Abstract
Background and Purpose—
Individual
markers of cerebral small vessel disease and cerebral atrophy explain a
small proportion of variance in vascular risk factors and cognitive
function. Combining these markers into a single measure of neurovascular
and neurodegenerative disease may be more powerful. We assessed this
using data contained in the Virtual International Stroke Trials Archive -
Prevention sub-archive.
Methods—
We
extracted white matter hyperintensities (WMH) and cerebrospinal fluid
(CSF) volumes from 317 people with ischemic stroke or transient ischemic
attack who had baseline magnetic resonance imaging. We assessed
progression of volumes in 208 people who had 2-year follow-up magnetic
resonance imaging. WMH and CSF volumes were segmented from fluid
attenuated inversion recovery and T1 images. The combined neurovascular
and neurodegenerative measure was the sum of WMH and CSF volume
normalized by intracranial volume. We assessed (1) the relationship
between baseline vascular risk factors and imaging markers; and (2) the
relationship between baseline imaging markers and Mini-Mental State
Examination score at follow-up using multiple linear regression. We also
assessed implications for sample size calculations using n=208
participants with follow-up magnetic resonance imaging.
Results—
Vascular risk factors accounted for 7%, 11%, and 12% of the variance in WMH, CSF, and combined volume, respectively (all P<0.001).
The association between baseline combined volume and 6-month follow-up
Mini-Mental State Examination (β=−0.442; SE, 0.07; P<0.0001) was 32% greater than WMH (β=−0.302; SE, 0.06; P<0.0001) and 12% greater than CSF (β=−0.391; SE, 0.07; P<0.0001)
alone. The combined volume required between 207 and 3305 (20%) fewer
patients per arm than WMH alone to detect reductions of 10% to 40% in
volume progression over 2 years.
Conclusions—
A
combined neurovascular and neurodegenerative magnetic resonance imaging
measure including WMH and CSF volume was more closely related to
vascular risk factors and cognitive function than either WMH or CSF
volume alone. The combined volume may be a more sensitive measurement
for clinical trials.
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