Cholesterol in midlife increases the risk of Alzheimer's disease during an up to 43-year follow-up

PurposeVascular risk factors in midlife may play a role in the development of cognitive decline, dementia and Alzheimer’ disease (AD). The role of serum total cholesterol has yielded inconsistent results in diverse cohorts.ObjectiveTo analyze the relationship between the midlife cholesterol level and AD in late life in a homogenous cohort of Caucasian men.MethodsThe Helsinki Businessmen Study is a cohort of male business executives who have been followed-up since 1964. Midlife cholesterol level was available in 3293 men, of whom 205 developed a register-verified AD. Cognitively intact men in 2007 (n = 844) served as controls, and logistic regression adjusted for age and cardiovascular risk factors was used to investigate the association between cholesterol and AD.ResultsAt baseline, the men with subsequent AD diagnosis had 0.4 mmol/L higher total cholesterol level than controls (6.7 vs 6.3 mmol/L). In adjusted analyses 1 mmol/L rise in total cholesterol was associated with a 22% increased risk of AD (odds ratio [OR] 1.22, 95% confidence interval 1.06 to 1.40, P = 0.005). Risk of AD (OR with 95% CI) also increased in a stepwise manner from the lowest to highest quartile of midlife cholesterol from 1.0 (referent) to 1.6 (1.01–2.6), 1.9 (1.2–3.0), and 2.0 (1.2–3.3), respectively.ConclusionIn this longitudinal study with up to 43 years of follow-up, higher serum total cholesterol in early midlife was clearly associated with a higher risk of AD in late life.     

Association of Epicardial Adipose Tissue With Progression of Coronary Artery Calcification Is More Pronounced in the Early Phase of Atherosclerosis: Results From the Heinz Nixdorf Recall Study

ObjectivesThis study sought to determine whether epicardial adipose tissue (EAT) volume predicts the progression of coronary artery calcification (CAC) score in the general population.BackgroundEAT predicts coronary events and is suggested to influence the development of atherosclerosis.MethodsWe included 3,367 subjects (mean age 59 ± 8 years; 47% male) from the population-based Heinz Nixdorf Recall study without known coronary artery disease at baseline. CAC was quantified from noncontrast cardiac electron beam computed tomography at baseline and after 5 years. EAT was defined as fat volume inside the pericardial sac and was quantified from axial computed tomography images. Association of EAT volume with CAC progression (log[CAC(follow-up) + 1] − log[CAC(baseline) + 1]) was depicted as percent progression of CAC + 1 per SD of EAT.ResultsSubjects with progression of CAC above the median had higher EAT volume than subjects with less CAC change (101.1 ± 47.1 ml vs. 84.4 ± 43.4 ml; p < 0.0001). In regression analysis, 6.3% (95% confidence interval [CI]: 2.3% to 10.4%; p = 0.0019) of progression of CAC + 1 was attributable to 1 SD of EAT, which persisted after adjustment for risk factors (6.1% [95% CI: 1.2% to 11.2%]; p = 0.014). For subjects with a CAC score of >0 to ≤100, progression of CAC + 1 by 20% (95% CI: 11% to 31%; p < 0.0001) was attributable to 1 SD of EAT. Effect sizes decreased with CAC at baseline, with no relevant link for subjects with a CAC score ≥400 (0.2% [95% CI: −3.5% to 4.2%]; p = 0.9). Likewise, subjects age <55 years at baseline showed the strongest association of EAT with CAC progression (20.6% [95% CI: 9.7% to 32.5%]; p < 0.0001). Interestingly, the effect of EAT on CAC progression was more pronounced in subjects with low body mass index (BMI), and decreased with degree of adiposity (BMI ≤25 kg/m²: 19.8% [95% CI: 9.2% to 31.4%]; p = 0.0001, BMI >40 kg/m²: 0.8% [95% CI: −26.7% to 38.9%]; p = 0.96).ConclusionsEAT is associated with the progression of CAC, especially in young subjects and subjects with low CAC score, suggesting that EAT may promote early atherosclerosis development.