Association Between White Matter Integrity and Cognitive Performance Among Diverse Older Hispanic/Latino Adults in SOL-INCA MRI

BACKGROUND AND OBJECTIVES: Hispanic/Latino Americans are disproportionately affected by vascular risk factors (VRFs) linked to cognitive decline, yet they remain underrepresented in neuroimaging research. The aim of this study was to determine how white matter (WM) injury imaging biomarkers relate to cognition among Hispanic/Latino adults of different heritage. METHODS: This study included 2,385 participants from the Study of Latinos-Investigation of Neurocognitive Aging MRI ancillary study, a cohort of self-identified Hispanic/Latino individuals. Cognitive performance was evaluated using standardized, log-transformed scores for Global Cognition Score (GCS), processing speed (Trail Making Test Part A), and executive function (Trail Making Test Part B). MRI data for each participant were acquired using standardized 3T protocols and WM injury measures, including WM hyperintensity (WMH) volume, free water (FW) fraction, and fractional anisotropy (FA). Multivariable regression models adjusted for age at MRI, sex, education, VRFs (diabetes, hypertension, smoking, self-reported history of prevalent stroke/TIA), years of US mainland residency, and heritage were used to assess the associations between imaging biomarkers and cognition. RESULTS: Significant differences in cognitive outcomes were observed across Hispanic/Latino heritage groups (p < 0.001). Compared with Central or South American participants, Dominican participants had lower GCS and TMT-A and TMT-B scores and Mexican participants had higher GCS and TMT-A and TMT-B scores (p < 0.05). Multivariable regression analyses using global diffusion MRI metrics revealed that higher FW and WMH and lower FA were significantly associated with worse global cognition, processing speed, and executive function (p < 0.001). WMH was the only imaging biomarker significantly associated with cognitive status, defined as impaired vs unimpaired (p < 0.001). Voxel-wise analyses identified robust FW-cognition associations in frontoparietal and temporal WM regions, including the corpus callosum, superior longitudinal fasciculus, anterior corona radiata, and retrolenticular internal capsule. DISCUSSION: In this large and diverse cohort of Hispanic/Latino adults, greater microstructural (FW, FA) and macrostructural (WMH) WM injury was associated with worse cognitive performance. FW was more strongly associated with continuous measures of cognition, whereas WMH was most strongly related to the categorical level of impairment. These results emphasize the complementary roles of microstructural and macrostructural measures of WM pathology in capturing different aspects of cognition.