Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Context: To study the prevalence and age dependency of senile plaques (SP) and neurofibrillary tangles (NFT), the brain changes characteristic of Alzheimer disease (AD), and their association with apolipoprotein E (APOE) genotypes in a community-dwelling normal population.', 'This neuropathological study used both silver staining and A beta immunohistochemistry in brain tissue microarrays, including SP coverage and NFT counts from frontal cortex and hippocampus, and APOE genotyping, and was performed on a consecutive prospective series of 603 subjects (aged between 0 and 97 years) of an unselected population living outside of institutions. Cases were subjected to autopsy following sudden or unexpected out-of-hospital death, covering 22.1% of the mortality of Tampere, Finland and its surroundings. None died of AD, although 22 (3.7%) were demented and 10 (1.7%) had memory problems.', 'Of the series, 30.8% had SP, and 42.1% had NFT; these occurred more commonly among females and showed a strong relationship with age. Both changes had already appeared at around 30 years of age, reaching an occurrence of almost 100% in the oldest. SP were more frequent in APOE epsilon 4-carriers compared with noncarriers in every age group except the oldest (>90 years). The difference was most evident during the ages 50 to 59 years, where 40.7% of epsilon 4-carriers had SP, compared with 8.2% in noncarriers (odds ratio, 8.39; 95% confidence interval, 2.55-27.62). The difference in NFT prevalence between APOE genotypes was not statistically significant in any age group.
Answer: The brain changes associated with AD may already begin developing early in middle age, especially among APOE epsilon 4 carriers.
Does apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begin in middle age?

Context: To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA).', "We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with 1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models.", 'Of 113677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged 50years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively.
Answer: Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.
Are longer durations of antitumour necrosis factor treatment associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis?

Context: Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2.', 'Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages.
Answer: Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis.
Does lipoicmethylenedioxyphenol reduce Experimental Atherosclerosis through Activation of Nrf2 Signaling?