Amyloid, tau, cerebrovascular disease, neurodegeneration, and cognition in middle‐aged adults from a racially and ethnically diverse, community‐based study

Abstract

AbstractBackgroundAlzheimer’s disease (AD) pathophysiology (i.e., amyloid‐induced tau) and cerebrovascular disease drive neurodegeneration and cognitive impairment. Our objective was to investigate moderation and mediation pathways among amyloid PET, tau PET, vascular MRI, and structural MRI in a middle‐aged, racially and ethnically diverse sample.MethodsIn an ongoing study, participants (n=63; 61±6 years old, 68% women, 13±4 years of education, 12% Non‐Latinx White/25% Non‐Latinx Black/63% Latinx) underwent amyloid PET (weighted average Florbetaben SUVR in Thaal phase regions), tau PET (average MK‐6240 SUVR in Braak stage I), vascular MRI (white matter hyperintensity (WMH) volume), and structural MRI (AD‐signature cortical thickness) in the Offspring Study of Racial and Ethnic Disparities in Alzheimer’s Disease. Serial parallel mediation was used to assess two pathways from age to neurodegeneration (i.e., age to amyloid to tau to neurodegeneration; age to WMH to tau to neurodegeneration).ResultsOlder age was associated with greater amyloid (7E‐3 [3E‐3, 0.01], p=0.001), which was in turn trend level associated with greater tau (0.55 [‐0.1, 1.2], p=0.09); tau was not associated with cortical thickness (‐6E‐3 [‐0.09, 0.08], p=0.88). The total indirect effect of this amyloid pathway was not significant (‐2E‐5 [‐3E‐4, 3E‐4], p=0.88). Older age was associated with greater WMH (0.01 [2E‐4, 0.02], p=0.048), but WMH was not associated with tau (0.01 [‐0.20, 0.22], p=0.91) or cortical thickness (‐8E‐3 [‐0.08, 0.06], p=0.82). The total indirect effect of this vascular pathway was not significant (‐9E‐7 [‐2E‐5, 2E‐5], p=0.93). The direct effect from age to neurodegeneration, given both indirect pathways, was significant (‐5E‐3 [‐9E‐3, ‐1E‐3], p=0.005).ConclusionsIn midlife, there is evidence of age‐related increases in cerebrovascular disease and amyloid‐induced tau, but the two pathways do not have an effect on neurodegeneration in this age group. Older age is the strongest predictor of neurodegeneration, but AD and cerebrovascular pathology may become stronger predictors later in the AD continuum.