Advanced searchCitation search
Skip main navigation
 
Original Research
7 July 2015

Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study

Authors: B. Gwen Windham, MD, MHS, Bradley Deere, MD, Michael E. Griswold, PhD, Wanmei Wang, MS, Daniel C. Bezerra, MD, PhD, Dean Shibata, MD, Kenneth Butler, PhD, David Knopman, MD, Rebecca F. Gottesman, MD, PhD, Gerardo Heiss, MD, PhD, and Thomas H. Mosley Jr., PhDAuthor, Article, & Disclosure Information
Publication: Annals of Internal Medicine
Volume 163, Number 1
https://doi.org/10.7326/M14-2057
Get Access

Submit a Comment

Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
Cancel

Abstract

Background:

Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored.

Objective:

To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs).

Design:

Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study.

Setting:

Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995.

Participants:

1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years.

Measurements:

Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models.

Results:

Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]).

Limitation:

Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes.

Conclusion:

Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates.

Primary Funding Source:

National Heart, Lung, and Blood Institute.

Get full access to this article

View all available purchase options and get full access to this article.

Get Access

References

1.
Fisher CM. Lacunar strokes and infarcts: a review. Neurology. 1982;32:871-6. [PMID: 7048128]
Crossref
PubMed
Google Scholar
2.
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;55:1217-25. [PMID: 9740116]
Crossref
PubMed
Google Scholar
3.
Bernick C, Kuller L, Dulberg C, Longstreth WT Jr, Manolio T, Beauchamp N, et al; Cardiovascular Health Study Collaborative Research Group. Silent MRI infarcts and the risk of future stroke: the Cardiovascular Health Study. Neurology. 2001;57:1222-9. [PMID: 11591840]
Crossref
PubMed
Google Scholar
4.
Bokura H, Kobayashi S, Yamaguchi S, Iijima K, Nagai A, Toyoda G, et al. 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. [PMID: 17904049]
Crossref
PubMed
Google Scholar
5.
Buyck JF, Dufouil C, Mazoyer B, Maillard P, Ducimetière P, Alpérovitch A, et al. Cerebral white matter lesions are associated with the risk of stroke but not with other vascular events: the 3-City Dijon Study. Stroke. 2009;40:2327-31. [PMID: 19443799]  doi: 10.1161/STROKEAHA.109.548222
Crossref
PubMed
Google Scholar
6.
Debette S, Beiser A, DeCarli C, Au R, Himali JJ, Kelly-Hayes M, et al. Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study. Stroke. 2010;41:600-6. [PMID: 20167919]  doi: 10.1161/STROKEAHA.109.570044
Crossref
PubMed
Google Scholar
7.
Folsom AR, Yatsuya H, Mosley TH Jr, Psaty BM, Longstreth WT Jr. Risk of intraparenchymal hemorrhage with magnetic resonance imaging-defined leukoaraiosis and brain infarcts. Ann Neurol. 2012;71:552-9. [PMID: 22522444]  doi: 10.1002/ana.22690
Crossref
PubMed
Google Scholar
8.
Gerdes VE, Kwa VI, ten Cate H, Brandjes DP, Büller HR, Stam J; Amsterdam Vascular Medicine Group. Cerebral white matter lesions predict both ischemic strokes and myocardial infarctions in patients with established atherosclerotic disease. Atherosclerosis. 2006;186:166-72. [PMID: 16098981]
Crossref
PubMed
Google Scholar
9.
Kobayashi S, Okada K, Koide H, Bokura H, Yamaguchi S. Subcortical silent brain infarction as a risk factor for clinical stroke. Stroke. 1997;28:1932-9. [PMID: 9341698]
Crossref
PubMed
Google Scholar
10.
Kuller LH, Longstreth WT Jr, Arnold AM, Bernick C, Bryan RN, Beauchamp NJ Jr; Cardiovascular Health Study Collaborative Research Group. White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke. Stroke. 2004;35:1821-5. [PMID: 15178824]
Crossref
PubMed
Google Scholar
11.
Longstreth WT Jr, Diehr P, Beauchamp NJ, Manolio TA. Patterns on cranial magnetic resonance imaging in elderly people and vascular disease outcomes [Letter]. Arch Neurol. 2001;58:2074. [PMID: 11735783]
Crossref
PubMed
Google Scholar
12.
Manolio TA, Kronmal RA, Burke GL, Poirier V, O'Leary DH, Gardin JM, et al. Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study. Stroke. 1994;25:318-27. [PMID: 8303738]
Crossref
PubMed
Google Scholar
13.
Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MM; Rotterdam Scan Study. Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke. 2003;34:1126-9. [PMID: 12690219]
Crossref
PubMed
Google Scholar
14.
Wong TY, Klein R, Sharrett AR, Couper DJ, Klein BE, Liao DP, et al; ARIC Investigators. Atherosclerosis Risk in Communities Study. Cerebral white matter lesions, retinopathy, and incident clinical stroke. JAMA. 2002;288:67-74. [PMID: 12090864]
Crossref
PubMed
Google Scholar
15.
Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9:689-701. [PMID: 20610345]  doi: 10.1016/S1474-4422(10)70104-6
Crossref
PubMed
Google Scholar
16.
Potter GM, Doubal FN, Jackson CA, Chappell FM, Sudlow CL, Dennis MS, et al. Enlarged perivascular spaces and cerebral small vessel disease. Int J Stroke. 2015;10:376-81. [PMID: 23692610]  doi: 10.1111/ijs.12054
Crossref
PubMed
Google Scholar
17.
Rouhl RP, van Oostenbrugge RJ, Knottnerus IL, Staals JE, Lodder J. Virchow-Robin spaces relate to cerebral small vessel disease severity. J Neurol. 2008;255:692-6. [PMID: 18286319]  doi: 10.1007/s00415-008-0777-y
Crossref
PubMed
Google Scholar
18.
Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013;12:483-97. [PMID: 23602162]  doi: 10.1016/S1474-4422(13)70060-7
Crossref
PubMed
Google Scholar
19.
Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125:e2-e220. [PMID: 22179539]  doi: 10.1161/CIR.0b013e31823ac046
Crossref
PubMed
Google Scholar
20.
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation. 2014;129:e28-e292. [PMID: 24352519]  doi: 10.1161/01.cir.0000441139.02102.80
Crossref
PubMed
Google Scholar
21.
Ohira T, Shahar E, Chambless LE, Rosamond WD, Mosley TH Jr, Folsom AR. Risk factors for ischemic stroke subtypes: the Atherosclerosis Risk in Communities study. Stroke. 2006;37:2493-8. [PMID: 16931783]
Crossref
PubMed
Google Scholar
22.
Price TR, Manolio TA, Kronmal RA, Kittner SJ, Yue NC, Robbins J, et al. 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;28:1158-64. [PMID: 9183343]
Crossref
PubMed
Google Scholar
23.
van der Flier WM, van Straaten EC, Barkhof F, Verdelho A, Madureira S, Pantoni L, et al. Small vessel disease and general cognitive function in nondisabled elderly: the LADIS study. Stroke. 2005;36:2116-20. [PMID: 16141425]
Crossref
PubMed
Google Scholar
24.
de Laat KF, Tuladhar AM, van Norden AG, Norris DG, Zwiers MP, de Leeuw FE. Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease. Brain. 2011;134:73-83. [PMID: 21156660]  doi: 10.1093/brain/awq343
Crossref
PubMed
Google Scholar
25.
Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ. 2010;341:c3666. [PMID: 20660506]  doi: 10.1136/bmj.c3666
Crossref
PubMed
Google Scholar
26.
Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al; American Heart Association Stroke Council. Council on Epidemiology and Prevention. Council on Cardiovascular Nursing. Council on Cardiovascular Radiology and Intervention. and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:2672-713. [PMID: 21778438]  doi: 10.1161/STR.0b013e3182299496
Crossref
PubMed
Google Scholar
27.
The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. Am J Epidemiol. 1989;129:687-702. [PMID: 2646917]
Crossref
PubMed
Google Scholar
28.
Bryan RN, Cai J, Burke G, Hutchinson RG, Liao D, Toole JF, et al. Prevalence and anatomic characteristics of infarct-like lesions on MR images of middle-aged adults: the Atherosclerosis Risk in Communities Study. AJNR Am J Neuroradiol. 1999;20:1273-80. [PMID: 10472985]
PubMed
Google Scholar
29.
Liao D, Cooper L, Cai J, Toole J, Bryan N, Burke G, et al. The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: the ARIC Study. Neuroepidemiology. 1997;16:149-62. [PMID: 9159770]
Crossref
PubMed
Google Scholar
30.
Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, et al; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12:822-38. [PMID: 23867200]  doi: 10.1016/S1474-4422(13)70124-8
Crossref
PubMed
Google Scholar
31.
Bezerra DC, Sharrett AR, Matsushita K, Gottesman RF, Shibata D, Mosley TH Jr, et al. Risk factors for lacune subtypes in the Atherosclerosis Risk in Communities (ARIC) Study. Neurology. 2012;78:102-8. [PMID: 22170882]  doi: 10.1212/WNL.0b013e31823efc42
Crossref
PubMed
Google Scholar
32.
Liao D, Cooper L, Cai J, Toole JF, Bryan NR, Hutchinson RG, et al. Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Atherosclerosis Risk in Communities Study. Stroke. 1996;27:2262-70. [PMID: 8969791]
Crossref
PubMed
Google Scholar
33.
Rosamond WD, Folsom AR, Chambless LE, Wang CH, McGovern PG, Howard G, et al. Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. Stroke. 1999;30:736-43. [PMID: 10187871]
Crossref
PubMed
Google Scholar
34.
Robins M, Baum HM. The National Survey of Stroke. Incidence. Stroke. 1981;12:I45-57. [PMID: 7222166]
PubMed
Google Scholar
35.
Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA, et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology. 2012;78:1043-50. [PMID: 22377814]  doi: 10.1212/WNL.0b013e31824e8e7f
Crossref
PubMed
Google Scholar
36.
Doubal FN, MacLullich AM, Ferguson KJ, Dennis MS, Wardlaw JM. Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease. Stroke. 2010;41:450-4. [PMID: 20056930]  doi: 10.1161/STROKEAHA.109.564914
Crossref
PubMed
Google Scholar
37.
Zhu YC, Tzourio C, Soumaré A, Mazoyer B, Dufouil C, Chabriat H. Severity of dilated Virchow-Robin spaces is associated with age, blood pressure, and MRI markers of small vessel disease: a population-based study. Stroke. 2010;41:2483-90. [PMID: 20864661]  doi: 10.1161/STROKEAHA.110.591586
Crossref
PubMed
Google Scholar
38.
Kalantarian S, Ay H, Gollub RL, Lee H, Retzepi K, Mansour M, et al. Association between atrial fibrillation and silent cerebral infarctions: a systematic review and meta-analysis. Ann Intern Med. 2014;161:650-8. [PMID: 25364886]  doi: 10.7326/M14-0538
Link
Google Scholar
39.
Vermeer SE, Longstreth WT Jr, Koudstaal PJ. Silent brain infarcts: a systematic review. Lancet Neurol. 2007;6:611-9. [PMID: 17582361]
Crossref
PubMed
Google Scholar
40.
Fu JH, Mok V, Lam W, Wong A, Chu W, Xiong Y, et al. Effects of statins on progression of subclinical brain infarct. Cerebrovasc Dis. 2010;30:51-6. [PMID: 20431290]  doi: 10.1159/000313614
Crossref
PubMed
Google Scholar
41.
Knopman DS, Penman AD, Catellier DJ, Coker LH, Shibata DK, Sharrett AR, et al. Vascular risk factors and longitudinal changes on brain MRI: the ARIC Study. Neurology. 2011;76:1879-85. [PMID: 21543737]  doi: 10.1212/WNL.0b013e31821d753f
Crossref
PubMed
Google Scholar

Comments

0 Comments
Sign In to Submit A Comment
Gauranga Dhar14 July 2015
Routine screening for WMH in elderly hypertensive patients is vital
White matter hyperintensities (WMH) are common in the elderly. Up to 30% of elderly population with hypertension found to have silent infarcts is found in routine MRI [1]. Take home message of this study is extremely vital to prevent further development of stroke and death.

Reference:
1. Vermeer SE, Longstreth WTJ, Koudstaal PJ. Silent brain infarcts: a systematic re-
view. Lancet Neurol 2007; 6: 611ñ619.

Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 163 • Number 1 • 7 July 2015
Pages: 22 - 31

History

Published online: 7 July 2015
Published in issue: 7 July 2015

Keywords

  1. Blood
  2. Brain
  3. Hazard ratio
  4. Infarction
  5. Ischemic stroke
  6. Lesions
  7. Longitudinal studies
  8. Medical risk factors
  9. Mortality
  10. Stroke

Copyright

© 2015 American College of Physicians.

Authors

Affiliations

B. Gwen Windham, MD, MHS
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Bradley Deere, MD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Michael E. Griswold, PhD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Wanmei Wang, MS
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Daniel C. Bezerra, MD, PhD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Dean Shibata, MD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Kenneth Butler, PhD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
David Knopman, MD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Rebecca F. Gottesman, MD, PhD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Gerardo Heiss, MD, PhD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Thomas H. Mosley Jr., PhD
From University of Mississippi Medical Center, Jackson, Mississippi; Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Washington Medical Center, Seattle, Washington; Mayo Clinic, Rochester, Minnesota; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
View all articles by this author
Acknowledgment: The authors thank the staff and participants of the ARIC Study for their important contributions and Mr. Seth Lirette for analytic assistance during the revision of the manuscript.
Financial Support: The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C, with the ARIC carotid MRI examination funded by U01HL075572-01.
Disclosures: Dr. Windham reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Griswold reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Butler reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. Knopman reports grants from TauRx Therapeutics and personal fees from Lundbeck, the Dominantly Inherited Alzheimer Network, and the American Academy of Neurology outside the submitted work. Dr. Mosley reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-2057.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement: Study protocol and data set: Protocols and data for the ARIC and ARIC Brain MRI Study may be obtained by approved persons through written agreements with the ARIC Steering Committee and the research sponsor (National Heart, Lung, and Blood Institute) (e-mail, [email protected]). Statistical code: Available from Dr. Griswold (e-mail, [email protected]).
Corresponding Author: B. Gwen Windham, MD, MHS, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216; e-mail, [email protected].
Current Author Addresses: Drs. Windham, Deere, Griswold, Butler, and Mosley and Ms. Wang: University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216.
Dr. Bezerra: Visconde Silva 52 / 804, Rio de Janeiro, Brazil 22271-092.
Dr. Shibata: University of Washington, 1959 NE Pacific Street, Seattle, WA 98195.
Dr. Knopman: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
Dr. Gottesman: Johns Hopkins Medicine, Phipps 446D, 600 North Wolfe Street, Baltimore, MD 21287.
Dr. Heiss: University of North Carolina at Chapel Hill, 137 East Franklin Street, Suite 306, Chapel Hill, NC 27514-4145.
Author Contributions: Conception and design: B.G. Windham, M.E. Griswold, T.H. Mosley.
Analysis and interpretation of the data: B.G. Windham, B. Deere, M.E. Griswold, W. Wang, D. Shibata, D. Knopman, R.F. Gottesman, T.H. Mosley.
Drafting of the article: B.G. Windham, B. Deere, M.E. Griswold, D.C. Bezerra.
Critical revision of the article for important intellectual content: B.G. Windham, M.E. Griswold, D.C. Bezerra, K. Butler, D. Knopman, R.F. Gottesman, T.H. Mosley.
Final approval of the article: B.G. Windham, M.E. Griswold, D.C. Bezerra, K. Butler, D. Knopman, R.F. Gottesman, G. Heiss, T.H. Mosley.
Provision of study materials or patients: G. Heiss, T.H. Mosley.
Statistical expertise: M.E. Griswold, W. Wang.
Obtaining of funding: G. Heiss, T.H. Mosley.
Administrative, technical, or logistic support: M.E. Griswold, G. Heiss.
Collection and assembly of data: D. Shibata, K. Butler, G. Heiss, T.H. Mosley.

Metrics & Citations

Metrics

Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.

For more information or tips please see 'Downloading to a citation manager' in the Help menu.

Format




Tips for downloading citations

Download article citation data for:
B. Gwen Windham, Bradley Deere, Michael E. Griswold, et al. Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study. Ann Intern Med.2015;163:22-31. [Epub 7 July 2015]. doi:10.7326/M14-2057

View More

Get Access

Login Options:
Purchase

You will be redirected to acponline.org to sign-in to Annals to complete your purchase.

buy this article subscribe

Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.

Create your Free Account

You will be redirected to acponline.org to create an account that will provide access to Annals.

create account learn more

Related in ACP Journals

View options

PDF/ePub

View PDF/ePub

Related in ACP Journals

Full Text

View Full Text

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media

View full text|Download PDF