Association of quantitative susceptibility mapping signal in gray matter with clinical characteristics and aging-related MRI markers: The Multi-Ethnic Study of Atherosclerosis

Background and objectives: In neuropathologic studies, iron accumulation in gray matter (GM) is associated with aging and specific neurological diseases, but less is known about its correlates in community-based populations. Methods: In the Multi-Ethnic Study of Atherosclerosis, brain MRI was conducted in 2018–2019. To estimate iron content, we derived the median quantitative susceptibility mapping (QSM) signal from four regions: the basal ganglia and cortical GM of the frontal, temporal, and parietal lobes. We examined cross-sectional associations with demographic and clinical characteristics, cognitive test performance, gait speed, and brain MRI measures of atrophy and small vessel disease. Results: We studied 943 participants (14 % Chinese, 25 % Black, 20 % Hispanic, 41 % White; mean age 74 years; 48 % men). In multivariable models, higher left basal ganglia QSM signal was associated with older age (7.2 ppb per 10 years; 95 %CI 4.6,9.9), smoking (7.1; 3.4,10.9), and diabetes (7.4; 2.5,12.3). Lower QSM signal was associated with Black race (−15.3; −20.6,-10, relative to White) and higher high-density lipoprotein cholesterol (−3.4 per 20 mg/dL; −5.8,-0.9). In cortical GM, QSM signal was associated with greater waist circumference, lifetime alcohol use, and log-transformed white matter hyperintensity (WMH) volume (0.08–0.12 SD units per SD, all p ≤ 0.002), but not with cognitive test performance or gait speed. Discussion: In cross-sectional analyses in a community-based cohort, older age, White race, smoking, diabetes, and greater WMH volume were associated with higher QSM signal in basal ganglia and/or cortical GM. Longitudinal studies are needed to further explore GM QSM signal in relation to cognition and gait in older individuals.