Original Contribution

Strictly Lobar Microbleeds Are Associated With Executive Impairment in Patients With Ischemic Stroke or Transient Ischemic Attack

Simone M. Gregoire, Grit Scheffler, Hans R. Jäger, Tarek A. Yousry, Martin M. Brown, Constantinos Kallis, Lisa Cipolotti, David J. Werring
https://doi.org/10.1161/STROKEAHA.111.000245
Stroke. 2013;44:1267-1272
Originally published April 22, 2013

This article has a correction. Please see:

Abstract

Background and Purpose—Cerebral microbleeds (CMBs) are a marker of small vessel diseases, including hypertensive arteriopathy and cerebral amyloid angiopathy, and may be associated with cognitive impairment. The relationship between CMBs and cognitive function in ischemic cerebrovascular disease remains uncertain. We, therefore, investigated the cognitive impact of CMBs in a cohort of patients with ischemic stroke or transient ischemic attack.

Methods—All patients underwent detailed and comprehensive neuropsychological testing and standardized MRI, including fluid attenuation inversion recovery, T1, T2, and gradient-recalled echo T2*-weighted sequences. CMBs, white matter changes, lacunes, and territorial cortical infarcts (defined by standardized criteria) were identified, and associations with cognition assessed.

Results—Three hundred twenty patients with a diagnosis of ischemic stroke or transient ischemic attack were included. Of these, 72 (22.5%) had at least 1 CMB. Of all the cognitive domains tested, only executive impairment was more prevalent in patients with CMBs than without (38% versus 25%; P=0.039). In univariate analysis, the presence of strictly lobar (but not deep) CMBs was associated with executive impairment (odds ratio, 2.49; 95% confidence interval, 1.16–5.36; P=0.019). In adjusted multivariate analyses, the presence (OR, 2.34; 95% confidence interval, 1.08–5.09; P=0.031) and number (OR, 1.33; 95% confidence interval, 1.04–1.69; P=0.022) of strictly lobar CMBs were significantly associated with executive impairment. CMBs were not associated with impairment in other cognitive domains.

Conclusions—Strictly lobar CMBs are independently associated with executive dysfunction in patients with ischemic stroke or transient ischemic attack. Our findings suggest that a microangiopathy related to strictly lobar CMBs (eg, cerebral amyloid angiopathy) contributes to cognitive impairment in this population.

Introduction

Cognitive impairment after stroke is associated with significant functional impact and high risk of dementia,1 which might be preventable with improved understanding of the underlying mechanisms. Cerebral small vessel disease plays a key role in cognitive dysfunction.2 Cerebral microbleeds (CMBs), detected on gradient-recalled echo T2*-weighted MRI, are an important marker of small vessel pathology; they correspond to small perivascular hemosiderin deposits related to vessels affected by hypertensive arteriopathy and cerebral amyloid angiopathy (CAA) and are presumed to represent focal areas of previous bleeding.3 Recent evidence suggests that CMBs are linked to cognitive impairment4,5 particularly executive function or processing speed.6–8 There is indirect evidence that CMB location reflects the underlying small vessel disease process (strictly lobar CMBs being a marker for CAA; deep CMBs for hypertensive arteriopathy),9 but the importance of CMB location with regard to cognition remains uncertain.

Some previous studies of CMBs and cognition have been limited by not considering a full spectrum of cerebrovascular lesions10 or using insensitive cognitive screening instruments. The role of CMBs in ischemic cerebrovascular disease without dementia remains largely unexplored. We, therefore, investigated the association of CMBs with detailed neuropsychological measures of cognition, taking account of other MRI markers of cerebrovascular disease, in a hospital-based ischemic stroke or transient ischemic attack (TIA) population. We hypothesized, based on observations described in our previous preliminary report,6 that CMBs are independently associated with domain-specific executive impairment in a larger cohort of patients with ischemic stroke or TIA, and also investigated whether lobar or deep CMBs were most strongly associated with cognitive dysfunction.

Methods

Patients

Patients referred to the stroke service at the National Hospital for Neurology and Neurosurgery, London, UK, and referred for detailed cognitive testing were considered. During the study period, the National Hospital for Neurology and Neurosurgery received all stroke referrals from the surrounding healthcare districts. Neuropsychological testing is performed routinely in all patients with adequate English, unless they are too unwell (eg, reduced conscious level) or have severe cognitive impairment (eg, severe dysphasia or dementia). Inclusion criteria were standardized adequate quality MRI, including gradient-recalled echo T2* T2-weighted and fluid attenuation inversion recovery (FLAIR), and complete neuropsychological data (including at least 1 measure of both executive function and speed and attention processing) within 3 months of the MRI scan. Exclusion criteria included previous traumatic brain injury or intracerebral hemorrhage, or known cause of cognitive impairment other than cerebrovascular disease.

All patients had detailed standardized clinical diagnostic assessment, including neurological examination, blood pressure measurement, ECG, and echocardiogram. We ascertained stroke mechanism using the Trial of Org 10172 in Acute Stroke criteria.11 The study was approved by the National Hospital for Neurology and Neurosurgery and Institute of Neurology joint research ethics committee.

Imaging

All patients had MR imaging according to a standardized protocol on a 1.5 Tesla scanner: Signa Echospeed (General Electric, Milwaukee, WI), including the following sequences: sagittal T1, axial T2-weighted Fast Spin Echo, axial T2*-weighted gradient-recalled echo (time to repetition, 300 ms; times to echo, 40 ms; flip angle, 20; field of view, 24×18; matrix, 256×160); and coronal FLAIR (time to repetition, 9895 ms; inversion time, 2473 ms; times to echo, 140 ms). For all these sequences, slice thickness was 5 mm and slice gap 1.5 mm.

Image analysis for CMBs was conducted by a neurologist trained in neuroimaging (S.M.G.) blinded to clinical details. CMBs were categorized as lobar, deep, or infratentorial using the Microbleed Anatomic Rating Scale,12 an instrument with good intrarater and interrater reliability for the presence of definite microbleeds in all brain locations using different MRI sequences and observer experience.12 CMBs in the insula were classified as lobar. White matter changes (WMC) were rated on axial T2-weighted and coronal FLAIR images using a validated scale13 by S.M.G. and another trained observer (G.S.). Interobserver agreement for WMC showed intraclass correlations between 0.84 and 0.96. Images were assessed for the number of lacunes, defined as cerebrospinal fluid–containing spaces, between 2 and 20 mm diameter, with high signal on T2-weighted or FLAIR images, or with a perilesional halo on FLAIR images.14 Territorial cortical infarcts were defined as involving the cortical territory of a large cerebral artery (not suggesting a perforating vessel occlusion), with a diameter above 15 mm.

Neuropsychological Data

Neuropsychological assessment (blinded to CMB status) comprised a standardized battery evaluating 7 cognitive domains: current intellectual functioning, verbal and visual memory, naming skills, perceptual functions, speed and attention, and executive functions. Executive functions were examined using ≥2 of the following: Stroop test,15 Word Fluency,16 Trail Making Test Part B,17 Weigl Color Form Sorting Task,18 and Modified Card Sorting Test.19 The tests used to evaluate the other cognitive domains are described in detail elsewhere.6 Derived scores were calculated for each test based on published normative data from a sample of individuals of comparable age. Each patient’s performance in each cognitive domain was classified as impaired or unimpaired, according to predefined criteria.6

Statistical Analysis

We used the Statistical Package for the Social Sciences version 16 (Chicago, IL) for the analysis. The characteristics of patients with and without CMBs were compared using 2-sided independent t test for normally distributed variables, Fisher exact test for comparison of proportions when the expected number of counts was <5 (otherwise χ2 test was used), and Mann–Whitney U test for comparison of non-normally distributed variables. Factors associated with executive impairment were investigated in unadjusted logistic regression analysis. Significant variables were subsequently entered into multivariate binary logistic regression analysis. Significance was declared at P<0.05.

Results

Of 1335 patients considered, 320 patients with a final diagnosis of ischemic stroke or TIA were included (Table 1; Figure 1). Of the 320 patients, 254 (79%) had an ischemic stroke and 66 (21%) had a TIA. At least 1 CMB was identified in 72 patients (22.5%). The CMB group included a higher proportion of men, a higher prevalence of hypertension, diabetes mellitus, antithrombotic use, previous ischemic stroke or TIA, a greater number of lacunes, and more severe WMC compared with the group without CMBs.

View this table:
Table 1.

Characteristics of the Patients

Figure 1.
Figure 1.

Flowchart describing patient selection.

Lobar CMBS were found in 51 patients (71%), deep CMBs in 37 (51%), and infratentorial CMBs in 21 (29%) patients. Lobar CMBs were most common in the temporal (n=31; 61%) followed by parieto-occipital (n=27; 53%) and frontal lobes (n=24; 47%). Thirty patients (42%) had strictly lobar CMBs; 16 (22%) had strictly deep CMBs. Among patients with strictly lobar CMBs, 6 had ≥5 CMBs.

Of the domains tested, only executive impairment was more prevalent in patients with CMBs compared with those without (38% versus 25%; P=0.039). There was no significant difference (P>0.10) between the CMB and non-CMB groups in the proportion impaired in the other cognitive domains (Table 2). In unadjusted binary logistic regression, executive impairment was associated with the presence of ≥1 strictly lobar CMBs and with ≥5 strictly lobar CMBs (Table 3). The number of lacunes and mean WMC severity were not associated with executive impairment. In multivariate analysis adjusted for age, WMC severity, and hypertension, the presence of ≥1 strictly lobar CMB and of ≥5 strictly lobar CMBs remained significantly associated with executive impairment (≥1: OR, 2.34; 95% CI, 1.08–5.09; P=0.031; ≥5: OR, 13.72; 95% CI, 1.55–121.57; P=0.019) (Table 4). The number of strictly lobar CMBs was associated with an increased likelihood of executive impairment (OR, 1.33 per additional CMB). CMB presence in the parieto-occipital lobes (adjusted OR, 3.05; 95% CI, 1.33–6.96; P=0.008) and insula (adjusted OR, 5.55; 95% CI, 1.58–19.53; P=0.008) was associated with executive impairment; the presence of infratentorial CMBs showed a nonsignificant trend toward association with executive function (OR, 2.39; 95% CI, 0.94–6.05; P=0.067). In other brain regions, CMBs presence was not associated with executive impairment.

View this table:
Table 2.

Proportions of Patients Impaired in Each Cognitive Domain

View this table:
Table 3.

Unadjusted Univariate Binary Logistic Regression Analyses Testing the Factors Associated With Executive Impairment

View this table:
Table 4.

Multivariate Binary Logistic Regression Analyses Testing the Factors Associated With Executive Impairment

Discussion

In patients with ischemic stroke or TIA, CMBs were associated with impairment in executive functions, but not other cognitive domains. Strictly lobar (but not deep) CMBs were associated with executive impairment, independent of age, hypertension, and the severity of WMC. The presence of at least 1 strictly lobar CMB more than doubled the likelihood of executive impairment, with evidence of a graded increase in the risk of impairment with an increasing number of strictly lobar CMBs.

CMBs have been reported to be common in various populations. However, links between CMBs and cognitive function have been inconsistent, probably because of the great variability in populations, MRI techniques, and cognitive rating instruments used.4,5,7,8,20–23 Nevertheless, consistent with our findings, a large recent study in community-based elderly subjects showed that CMBs were independently associated with lower scores in processing speed and executive functions.20 Another study in a large European population-based cohort22 reported robust associations between strictly lobar CMBs and cognitive function (information processing speed and motor speed), but only weak associations for deep or infratentorial CMBs.

The association between CMBs and cognitive function in stroke cohorts24 is largely unknown. In a small case–control study of 55 patients referred to a neurovascular clinic, we found that executive impairment was twice as common in patients with CMBs as in matched microbleed-free controls, independent of WMC.6 These effects were hypothesized to be mediated by CMBs in frontal and basal ganglia regions. In the current study, executive dysfunction was associated only with strictly lobar CMBs, with no significant association with deep or infratentorial CMBs. The different findings in the present study may be explained by the inclusion of only outpatients with less severe cerebrovascular disease and mainly deep CMBs in the previous report.6 A study in patients with neuroimaging evidence of small vessel disease reported that frontal and temporal lobe CMBs were related to global cognitive function, psychomotor speed, and attention.21 Finally, a hospital-based study of 411 patients with ischemic stroke, hemorrhagic stroke, and nonstroke25 found that dementia was associated with CMBs in the ischemic stroke subgroup, but the study did not report adjusted analyses nor the criteria used to define dementia.

Our study provides evidence for a link between a process associated with strictly lobar CMBs and executive function in ischemic cerebrovascular disease. Strictly lobar CMBs are a putative marker for CAA,26 making this a possible risk factor for cognitive impairment, even in patients in whom CAA was clinically not suspected. Our finding of frequent CMBs in the temporal and parieto-occipital regions is in keeping with the anatomic predilection of CAA.21,26 CAA, although most often clinically recognized as a cause of lobar intracerebral hemorrhage in the elderly, is also associated with dementia.27 CAA pathology is more prevalent at autopsy in the brains of individuals who were previously demented than those who were not demented.28 The severity of CAA may also increase the risk of future cognitive decline; in a prospective cohort study of patients with lobar intracerebral hemorrhage, the risk of cognitive impairment at 2 years increased with increasing baseline CMB burden (hazard ratio, 1.9; 95% CI, 1.2–2.8, for each increase in CMB category).29 Community-based pathological studies, including the Honolulu–Asia Aging Study and MRC Cognitive Function and Aging Study, found CAA to be associated with cognition even after controlling for age and neurodegenerative pathology.28,30 The Religious Orders Study showed that moderate-to-severe CAA was linked to impairment in specific cognitive domains, particularly perceptual speed, assessed with the Symbol Digit Modalities Tests and Number Comparison tests31; however, we found no association between CMBs and speed and attention functions, also assessed by the Symbol Digit Modalities test. Possible explanations include the following: first, our patients all attended hospital with ischemic stroke or TIA, whereas the Religious Orders Study included community-based subjects, in whom only 36% had cerebral infarction at autopsy; and second, the Religious Orders Study found associations with moderate-to-severe CAA pathology, whereas our patients with strictly lobar CMBs probably have less severe CAA pathology. Indeed, without pathological data, we do not know the true prevalence or severity of definite CAA pathology. Nevertheless, we suggest that our data add to emerging evidence that CAA has an independent association with cognitive function in a range of populations.

It is unclear whether CMBs are a direct cause of cognitive impairment or are a general marker for the severity of microangiopathic disease23; our finding that CMBs in the parieto-occipital lobes and insula were associated with executive impairment most favors an indirect link. Mechanisms by which lobar CMBs (reflecting CAA) could be linked with cognitive impairment include vascular β-amyloid damaging the neurovascular unit,32 hypoperfusion from small vessel stenosis, or even small areas of microinfarction.33 Some CMBs may have a direct effect on surrounding or connected brain regions, a notion supported by tissue necrosis seen in histopathologic studies.3,34 Precise mapping of CMBs throughout the brain, with assessment of damage to surrounding tissues and the whole brain using quantitative MRI techniques (eg, diffusion tensor imaging) may be a helpful future approach.21

The pattern of CMBs we observed (prevalent in the temporal, parieto-occipital, and frontal lobes) has previously been associated with cognitive dysfunction in different populations.8,35 A recent study of non-demented elderly subjects also noted that frontal and temporal CMBs were associated with poor cognitive performance,21 although this cohort was restricted to patients with small vessel disease, with a much lower prevalence of cortical infarcts than ours.

Strengths of our study include the standardized, detailed neuropsychological battery; the standardized MRI protocol tailored to the detection of cerebrovascular disease; and the use of validated rating scales by trained raters blinded to clinical details. We considered a range of cerebrovascular lesions (lacunes, WMC, and cortical infarcts) and adjusted analyses for potential confounding factors. Despite these factors, we cannot exclude an effect of other unmeasured confounders (eg, cerebral volume loss). There may have been selection bias because of our inclusion criteria: patients with very severe stroke who died soon afterward will not have had MRI or neuropsychology and patients with severe dementia are unlikely to have been referred to our outpatient service. However, the routine use of neuropsychology means that our results are likely to be generalizable to other stroke service cohorts of stroke survivors able to undergo neuropsychological testing. The use of a routine clinical MRI without optimized sequence parameters or advanced postprocessing may have underestimated the prevalence of CMBs, although such technical factors do not seem to markedly affect the relationship between CMBs and cognition.21,36 Nevertheless, it remains possible that highly optimized sequences (eg, high field strength) could affect the relationship between CMBs and cognition.37 Finally, we were not able to definitely confirm that strictly lobar CMBs were correlated with histopathologic or in vivo amyloid imaging evidence of CAA.

Conclusions

Strictly lobar CMBs are an independent risk factor for executive impairment in patients with ischemic cerebrovascular disease. Our findings support the hypothesis that a microangiopathy related to strictly lobar microbleeds (eg, CAA) contributes to cognitive impairment in this population. With increasing knowledge of the pathophysiology and clinical–radiological spectrum of CAA,27 our findings may have implications for the diagnosis, treatment, and prevention of cognitive impairment in stroke populations.

Sources of Funding

Dr Gregoire was supported by the Stroke Association (TSA 2006/08). The imaging was conducted at the National Hospital for Neurology and Neurosurgery. Professor Brown’s Chair in Stroke Medicine at University College London is supported by the Reta Lila Weston Trust for Medical Research. Dr Werring receives research support from a Department of Health/Higher Education Funding Council for England Clinical Senior Lectureship Award. This work was undertaken at University College London Hospitals/University College London who received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme.

Disclosures

None.

  • Received November 21, 2012.
  • Revision received February 8, 2013.
  • Accepted February 13, 2013.

References

  1. 1.↵
    1. Wentzel C,
    2. Rockwood K,
    3. MacKnight C,
    4. Hachinski V,
    5. Hogan DB,
    6. Feldman H,
    7. et al
    . Progression of impairment in patients with vascular cognitive impairment without dementia. Neurology. 2001;57:714–716.
    OpenUrlCrossRef
  2. 2.↵
    A united approach to vascular disease and neurodegeneration. Lancet Neurol. 2012;11:293.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Fazekas F,
    2. Kleinert R,
    3. Roob G,
    4. Kleinert G,
    5. Kapeller P,
    6. Schmidt R,
    7. et al
    . 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. Am J Neuroradiol. 1999;20:637–642.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Cordonnier C,
    2. van der Flier WM,
    3. Sluimer JD,
    4. Leys D,
    5. Barkhof F,
    6. Scheltens P
    . Prevalence and severity of microbleeds in a memory clinic setting. Neurology. 2006;66:1356–1360.
    OpenUrlCrossRef
  5. 5.↵
    1. Goos JD,
    2. Kester MI,
    3. Barkhof F,
    4. Klein M,
    5. Blankenstein MA,
    6. Scheltens P,
    7. et al
    . Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition. Stroke. 2009;40:3455–3460.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Werring DJ,
    2. Frazer DW,
    3. Coward LJ,
    4. Losseff NA,
    5. Watt H,
    6. Cipolotti L,
    7. et al
    . Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI. Brain. 2004;127:2265–2275.
    OpenUrlAbstract/FREE Full Text
  7. 7.↵
    1. Yakushiji Y,
    2. Nishiyama M,
    3. Yakushiji S,
    4. Hirotsu T,
    5. Uchino A,
    6. Nakajima J,
    7. et al
    . Brain microbleeds and global cognitive function in adults without neurological disorder. Stroke. 2008;39:3323–3328.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Seo SW,
    2. Hwa Lee B,
    3. Kim EJ,
    4. Chin J,
    5. Sun Cho Y,
    6. Yoon U,
    7. et al
    . Clinical significance of microbleeds in subcortical vascular dementia. Stroke. 2007;38:1949–1951.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Poels MM,
    2. Vernooij MW,
    3. Ikram MA,
    4. Hofman A,
    5. Krestin GP,
    6. van der Lugt A,
    7. et al
    . Prevalence and risk factors of cerebral microbleeds: an update of the Rotterdam scan study. Stroke. 2010;41:S103–S106.
    OpenUrlAbstract/FREE Full Text
  10. 10.↵
    1. Fisher M
    . The challenge of mixed cerebrovascular disease. Ann N Y Acad Sci. 2010;1207:18–22.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Adams HP Jr.,
    2. Bendixen BH,
    3. Kappelle LJ,
    4. Biller J,
    5. Love BB,
    6. Gordon DL,
    7. et al
    . Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35–41.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Gregoire SM,
    2. Chaudhary UJ,
    3. Brown MM,
    4. Yousry TA,
    5. Kallis C,
    6. Jäger HR,
    7. et al
    . The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology. 2009;73:1759–1766.
    OpenUrlCrossRef
  13. 13.↵
    1. Wahlund LO,
    2. Barkhof F,
    3. Fazekas F,
    4. Bronge L,
    5. Augustin M,
    6. Sjögren M,
    7. et al
    .; European Task Force on Age-Related White Matter Changes. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke. 2001;32:1318–1322.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Vermeer SE,
    2. Longstreth WT Jr.,
    3. Koudstaal PJ
    . Silent brain infarcts: a systematic review. Lancet Neurol. 2007;6:611–619.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Trennary M
    . Stroop Neuropsychological Screening Test (snst). Odessa, FL: Psychological Assessment Resources Inc.; 1989.
  16. 16.↵
    1. Spreen O
    . Neurosensory Center Comprehensive Examination for Aphasia. Victoria, BC: Neuropsychology Laboratory, University of Victoria;1969.
  17. 17.↵
    1. Battery AIT
    . Manual and Directions for Scoring. Washington, DC: War Department, Adjunct General’s Office;1944.
  18. 18.↵
    1. Weigl E
    . On the psychology of so-called processes of abstraction. J Abnormal Soc Psychol 1941;36:3–33.
    OpenUrlCrossRef
  19. 19.↵
    1. Nelson HE
    . A modified card sorting test sensitive to frontal lobe defects. Cortex. 1976;12:313–324.
    OpenUrlCrossRefPubMed
  20. 20.↵
    1. Qiu C,
    2. Cotch MF,
    3. Sigurdsson S,
    4. Jonsson PV,
    5. Jonsdottir MK,
    6. Sveinbjrnsdottir S,
    7. et al
    . Cerebral microbleeds, retinopathy, and dementia: the AGES-Reykjavik Study. Neurology. 2010;75:2221–2228.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. van Norden AG,
    2. van den Berg HA,
    3. de Laat KF,
    4. Gons RA,
    5. van Dijk EJ,
    6. de Leeuw FE
    . Frontal and temporal microbleeds are related to cognitive function: the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) Study. Stroke. 2011;42:3382–3386.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Poels MM,
    2. Ikram MA,
    3. van der Lugt A,
    4. Hofman A,
    5. Niessen WJ,
    6. Krestin GP,
    7. et al
    . Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study. Neurology. 2012;78:326–333.
    OpenUrlCrossRef
  23. 23.↵
    1. Werring DJ,
    2. Gregoire SM,
    3. Cipolotti L
    . Cerebral microbleeds and vascular cognitive impairment. J Neurol Sci. 2010;299:131–135.
    OpenUrlCrossRefPubMed
  24. 24.↵
    1. Werring DJ,
    2. Coward LJ,
    3. Losseff NA,
    4. Jäger HR,
    5. Brown MM
    . Cerebral microbleeds are common in ischemic stroke but rare in TIA. Neurology. 2005;65:1914–1918.
    OpenUrlCrossRef
  25. 25.↵
    1. Yamada S,
    2. Saiki M,
    3. Satow T,
    4. Fukuda A,
    5. Ito M,
    6. Minami S,
    7. et al
    . Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age. Eur J Neurol. 2012;19:98–104.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Vernooij MW,
    2. van der Lugt A,
    3. Ikram MA,
    4. Wielopolski PA,
    5. Niessen WJ,
    6. Hofman A,
    7. et al
    . Prevalence and risk factors of cerebral microbleeds: the Rotterdam Scan Study. Neurology. 2008;70:1208–1214.
    OpenUrlCrossRef
  27. 27.↵
    1. Charidimou A,
    2. Gang Q,
    3. Werring DJ
    . Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatr. 2012;83:124–137.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Pfeifer LA,
    2. White LR,
    3. Ross GW,
    4. Petrovitch H,
    5. Launer LJ
    . Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology. 2002;58:1629–1634.
    OpenUrlCrossRef
  29. 29.↵
    1. Greenberg SM,
    2. Eng JA,
    3. Ning M,
    4. Smith EE,
    5. Rosand J
    . Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke. 2004;35:1415–1420.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Wharton SB,
    2. Brayne C,
    3. Savva GM,
    4. Matthews FE,
    5. Forster G,
    6. Simpson J,
    7. et al
    .; Medical Research Council Cognitive Function and Aging Study. Epidemiological neuropathology: the MRC Cognitive Function and Aging Study experience. J Alzheimers Dis. 2011;25:359–372.
    OpenUrlPubMed
  31. 31.↵
    1. Arvanitakis Z,
    2. Leurgans SE,
    3. Wang Z,
    4. Wilson RS,
    5. Bennett DA,
    6. Schneider JA
    . Cerebral amyloid angiopathy pathology and cognitive domains in older persons. Ann Neurol. 2011;69:320–327.
    OpenUrlCrossRefPubMed
  32. 32.↵
    1. Iadecola C,
    2. Park L,
    3. Capone C
    . Threats to the mind: aging, amyloid, and hypertension. Stroke. 2009;40:S40–S44.
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    1. Gregoire SM,
    2. Charidimou A,
    3. Gadapa N,
    4. Dolan E,
    5. Antoun N,
    6. Peeters A,
    7. et al
    . Acute ischaemic brain lesions in intracerebral haemorrhage: multicentre cross-sectional magnetic resonance imaging study. Brain. 2011;134:2376–2386.
    OpenUrlAbstract/FREE Full Text
  34. 34.↵
    1. Schrag M,
    2. McAuley G,
    3. Pomakian J,
    4. Jiffry A,
    5. Tung S,
    6. Mueller C,
    7. et al
    . Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study. Acta Neuropathol. 2010;119:291–302.
    OpenUrlCrossRefPubMed
  35. 35.↵
    1. Pettersen JA,
    2. Sathiyamoorthy G,
    3. Gao FQ,
    4. Szilagyi G,
    5. Nadkarni NK,
    6. St George-Hyslop P,
    7. et al
    . Microbleed topography, leukoaraiosis, and cognition in probable Alzheimer disease from the Sunnybrook dementia study. Arch Neurol. 2008;65:790–795.
    OpenUrlCrossRefPubMed
  36. 36.↵
    1. Goos JD,
    2. van der Flier WM,
    3. Knol DL,
    4. Pouwels PJ,
    5. Scheltens P,
    6. Barkhof F,
    7. et al
    . Clinical relevance of improved microbleed detection by susceptibility-weighted magnetic resonance imaging. Stroke. 2011;42:1894–1900.
    OpenUrlAbstract/FREE Full Text
  37. 37.↵
    1. Conijn MM,
    2. Geerlings MI,
    3. Biessels GJ,
    4. Takahara T,
    5. Witkamp TD,
    6. Zwanenburg JJ,
    7. et al
    . Cerebral microbleeds on MR imaging: comparison between 1.5 and 7T. Am J Neuroradiol. 2011;32:1043–1049.
    OpenUrlAbstract/FREE Full Text
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  • Strictly Lobar Microbleeds Are Associated With Executive Impairment in Patients With Ischemic Stroke or Transient Ischemic Attack
    Simone M. Gregoire, Grit Scheffler, Hans R. Jäger, Tarek A. Yousry, Martin M. Brown, Constantinos Kallis, Lisa Cipolotti and David J. Werring
    Stroke. 2013;44:1267-1272, originally published April 22, 2013
    https://doi.org/10.1161/STROKEAHA.111.000245
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