Executive dysfunction in cerebral small vessel disease: A subdomain analysis with conventional and experimental assessment methods

Abstract

Introduction: Executive functions and processing speed have been regarded as core cognitive domains affected in cerebral small vessel disease (SVD). Executive functions, as an umbrella concept, consist of a variety of different subcomponents, yet in research these abilities are often evaluated with single tests or summary scores. Currently, it is unknown whether all executive abilities are equally affected by SVD brain changes and whether some tests are more sensitive in detecting deficits than others. We investigated the associations of white matter hyperintensity (WMH) volume with specific executive abilities (cognitive flexibility, response inhibition, working memory) and processing speed by using an extensive set of paper-and-pencil and computerised neuropsychological tests. Methods: In the Helsinki Small Vessel Disease Study, 152 subjects (age 65-75 years) with varying degrees of WMH but no clinical stroke or dementia were evaluated with quantitative automated MRI analysis and a comprehensive neuropsychological examination. Executive functions and processing speed measures included the Wechsler adult intelligence scale (WAIS-IV) Coding subtest, Stroop test, Hayling sentence completion test, Brixton spatial anticipation test, verbal fluency test, Wechsler memory scale (WMS-III) Digit span and Number-letter sequencing subtasks, and the more experimental Flexible attention test (FAT), Simon task and Sustained attention to response task (SART). Results: Linear regression analyses controlling for age, sex and education revealed significant associations between WMH volume and measures within all evaluated subdomains. However, marked differences were found between individual test Results: The strongest associations were observed for FAT Numbers and Number-letter task (computerised tests based on the Trail making test), FAT Visuospatial span, Simon task and verbal fluency (animals), while some of the widely used tests failed to reach significance. Discussion: WMH are related to significant deficits in processing speed and executive functions subdomains of flexibility, inhibition and working memory. The strength of associations within subdomains is nevertheless highly dependent on the evaluation method in use. Computerised tests providing precise measures of reaction times and response accuracy seem to outperform many of the conventional paper-and-pencil tests. These results have implications for observational studies and intervention trials, where the selection of sensitive outcome measures is crucial.