The epidemiology of silent brain infarction: a systematic review of population-based cohorts

Jonathon P Fanning, Andrew A Wong, John F Fraser, Jonathon P Fanning, Andrew A Wong, John F Fraser

Abstract

Background: Cerebral infarction is a commonly observed radiological finding in the absence of corresponding, clinical symptomatology, the so-called silent brain infarction (SBI). SBIs are a relatively new consideration as improved imaging has facilitated recognition of their occurrence. However, the true incidence, prevalence and risk factors associated with SBI remain controversial.

Methods: Systematic searches of the Medline and EMBASE databases from 1946 to December 2013 were performed to identify original studies of population-based adult cohorts derived from community surveys and routine health screening that reported the incidence and prevalence of magnetic resonance imaging (MRI)-determined SBI.

Results: The prevalence of SBI ranges from 5% to 62% with most studies reported in the 10% to 20% range. Longitudinal studies suggest an annual incidence of between 2% and 4%. A strong association was seen to exist between epidemiological estimates of SBI and age of the population assessed. Hypertension, carotid stenosis, chronic kidney disease and metabolic syndrome all showed a strong association with SBI. Heart failure, coronary artery disease, hyperhomocysteinemia and obstructive sleep apnea are also likely of significance. However, any association between SBI and gender, ethnicity, tobacco or alcohol consumption, obesity, dyslipidemia, atrial fibrillation and diabetes mellitus remains unclear.

Conclusions: SBI is a remarkably common phenomenon and endemic among older people. This systematic review supports the association of a number of traditional vascular risk factors, but also highlights disparities between clinically apparent and silent strokes, potentially suggesting important differences in pathophysiology and warranting further investigation.

Figures

Figure 1
Figure 1
Mean Prevalence of SBI, by Mean Age in Clinic Patients Undergoing Routine Health Screening.
Figure 2
Figure 2
Mean Prevalence of SBI, by Mean Age in General Community Surveys.
Figure 3
Figure 3
Mean Prevalence of SBI, by Mean Age in population-based cohorts (combining Figures1and2).

References

    1. Fisher CM. Lacunes: small, deep cerebral infarcts. Neurology. 1965;15:774–784. doi: 10.1212/WNL.15.8.774.
    1. Avdibegovic E, Becirovic E, Salimbasic Z, Hasanovic M, Sinanovic O. Cerebral cortical atrophy and silent brain infarcts in psychiatric patients. Psychiatr Danub. 2007;19:49–55.
    1. Price TR, Manolio TA, Kronnal RA, Kittner SJ, Yue NC, Robbins J, Anton-Culver H, O'Leary DH. Silent brain infarction on magnetic resonance imaging and neurological abnormalities in community-dwelling older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Stroke. 1997;28:1158–1164. doi: 10.1161/01.STR.28.6.1158.
    1. Liebetrau M, Steen B, Hamann GF, Skoog I. Silent and symptomatic infarcts on cranial computerized tomography in relation to dementia and mortality: a population-based study in 85-year-old subjects. Stroke. 2004;35:1816–1820. doi: 10.1161/01.STR.0000131928.47478.44.
    1. Song IU, Kim JS, Kim YI, Eah KY, Lee KS. Clinical significance of silent cerebral infarctions in patients with Alzheimer disease. Cogn Behav Neurol. 2007;20:93–98. doi: 10.1097/WNN.0b013e31805d859e.
    1. Wright CB, Festa JR, Paik MC, Schmeidigen A, Brown TR, Yoshita M, DeCarli C, Sacco R, Stern Y. White matter hyperintensities and subclinical infarction: associations with psychomotor speed and cognitive flexibility. Stroke. 2008;39:800–805. doi: 10.1161/STROKEAHA.107.484147.
    1. Fujikawa T, Yamawaki S, Touhouda Y. Silent cerebral infarctions in patients with late-onset mania. Stroke. 1995;26:946–949. doi: 10.1161/01.STR.26.6.946.
    1. Hamada T, Murata T, Omori M, Takahashi T, Kosaka H, Wada Y, Yoshida H. Abnormal nocturnal blood pressure fall in senile-onset depression with subcortical silent cerebral infarction. Neuropsychobiology. 2003;47:187–191. doi: 10.1159/000071213.
    1. Yamashita H, Fujikawa T, Yanai I, Morinobu S, Yamawaki S. Cognitive dysfunction in recovered depressive patients with silent cerebral infarction. Neuropsychobiology. 2002;45:12–18. doi: 10.1159/000048667.
    1. Bokura H, Kobayashi S, Yamaguchi S, Iijima K, Nagai A, Toyoda G, Oguro H, Takahashi K. Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study. J Stroke Cerebrovasc Dis. 2006;15:57–63. doi: 10.1016/j.jstrokecerebrovasdis.2005.11.001.
    1. Kobayashi S, Okada K, Koide H, Bokura H, Yamaguchi S. Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke. 1997;28:1932–1939. doi: 10.1161/01.STR.28.10.1932.
    1. Putaala J, Haapaniemi E, Kurkinen M, Salonen O, Kaste M, Tatlisumak T. Silent brain infarcts, leukoaraiosis, and long-term prognosis in young ischemic stroke patients. Neurology. 2011;76:1742–1749. doi: 10.1212/WNL.0b013e31821a44ad.
    1. Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MM. Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke. 2003;34:1126–1129. doi: 10.1161/01.STR.0000068408.82115.D2.
    1. Longstreth WT, Dulberg C, Manolio TA, Lewis MR, Baeuchamp NJ, O'Leary D, Carr J, Furberg CD. Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study. Stroke. 2002;33:2376–2382. doi: 10.1161/01.STR.0000032241.58727.49.
    1. Asumi M, Yamaguchi T, Saito K, Kodama S, Miyazawa H, Matsui H, Suzuki E, Fukuda H, Sone H. Are serum cholesterol levels associated with silent brain infarcts? The Seiryo Clinic Study. Atherosclerosis. 2010;210:674–677. doi: 10.1016/j.atherosclerosis.2010.01.008.
    1. Bokura H, Nagai A, Oguro H, Kobayashi S, Yamaguchi S. The association of metabolic syndrome with executive dysfunction independent of subclinical ischemic brain lesions in Japanese adults. Dement Geriatr Cog Disord. 2010;30:479–485. doi: 10.1159/000322057.
    1. Kwon HM, Kim BJ, Lee SH, Choi SH, Oh BH, Yoon BW. Metabolic syndrome as an independent risk factor of silent brain infarction in healthy people. Stroke. 2006;37:466–470. doi: 10.1161/01.STR.0000199081.17935.81.
    1. Kwon HM, Kim BJ, Park JH, Ryu WS, Kim CK, Lee SH, Ko SB, Nam H, Lee SH, Lee YS, Yoon BW. Significant association of metabolic syndrome with silent brain infarction in elderly people. J Neurol. 2009;256:1825–1831. doi: 10.1007/s00415-009-5201-8.
    1. Lee SC, Park SJ, Ki HK, Gwon HC, Chung CS, Byun HS, Shin KJ, Shin MH, Lee WR. Prevalence and risk factors of silent cerebral infarction in apparently normal adults. Hypertension. 2000;36:73–77. doi: 10.1161/01.HYP.36.1.73-a.
    1. Matsumoto M, Inoue K, Moriki A. Associations of brachial-ankle pulse wave velocity and carotid atherosclerotic lesions with silent cerebral lesions. Hypertension Res. 2007;30:767–773. doi: 10.1291/hypres.30.767.
    1. Nakagawa T, Sekizawa K, Nakajoh K, Tanji H, Arai H, Sasaki H. Silent cerebral infarction: a potential risk for pneumonia in the elderly. J Intern Med. 2000;247:255–259. doi: 10.1046/j.1365-2796.2000.00599.x.
    1. Saji N, Kimura K, Shimizu H, Kita Y. Silent brain infarct is independently associated with arterial stiffness indicated by cardio-ankle vascular index (CAVI) Hypertension Res. 2012;35:756–760. doi: 10.1038/hr.2012.20.
    1. Saji N, Kimura K, Shimizu H, Kita Y. Association between silent brain infarct and arterial stiffness indicated by brachial-ankle pulse wave velocity. Intern Med. 2012;51:1003–1008. doi: 10.2169/internalmedicine.51.6852.
    1. Uehara T, Tabuchi M, Mori R. Risk factors for silent cerebral infarcts in subcortical white matter and basal ganglia. Stroke. 1999;30:378–382. doi: 10.1161/01.STR.30.2.378.
    1. Yi CC, Zhang YQ, Liu WW, Guo ZJ, Yin RF. Prevalence and risk factors of silent cerebral infarction in a Chinese population. Acad J Sec Military Med Univ. 2011;32:537–540. doi: 10.3724/SP.J.1008.2011.00537.
    1. Yoshida M, Higashi K, Kobayashi E, Saeki N, Wakui K, Kusaka T, Takizawa H, Kashiwado K, Suzuki N, Fukuda K, Nakamura T, Watanabe S, Tada K, Machi Y, Mizoi M, Toida T, Kanzaki T, Tomitori H, Kashiwagi K, Igarashi K. Correlation between images of silent brain infarction, carotid atherosclerosis and white matter hyperintensity, and plasma levels of acrolein, IL-6 and CRP. Atherosclerosis. 2010;211:475–479. doi: 10.1016/j.atherosclerosis.2010.03.031.
    1. Cho ER, Kim H, Seo HS, Suh S, Lee SK, Shin C. Obstructive sleep apnea as a risk factor for silent cerebral infarction. J Sleep Res. 2013;22:452–458. doi: 10.1111/jsr.12034.
    1. Park K, Yasuda N, Toyonaga S, Tsubosaki E, Nakabayashi H, Shimizu K. Significant associations of metabolic syndrome and its components with silent lacunar infarction in middle aged subjects. J Neurol Neurosurg Psychiatry. 2008;79:719–721. doi: 10.1136/jnnp.2007.134809.
    1. Chou CC, Lien LM, Chen WH, Wu MS, Lin SM, Chiu HC, Chiou HY, Bai CH. Adults with late stage 3 chronic kidney disease are at high risk for prevalent silent brain infarction: a population-based study. Stroke. 2011;42:2120–2125. doi: 10.1161/STROKEAHA.110.597930.
    1. Kohara K, Fujisawa M, Ando F, Tabara Y, Nino N, Miki T, Shimokata H. MTHFR gene polymorphism as a risk factor for silent brain infarcts and white matter lesions in the Japanese general population: the NILS-LSA Study. Stroke. 2003;34:1130–1135. doi: 10.1161/01.STR.0000069163.02611.B0.
    1. Das RR, Seshadri S, Beiser AS, Kelly-Hayes M, Au R, Himali JJ, Kase CS, Benjamin EJ, Polak JF, O'Donnell CJ, Yoshita M, D'Agostino RB Sr, DeCarli C, Wolf PA. Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study. Stroke. 2008;39:2929–2935. doi: 10.1161/STROKEAHA.108.516575.
    1. DeCarli C, Massaro J, Harvey D, Hald J, Tullberg M, Au R, Beiser A, D'Agostino R, Wolf PA. Measures of brain morphology and infarction in the framingham heart study: establishing what is normal. Neurobiol Aging. 2005;26:491–510. doi: 10.1016/j.neurobiolaging.2004.05.004.
    1. Howard G, Wagenknecht LE, Cai J, Cooper L, Kraut MA, Toole JF. Cigarette smoking and other risk factors for silent cerebral infarction in the general population. Stroke. 1998;29:913–917. doi: 10.1161/01.STR.29.5.913.
    1. Schmidt R, Schmidt H, Pichler M, Enzinger C, Pertovic K, Niederkorn K, Horner S, Ropele S, Watzinger N, Schumacher M, Berghold A, Kostner GM, Fazekas F. C-reactive protein, carotid atherosclerosis, and cerebral small-vessel disease: results of the Austrian Stroke Prevention Study. Stroke. 2006;37:2910–2916. doi: 10.1161/01.STR.0000248768.40043.f9.
    1. Aono Y, Ohkubo T, Kikuya M, Hara A, Kondo T, Obara T, Metoki H, Inoue R, Asayama K, Shintani Y, Hashimoto J, Totsune K, Hoshi H, Satoh H, Izumi S, Imai Y. Plasma fibrinogen, ambulatory blood pressure, and silent cerebrovascular lesions: the Ohasama study. Arterioscler Thromb Vasc Biol. 2007;27:963–968. doi: 10.1161/01.ATV.0000258947.17570.38.
    1. Willey JZ, Moon YP, Paik MC, Yoshita M, DeCarli C, Sacco RL, Elkind MS, Wright CB. Lower prevalence of silent brain infarcts in the physically active: the Northern Manhattan Study. Neurology. 2011;76:2112–2118. doi: 10.1212/WNL.0b013e31821f4472.
    1. Schmidt WP, Roesler A, Kretzschmar K, Ladwig KH, Junker R, Berger K. Functional and cognitive consequences of silent stroke discovered using brain magnetic resonance imaging in an elderly population. J Am Geriatr Soc. 2004;52:1045–1050. doi: 10.1111/j.1532-5415.2004.52300.x.
    1. Vermeer SE, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM. Prevalence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke. 2002;33:21–25. doi: 10.1161/hs0102.101629.
    1. Fukuda K, Takashima Y, Hashimoto M, Uchino A, Yuzuriha T, Yao H. Early menopause and the risk of silent brain infarction in community-dwelling elderly subjects: the Sefuri Brain MRI Study. J Stroke Cerebrovasc Dis. 2014;23:817–822. doi: 10.1016/j.jstrokecerebrovasdis.2013.07.005.
    1. Satizabal C, Zhu Y, Mazoyer B, Dufouil C, Tzourio C. Circulating IL-6 and CRP are associated with MRI findings in the elderly: The 3C-Dijon Study. Neurology. 2012;78:720–727. doi: 10.1212/WNL.0b013e318248e50f.
    1. Choi P, Ren M, Phan T, Callisaya M, Ly J, Beare R, Chong W, Srikanth V. Silent infarcts and cerebral microbleeds modify the associations of white matter lesions with gait and postural stability: population based study. Stroke. 2012;43:1505–1510. doi: 10.1161/STROKEAHA.111.647271.
    1. Russo C, Jin Z, Liu R, Iwata S, Tugcu A, Yoshita M, Homma S, Elkind MS, Rundek T, Decarli C, Wright CB, Sacco RL, Di Tullio MR. LA volumes and reservoir function are associated with subclinical cerebrovascular disease: the CABL (Cardiovascular Abnormalities and Brain Lesions) study. JACC Cardiovasc Imaging. 2013;6:313–323. doi: 10.1016/j.jcmg.2012.10.019.
    1. Cheung N, Mosley T, Islam A, Kawasaki R, Sharrett AR, Klein R, Coker LH, Knopman DS, Shibata DK, Catellier D, Wong TY. Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study. Brain. 2010;133:1987–1993. doi: 10.1093/brain/awq127.
    1. Vermeer SE, den Heijer T, Koudstaal PJ, Oudkerk M, Hofman A, Breteler MM. Incidence and risk factors of silent brain infarcts in the population-based Rotterdam Scan Study. Stroke. 2003;34:392–396. doi: 10.1161/01.STR.0000052631.98405.15.
    1. Longstreth WT Jr, Bernick C, Manolio TA, Bryan N, Jungreis CA, Price TR. Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study. Arch Neurol. 1998;55:1217–1225. doi: 10.1001/archneur.55.9.1217.
    1. Morrison AC, Fornage M, Liao D, Boerwinkle E. Parental history of stroke predicts subclinical but not clinical stroke: the Atherosclerosis Risk in Communities Study. Stroke. 2000;31:2098–2102. doi: 10.1161/01.STR.31.9.2098.
    1. Pathak EB, Sloan MA. Recent racial/ethnic disparities in stroke hospitalizations and outcomes for young adults in Florida, 2001–2006. Neuroepidemiology. 2009;32:302–311. doi: 10.1159/000208795.
    1. Takashima Y, Miwa Y, Mori T, Hashimoto M, Uchino A, Yuzuriha T, Sasaguri T, Yao H. Sex differences in the risk profile and male predominance in silent brain infarction in community-dwelling elderly subjects: the Sefuri brain MRI study. Hypertens Res. 2010;33:748–752. doi: 10.1038/hr.2010.69.
    1. Moore RD, Pearson TA. Moderate alcohol consumption and coronary artery disease: a review. Medicine. 1986;65:242–267. doi: 10.1097/00005792-198607000-00004.
    1. Mukamal KJ, Longstreth WT Jr, Mittleman MA, Crum RM, Siscovick DS. Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the Cardiovascular Health Study. Stroke. 2001;32:1939–1946. doi: 10.1161/hs0901.095723.
    1. Fukuda K, Yuzuriha T, Kinukawa N, Murakawa R, Takashima Y, Uchino A, Ibayashi S, Iida M, Yao H, Hirano M. Alcohol intake and quantitative MRI findings among community dwelling Japanese subjects. J Neurol Sci. 2009;278:30–34. doi: 10.1016/j.jns.2008.11.007.
    1. Bokura H, Yamaguchi S, Iijima K, Nagai A, Oguro H. Metabolic syndrome is associated with silent ischemic brain lesions. Stroke. 2008;39:1607–1609. doi: 10.1161/STROKEAHA.107.508630.
    1. Pezzini A, Del Zotto E, Padovani A. Homocysteine and cerebral ischemia: pathogenic and therapeutical implications. Curr Med Chem. 2007;14:249–263. doi: 10.2174/092986707779941140.
    1. Wu XQ, Ding J, Ge AY, Liu FF, Wang X, Fan W. Acute phase homocysteine related to severity and outcome of atherothrombotic stroke. Eur J Intern Med. 2013;24:362–367. doi: 10.1016/j.ejim.2013.01.015.
    1. Vermeer SE, van Dijk EJ, Koudstaal PJ, Oudkerk M, Hofman A, Clarke R, Breteler MM. Homocysteine, silent brain infarcts, and white matter lesions: the Rotterdam Scan Study. Ann Neurol. 2002;51:285–289. doi: 10.1002/ana.10111.
    1. Seshadri S, Wolf PA, Beiser AS, Selhub J, Au R, Jacques PF, Yoshita M, Rosenberg IH, D'Agostino RB, DeCarli C. Association of plasma total homocysteine levels with subclinical brain injury: cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study. Arch Neurol. 2008;65:642–649. doi: 10.1001/archneur.65.5.642.
    1. Manolio T, Burke G, O’Leary D, Evans G, Beauchamp N, Knepper L, Ward B. Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults: the cardiovascular health study. Atheroscler Thromb Vasc Biol. 1999;19:356–365. doi: 10.1161/01.ATV.19.2.356.
    1. Seliger SL, Longstreth WT Jr, Katz R, Manolio TA, Fried LF, Shlipak M, Stehman-Breen CO, Newman A, Sarnak M, Gillen DL, Bleyer A, Siscovick DS. Cystatin C and subclinical brain infarction. J Am Soc Nephrol. 2005;16:3721–3727. doi: 10.1681/ASN.2005010006.
    1. Heo SH, Lee SH. High levels of serum uric acid are associated with silent brain infarction. J Neurol Sci. 2010;297:6–10. doi: 10.1016/j.jns.2010.07.007.
    1. Knuiman MW, Folsom AR, Chambless LE, Liao D, Wu KK. Association of hemostatic variables with MRI-detected cerebral abnormalities: the atherosclerosis risk in communities study. Neuroepidemiology. 2001;20:96–104. doi: 10.1159/000054767.
    1. Zhu YC, Dufouil C, Tzourio C, Chabriat H. Silent brain infarcts: a review of MRI diagnostic criteria. Stroke. 2011;42:1140–1145. doi: 10.1161/STROKEAHA.110.600114.
    1. Koch S, McClendon MS, Bhatia R. Imaging evolution of acute lacunar infarction: Leukoariosis or lacune? Neurology. 2011;77:1091–1095. doi: 10.1212/WNL.0b013e31822e1470.
    1. Potter GM, Marlborough FJ, Wardlaw JM. Wide variation in definition, detection, and description of lacunar lesions on imaging. Stroke. 2011;42:359–366. doi: 10.1161/STROKEAHA.110.594754.
    1. Bokura H, Kobayashi S, Yamaguchi S. Distinguishing silent lacunar infarction from enlarged Virchow-Robin spaces: a magnetic resonance imaging and pathological study. J Neurol. 1998;245:116–122. doi: 10.1007/s004150050189.
    1. Reitz C, Schupf N, Luchsinger JA, Brickman AM, Manly JJ, Andrews H, Tang MX, DeCarli C, Brown TR, Mayeux R. Validity of self-reported stroke in elderly African Americans, Caribbean Hispanics, and Whites. Arch Neurol. 2009;66:834–840. doi: 10.1001/archneurol.2009.83.
    1. Howard VJ, McClure LA, Meschia JF, Pulley L, Orr SC, Friday GH. High prevalence of stroke symptoms among persons without a diagnosis of stroke or transient ischemic attack in a general population: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Arch Intern Med. 2006;166:1952–1958. doi: 10.1001/archinte.166.18.1952.
    1. Sterne JA, Egger M, Smith GD. Investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001;323:101–105. doi: 10.1136/bmj.323.7304.101.
    1. Rockwood K, Gubitz G. Silent cerebral infarction: are we listening? Stroke. 2008;39:2919–2920. doi: 10.1161/STROKEAHA.108.523803.
    1. Fanning JP, Walters DL, Platts DG, Eeles E, Bellapart J, Fraser JF. Characterization of neurological injury in transcatheter aortic valve implantation: how clear is the picture? Circulation. 2014;129:504–515. doi: 10.1161/CIRCULATIONAHA.113.004103.
    1. Fanning JP, Wesley AJ, Platts DG, Walters DL, Eeles EM, Seco M, Tronstad O, Strugnell W, Barnett AG, Clarke AJ, Bellapart J, Vallely MP, Tesar PJ, Fraser JF. The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY): concept, design and rationale. BMC Cardiovasc Disord. 2014;14:45. doi: 10.1186/1471-2261-14-45.

Source: PubMed

3
購読する