Background: Cerebral microbleeds (CMBs) are associated with focal hemosiderin deposits and represent a form of cerebral small vessel disease. To date, indefinite and inconsistent reports are available regarding the association between serum lipid fractions and CMBs. In addition, these previous studies did not include Asian populations, who may have a higher risk of cerebral hemorrhage. The purpose of this study was to examine the associations between serum lipid fractions and CMBs in healthy Japanese subjects. Methods: We performed a cross-sectional study involving 4,024 neurologically normal Japanese subjects (mean age 61.6 years). All the participants underwent 1.5-Tesla magnetic resonance imaging scan, and CMBs were classified into 3 groups based on their locations. The concentrations of lipid fractions were categorized into quartiles and the association between the lipid fractions and CMBs were investigated using logistic regression analysis. Results: CMBs were observed in 164 (4.1%) of participants. Of these participants with CMBs, 33 (20.1%) had lobar CMBs and 91 (55.5%) had deep CMBs. Subjects with deep CMBs had lower total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels. After adjusting for confounding factors, lower TC and HDL-C levels were still associated with the presence of deep CMBs (OR for the highest vs. the lowest quartiles of TC and HDL-C was 2.28 [95% CI 1.05-4.94], and 1.93 [95% CI 1.02-3.65], respectively). The presence of subcortical infarcts and periventricular hyperintensities was more frequently observed in deep CMBs, whereas white matter hyperintensities were more frequently observed in lobar CMBs. Conclusions: Our results suggest that low serum TC and HDL-C levels are closely associated with deep CMBs.

1.
Fazekas F, Kleinert R, Roob G, Kleinert G, Kapeller P, Schmidt R, Hartung HP: Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. AJNR Am J Neuroradiol 1999;20:637-642.
2.
Wardlaw JM, Lewis SC, Keir SL, Dennis MS, Shenkin S: Cerebral microbleeds are associated with lacunar stroke defined clinically and radiologically, independently of white matter lesions. Stroke 2006;37:2633-2636.
3.
Thijs V, Lemmens R, Schoofs C, Gorner A, Van Damme P, Schrooten M, Demaerel P: Microbleeds and the risk of recurrent stroke. Stroke 2010;41:2005-2009.
4.
Jeerakathil T, Wolf PA, Beiser A, Hald JK, Au R, Kase CS, Massaro JM, DeCarli C: Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham study. Stroke 2004;35:1831-1835.
5.
Bokura H, Saika R, Yamaguchi T, Nagai A, Oguro H, Kobayashi S, Yamaguchi S: Microbleeds are associated with subsequent hemorrhagic and ischemic stroke in healthy elderly individuals. Stroke 2011;42:1867-1871.
6.
Nishikawa T, Ueba T, Kajiwara M, Fujisawa I, Miyamatsu N, Yamashita K: Cerebral microbleeds predict first-ever symptomatic cerebrovascular events. Clin Neurol Neurosurg 2009;111:825-828.
7.
Lee SH, Bae HJ, Yoon BW, Kim H, Kim DE, Roh JK: Low concentration of serum total cholesterol is associated with multifocal signal loss lesions on gradient-echo magnetic resonance imaging: analysis of risk factors for multifocal signal loss lesions. Stroke 2002;33:2845-2849.
8.
Romero JR, Preis SR, Beiser A, DeCarli C, Viswanathan A, Martinez-Ramirez S, Kase CS, Wolf PA, Seshadri S: Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham heart study. Stroke 2014;45:1492-1494.
9.
Vernooij MW, van der Lugt A, Ikram MA, Wielopolski PA, Niessen WJ, Hofman A, Krestin GP, Breteler MM: Prevalence and risk factors of cerebral microbleeds: the Rotterdam scan study. Neurology 2008;70:1208-1214.
10.
Wieberdink RG, Poels MM, Vernooij MW, Koudstaal PJ, Hofman A, van der Lugt A, Breteler MM, Ikram MA: Serum lipid levels and the risk of intracerebral hemorrhage: the Rotterdam study. Arterioscler Thromb Vasc Biol 2011;31:2982-2989.
11.
Ding J, Sigurdsson S, Garcia M, Phillips CL, Eiriksdottir G, Gudnason V, van Buchem MA, Launer LJ: Risk factors associated with incident cerebral microbleeds according to location in older people: the age, gene/environment susceptibility (AGES)-Reykjavik study. JAMA Neurol 2015;72:682-688.
12.
van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ: Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010;9:167-176.
13.
Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, Amaducci L, Orgogozo JM, Brun A, Hofman A, et al: Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 1993;43:250-260.
14.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: 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. Neurology 1984;34:939-944.
15.
Fazekas F, Kleinert R, Offenbacher H, Payer F, Schmidt R, Kleinert G, Radner H, Lechner H: The morphologic correlate of incidental punctate white matter hyperintensities on MR images. AJNR Am J Neuroradiol 1991;12:915-921.
16.
Chen YW, Lee MJ, Smith EE: Cerebral amyloid angiopathy in East and West. Int J Stroke 2010;5:403-411.
17.
Reed DM: The paradox of high risk of stroke in populations with low risk of coronary heart disease. Am J Epidemiol 1990;131:579-588.
18.
Choudhury RP, Rong JX, Trogan E, Elmalem VI, Dansky HM, Breslow JL, Witztum JL, Fallon JT, Fisher EA: High-density lipoproteins retard the progression of atherosclerosis and favorably remodel lesions without suppressing indices of inflammation or oxidation. Arterioscler Thromb Vasc Biol 2004;24:1904-1909.
19.
Navab M, Berliner JA, Subbanagounder G, Hama S, Lusis AJ, Castellani LW, Reddy S, Shih D, Shi W, Watson AD, Van Lenten BJ, Vora D, Fogelman AM: HDL and the inflammatory response induced by LDL-derived oxidized phospholipids. Arterioscler Thromb Vasc Biol 2001;21:481-488.
20.
Rouhl RP, Damoiseaux JG, Lodder J, Theunissen RO, Knottnerus IL, Staals J, Henskens LH, Kroon AA, de Leeuw PW, Tervaert JW, van Oostenbrugge RJ: Vascular inflammation in cerebral small vessel disease. Neurobiol Aging 2012;33:1800-1806.
21.
Charidimou A, Werring DJ: A raging fire in acute lacunar stroke: inflammation, blood-brain barrier dysfunction and the origin of cerebral microbleeds. J Neurol Sci 2014;340:1-2.
22.
Mulder M, Terwel D: Possible link between lipid metabolism and cerebral amyloid angiopathy in Alzheimer's disease: a role for high-density lipoproteins? Haemostasis 1998;28:174-194.
23.
Wardlaw JM, Sandercock PA, Dennis MS, Starr J: Is breakdown of the blood-brain barrier responsible for lacunar stroke, leukoaraiosis, and dementia? Stroke 2003;34:806-812.
24.
Smith EE, Greenberg SM: Beta-amyloid, blood vessels, and brain function. Stroke 2009;40:2601-2606.
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