Age- and sex-specific rates of leukoaraiosis in TIA and stroke patients

Abstract

Objective: To determine any sex differences in age-specific prevalence or severity of leukoaraiosis, a marker of white matter ischemia, in population-based and clinic cohorts of TIA/stroke and in a systematic review of the literature.Methods: Age-specific sex differences were calculated for both CT and MRI in the Oxford Vascular Study (OXVASC) and in an MRI-based clinic cohort. We pooled odds ratios (ORs) for leukoaraiosis in women vs men from published studies by fixed-effect meta-analysis, stratified by patient characteristics (stroke vs nonstroke) and CT vs MRI. Results:Among 10 stroke studies (all CT-based), leukoaraiosis was most frequent in women (OR ϭ 1.42, 95% confidence interval [CI] 1.27-1.57, p Ͻ 0.0001), with little heterogeneity between studies (p ϭ 0.28). However, no such excess was seen in 10 reports of nonstroke cohorts (0.91, 0.67-1.24, p ϭ 0.56). Moreover, excess leukoaraiosis in women on CT-imaging in OXVASC (1.38, 1.15-1.67, p ϭ 0.001) was explained by their older age (age-adjusted OR ϭ 1.01, 0.82-1.25, p ϭ 0.90). Leukoaraiosis was more severe in older (Ն75) women (CT-1.50, 1.14-1.97, p ϭ 0.004 in OXVASC; MRI-1.70, 1.17-2.48, p ϭ 0.006 in OXVASC and clinic cohort). However, leukoaraiosis was independently associated with early mortality (hazard ratio ϭ 1.46, 1.23-1.73, p Ͻ 0.0001), suggesting that comparisons in older age groups will be biased by prior premature death of men with leukoaraiosis. Sex differences in severity of leukoaraiosis were not addressed in previous studies. Conclusions:Previously reported excess leukoaraiosis in women with TIA/stroke is likely to be confounded by age and apparently greater severity in older women is likely to be biased by premature death in men with leukoaraiosis. Neurology Onset of coronary artery disease is delayed in women compared to men, 1,2 and women have a lower prevalence of peripheral and carotid artery disease, particularly before 75 years of age. 3 However, the overall age-specific incidence of stroke differs much less between the sexes, 4 the lifetime risk of stroke is similar in men and women, 5,6 and stroke in women appears to be more severe and to lead to more disability than in men. 7,8 This greater relative susceptibility to stroke than to coronary artery disease and the increased severity of stroke in women are unexplained, but could be due to a greater susceptibility to microvascular cerebral ischemia. Women have been reported to have a higher prevalence and severity of leukoaraiosis than men in some studies 9 -12 and a higher progression rate of leukoaraiosis by longitudinal MRI studies, 13,14 although not all studies have confirmed this difference. [15][16][17] To clarify whether leukoaraiosis is more prevalent or more severe in women than in men, or if the previously observed differences might be due to confounding by age, or be secondary to competing risk of earlier vascular death in men, we did a systematic review of the literature on leukoaraiosis and its association to sex,

Leukoaraiosis Predicts a Poor 90-Day Outcome after Endovascular Stroke Therapy

“…Leukoaraiosis may represent a viable biomarker because it can be determined by standard neuroimaging and has been consistently shown to predict a higher risk for poor poststroke outcome. [5][6][7][8]15,18 How leukoaraiosis contributes to worse poststroke outcomes Functional improvement of patients who were alive at the time of discharge (n ϭ 87) according to leukoaraiosis severity (unadjusted). Compared with patients with absent-to-moderate leukoaraiosis, patients with severe leukoaraiosis are significantly less likely to have any improvement on the mRS from discharge to 90 days (50% versus 79% of surviving patients [21% versus 59% of all patients, respectively]; P ϭ .034; darker shades indicate less improvement).…”

“…2 While numerous studies have focused on procedural aspects, treatment window, and neuroimaging signatures of acute tissue injury, little is known regarding the potential contribution of preexisting white matter rarefaction (leukoaraiosis) on outcome. [3][4][5] Yet, leukoaraiosis is frequently encountered in the elderly 6,7 and is well-known to contribute to worse outcomes after acute ischemic stroke. 7,8 Given the expected tripling of the number of persons aged 60 or older in developed nations by 2050 9 and the increasing prevalence of stroke with advancing age, 10,11 it is expected that an increasing number of patients with pre-existing leukoaraiosis will be treated with EST.…”

Posterior white matter disease distribution as a predictor of amyloid angiopathy

“…12,27,28 Because it appears that WM damage in normal elderly subjects tends to be frontal in predominance regardless of sex, 12,29 this may explain why we found women to have a higher burden of frontal WMH. Alternatively, sex-based differences in WMH burden may be the result of premature death in men with high WMH burden.…”

“…Alternatively, sex-based differences in WMH burden may be the result of premature death in men with high WMH burden. 28 Thus, further well-designed pathophysiologic and population-based studies are required to more definitely address this issue.…”

Age-specific association of migraine with cryptogenic TIA and stroke

“…Moreover, markers of small vessel disease on brain imaging were prospectively coded in OXVASC and have been published previously. 18 The Age-Related White Matter Changes (ARWMC) scale was applied for both CT and MRI, rating 5 different regions in both hemispheres according to a 0-3 score. Total score was categorized as absent (0), mild (1-5), moderate (6-10), or severe (.10) white matter disease (WMC).…”