Alzheimer's disease and related dementias are influenced by genetic and environmental risk factors. We investigated the relationship between contextual exposures and cognitive outcomes, independent of Show more
Alzheimer's disease and related dementias are influenced by genetic and environmental risk factors. We investigated the relationship between contextual exposures and cognitive outcomes, independent of and in interaction with polygenic risk. Using the Multi-Ethnic Study of Atherosclerosis (N = 5687), we assessed the associations of contextual determinants representing the social, chemical, and built environment with incident dementia and late-life cognition using proportional hazards regression and generalized estimating equation models, then evaluated their joint effects stratified by genetic risk via Bayesian kernel machine regression. Neighborhood disadvantage was associated with higher dementia risk and poorer cognitive scores after adjusting for genetic risk and other individual-level covariates. Joint analysis of all contextual determinants indicated that more deleterious mixtures of contextual determinants are associated with lower late-life cognition among apolipoprotein E ɛ4 non-carriers with intermediate polygenic risk. Contextual determinants are associated with dementia and late-life cognition after adjusting for age, sex, education, and genetic risk. Show less
Both lipoprotein(a) [Lp(a)] and peripheral artery disease (PAD) are associated with ischaemic events. We sought to assess the association between Lp(a) and major adverse cardiovascular events (MACE) a Show more
Both lipoprotein(a) [Lp(a)] and peripheral artery disease (PAD) are associated with ischaemic events. We sought to assess the association between Lp(a) and major adverse cardiovascular events (MACE) and major lower extremity events (MALE) among patients with baseline PAD. The Mass General Brigham (MGB) Lp(a) registry includes all individuals with Lp(a) measured at two tertiary care centres from 2000 to 2019. Those with PAD were grouped according to Lp(a) percentile: 1st-25th [Q1, Lp(a) ≤ 14 nmol/L], 26th-50th (Q2, 14-<42 nmol/L), 51st-75th (Q3, 42-<132 nmol/L), and 76th-100th (Q4, 132-855 nmol/L). Outcomes were MACE [composite of cardiovascular (CV) death, myocardial infarction, or coronary revascularization] and MALE (composite of peripheral revascularization, acute limb ischaemia, or major lower extremity amputation). Cox proportional hazard modelling was used to assess the association between Lp(a) and the outcomes of interest after adjusting for traditional risk factors. Among 3757 individuals with PAD [39% female, median age 68 (IQR: 58-77)], individuals with Lp(a) levels in the third and fourth quartiles had a 24 and 30% increased hazard of MACE, respectively [adj. hazard ratio (HR): 1.24, P = 0.005; adj. HR: 1.30, P = 0.001] when compared with those in the first quartile. Individuals in the fourth quartile had a 19% greater hazard of MALE (adj. HR: 1.19, P = 0.043). Elevated Lp(a) in patients with PAD was associated with an increased risk of both MACE and MALE. Accordingly, measurement of Lp(a) may convey important prognostic value and allow for further risk stratification within this high-risk population. Show less