Association of vascular brain injury, neurodegeneration, amyloid, and cognitive trajectory

OBJECTIVE: To determine whether vascular and neurodegenerative factors influence cognition before clinically relevant Alzheimer disease pathology, we analyzed MRI measures and amyloid imaging in an ethnoracially diverse cohort of cognitively normal individuals older than 60 years. METHODS: Participants (n = 154; mean age 74.15 ± 6.94; 50% female; 54% Caucasian, 22.1% Hispanic, 14.9% African American) were recruited from the University of California, Davis Alzheimer's Disease Research Center, who were cognitively normal at baseline, time of PET, and MRI, and received yearly cognitive assessment for 6.23 ± 4.16 years. Mixed model regression with random slope and intercept was calculated for episodic memory and executive function, adjusting for age, sex, education, and ethnicity. RESULTS: Vascular burden score was associated with total white matter hyperintensity (WMH) volume (β, 0.171; 95% confidence interval [CI], 0.024-0.318). WMH volume was associated with low baseline executive function (-0.115; -0.226 to -0.003) and rate of change in memory (-0.029; -0.045 to -0.012). Hippocampal volume was associated with the rate of change in memory (0.040; 0.021-0.059) and executive function (0.024; 0.008-0.039). Continuous measures of amyloid status influenced change in memory (-0.026; -0.044 to -0.008) and executive function (-0.033; -0.046 to -0.021) independently of MRI measures. CONCLUSION: Vascular brain injury and neurodegeneration are associated with baseline cognitive performance and the rate of longitudinal change independent of amyloid status among community-dwelling, ethnicity diverse cognitively normal individuals, supporting the role of vascular diseases as risk factors for later-life dementia.