Supplementary Material for: Brain Imaging Features Associated with 20-Year Cognitive Decline in a Community-Based Multiethnic Cohort Without Dementia

Introduction: This study aimed to characterize the association of cognitive decline starting in midlife with brain pathology in late-life in the absence of dementia. Methods: Non-demented Atherosclerosis Risk in Communities (ARIC) participants with brain imaging, all cognitive factor scores (CFS), and non-missing covariates were included. CFS were collected at three visits across 21 years (1990-2013) (short-term cognitive change [1990-1996], long-term cognitive change [1990-2013]), and brain magnetic resonance imaging (MRI) and florbetapir positron emission tomography (PET) imaging were collected in 2011-13 (PET subset n=327). Outcomes of interest were total and regional brain volumes (cm3), log2(white matter hyperintensity volume), white matter integrity (fractional anisotropy, mean diffusivity), ≥1 lacunar infarct (3-20 mm), and elevated brain -amyloid (SUVR >1.2). Multivariable linear/logistic regression related outcomes to CFS slopes after adjusting for demographics and total intracranial volume. Results: At baseline, the 1734 participants had a mean (SD) age of 55 (5.2) years, were 60% female, and 26% Black. After adjustment, a 1-SD larger long-term decline in CFS was associated with a smaller relative total brain volume by 1.2% [95%CI: 1.0, 1.5], a smaller relative temporal lobe meta region volume by 1.9% [1.5, 2.3], a 13% [9, 17] larger volume of white matter hyperintensities, a 1.3-fold [1.2, 1.4] higher odds of having ≥1 lacune, and 1.7-fold [1.3, 2.2] higher odds of elevated brain -amyloid deposition, and worse white matter integrity. Some long-term associations were also found for midlife short-term declines in CFS. Conclusions: This study provides evidence that starting in midlife, short-term and long-term declines in cognition are associated with multiple deleterious late-life differences in non-demented brains.