairment. J Neurol Sci2017;
380: 1–10.
55.
NieboerDDouwLVan DijkBW, et al.
Relation between carotid stiffness, cognitive performance and brain connectivity in a healthy Middle-aged population: an observational neurophysiological cohort study with magnetoencephalography. 2016;
6: e13441.
56.
MuelaHCSCosta-HongVAYassudaMS, et al.
Higher arterial stiffness is associated with lower cognitive performance in patients with hypertension. J Clin Hypertens (Greenwich)2018;
20: 22–30.
57.
ChirinosJASegersPHughesT, et al.
Large-artery stiffness in health and disease: JACC state-of-the-art review. J Am Coll Cardiol2019;
74: 1237–1263.
58.
PierceGLCoutinhoTADuboseLE, et al.
Is it good to have a stiff aorta with aging? Causes and consequences. Physiology (Bethesda)2022;
37: 154–173.
59.
StewartCRStringerMSShiY, et al.
Associations between white matter hyperintensity burden, cerebral blood flow and transit time in small vessel disease: an updated Meta-Analysis. Front Neurol2021;
12: 647848.
60.
JeongSKRosensonRS.and Shear rate specific blood viscosity and shear stress of carotid artery duplex ultrasonography in patients with lacunar infarction. BMC Neurol2013;
13: 36–37.
61.
PewowarukRJTedlaYKorcarzCE, et al.
Carotid artery stiffening with aging: structural versus load-dependent mechanisms in MESA (the multi-ethnic study of atherosclerosis). Hypertension2022;
79: 150–158.
62.
DuivenvoordenRVanBavelEDe GrootE, et al.
Endothelial shear stress a critical determinant of arterial remodeling and arterial stiffness in humans – a carotid 3.0-T MRI study. Circ: Cardiovascular Imaging2010;
3: 578–585.
63.
LiaoDArnettDKTyrolerHA, et al.
Arterial stiffness and the development of hypertension. Hypertension1999;
34: 201–206.
64.
KaessBMRongJLarsonMG, et al.
Aortic stiffness, blood pressure progression, and incident hypertension. JAMA2012;
308: 875–881.
65.
PainiABoutouyriePCalvetD, et al.
Carotid and aortic stiffness. Hypertension2006;
47: 371–376.
66.
AizawaKShoemakerJKOverendTJ, et al.
Effects of lifestyle modification on central artery stiffness in metabolic syndrome subjects with pre-hypertension and/or pre-diabetes. Diabetes Res Clin Pract2009;
83: 249–256.
67.
MizuguchiYOishiYMiyoshiH, et al.
Impact of statin therapy on left ventricular function and carotid arterial stiffness in patients with hypercholesterolemia. Circ J2008;
72: 538–544.
68.
WangWNorbyFLGeorgeKM, et al.
Association of carotid intima‐media thickness and other carotid ultrasound features with incident dementia in the ARIC‐NCS. 2021;
10: 20489.
69.
de la TorreJC. and
Alzheimer’s disease prevalence can be lowered with non-invasive testing. J Alzheimers Dis2008;
14: 353–359.
70.
GomezCR. and
Carotid plaque morphology and risk for stroke. Stroke1990;
21: 148–151.
71.
JohnstonSCO’MearaESManolioTA, et al.
Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med2004;
140: 237–247.
72.
CarcaillonLPlichartMZureikM, et al.
Carotid plaque as a predictor of dementia in older adults: the three-city study. Alzheimers Dement2015;
11: 239–248.
73.
WeiYWangMGuiY, et al.
Carotid artery stiffness in rural adult Chinese: a cross-sectional analysis of the community-based China stroke cohort study. BMJ Open2020;
10: e036398.
74.
van PopeleNMGrobbeeDEBotsML, et al.
Association between arterial stiffness and atherosclerosis: the Rotterdam study. Stroke2001;
32: 454–460.
75.
Peter-MarskeKMMeyerMTanakaH, et al.
Central arterial stiffening and intracranial atherosclerosis: the atherosclerosis risk in communities neurocognitive study (ARIC-NCS): aortic stiffness & intracranial atherosclerosis. J Stroke Cerebrovasc Dis2024;
33: 107477.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
