Abstract
Background and ObjectivesThe severity of white matter hyperintensities (WMH) at presentation with stroke is associated with poststroke dementia and dependency. However, WMH can decrease or increase after stroke; prediction of cognitive decline is imprecise; and there are few data assessing longitudinal interrelationships among changing WMH, cognition, and function after stroke, despite the clinical importance.MethodsWe recruited patients within 3 months of a minor ischemic stroke, defined as NIH Stroke Scale (NIHSS) score <8 and not expected to result in a modified Rankin Scale (mRS) score >2. Participants repeated MRI at 1 year and cognitive and mRS assessments at 1 and 3 years. We ran longitudinal mixed-effects models assessing change in Addenbrooke’s Cognitive Examination–Revised (ACE-R) and mRS scores. For mRS score, we assessed longitudinal WMH volumes (cube root; percentage intracranial volume [ICV]), adjusting for age, NIHSS score, ACE-R, stroke subtype, and time to assessment. For ACE-R score, we additionally adjusted for ICV, mRS, premorbid IQ, and vascular risk factors. We then used a multivariate model to jointly assess changing cognition/mRS score, adjusted for prognostic variables, using all available data.ResultsWe recruited 264 patients; mean age was 66.9 (SD 11.8) years; 41.7% were female; and median mRS score was 1 (interquartile range 1–2). One year after stroke, normalized WMH volumes were associated more strongly with 1-year ACE-R score (β = −0.259, 95% CI −0.407 to −0.111 more WMH per 1-point ACE-R decrease, p = 0.001) compared to subacute WMH volumes and ACE-R score (β = 0.105, 95% CI −0.265 to 0.054, p = 0.195). Three-year mRS score was associated with 3-year ACE-R score (β = −0.272, 95% CI −0.429 to −0.115, p = 0.001). Combined change in baseline-1-year jointly assessed ACE-R/mRS scores was associated with fluctuating WMH volumes (F = 9.3, p = 0.03).DiscussionAfter stroke, fluctuating WMH mean that 1-year, but not baseline, WMH volumes are associated strongly with contemporaneous cognitive scores. Covarying longitudinal decline in cognition and independence after stroke, central to dementia diagnosis, is associated with increasing WMH volumes.
Highlights
Cerebral small vessel disease (SVD) is common in patients with stroke and is a common cause of stroke and vascular dementia.[1]
We found that co-varying longitudinal change in cognition and modified Rankin Scale (mRS) post-stroke independently associates with change in total white matter hyperintensities (WMH) volumes between baseline and one year
Of particular relevance to dementia after stroke, we show that longitudinal change in co-varying cognition and mRS in the first year post-stroke is associated with age, intracranial volume (ICV), change in WMH volumes and NIHSS
Summary
Cerebral small vessel disease (SVD) is common in patients with stroke and is a common cause of stroke and vascular dementia.[1]. In cross-sectional studies, worse white matter hyperintensities (WMH) at stroke presentation are associated with worse cognition assessed concurrently as well as long term.[10,11] it is less clear whether longitudinal WMH change predicts coexistent post-stroke cognitive or functional impairment. Small MRI studies assessing WMH progression and post-stroke cognitive decline have not detected a longitudinal association, follow-up sample sizes may have been underpowered, ranging from n=30 to n=94 participants[12,13,14,15,16,17] (systematic search for relevant papers and summary of their characteristics are described in eTable 1 and eTable 2 in the Supplement). WMH can decrease or increase after stroke, prediction of cognitive decline is imprecise, and there are few data assessing longitudinal interrelationships between changing WMH, cognition, and function after stroke, despite the clinical importance
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