Abstract 109: Manipulative Dexterity is Associated with Occult White Matter Ischemic Lesions in Healthy Asymptomatic Persons at Increased Risk for Cardiovascular Disease
Introduction: Persons with a family history of early-onset coronary artery disease (CAD) have an excess risk of stroke and CAD. White matter lesions (WML) on MRI represent small vessel ischemic cerebrovascular disease and are associated with incident stroke and neurocognitive decline with age. We hypothesized manipulative manual dexterity, an integration of fine motor, visual spatial, and cognition function, may be affected by increased WML burden in task-relevant brain regions across age ranges in persons at risk for pre-clinical occult vascular disease. We tested this in a large population with a family history of early CAD. Methods: Healthy 29-74 year old subjects (N=714; mean age 51± 11 years; mean education 14 ± 3 years; 42% male, 38% Black) were identified from probands with CAD <60 years. WML location and volumes were measured on 3T FLAIR MRI. Manipulative manual dexterity was measured with standardized timed grooved pegboard test. Left and right pegboard scores were averaged. Results: WML were observed in all age groups; mean overall pegboard scores were 108±18, and were within reference norms. In unadjusted analysis, pegboard scores were highly correlated in the expected direction with total WML volumes, r=0.34, p=<.0001; subcortical volumes r=0.30, <.0001 periventricular volumes r=0.31, <.0001; and with most regional WML volumes; frontal 0.34, <.0001; insula r=0.31, p<.0001, parietal r=0.31, p<.0001, and temporal volumes r=0.17, p <.0001. In separate multivariate regression analyses predicting (log) pegboard score adjusted for age, sex, race, education and nonindependence of families (GEE), total WML volume became more statistically significant ( p=5.79E-05) while other regions retained statistical significance, p< 0.01. Conclusions: Our findings in a large population-based sample with a family history of early CAD confirm that greater WML volumes in multiple brain locations are associated with higher pegboard scores (worse performance) independent of age, sex, race, and education. This suggests that small vessel cerebrovascular disease is present in an early preclinical state and that WML volumes impact manipulative manual dexterity in healthy middle-aged and younger individuals with excess risk for clinical vascular disease.