Neurodegeneration Over 3 Years Following Ischaemic Stroke: Findings From the Cognition and Neocortical Volume After Stroke Study

Abstract

Background: Stroke survivors are at high risk of dementia, associated with increasing age and vascular burden and with pre-existing cognitive impairment, older age. Brain atrophy patterns are recognised as signatures of neurodegenerative conditions, but the natural history of brain atrophy after stroke remains poorly described. We sought to determine whether stroke survivors who were cognitively normal at time of stroke had greater total brain (TBV) and hippocampal volume (HV) loss over 3 years than controls. We examined whether stroke survivors who were cognitively impaired (CI) at 3 months following their stroke had greater brain volume loss than cognitively normal (CN) stroke participants over the next 3 years.Methods: Cognition And Neocortical Volume After Stroke (CANVAS) study is a multi-centre cohort study of first-ever or recurrent adult ischaemic stroke participants compared to age- and sex-matched community controls. Participants were followed with MRI and cognitive assessments over 3 years and were free of a history of cognitive impairment or decline at inclusion. Our primary outcome measure was TBV change between 3 months and 3 years; secondary outcomes were TBV and HV change comparing CI and CN participants. We investigated associations between group status and brain volume change using a baseline-volume adjusted linear regression model with robust standard error.Results: Ninety-three stroke (26 women, 66.7 ± 12 years) and 39 control participants (15 women, 68.7 ± 7 years) were available at 3 years. TBV loss in stroke patients was greater than controls: stroke mean (M) = 20.3 cm3 ± SD 14.8 cm3; controls M = 14.2 cm3 ± SD 13.2 cm3; [adjusted mean difference 7.88 95%CI (2.84, 12.91) p-value = 0.002]. TBV decline was greater in those stroke participants who were cognitively impaired (M = 30.7 cm3; SD = 14.2 cm3) at 3 months (M = 19.6 cm3; SD = 13.8 cm3); [adjusted mean difference 10.42; 95%CI (3.04, 17.80), p-value = 0.006]. No statistically significant differences in HV change were observed.Conclusions: Ischaemic stroke survivors exhibit greater neurodegeneration compared to stroke-free controls. Brain atrophy is greater in stroke participants who were cognitively impaired early after their stroke. Early cognitive impairment was associated greater subsequent atrophy, reflecting the combined impacts of stroke and vascular brain burden. Atrophy rates could serve as a useful biomarker for trials testing interventions to reduce post-stroke secondary neurodegeneration.Clinical Trail Registration:http://www.clinicaltrials.gov, identifier: NCT02205424.

Cortical thinning 3 years after ischaemic stroke is associated with cognitive impairment and APOE ε4

“…We reported lower total brain volume 3 years post-stroke in survivors who were cognitively impaired (CI) at 3 months. ( Brodtmann, 2021 ) We also reported greater degeneration of structural brain networks in subacute stroke, associated with attention, executive function, language, memory, and visuospatial function impairment. ( Veldsman, 2020 , Veldsman, 2020 ) Moreover, we found carriers of the APOE ε4 allele to have worse verbal memory performance and reduced entorhinal volume 1-year post-stroke.…”

“…We also screened for anxiety (GAD-7 score) and depression (PHQ-9 score). A cognitive evaluation panel ( Brodtmann, 2021 ) was tasked with assigning a cognitive status (CI, CN, or dementia) to each participant based on cognitive z-scores, mood scores, and information from clinical interviews.…”

Longitudinal Brain Changes After Stroke and the Association With Cognitive Decline

“…Stroke and dementia both pose risks for each other and share many of the same neurodegenerative and cerebrovascular risk factors (2), with preexisting structural brain pathology being a frequent finding in stroke patients (3). Early onset (<3 months) of post-stroke dementia (PSD) has been found to be primarily associated with stroke lesion volume and white matter hyperintensity (WMH) load (4)(5)(6)(7). The likelihood of developing cognitive impairment after a stroke does however remain elevated for many years after the incident (8), with late onset (>6 months) being mainly associated with the presence of lacunes and a history of ischemic heart disease and stroke (9).…”

Blood Pressure and Vascular Cognitive Impairment

“…85 Brain atrophy rates could serve as an objective quantitative biomarker independent of educational status or language. 86,87…”

“…85 Brain atrophy rates could serve as an objective quantitative biomarker independent of educational status or language. 86,87 The disadvantage of both imaging-based measures is repeated MRI, which is not accessible to all populations and may limit participant inclusion. However, large randomized controlled trials could use these end points for Phase IIb studies before translating to functional and cognitive outcomes.…”