Incidence, Manifestations, and Predictors of Worsening White Matter on Serial Cranial Magnetic Resonance Imaging in the Elderly The Cardiovascular Health Study

University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Stroke (Impact Factor: 5.72). 01/2005; 36(1):56-61. DOI: 10.1161/01.STR.0000149625.99732.69
Source: PubMed


Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging.
The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade.
Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk.
Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.

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Available from: Norman Beauchamp, May 28, 2014
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    • "The severity of WMHs could be accessed by several methods, from the visual scoring systems [11], [14]–[15] or semi-automated [12] to automated methods of analysis [16]–[20]. A semi-automated method was reported to be better correlated with WMHs progression than visual scoring systems [21]. "
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    ABSTRACT: White matter hyperintensities (WMHs) of presumed vascular origin are common in ageing population, especially in patients with acute cerebral infarction and the volume has been reported to be associated with mental impairment and the risk of hemorrhage from antithrombotic agents. WMHs delineation can be computerized to minimize human bias. However, the presence of cerebral infarcts greatly degrades the accuracy of WMHs detection and thus limits the application of computerized delineation to patients with acute cerebral infarction. We propose a computer-assisted segmentation method to depict WMHs in the presence of cerebral infarcts in combined T1-weighted, fluid attenuation inversion recovery, and diffusion-weighted magnetic resonance imaging (MRI). The proposed method detects WMHs by empirical threshold and atlas information, with subtraction of white matter voxels affected by acute infarction. The method was derived using MRI from 25 hemispheres with WMHs only and 13 hemispheres with both WMHs and cerebral infarcts. Similarity index (SI) and correlation were utilized to assess the agreement between the new automated method and a gold standard visually guided semi-automated method done by an expert rater. The proposed WMHs segmentation approach produced average SI, sensitivity and specificity of 83.142±11.742, 84.154±16.086 and 99.988±0.029% with WMHs only and of 68.826±14.036, 74.381±18.473 and 99.956±0.054% with both WMHs and cerebral infarcts in the derivation cohort. The performance of the proposed method with an external validation cohort was also highly consistent with that of the experienced rater.
    PLoS ONE 08/2014; 9(8):e104011. DOI:10.1371/journal.pone.0104011 · 3.23 Impact Factor
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    • "Furthermore, a significant relationship was found between the presence of apathy and leukoaraiosis in both MCI and AD, a finding that has been little studied [20] and that may open new avenues of research linking the presence of both as a prognostic factor for the evolution and severity of dementia. We also found a statistical significance between the presence of leukoaraiosis and hypertension in patients, a finding supported by the literature, with various research linking leukoaraiosis with cardiovascular disease [12,14,19] as leukoaraiosis is associated with a reduction in blood perfusion in areas where it appears [42]. These results are consistent with the findings of other studies that found a high prevalence of apathy and leukoaraiosis in patients with dementia. "
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    ABSTRACT: Aims The aim is to study the prevalence and possible relationship of apathy and leukoaraiosis in cases of cognitive impairment of varying severity in Spain. Methods We conducted a cross-sectional, descriptive, multicenter study involving 109 patients with Alzheimer's disease (AD) and 59 with mild cognitive impairment (MCI). Results The older group with AD had a higher prevalence of leukoaraiosis and apathy, with significant differences compared to the MCI group. Conclusions To our knowledge, this is the first multicenter study in our country that jointly analyzes the presence of apathy and leukoaraiosis in the institutionalized elderly with varying degrees of cognitive impairment according to the most recent criteria for detecting apathy in dementia.
    05/2014; 4(2):228-35. DOI:10.1159/000363227
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    • "White matter lesions (WML) are common in older people and in patients with stroke [1] and are associated with cognitive impairment and dementia, particularly in those with WML progression [2,3,4]. WML are of increased signal on T2-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging and decreased on T1-weighted relative to normal white and grey matter. "
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    ABSTRACT: Background White matter lesions (WML) and brain atrophy are important biomarkers in stroke and dementia. Stroke lesions, either acute or old, symptomatic or silent, are common in older people. Such stroke lesions can have similar signals to WML and cerebrospinal fluid (CSF) on magnetic resonance (MR) images, and may be classified accidentally as WML or CSF by MR image processing algorithms, distorting WML and brain atrophy volume from the true volume. We evaluated the effect that acute or old stroke lesions at baseline, and new stroke lesions occurring during follow-up, could have on measurement of WML volume, cerebral atrophy and their longitudinal progression. Methods We used MR imaging data from patients who had originally presented with acute lacunar or minor cortical ischaemic stroke symptoms, recruited prospectively, who were scanned at baseline and about 3 years later. We measured WML and CSF volumes (ml) semi-automatically. We manually outlined the acute index stroke lesion (ISL), any old stroke lesions present at baseline, and new lesions appearing de novo during follow-up. We compared baseline and follow-up WML volume, cerebral atrophy and their longitudinal progression excluding and including the acute ISL, old and de novo stroke lesions. A non-parametric test (Wilcoxon's signed rank test) was used to compare the effects. Results Among 46 patients (mean age 72 years), 33 had an ISL visible on MR imaging (median volume 2.05 ml, IQR 0.88–8.88) and 7 of the 33 had old lacunes at baseline: WML volume was 8.54 ml (IQR 5.86–15.80) excluding versus 10.98 ml (IQR 6.91–24.86) including ISL (p < 0.001). At follow-up, median 39 months later (IQR 30–45), 3 patients had a de novo stroke lesion; total stroke lesion volume had decreased in 11 and increased in 22 patients: WML volume was 12.17 ml (IQR 8.54–19.86) excluding versus 14.79 ml (IQR 10.02–38.03) including total stroke lesions (p < 0.001). Including/excluding lacunes at baseline or follow-up also made small differences. Twenty-two of the 33 patients had tissue loss due to stroke lesions between baseline and follow-up, resulting in a net median brain tissue volume loss (i.e. atrophy) during follow-up of 24.49 ml (IQR 12.87–54.01) excluding versus 24.61 ml (IQR 15.54–54.04) including tissue loss due to stroke lesions (p < 0.001). Including stroke lesions in the WML volume added substantial noise, reduced statistical power, and thus increased sample size estimated for a clinical trial. Conclusions Failure to exclude even small stroke lesions distorts WML volume, cerebral atrophy and their longitudinal progression measurements. This has important implications for design and sample size calculations for observational studies and randomised trials using WML volume, WML progression or brain atrophy as outcome measures. Improved methods of discriminating between stroke lesions and WML, and between tissue loss due to stroke lesions and true brain atrophy are required.
    Cerebrovascular Diseases 11/2012; 34(5-6):336-342. DOI:10.1159/000343226 · 3.75 Impact Factor
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