Longitudinal Brain Changes After Stroke and the Association With Cognitive Decline

So you described something, but nothing here is going to get survivors better recovery. Useless.

 ipsilesional (not comparable) (pathology, medicine) On the same side as a lesion.

contralesional (not comparable) (medicine) Describing the half of a patient's brain or body away from the site of a lesion.

Longitudinal Brain Changes After Stroke and the Association With Cognitive Decline

Eva B. Aamodt^1,2*, Stian Lydersen³, Dag Alnæs⁴, Till Schellhorn^1,2, Ingvild Saltvedt^5,6, Mona K. Beyer^1,2 and Asta Håberg^5,7

• ¹Institute of Clinical Medicine, University of Oslo, Oslo, Norway
• ²Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
• ³Regional Centre for Child and Youth Mental Health and Child Welfare, Department of Mental Health, NTNU – Norwegian University of Science and Technology, Trondheim, Norway
• ⁴Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway
• ⁵Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Science, NTNU – Norwegian University of Science and Technology, Trondheim, Norway
• ⁶Department of Geriatrics, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
• ⁷Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway

Background: Cognitive impairment is common after stroke. So is cortical- and subcortical atrophy, with studies reporting more atrophy in the ipsilesional hemisphere than the contralesional hemisphere. The current study aimed to investigate the longitudinal associations between (I) lateralization of brain atrophy and stroke hemisphere, and (II) cognitive impairment and brain atrophy after stroke. We expected to find that (I) cortical thickness and hippocampal-, thalamic-, and caudate nucleus volumes declined more in the ipsilesional than the contralesional hemisphere up to 36 months after stroke. Furthermore, we predicted that (II) cognitive decline was associated with greater stroke volumes, and with greater cortical thickness and subcortical structural volume atrophy across the 36 months.

Methods: Stroke survivors from five Norwegian hospitals were included from the multisite-prospective “Norwegian Cognitive Impairment After Stroke” (Nor-COAST) study. Analyses were run with clinical, neuropsychological and structural magnetic resonance imaging (MRI) data from baseline, 18- and 36 months. Cortical thicknesses and subcortical volumes were obtained via FreeSurfer segmentations and stroke lesion volumes were semi-automatically derived using ITK-SNAP. Cognition was measured using MoCA.

Results: Findings from 244 stroke survivors [age = 72.2 (11.3) years, women = 55.7%, stroke severity NIHSS = 4.9 (5.0)] were included at baseline. Of these, 145 (59.4%) had an MRI scan at 18 months and 72 (49.7% of 18 months) at 36 months. Most cortices and subcortices showed a higher ipsi- compared to contralesional atrophy rate, with the effect being more prominent in the right hemisphere. Next, greater degrees of atrophy particularly in the medial temporal lobe after left-sided strokes and larger stroke lesion volumes after right-sided strokes were associated with cognitive decline over time.

Conclusion: Atrophy in the ipsilesional hemisphere was greater than in the contralesional hemisphere over time. This effect was found to be more prominent in the right hemisphere, pointing to a possible higher resilience to stroke of the left hemisphere. Lastly, greater atrophy of the cortex and subcortex, as well as larger stroke volume, were associated with worse cognition over time and should be included in risk assessments of cognitive decline after stroke.

Introduction

Although the chances of surviving a stroke have become high, its aftermath often involves the development of cognitive problems (1). About 30% of stroke survivors develop cognitive impairments after a first-ever stroke, with the incidence of dementia within the first year after a major stroke being almost 50 times higher than in the general population, and nearly 6 times higher after a minor one (1). Stroke and dementia both pose risks for each other and share many of the same neurodegenerative and cerebrovascular risk factors (2), with pre-existing 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 (4–7). 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). Moreover, early deficits in cognition after a stroke does not necessarily mean long-term problems and some studies report that about ¼ of patients with cognitive impairment at time of discharge show improvement already within the first year after a stroke event (10). Discovering reliable methods of identifying stroke patients at risk of dementia vs. only transitory cognitive impairment therefore has major implications in the development of tailorized follow-up strategies for patients, thereby decreasing both the personal and the societal disease burden of PSD.

Accelerated post-stroke cortical and subcortical atrophy is common, but the pattern it occurs in remains somewhat unclear. Stroke has been found to be associated with an overall accelerated atrophy rate for at least 3–12 months after a stroke incident, with the atrophy taking place irrespective of stroke lesion location (11). This could either be explained by distant neurophysiological changes, also called diachisis (12) or by secondary atrophy, also called Wallerian degeneration, affecting descending fiber tracts from the locus of the stroke, leading to structural changes also in areas distal to the stroke (13). In stroke there may also be a greater atrophy rate in the ipsi- (same side as the stroke) than the contralesional (opposite side of the stroke) hemisphere. Ipsilesional cortices and subcortical structures have been found to decrease more than its contralesional counterparts (11, 14), although some structures, such as the hippocampus, have also been reported to shrink equally in both hemispheres (15). Additionally, some studies report that the ipsilesional hemisphere atrophies more than the contralesional hemisphere only if the stroke was located to the middle cerebral artery territory (16). These somewhat diverging findings call for further clarification.

Although the exact spatial pattern of atrophy remains unclear, the effects of a stroke has been shown to last for years, with findings showing persistent greater brain atrophy up to 6 years after a stroke insult (17). Moreover, ipsilesional cortical and subcortical atrophy as opposed to contralesional atrophy rates have been found to be 2–4 times greater at 1 year compared to at 3 months after a stroke (11). These findings suggest that a stroke leads to protracted atrophy in the ipsilesional cortex more so than in other parts of the brain. Still, the temporal profile of the atrophy is yet to be fully understood. Longitudinal designs are therefore required to map out a potential difference in atrophy pattern trajectories between anatomical regions following a stroke.

Both cortical and subcortical atrophy have been shown to be associated with cognitive decline (14, 18). The brain changes reported as providing the greatest risk of cognitive decline in cross-sectional and longitudinal studies lasting up to 3–12 months are global brain atrophy, medial temporal lobe (including hippocampal) atrophy, and WMH load (4, 19–22). Since accelerated brain atrophy is demonstrated for a longer time period, potentially important changes in brain structure-function relationship over time may be overlooked due to relatively short follow-up times in previous studies. The current study therefore aimed to use a longitudinal follow-up design including both cognition and structural brain imaging assessed three times across 36 months in contrast to the typical 3–12 months follow-up.

The current prospective 36-months follow-up study of stroke patients aimed to investigate the longitudinal associations between (I) brain structure atrophy and stroke hemisphere, and (II) cognitive impairment and brain structure atrophy after stroke. We expected to find that (I) cortical thickness and hippocampal-, thalamic-, and caudate nucleus volumes declined more in the ipsilesional than the contralesional hemisphere at both 18- and 36 months after stroke. We also expected that (II) cognitive decline was associated with a larger stroke volume, and with greater cortical thickness and hippocampal-, thalamic-, and caudate nucleus volume atrophy at each timepoint.

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