White matter lesion progression, brain atrophy, and cognitive decline: The Austrian stroke prevention study

Abstract

White matter lesions progress over time, but the clinical consequences are widely unknown. Three-hundred twenty-nine elderly community-dwelling volunteers underwent serial magnetic resonance imaging scanning and cognitive testing at baseline and at 3- and 6-year follow-up. We measured the changes in white matter lesion and brain parenchymal volumes. After 6 years, the median increase in white matter lesion load was 0.2 cm3 (interquartile range [IQR], 0.0-0.80 cm3) with a maximum of 31.4 cm3. The median loss of brain volume was 2.3% (IQR, 1.13-3.58%). Increasing white matter lesion volume was correlated with loss of brain volume (p < 0.0001) and performance decline in tests of memory (p = 0.022), conceptualization (p = 0.046), and visuopractical skills (p = 0.005). Associations between changes in white matter lesion load and cognitive functioning were no longer significant when adding change in brain volume to the models, suggesting that cognitive decline related directly to loss of brain substance with progression of lesion burden.

Brain volumetric changes and cognitive ageing during the eighth decade of life

“…Imaging‐detected infarcts included historical and/or silent stroke lesions that occurred in approximately 13% of participants (58 of the 459 participants with repeated MRI data); these were excluded from all tissue volumes. This incidence is approximately equal to the average incidence of infarcts in other large ageing cohorts [Schmidt et al, 2005; van Dijk et al, 2008]; we did not exclude these participants to ensure that our sample was as representative as possible of the wider population of older adults. Infarcts were identified by their cortical wedge‐shaped distribution in a typical arterial territory or, if subcortical, by their size larger than 2 cm indicating a striatocapsular aetiology.…”

“…Schmidt et al, 2005). Most relevant for the present analysis, Schmidt et al [2005] showed in a sample of 329 adults aged approximately 60 years that total brain volume loss across six years was correlated with decline in multiple cognitive skills. Other longitudinal studies have found similar results for loss of tissue in more specific brain regions, such as grey and white matter [e.g.…”

“…This is especially true for studies of healthy brain tissue: Only a few longitudinal studies have attempted to estimate either the predictive value of healthy brain tissue volume measured at baseline for subsequent cognitive decline (level‐change correlations; [Cardenas et al, 2011]), or the extent of coupled change in brain volume and cognitive ability (change‐change correlations; e.g. Schmidt et al, 2005). Most relevant for the present analysis, Schmidt et al [2005] showed in a sample of 329 adults aged approximately 60 years that total brain volume loss across six years was correlated with decline in multiple cognitive skills.…”

“…The small number of studies in the area, however, makes it difficult to draw solid conclusions on the effect sizes involved. For instance, as shown by Kloppenborg et al's [2014] meta‐analysis, only four age‐heterogeneous studies have examined change‐change correlations between WMH volume and processing speed, with Fisher's z estimates ranging widely, from −0.02 [Schmidt et al, 2005] to −0.42 [Wolfson et al, 2013]. …”

A fully automated method for quantifying and localizing white matter hyperintensities on MR images

“…The normalized WMH results were also significantly correlated to the visual grades (R-squared = 0.909, F(1,18) = 170.3, P < 0.0001). This WM normalization method may not be the best way for whole brain adjustment, since previous studies have showed that WMH are significantly related to atrophy (Capizzano, et al 2004;Schmidt, et al 2005). A whole brain normalization method, which takes brain atrophy into consideration, may be better for WMH assessment.…”