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Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

ABSTRACT: Introduction:It has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke lesion itself. The present study aimed to investigate associations between imaging markers of lesion-related and generalised brain pathology and the development of PSA and PSD during a one-year follow-up. Patients and methods:In a prospective cohort study, 188 stroke patients received 3-Tesla MRI at baseline (three months post-stroke) for evaluation of lesion-related, vascular, and degenerative brain pathology. Presence of lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces was summed to provide a measure of total cerebral small vessel disease (cSVD) burden (range 0-4). The Mini International Neuropsychiatric Interview and Apathy Evaluation Scale were administered at baseline and repeated at 6- and 12-month follow-up to define presence of PSD and PSA, respectively. Results:Population-averaged logistic regression models showed that global brain atrophy and severe cSVD burden (score 3-4) were significantly associated with the odds of having PSA (ORGEE 5.33, 95% CI 1.99-14.25 and 3.04, 95% CI 1.20-7.69, respectively), independent of stroke lesion volume and co-morbid PSD. Medium cSVD burden (score 2) was significantly associated with the odds of having PSD (ORGEE 2.92, 95% CI 1.09-7.78), independent of stroke lesion volume, co-morbid PSA, and pre-stroke depression. No associations were found with lesion-related markers. Conclusions:The results suggest that generalised degenerative and vascular brain pathology, rather than lesion-related pathology, is an important predictor for the development of PSA, and less strongly for PSD.

SUBMITTER: Douven E

PROVIDER: S-EPMC7092734 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

Douven Elles E Staals Julie J Freeze Whitney M WM Schievink Syenna Hj SH Hellebrekers Danique Mj DM Wolz Robin R Jansen Jacobus Fa JF van Oostenbrugge Robert J RJ Verhey Frans Rj FR Aalten Pauline P Köhler Sebastian S

European stroke journal 20191016 1

<h4>Introduction</h4>It has been suggested that the development of post-stroke apathy (PSA) and depression (PSD) may be more strongly associated with generalised brain pathology, rather than the stroke lesion itself. The present study aimed to investigate associations between imaging markers of lesion-related and generalised brain pathology and the development of PSA and PSD during a one-year follow-up.<h4>Patients and methods</h4>In a prospective cohort study, 188 stroke patients received 3-Tes ...[more]

PMID: 32232173

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Project description:Cognitive impairment and neuropsychiatric syndromes, like depression and apathy, are frequent residual consequences of stroke. These have a large impact on quality of life and long-term prognosis. Several factors are involved in the development of these residual syndromes, although their exact role and their interrelationships remain still rather unclear. The Cognition and Affect after Stroke: a Prospective Evaluation of Risks (CASPER) study has been primarily designed to examine whether stroke-specific (e.g. lesion location, volume, type, severity), cerebrovascular and neurodegenerative (e.g. white matter changes, atrophy, microbleeds, perivascular spaces), inflammatory, endothelial, and (epi)genetic markers are associated with cognitive impairment, post-stroke depression, and post-stroke apathy, and whether they predict their course over 12 months. The secondary aims are to investigate how the above-mentioned markers interact with each other, and to determine if patients with apathy and depression after stroke differ in pathogenesis, course, and outcome (e.g. functional outcome, neurocognitive performance, quality of life).CASPER is a 1-year prospective clinical cohort follow-up study in 250 stroke patients recruited at the neurological in- and outpatient services at Maastricht University Medical Center (MUMC+, Maastricht, The Netherlands), and Zuyderland Medical Center (Sittard and Heerlen, The Netherlands). At baseline (3 months post-stroke), a neuropsychological assessment, neuropsychiatric interview, blood sample, and brain magnetic resonance imaging (MRI) scan are conducted. Assessment of neuropsychiatric and neurocognitive status are repeated 6 and 12 months later.The CASPER study investigates stroke-specific, vascular, neurodegenerative, inflammatory, and genetic markers of the development of vascular cognitive impairment, depression, and apathy after stroke. This creates the possibility to study not only the contribution of these individual markers but also their joint contribution, which differentiates this study from earlier stroke cohorts who lacked long-term follow-up data, a large sample size, an extensive MRI protocol, and markers from the blood. The knowledge we derive from this study might help in identifying markers that are associated with, or can predict the onset, maintenance, and progression of vascular cognitive impairment, depression, and apathy after stroke, and could provide new insights into possibilities for treatment and rehabilitation that result in better functional outcome after stroke.ClinicalTrials.gov NCT02585349.

Project description:Importance: Given the importance of apathy for stroke, we felt it was time to scrutinize the psychometric properties of the commonly used Starkstein Apathy Scale (SAS) for this purpose. Objectives: The objectives were to: (i) estimate the extent to which the SAS items fit a hierarchical continuum of the Rasch Model; and (ii) estimate the strength of the relationships between the Rasch analyzed SAS and converging constructs related to stroke outcomes. Methods: Data was from a clinical trial of a community-based intervention targeting participation. A total of 857 SAS questionnaires were completed by 238 people with stroke from up to 5 time points. SAS has 14 items, rated on a 4-point scale with higher values indicating more apathy. Psychometric properties were tested using Rasch partial-credit model, correlation, and regression. Items were rescored so higher scores are interpreted as lower apathy levels. Results: Rasch analysis indicated that the response options were disordered for 8/14 items, pointing to unreliability in the interpretation of the response options; they were consequently reduced from 4 to 3. Only 9/14 items fit the Rasch model and therefore suitable for creating a total score. The new rSAS was deemed unidimensional (residual correlations: < 0.3), reasonably reliable (person separation index: 0.74), with item-locations uniform across time, age, sex, and education. However, 30% of scores were > 2 SD above the standardized mean but only 2/9 items covered this range (construct mistargeting). Apathy (rSAS/SAS) was correlated weakly with anxiety/depression and uncorrelated with physical capacity. Regression showed that the effect of apathy on participation and health perception was similar for rSAS/SAS versions: R2 participation measures ranged from 0.11 to 0.29; R2 for health perception was ∼0.25. When placed on the same scale (0-42), rSAS value was 6.5 units lower than SAS value with minimal floor/ceiling effects. Estimated change over time was identical (0.12 units/month) which was not substantial (1.44 units/year) but greater than expected assuming no change (t: 3.6 and 2.4). Conclusion: The retained items of the rSAS targeted domains of behaviors more than beliefs and results support the rSAS as a robust measure of apathy in people with chronic stroke.

Project description:BACKGROUND:Cognitive impairment is an important consequence of stroke and transient ischaemic attack, but its determinants are not fully understood. Simple univariable or multivariable models have not shown clinical utility for predicting cognitive impairment. Cardiovascular risk factors may influence cognition through multiple, direct, and indirect pathways, including effects on prior cognition and stroke severity. Understanding these complex relationships may help clinical teams plan intervention and follow-up strategies. METHODS:We analysed clinical and demographic data from consecutive patients admitted to an acute stroke ward. Cognitive assessment comprised Abbreviated Mental Test and mini-Montreal Cognitive Assessment. We constructed bias-corrected confidence intervals to test indirect effects of cardiovascular risk factors (hypertension, vascular disease, atrial fibrillation, diabetes mellitus, previous stroke) on cognitive function, mediated through stroke severity and history of dementia, and we assessed moderation effects due to comorbidity. RESULTS:From 594 eligible patients, we included 587 in the final analysis (age range 26-100; 45% female). Our model explained R2?=?62.10% of variance in cognitive test scores. We found evidence for an indirect effect of previous stroke that was associated with increased risk of prevalent dementia and in turn predicted poorer cognitive score (estimate?=?-?0.39; 95% bias-corrected CI, -?0.75 to -?0.13; p?=?0.02). Atrial fibrillation was associated with greater stroke severity and in turn with a poorer cognitive score (estimate?=?-?0.27; 95% bias-corrected CI, -?0.49 to -?0.05; p?=?0.02). Conversely, previous TIA predicted decreased stroke severity and, through that, lesser cognitive impairment (estimate?=?0.38; 95% bias-corrected CI, 0.08 to 0.75; p?=?0.02). Through an association with reduced stroke severity, vascular disease was associated with lesser cognitive impairment, conditional on presence of hypertension and absence of diabetes mellitus (estimate?=?0.36; 95% bias-corrected CI, 0.03 to 0.68; p?=?0.02), although the modelled interaction effects did not reach statistical significance. CONCLUSIONS:We have shown that relationships between cardiovascular risk factors and cognition are complex and simple multivariable models may be overly reductionist. Including direct and indirect effects of risk factors, we constructed a model that explained a substantial proportion of variation in cognitive test scores. Models that include multiple paths of influence and interactions could be used to create dementia prognostic tools for use in other healthcare settings.

Dataset Information

Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

Publications

Imaging markers associated with the development of post-stroke depression and apathy: Results of the Cognition and Affect after Stroke - a Prospective Evaluation of Risks study.

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