[o3–07–05]: the impact of small vessel disease burden on executive functioning in individuals with or at risk for dementia

Cerebral small vessel disease (SVD) is common in Alzheimer's disease (AD) and worsens cognition, particularly executive functions. Previous work on this topic used composite measures of executive functions despite ample evidence that they are a collection of individual processes, not a unitary construct. We aimed to elucidate specific associations between regional SVD burden and individual executive measures, using white matter hyperintensities (WMH) as a measure of SVD burden. Participants were 470 adults (aged 50–89) from the Sunnybrook Dementia Study (ClinicalTrials.gov NCT01800214). Ninety-nine were cognitively normal (CN), 56 had mild cognitive impairment, no dementia (CIND) and 315 had AD. Participants with stroke, head trauma, substance abuse, or psychiatric/neurological disorders other than AD were not included. All underwent 1.5T MRI and neuropsychological assessment. Executive measures included phonemic/semantic fluency, forward/backward digit span, Rey figure copy, Wisconsin Card-Sorting Task (WCST), Trails A/B, Stroop, and Digit-Symbol Substitution. Raw scores were standardized against the CN group adjusted for age, sex and education. Regional (dorsolateral, superior medial, inferior medial) WMH volumes were quantified using Lesion Explorer segmentation software, corrected for head-size and normalized using log-transformation. These were entered together as predictors in linear regression models with Z scores on each test as the outcome measures, along with age, sex, and education as covariates. Models included all participants so that WMH/cognition relationships could be explored independently from diagnostic category. Right dorsolateral WMH volumes were negatively associated with Rey copy score (β=-2.6, p