Repository logo
 

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


Type

Article

Change log

Authors

Lawrence, Andrew J 
Brookes, Rebecca L 
Zeestraten, Eva A 
Barrick, Thomas R 
Morris, Robin G 

Abstract

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.

Description

Keywords

Aged, Cerebral Small Vessel Diseases, Cognition, Cognition Disorders, Female, Humans, Longitudinal Studies, Male, Memory, Short-Term, Middle Aged, Neuropsychological Tests, Prospective Studies

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

10

Publisher

Public Library of Science (PLoS)
Sponsorship
Stroke Association (TSA 2010/08)
This work was supported by the Wellcome Trust [grant number 081589] and Alzheimer's Research UK [grant number ARUK-PG2013-2].