PT  - JOURNAL ARTICLE
AU  - Pettigrew, Corinne
AU  - Soldan, Anja
AU  - Wang, Jiangxia
AU  - Wang, Mei-Cheng
AU  - Arthur, Karissa
AU  - Moghekar, Abhay
AU  - Gottesman, Rebecca F.
AU  - Albert, Marilyn
TI  - Association of midlife vascular risk and AD biomarkers with subsequent cognitive decline
AID  - 10.1212/WNL.0000000000010946
DP  - 2020 Dec 08
TA  - Neurology
PG  - e3093--e3103
VI  - 95
IP  - 23
4099  - http://n.neurology.org/content/95/23/e3093.short
4100  - http://n.neurology.org/content/95/23/e3093.full
SO  - Neurology2020 Dec 08; 95
AB  - Objective To determine whether vascular risk and Alzheimer disease (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 (mean 56.4 years, SD 10.9 years) 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 β-amyloid (Aβ)1–42, 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 (mean follow-up 13.9 years) and change in CSF biomarkers (mean follow-up 4.2 years).Results There was no evidence of a synergistic relationship between the vascular risk score and CSF AD biomarkers and cognitive decline. Instead, the vascular risk score (estimate −0.022, 95% confidence interval [CI] −0.043 to −0.002, p = 0.03) and AD biomarkers (estimate −0.060, 95% 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.Aβ=β-amyloid; AD=Alzheimer disease; BIOCARD=Biomarkers for Older Controls at Risk for Dementia; CDR=Clinical Dementia Rating; CI=confidence interval; CVD=cerebrovascular disease; JHU=Johns Hopkins University; MCI=mild cognitive impairment; p-tau=phosphorylated tau; t-tau=total tau