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(Stroke. 1995;26:588-592.)
© 1995 American Heart Association, Inc.

Articles

Leukoaraiosis in Stroke Patients

The Copenhagen Stroke Study

Henrik Stig Jørgensen, MD; Hirofumi Nakayama, MD; Hans Otto Raaschou, MD Tom Skyhøj Olsen, MD, PhD

From the Departments of Neurology and Radiology (H.O.R.), Bispebjerg Hospital, Copenhagen, Denmark.

Correspondence to Henrik Stig Jørgensen, MD, Department of Neurology, Bispebjerg Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose This study was undertaken to determine factors of importance for the development of leukoaraiosis and to evaluate whether leukoaraiosis influences stroke outcome.

Methods The study was prospective and consecutive and included 1084 unselected patients with acute stroke and transient ischemic attack admitted from the community of Bispebjerg (Copenhagen, Denmark) during a 25-month period from September 1, 1991, to September 30, 1993. All patients were treated in a stroke unit from the time of acute admission to completion of rehabilitation. Daily alcohol consumption and other putative risk factors were registered on admission, and patients were evaluated weekly to death or time of completed rehabilitation by means of neurological (Scandinavian Stroke Scale) and functional (Barthel Index) scores. Leukoaraiosis was diagnosed on computed tomographic scan. Multivariate analyses were applied to test relations independent of other influencing factors.

Results Leukoaraiosis was present in 15% of the patients. Age was the only factor that significantly increased the risk of leukoaraiosis (odds ratio [OR] per 10-year increase, 2.4; 95% confidence interval [CI], 1.8 to 3.1), whereas the presence of atrial fibrillation was adversely related to leukoaraiosis (OR, 0.26; 95% CI, 0.13 to 0.52). Moderate daily alcohol consumption (1 to 5 drinks) reduced the risk of leukoaraiosis (OR, 0.50; 95% CI, 0.28 to 0.87), whereas heavy daily alcohol consumption (>5 drinks) tended to increase the risk (OR, 1.3; 95% CI, 0.5 to 3.3). Leukoaraiosis was not related to the presence of hypertension, diabetes, ischemic heart disease, atrial fibrillation, intermittent claudication, smoking, or sex. The presence of leukoaraiosis had no influence on neurological outcome (P=.20), functional outcome (P=.47), length of hospital stay (P=.75), or mortality (P=.31).

Conclusions Moderate daily alcohol intake seems associated with a decreased risk of leukoaraiosis in stroke patients. The relation between alcohol intake and leukoaraiosis may even be U-shaped, like the relation between alcohol intake and coronary heart disease, alcohol intake and mortality, and alcohol intake and stroke. The presence of leukoaraiosis does not seem to influence the rehabilitation process or outcome of stroke.

Key Words: cerebrovascular disorders • leukoaraiosis • prognosis • risk factors

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Leukoaraiosis is the rarefaction of the white matter in the brain as seen on computed tomography (CT) or magnetic resonance imaging (MRI).¹ Leukoaraiosis may be associated with mental dysfunction in healthy elderly subjects,^{2 3 4 5 6} with the development of both vascular dementia and Alzheimer's type of dementia,^{1 7 8 9 10 11 12} and with cerebrovascular disease.^{1 8 9 13 14 15} In studies in which CT was used, the frequency of leukoaraiosis was reported to range from 9% to 19% in the elderly,¹⁶ from 3% to 44% in stroke patients,^{8 9 12} and from 30% to 60% in patients with Alzheimer's disease^{16 17} ; it was also determined that 50% of 23 patients with vascular dementia had leukoaraiosis.¹⁷ The wide variation in the frequency of leukoaraiosis reported probably reflects differences in age distribution and in diagnostic criteria used between studies. In studies in which MRI was used, the frequency of leukoaraiosis may be even higher than that reported from CT studies.¹⁶

The causes of the development of leukoaraiosis are uncertain. The frequency of leukoaraiosis increases with age,^{1 6 7 8 14 17} but an increased risk of leukoaraiosis has also been connected to hypertension^{1 7 9 10 11 14 18 19} and to heart disease.^{8 10 11} Cerebral blood flow is reduced in both patients and healthy elderly subjects with leukoaraiosis.^{11 17 20 21 22} Pathological studies have consistently linked leukoaraiosis with demyelination, gliosis, necrosis, cavitation, and vacuolization, conditions commonly associated with cerebrovascular disease.^{16 23 24}

In this prospective, community-based study we investigated factors of importance in the development of leukoaraiosis by characterizing stroke and transient ischemic attack (TIA) patients with leukoaraiosis. Patients were characterized in terms of clinical and radiological features and in terms of putative risk factors: hypertension, atrial fibrillation, ischemic heart disease, diabetes, smoking, and alcohol intake. Our purpose was also to describe the impact of leukoaraiosis on the prognosis of the stroke patient.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Inclusion Criteria
The study was consecutive and prospective. Included were all patients with acute stroke and TIA admitted to the neurological department of Bispebjerg Hospital, Copenhagen, in a 25-month period from September 1, 1991, to September 30, 1993. A total of 1351 patients with acute cerebrovascular disease were admitted in the inclusion period.

We excluded 267 patients (19.8%) in whom a CT scan could not be performed: 138 patients died before the scan could be completed, 27 were unable to undergo the examination because of poor condition, 45 could not cooperate sufficiently to complete the examination, 37 refused the examination, and 20 patients were not scanned for other reasons. Consequently, a total of 1084 patients were included in the study.

The study population was community based, as described elsewhere.²⁵ Initial diagnostic procedures and treatment as well as all stages of rehabilitation took place in the neurological department. This occurred regardless of the age of the patient, the severity of the stroke, and the condition of the patient before the stroke.

Stroke was defined according to World Health Organization criteria: rapidly developed clinical signs of focal disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than vascular origin. If the signs lasted less than 24 hours the diagnosis was TIA. Subarachnoid bleeding was not included.²⁶

This study was approved by the Ethics Committee of Copenhagen (approval No. V. 100.2263/91).

Computed Tomography
CT was performed with a Siemens Somatom DRG scanner. The time from onset of stroke to CT examination was dependent on the accessibility of the scanner, which varied during the study period. The median time from stroke onset to CT was 8 days. All scans were described by the same radiologist (H.O.R.), who was blinded to clinical data. In each patient it was decided whether leukoaraiosis was present or absent. Leukoaraiosis was defined as diffuse or patchy lucencies of the white matter or centrum ovale, ie, poorly delineated hypodense areas (Fig 1). An area was considered hypodense if its density was between that of normal white matter and that of the cerebrospinal fluid. In determining whether leukoaraiosis was present or absent, only cases in which leukoaraiosis was evident were classified as present; other cases were classified as absent. A silent infarct was diagnosed if CT revealed an infarct that could not be related to either the present stroke or to a former stroke.

View larger version (149K): [in this window] [in a new window]   Figure 1. Computed tomographic scan showing leukoaraiosis.

Clinical Evaluation
The following putative risk factors were considered: age, sex, current smoking (daily), atrial fibrillation (verified on electrocardiogram obtained on admission), intermittent claudication, hypertension (in treatment with antihypertensive drugs at the time of admission or hypertension diagnosed during the hospital stay [repeated blood pressure measurements >160/90 mm Hg after the first week following stroke]), diastolic and systolic blood pressure on admission, diabetes mellitus (a history of diabetes or diabetes diagnosed during the hospital stay [repeated blood glucose levels diagnostic for diabetes or blood glucose level on admission >11 mmol/L in patients without known diabetes who died before further diagnosis could be made²⁷ ]), and ischemic heart disease (a history of ischemic heart disease or ischemic heart disease diagnosed during the hospital stay).

Alcohol consumption was graded into three categories: (1) abstainers/less than 1 drink per day on average (no daily alcohol consumption); (2) between 1 and 5 drinks per day on average (moderate daily alcohol consumption); and (3) more than 5 drinks per day on average (heavy daily alcohol consumption). A drink was approximately 12 g alcohol, corresponding to a bottle of beer, a glass of wine, or a single tot of spirits.

Comorbidity was defined as concurrent disease with potential influence on the ability to perform activities of daily living, eg, former stroke with sequelae, amputation, heart failure, or parkinsonism.

The Scandinavian Stroke Scale was used to assess neurological deficits.^{28 29} The Scandinavian Stroke Scale evaluates level of consciousness; eye movement; power in arm, hand, and leg; orientation; aphasia; facial paresis; and gait. The total score ranges from 0 to 58 points. It was performed on admission, the day after admission, every week during the hospital stay, and at discharge. The weekly assessment was performed by the same neurologist (H.S.J.) in all patients.

The Barthel Index score was used to assess functional ability³⁰ weekly during the hospital stay and at discharge. It evaluates 10 different activities of daily life and ranges in total score from 0 to 100 points.

Statistical Analysis
We performed statistical analyses using the SPSS package.³¹ In univariate analysis Student's t test was used for continuous data, and the ² test was used for noncontinuous data. For risk factors, a multiple logistic regression model was used to test for independence of other factors. A multiple linear regression model was used to test the independent influence of leukoaraiosis on initial stroke severity, speed of recovery, functional and neurological outcome of stroke, and length of hospital stay. A multiple logistic regression model was used to test the independent influence of leukoaraiosis on mortality. All variables of interest were tested with the backward procedure. The level of significance was chosen as P<.05. The large number of patients included in the study justifies the use of the multiple regression model. Only factors with a potential relation to the dependent variable were included in the model. Evaluation of the results should, however, be done with the multiple comparison nature of the analysis in mind.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Leukoaraiosis
Leukoaraiosis was present in 163 (15%) of the 1084 patients. Table 1 shows a univariate comparison of basic characteristics and CT data in patients with and without leukoaraiosis. The frequency of stroke versus TIA and that of infarction versus hemorrhage did not differ between patients with and without leukoaraiosis. Patients with leukoaraiosis were older, more often had other disabling diseases, more often were women, and less often had cortical involvement of the stroke than patients without leukoaraiosis. Leukoaraiosis and silent infarct also seemed related. However, this association was mainly explained by the fact that both conditions are associated with increasing age.

View this table: [in this window] [in a new window]   Table 1. Basic Characteristics and Computed Tomographic Data in Patients With and Patients Without Leukoaraiosis

Risk Factors
In the univariate analysis (Table 2), age, female sex, daily alcohol consumption, and smoking were significantly related to leukoaraiosis. Female sex and increasing age were related to an increased risk of leukoaraiosis, and daily alcohol consumption and smoking were related to a decreased risk of leukoaraiosis: 6 (9.5%) of 63 patients with heavy daily alcohol consumption had leukoaraiosis, 23 (9.2%) of 249 patients with moderate daily alcohol consumption had leukoaraiosis, and 117 (18%) of 648 patients with no daily alcohol consumption had leukoaraiosis. Hypertension, blood pressure on admission, ischemic heart disease, and other stroke risk factors were not related to leukoaraiosis.

View this table: [in this window] [in a new window]   Table 2. Univariate Analysis of Risk Factors in Patients With and Patients Without Leukoaraiosis

In the multiple regression analysis, age (odds ratio [OR] per 10-year increase, 2.4; 95% confidence interval [CI], 1.8 to 3.1) was the only factor to increase the risk of leukoaraiosis independent of other factors, whereas both atrial fibrillation (OR, 0.26; 95% CI, 0.13 to 0.52) and moderate daily alcohol consumption compared with no daily alcohol consumption (OR, 0.50; 95% CI, 0.28 to 0.87) decreased the risk of leukoaraiosis independent of other factors (Fig 2). Despite a decreased frequency of leukoaraiosis in patients with heavy daily alcohol consumption, the multivariate analysis showed a tendency toward an increased risk of leukoaraiosis in these patients compared with patients with no daily alcohol consumption (OR, 1.3; 95% CI, 0.5 to 3.3). This discrepancy was explained by an association between age and daily alcohol intake: Patients with heavy daily alcohol consumption (mean age, 61.7 years; SD, 11.5) were younger than patients with moderate daily alcohol consumption (mean age, 70.5 years; SD, 11.0), who in turn were younger than patients with no daily alcohol consumption (mean age, 74.8 years; SD, 11.0) (P<.0001). The univariate relations between sex and leukoaraiosis and between smoking and leukoaraiosis disappeared in the multivariate analysis. This was explained by an association between age and sex: Mean age was higher in women (76.0 years; SD, 10.5) than in men (70.0 years; SD, 11.8). It was also explained by an association between daily alcohol consumption and smoking: Patients with daily alcohol consumption were more frequently smokers than patients without daily alcohol consumption.

View larger version (11K): [in this window] [in a new window]   Figure 2. Line graph showing relative risk of leukoaraiosis in relation to alcohol intake. Risk was set at 1.00 in patients with an alcohol consumption of less than 1 drink daily. Stars mark the odds ratio for leukoaraiosis at given levels of daily alcohol consumption as indicated, and vertical lines show the corresponding 95% confidence intervals.

Stroke Prognosis
Table 3 shows the results of the multiple regression analyses of the relation between leukoaraiosis and initial stroke severity and the relation between leukoaraiosis and different outcome measures of stroke, independent of other influencing factors. Patients with TIA were excluded in these analyses. It appears from Table 3 that the presence of leukoaraiosis had no influence on initial stroke severity, mortality, length of hospital stay, or either of the outcome measures at the end of rehabilitation, ie, neurological and functional outcome.

View this table: [in this window] [in a new window]   Table 3. Multiple Logistic Regression Analyses of the Influence of Leukoaraiosis and Other Factors on Stroke Severity, Speed of Recovery, Neurological Outcome, Functional Outcome, and Mortality

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The diagnosis of leukoaraiosis is based on the observer's visual impression of the CT scan. Some interobserver variation in diagnostic sensitivity is therefore to be expected; mild cases of leukoaraiosis may be diagnosed by some but not by others. Intraobserver variation may even be present in mild cases of leukoaraiosis. In this study only cases in which leukoaraiosis was evident were classified as leukoaraiosis; other cases were classified as without leukoaraiosis. This presents a bias to the present study because some mild cases of leukoaraiosis may not have been diagnosed. On the other hand, including only patients in whom the diagnosis is certain increases the specificity of the diagnosis, although we did not study intraobserver reliability. The frequency of leukoaraiosis in this study is, however, well within the range of frequencies found in previous studies of stroke patients.^{8 9 12}

The relation between leukoaraiosis and alcohol consumption has not been studied before. This community-based study of 1084 patients with acute cerebrovascular disease shows that the relation between leukoaraiosis and daily alcohol intake is U-shaped when accounting for possible confounding factors such as age, sex, hypertension, and smoking. Patients with a moderate daily alcohol consumption had a significantly reduced risk of leukoaraiosis compared with patients with no daily alcohol consumption, whereas the risk tended to be increased in patients with a daily alcohol consumption of more than 5 drinks per day.

Patients who had discontinued substantial daily alcohol intake and consequently appear as abstainers in the study may represent a bias to these results and contribute to the explanation of the U-shaped curve. However, the number of the patients in question is probably very small in this population of mainly elderly people, and their impact on the result would therefore be negligible. Furthermore, a study that separated former drinkers from abstainers showed that with respect to coronary heart disease, former drinkers had a lower disease risk.³²

The validity of self-reported alcohol intake can be questioned. However, no other method to obtain this information has proved more valid.³³ Patients had no reason to conceal their alcohol intake, as may be the case, for example, in data collection for insurance purposes. Nevertheless, underreporting is possible. This would imply that the true risk curve for leukoaraiosis is to the right of the observed curve, moving the maximal reduced risk to levels of alcohol consumption that are higher than here reported. In addition, the reduced risk was found in patients with an average daily alcohol intake ranging from 1 to 5 drinks. Unless the risk reduction is constant within this range, it may be even greater in patients with an alcohol intake of, for example, 2 or 3 drinks daily. Likewise, in the group of patients with a large daily alcohol intake, a very large daily alcohol consumption could be related to an even higher increased risk than here reported. Such detailed information is, however, not available because of the difficulties of obtaining a detailed history of alcohol consumption in acutely ill stroke patients. A semiquantitative scale with only three categories was used. This crude grading of daily alcohol consumption was established to quantify alcohol consumption at least to some extent.

The apparent beneficial effect of light to moderate daily alcohol consumption and the possible detrimental effect of more considerable alcohol consumption have been observed previously in studies relating alcohol intake and morbidity and mortality from coronary heart disease,^{32 34 35 36} mortality in general,³⁷ and incidence of stroke.^{38 39 40 41 42 43} The protective effect of alcohol intake on vascular disease may be due to the positive correlation between moderate alcohol intake and plasma concentrations of high-density lipoprotein cholesterol^{36 44} and an inverse relation between alcohol intake and platelet aggregability.⁴⁵

This study confirms previous findings that leukoaraiosis is related to age^{1 7 8 14 17} but not to sex, smoking, or diabetes. Age was the only factor found to increase the risk of leukoaraiosis significantly in the present study. A 10-year increase in age more than doubled the risk. Former studies performed in individuals without stroke found leukoaraiosis connected to hypertension.^{1 7 9 10 14 19 22} Such a relation was not present in our population of stroke and TIA patients, confirming the findings of previous studies of stroke patients.^{8 13} Furthermore, no relation was found between leukoaraiosis and ischemic heart disease or intermittent claudication. These negative findings in a stroke population do not, however, indicate that a relation between leukoaraiosis and one or several of these stroke risk factors does not exist in individuals without stroke. Any factor (ie, hypertension, ischemic heart disease, intermittent claudication) associated with generalized atherosclerosis present in most stroke patients may be responsible for the development of leukoaraiosis, but these relations are blurred in a stroke population in which most stroke patients have generalized cerebrovascular disease. That atrial fibrillation was related to a reduced frequency of leukoaraiosis in this study supports this theory. Patients with atrial fibrillation constitute a special subgroup of the stroke population. In these patients stroke is in most cases caused by embolic material from the heart and thus not related to intracerebral vascular disease. This may explain why stroke patients with atrial fibrillation had a reduced risk of having leukoaraiosis. In future studies grading of leukoaraiosis according to severity may produce additional information because different grades of leukoaraiosis may theoretically reflect different histopathologic substrates.

Stroke prognosis was not influenced by the presence of leukoaraiosis in this study. This is in contrast to a study of 215 stroke patients with lacunar infarcts, in which a poorer prognosis for patients with leukoaraiosis regarding mortality and activities of daily living was reported.⁸ However, only univariate analyses were used.

It is possible that the different outcome measures that we used are too insensitive to detect the impact of possible small impairments of brain function on stroke outcome. The neurological and functional scores used in our study are not designed to measure in detail functions specifically dependent on high intellectual performance. However, they provide practical, useful information. Leukoaraiosis in stroke patients does not worsen the prognosis for recovery in activities of daily living and neurological functions and does not retard recovery from stroke.

	Acknowledgments

 
This study was supported by grants from the Danish Health Foundation, the Danish Heart Foundation, Ebba Celinders Foundation, and the Gangsted Foundation.

Received September 23, 1994; revision received December 19, 1994; accepted December 23, 1994.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Hachinski VC, Potter P, Merskey H. Leuco-araiosis. Arch Neurol. 1987;44:21-23. [Abstract]
2. Kluger A, Glanutsos J, Leon MJ, George AE. Significance of age-related white matter lesions. Stroke. 1988;19:1054-1055. [Free Full Text]
3. Junqué C, Pujol J, Vendrell P, Bruna A, Jódar M, Ribas JC, Vinas J, Capdevila A, Marti-Vilalta JL. Leuco-araiosis on magnetic resonance imaging and speed of mental processing. Arch Neurol. 1990;47:151-156. [Abstract]
4. Boone KB, Miller BL, Lesser IM, Mehringer CM, Hill-Gutierrez E, Goldberg MA, Berman NG. Neuropsychological correlates of white-matter lesions in healthy elderly subjects: a threshold effect. Arch Neurol. 1992;49:549-554. [Abstract]
5. van Swieten JC, Geyskes GG, Derix MMA, Peeck BM, Ramos LMP, van Latum JC, van Gijn J. Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol. 1991;30:825-830. [Medline] [Order article via Infotrieve]
6. Ylikoski R, Ylikoski A, Erkinjuntti T, Sulkava R, Raininko R, Tilvis R. White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol. 1993;50: 818-824.
7. Steingart A, Hachinski VC, Lau C, Fox AJ, Fox H, Lee D, Inzitari D, Merskey H. Cognitive and neurologic findings in demented patients with diffuse matter lucencies on computed tomographic scan (leuco-araiosis). Arch Neurol. 1987;44:36-39. [Abstract]
8. Miyao S, Takano A, Teramoto J, Takahashi A. Leukoaraiosis in relation to prognosis for patients with lacunar infarction. Stroke. 1992;23:1434-1438. [Abstract/Free Full Text]
9. Bogousslavsky J, Regli F, Uske A. Leukoencephalopathy in patients with ischemic stroke. Stroke. 1987;18:896-899. [Abstract/Free Full Text]
10. Gupta SR, Naheedy MH, Young JC, Ghobrial M, Rubino FA, Hindo W. Periventricular white matter changes and dementia. Arch Neurol. 1988;45:637-641. [Abstract]
11. Terayama Y, Meyer JS, Kawamura J, Weathers S, Mortel KF. Patterns of cerebral hypoperfusion compared among demented and nondemented patients with stroke. Stroke. 1992;23:686-692. [Abstract/Free Full Text]
12. Diaz JF, Merskey H, Hachinski VC, Lee DH, Boniferro M, Wong CJ, Mirsen TR, Fox H. Improved recognition of leucoaraiosis and cognitive impairment in Alzheimer's disease. Arch Neurol. 1991;48:1022-1025. [Abstract]
13. Hijdra A, Verbeeten B, Verhulst JAPM. Relation of leukoaraiosis to lesion type in stroke patients. Stroke. 1990;21:890-894. [Abstract/Free Full Text]
14. Awad IA, Spetzler RF, Hodak JA, Awad CA, Carey R. Incidental subcortical lesions identified on magnetic resonance in the elderly, I: correlation with age and cerebrovascular risk factors. Stroke. 1986;17:1084-1089. [Abstract/Free Full Text]
15. Lopez OL, Becker JT, Rezek D, Wess J, Boller F, Reynolds CF, Panisset M. Neuropsychiatric correlates of cerebral white-matter radiolucencies in probable Alzheimer's disease. Arch Neurol. 1992;4:828-834.
16. Tatemichi TK. How acute brain failure becomes chronic: a view of the mechanisms of dementia related to stroke. Neurology. 1990;40: 1652-1659.
17. Kobari M, Meyer JS, Ichijo M. Leuko-araiosis, cerebral atrophy, and cerebral perfusion in normal ageing. Arch Neurol. 1990; 47:161-165.
18. Inzitari D, Diaz F, Fox A, Hachinski VC, Steingart A, Lau C, Donald A, Wade J, Mulic H, Merskey H. Vascular risk factors and leuco-araiosis. Arch Neurol. 1987;44:42-47. [Abstract]
19. Dominguez R, Famulari A, Garcia G, Bartolome E, D'Abraccio G, Vila J, Gallo A, Cannata M. Early onset of leuko-araiosis in hypertensive patients. Arch Neurol. 1993;50:13-14. [Medline] [Order article via Infotrieve]
20. Yao H, Sadoshima S, Ibayashi S, Kuwabara Y, Ichiya Y, Fujishima M. Leukoaraiosis and dementia in hypertensive patients. Stroke. 1992;23:1673-1677. [Abstract/Free Full Text]
21. Herholz K, Heindel W, Rackl A, Neubauer I, Steinbrich W, Pietrzyk U, Erasmi-Körber H, Heiss WD. Regional cerebral blood flow in patients with leuko-araiosis and atherosclerotic carotid artery disease. Arch Neurol. 1990;47:392-396. [Abstract]
22. Fazekas F, Niederkorn K, Schmidt R, Offenbacher H, Horner S, Berta G, Lechner H. White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors. Stroke. 1988;19:1285-1288. [Abstract/Free Full Text]
23. Munoz DG, Hastak SM, Harper B, Lee D, Hachinski VC. Pathologic correlates of increased signals of the centrum ovale on magnetic resonance imaging. Arch Neurol. 1993;50:492-497. [Abstract]
24. van Swieten JC, van den Hout JHW, van Ketel BA, Hildra A, Wokke JHJ, van Gijn J. Periventricular lesions in the white matter on magnetic resonance imaging in the elderly: a morphometric correlation with arteriosclerosis and dilated perivascular spaces. Brain. 1991;114:761-774. [Abstract/Free Full Text]
25. Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. The effect of blood pressure and diabetes on stroke in progression. Lancet. 1994;344:156-159. [Medline] [Order article via Infotrieve]
26. Report of the WHO Task Force on Stroke and Other Cerebrovascular Disorders. Stroke—1989: recommendations on stroke prevention, diagnosis and therapy. Stroke. 1989;20:1407-1431. [Free Full Text]
27. Jørgensen HS, Nakayama H, Raaschou HO, Olsen TS. Stroke in patients with diabetes: the Copenhagen Stroke Study. Stroke. 1994;25:1977-1984. [Abstract]
28. Scandinavian Stroke Study Group. Multicenter trial of hemodilution in ischemic stroke: background and study protocol. Stroke. 1985;16:885-890. [Free Full Text]
29. Lindenstrøm E, Boysen G, Christiansen LW, á Rogvi Hansen B, Nielsen BW. Reliability of Scandinavian Stroke Scale. Cerebrovasc Dis. 1991;1:103-107.
30. Mahoney FD, Barthel DW. Functional evaluation: the Barthel Index. Md State Med J. 1965;14:61-63. [Medline] [Order article via Infotrieve]
31. SPSS, Statistical Package for Social Sciences. Chicago, Ill: SPSS Inc; 1992. Windows version, release 5.0.
32. Jackson R, Scragg R, Beaglehole R. Alcohol consumption and risk of coronary heart disease. BMJ. 1991;303:211-216.
33. Midanik L. The validity of self-reported alcohol consumption and alcohol problems: a literature review. Br J Addict. 1982;77:357-382. [Medline] [Order article via Infotrieve]
34. Shaper AG, Wannamethee G, Walker M. Alcohol and mortality in British men: explaining the U-shaped curve. Lancet. 1988;1: 1267-1273.
35. Marmot M, Brunner E. Alcohol and cardiovascular disease: the status of the U shaped curve. BMJ. 1991;303:565-568.
36. Suh I, Shaten BJ, Cutler JA, Kuller LH. Alcohol use and mortality from coronary heart disease: the role of high-density lipoprotein cholesterol. Ann Intern Med. 1992;116:881-887.
37. Grønbæk M, Deis A, Sørensen TIA, Becker U, Borch-Johnsen K, Muller C, Schnohr P, Jensen G. Influence of sex, age, body mass index, and smoking on alcohol intake and mortality. BMJ. 1994;308:302-306. [Abstract/Free Full Text]
38. Gill JS, Zezulka AV, Shipley MJ, Gill SK, Beevers DG. Stroke and alcohol consumption. N Engl J Med. 1986;315:1041-1046. [Abstract]
39. Klatsky AL, Armstrong MA, Friedmann GD. Alcohol use and subsequent cerebrovascular disease hospitalizations. Stroke. 1989; 20:741-746.
40. Camargo CA. Moderate alcohol consumption and stroke: the epidemiological evidence. Stroke. 1989;20:1611-1626. [Abstract/Free Full Text]
41. Gill JS, Shipley MJ, Tsementzis SA, Hornby RS, Gill SK, Hitchcock ER, Beevers DG. Alcohol consumption: a risk factor for hemorrhagic and non-hemorrhagic stroke. Am J Med. 1991;90:489-497. [Medline] [Order article via Infotrieve]
42. Shaper AG, Phillips AN, Pocock SJ, Walker M, Macfarlane PW. Risk factors for stroke in middle aged British men. BMJ. 1991; 302:1111-1115.
43. Palomäki H, Kaste M. Regular light-to-moderate intake of alcohol and the risk of ischemic stroke: is there a beneficial effect? Stroke. 1993;24:1828-1832. [Abstract/Free Full Text]
44. Criqui MH. The reduction of coronary heart disease with light to moderate alcohol consumption: effect or artificial? Br J Addict. 1990;85:854-857.
45. Renaud S, de Longeril M. Wine, alcohol, platelets and the French paradox for coronary heart disease. Lancet. 1992;339:1523-1526.[Medline] [Order article via Infotrieve]

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				J. Y. Streifler, M. Eliasziw, O. R. Benavente, S. Alamowitch, A. J. Fox, V. Hachinski, and H. J.M. Barnett Development and Progression of Leukoaraiosis in Patients With Brain Ischemia and Carotid Artery Disease Stroke, August 1, 2003; 34(8): 1913 - 1916. [Abstract] [Full Text] [PDF]

				M. Wiszniewska, G. Devuyst, J. Bogousslavsky, J. Ghika, and G. van Melle What Is the Significance of Leukoaraiosis in Patients With Acute Ischemic Stroke? Arch Neurol, July 1, 2000; 57(7): 967 - 973. [Abstract] [Full Text] [PDF]

				H. Sawada, F. Udaka, Y. Izumi, K. Nishinaka, H. Kawakami, S. Nakamura, and M. Kameyama Cerebral white matter lesions are not associated with apoE genotype but with age and female sex in Alzheimer's disease J. Neurol. Neurosurg. Psychiatry, May 1, 2000; 68(5): 653 - 656. [Abstract] [Full Text]

				D. P. Briley, S. Haroon, S. M. Sergent, and S. Thomas Does leukoaraiosis predict morbidity and mortality? Neurology, January 11, 2000; 54(1): 90 - 90. [Abstract] [Full Text] [PDF]

				V. I. H. Kwa, J. Stam, L. M. Blok, B. Verbeeten Jr, and f. t. A. V. M. Group T2-Weighted Hyperintense MRI Lesions in the Pons in Patients With Atherosclerosis Stroke, July 1, 1997; 28(7): 1357 - 1360. [Abstract] [Full Text]

				H. S. Jorgensen, H. Nakayama, J. Reith, H. O. Raaschou, and T. S. Olsen Acute Stroke With Atrial Fibrillation: The Copenhagen Stroke Study Stroke, October 1, 1996; 27(10): 1765 - 1769. [Abstract] [Full Text]

				A. V. Salgado, J. M. Ferro, and A. Gouveia-Oliveira Long-term Prognosis of First-Ever Lacunar Strokes : A Hospital-Based Study Stroke, April 1, 1996; 27(4): 661 - 666. [Abstract] [Full Text]

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