Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study.
OBJECTIVE
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.
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
Andrew J
AJ
Lawrence
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
Rebecca L
RL
Brookes
Neurosciences Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, United Kingdom.
Eva A
EA
Zeestraten
Neurosciences Research Centre, Cardiovascular and Cell Sciences Research Institute, St George's University of London, London, United Kingdom.
Thomas R
TR
Barrick
Department of Psychology, King's College Institute of Psychiatry, Psychology and Neurosciences, London, United Kingdom.
Robin G
RG
Morris
Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.
Hugh S
HS
Markus
D000368:Aged; D059345:Cerebral Small Vessel Diseases / Q000503:physiopathology*; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies