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Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

OBJECTIVES: Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in...

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Autores principales: Lawrence, Andrew J., Brookes, Rebecca L., Zeestraten, Eva A., Barrick, Thomas R., Morris, Robin G., Markus, Hugh S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537104/
https://www.ncbi.nlm.nih.gov/pubmed/26273828
http://dx.doi.org/10.1371/journal.pone.0135523
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author Lawrence, Andrew J.
Brookes, Rebecca L.
Zeestraten, Eva A.
Barrick, Thomas R.
Morris, Robin G.
Markus, Hugh S.
author_facet Lawrence, Andrew J.
Brookes, Rebecca L.
Zeestraten, Eva A.
Barrick, Thomas R.
Morris, Robin G.
Markus, Hugh S.
author_sort Lawrence, Andrew J.
collection PubMed
description OBJECTIVES: Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline. METHODS: 121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points. RESULTS: Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up. CONCLUSIONS: The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease.
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spelling pubmed-45371042015-08-20 Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study Lawrence, Andrew J. Brookes, Rebecca L. Zeestraten, Eva A. Barrick, Thomas R. Morris, Robin G. Markus, Hugh S. PLoS One Research Article OBJECTIVES: Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline. METHODS: 121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points. RESULTS: Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up. CONCLUSIONS: The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease. Public Library of Science 2015-08-14 /pmc/articles/PMC4537104/ /pubmed/26273828 http://dx.doi.org/10.1371/journal.pone.0135523 Text en © 2015 Lawrence et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lawrence, Andrew J.
Brookes, Rebecca L.
Zeestraten, Eva A.
Barrick, Thomas R.
Morris, Robin G.
Markus, Hugh S.
Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study
title Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study
title_full Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study
title_fullStr Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study
title_full_unstemmed Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study
title_short Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study
title_sort pattern and rate of cognitive decline in cerebral small vessel disease: a prospective study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537104/
https://www.ncbi.nlm.nih.gov/pubmed/26273828
http://dx.doi.org/10.1371/journal.pone.0135523
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