Interaction between cognitive reserve and age moderates effect of lesion load on stroke outcome

Roza M Umarova,Markus Martin,Lena V Schumacher,Jürgen Hennig,Stefan Klöppel,Christoph P Kaller,Horst Urbach,Karl Egger,Charlotte S M Schmidt

doi:10.1038/s41598-021-83927-1

Abstract

The concepts of brain reserve and cognitive reserve were recently suggested as valuable predictors of stroke outcome. To test this hypothesis, we used age, years of education and lesion size as clinically feasible coarse proxies of brain reserve, cognitive reserve, and the extent of stroke pathology correspondingly. Linear and logistic regression models were used to predict cognitive outcome (Montreal Cognitive Assessment) and stroke-induced impairment and disability (NIH Stroke Scale; modified Rankin Score) in a sample of 104 chronic stroke patients carefully controlled for potential confounds. Results revealed 46% of explained variance for cognitive outcome (p < 0.001) and yielded a significant three-way interaction: Larger lesions did not lead to cognitive impairment in younger patients with higher education, but did so in younger patients with lower education. Conversely, even small lesions led to poor cognitive outcome in older patients with lower education, but didn’t in older patients with higher education. We observed comparable three-way interactions for clinical scores of stroke-induced impairment and disability both in the acute and chronic stroke phase. In line with the hypothesis, years of education conjointly with age moderated effects of lesion on stroke outcome. This non-additive effect of cognitive reserve suggests its post-stroke protective impact on stroke outcome.

Highlights

The concepts of brain reserve and cognitive reserve were recently suggested as valuable predictors of stroke outcome
We recently suggested that the concepts of brain and cognitive reserve might constitute a theoretical framework to capture inter-individual variability and to improve prediction of outcome in stroke: Stroke outcome might result from the interaction between pre-stroke brain reserve and cognitive reserve and severity of stroke damage (Fig. 1)[8,9]
Explorative analysis revealed that both age and years of education correlated with chronic stroke outcome as measured by the Montreal Cognitive Assessment (MoCA) (r = − 0.428, p < 0.001; r = 0.379, p < 0.001 correspondingly) and with the routine clinical scores, i.e. chronic NIH Stroke Scale (NIHSS) (τ = 0.104, p = 0.046; τ = − 0.202, p = 0.001) and chronic modified Rankin Scale (mRS) (τ = 0.169, p = 0.004; τ = − 0.200, p = 0.001)

Summary

Introduction

The concepts of brain reserve and cognitive reserve were recently suggested as valuable predictors of stroke outcome To test this hypothesis, we used age, years of education and lesion size as clinically feasible coarse proxies of brain reserve, cognitive reserve, and the extent of stroke pathology correspondingly. In line with the hypothesis, years of education conjointly with age moderated effects of lesion on stroke outcome This non-additive effect of cognitive reserve suggests its post-stroke protective impact on stroke outcome. Plenty of factors have been reported to impact stroke outcome: Demographic factors (e.g. older age, female sex, lower educational attainment) and clinical and stroke characteristics (initial stroke severity, lesion load) constitute significant predictors for poorer post-stroke cognitive functioning[2,3,4]. For disentangling the individual contributions of these three determinants of stroke outcome, we (i) applied a paired-matching approach[17,18] to remove the confounds between them and (ii) statistically accounted for their interplay by explicitly modeling the respective two- and three-way interactions[19]

Methods

Results

Discussion

Conclusion