Abstract WMP20: Association Of Periventricular And Deep White Matter Hyperintensity With Cognitive Performance In A Middle-aged Population

Abstract

Introduction: White matter hyperintensity (WMH) has been associated with manual dexterity performance in apparently healthy middle-aged population. However, the relative effect of WMH topographic distribution on cognition remains unknown. We hypothesized that periventricular WMH (PVWMH) is more strongly associated with manual dexterity and cognitive measures compared to deep WMH (DWMH) given its proximity to the white matter tracts involved in motor and executive functions. Methods: Apparently healthy middle-aged participants in the Genetic Study of Atherosclerosis Risk with brain MRI and cognitive measurements were selected. Cognitive measures included delayed word recall short (DWRS) and long (DWRL), digit symbol substitution (DSS), word fluency (WF), digit span forward test (DSFT), backward (DSBT) and total (DSTS), and grooved peg board test (GPBT) including the dominant and non-dominant hand (GPBTD, GPBTnD). PVWMH and DWMH volumes were measured using semi-automated segmentation paradigm. The relative associations of these measurements with PVWMH and DWMH volumes as multiple measurements within the same individual further nested within families were determined using multilevel linear models adjusting for intracranial volume, age, sex and cardiovascular risk factors. Results: 782 subjects were included (age 51.1±10.6, 58.4% female and 39% African American, PVWMH volume 437.4 [0-1646] mm 3 , DWMH volume 273.5 [76-665] mm 3 ). Within the same subject, PVWMH showed greater association than DWMH with worse performance on GPBT, GPBTD, GPBTnD, DWRS, and DWRL (P=0.006, 0.01, 0.01, 0.01 and 0.03, respectively) after adjusting for age and other cardiovascular risk factors. There was no difference in the association of PVWMH versus DWMH volumes with DSS, WF, DSFT, DSBT, DSTS (P=0.19, 0.52, 0.13, 0.6, and 0.6, respectively). Conclusions: PVWMH shows greater association than DWMH with cognitive measures of manipulative manual dexterity and recall suggesting that PVWMH and DWMH may have different cognitive phenotypes in middle-aged population with cerebral small vessel disease.