Age- and sex-specific rates of leukoaraiosis in TIA and stroke patients: population-based study

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 = 1.42, 95% confidence interval [CI] 1.27-1.57, p < 0.0001), with little heterogeneity between studies (p = 0.28). However, no such excess was seen in 10 reports of nonstroke cohorts (0.91, 0.67-1.24, p = 0.56). Moreover, excess leukoaraiosis in women on CT-imaging in OXVASC (1.38, 1.15-1.67, p = 0.001) was explained by their older age (age-adjusted OR = 1.01, 0.82-1.25, p = 0.90). Leukoaraiosis was more severe in older (≥ 75) women (CT-1.50, 1.14-1.97, p = 0.004 in OXVASC; MRI-1.70, 1.17-2.48, p = 0.006 in OXVASC and clinic cohort). However, leukoaraiosis was independently associated with early mortality (hazard ratio = 1.46, 1.23-1.73, p < 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.

Figure 1. Meta-analysis of studies identified by a systematic review of the published literature on the prevalence of leukoaraiosis stratified by sex

Pooled odds ratios for difference in prevalence of leukoaraiosis between sexes are shown. The studies have been stratified according to patient setting (stroke vs nonstroke patients), and according to the type of imaging used (CT or MRI). See supplemental data at www.neurology.org for e-references. CI = confidence interval; OR = odds ratio.

Figure 2. Age- and sex-specific distribution of leukoaraiosis on CT and MRI scans

Distribution of leukoaraiosis on CT scans of Oxford Vascular Study (OXVASC) patients (A) and MRI scans of OXVASC (B) and Stoke-Mandeville (C) patients, according to sex and age. The severity of leukoaraiosis is rated according to the ARWMC scale. Numbers of patients in each category are reported below the columns, and mean age for men and women in each age category is reported.