Association of midlife vascular risk and AD biomarkers with subsequent cognitive decline.

OBJECTIVE: To determine whether vascular risk and AD biomarkers have independent or synergistic effects on cognitive decline, and whether vascular risk is associated with the accumulation of AD pathology, as measured by change in biomarkers over time.

METHODS: At baseline, participants (N = 168) were cognitively normal and primarily middle-aged (M = 56.4, SD = 10.9), and had both vascular risk factor status and proximal CSF biomarkers available. Baseline vascular risk was quantified with a composite vascular risk score reflecting the presence or absence of: hypertension, hypercholesterolemia, diabetes, current smoking, and obesity. CSF biomarkers of Aβ1-42 , total tau (t-tau), and phosphorylated tau (p-tau) were used to create dichotomous "high" and "low" AD biomarker groups (based on Aβ1-42 and tau). Linear mixed effects models were used to examine change in a cognitive composite score (M follow-up = 13.9 years) and change in CSF biomarkers (M follow-up = 4.2 years).

RESULTS: There was no evidence of a synergistic relationship between the vascular risk score and CSF AD biomarkers on cognitive decline. Instead, the vascular risk score ( estimate = -0.022, CI = -0.043 to -0.002, p = 0.03) and AD biomarkers ( estimate = -0.060, CI = -0.096 to -0.024, p = 0.001) were independently and additively associated with cognitive decline. In addition, the vascular risk score was unrelated to levels of, or rate of change in CSF Aβ1-42 , t-tau, or p-tau.

CONCLUSIONS: The results of this observational cohort study suggest that vascular risk and biomarkers of AD pathology, when measured in midlife, act along independent pathways, and underscore the importance of accounting for multiple risk factors for identifying cognitively normal individuals at the greatest risk of cognitive decline.