High circulating levels of midregional proenkephalin A predict vascular dementia: a population-based prospective study.

Midregional Pro-enkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) have been associated with vascular dementia. However, the longitudinal relationship between these biomarkers and incident dementia has not been fully investigated. In the population-based Malmö Preventive Project, circulating levels of MR-PENK A and NT-PTA were determined in a random sample of 5,323 study participants (mean age: 69 ± 6 years) who were followed-up over a period of 4.6 ± 1.6 years. The study sample included 369 patients (7%) who were diagnosed in the same period with dementia. We analyzed relationship of MR-PENK A and NT-PTA with the risk of developing dementia by using multivariable-adjusted Cox regression models adjusted for traditional risk factors. Increased plasma levels of MR-PENK A were associated with higher risk of incident vascular dementia whereas no associations were found with all-cause or Alzheimer dementia. The risk of vascular dementia was mainly conferred by the highest quartile of MR-PENK as compared with lower quartiles. Elevated levels of NT-PTA yielded significant association with all-cause dementia or dementia subtypes. Elevated plasma concentration of MR-PENK A independently predicts vascular dementia in the general population. MR-PENK A may be used as an additional tool for identifying vascular subtype in ambiguous dementia cases.

Beta-blocker therapy and risk of vascular dementia: A population-based prospective study.

There are a few studies that report cognitive impairment as a complication of treatment with beta- blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimer's and mixed dementia in the prospective population-based Malmö Preventive Project. We included 18,063 individuals (mean age 68.2, males 63.4%) followed up for 84,506 person-years. Dementia cases were retrieved from the Swedish National Patient Register and validated by review of medical records and neuroimaging data. We performed propensity score matching analysis, resulting in 3720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazards regression. Overall, 122 study participants (1.6%) were diagnosed with dementia during the follow-up. Beta-blocker therapy was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95%CI 1.01-3.78; p = .048). Conversely, treatment with beta-blockers was not associated with increased risk of all-cause, Alzheimer's and mixed dementia (HR:1.15; 95%CI 0.80-1.66; p = .44; HR:0.85; 95%CI 0.48-1.54; P = .59 and HR:1.35; 95%CI 0.56-3.27; p = .50, respectively). We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta- blockers and increased risk of vascular dementia.

Global transport of perfluoroalkyl acids via sea spray aerosol.

Perfluoroalkyl acids (PFAAs) are persistent organic pollutants found throughout the world's oceans. Previous research suggests that long-range atmospheric transport of these substances may be substantial. However, it remains unclear what the main sources of PFAAs to the atmosphere are. We have used a laboratory sea spray chamber to study water-to-air transfer of 11 PFAAs via sea spray aerosol (SSA). We observed significant enrichment of all PFAAs relative to sodium in the SSA generated. The highest enrichment was observed in aerosols with aerodynamic diameter < 1.6 µm, which had aerosol PFAA concentrations up to ∼62 000 times higher than the PFAA water concentrations in the chamber. In surface microlayer samples collected from the sea spray chamber, the enrichment of the substances investigated was orders of magnitude smaller than the enrichment observed in the aerosols. In experiments with mixtures of structural isomers, a lower contribution of branched PFAA isomers was observed in the surface microlayer compared to the bulk water. However, no clear trend was observed in the comparison of structural isomers in SSA and bulk water. Using the measured enrichment factors of perfluorooctanoic acid and perfluorooctane sulfonic acid versus sodium we have estimated global annual emissions of these substances to the atmosphere via SSA as well as their global annual deposition to land areas. Our experiments suggest that SSA may currently be an important source of these substances to the atmosphere and, over certain areas, to terrestrial environments.

Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population-based prospective study.

BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults. METHODS: A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6 ± 1.3 years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis. RESULTS: Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P = 0.002, and 1.52; 1.21-1.89; P < 0.001, respectively). Risk of all-cause dementia increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145-1681 pmol L-1 vs. Q1, 22-77 pmol L-1 : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmol L-1 (Q3-Q4, 68-432 pmol L-1 vs. Q1-Q2,4-68 pmol L-1 ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors. CONCLUSIONS: Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia.

Associations of central and brachial blood pressure with cognitive function: a population-based study.

Previous observational studies on the association between brachial blood pressure (BP) and cognition have reported conflicting results. Central BP has been hypothesized to be more strongly related to cognition than brachial BP. The aim of this study was to assess the association between brachial as well as central BP and cognitive function, both cross-sectionally and with brachial BP measured 17 years before cognitive testing. The study population comprised 2548 individuals aged 61-85 years at follow-up (61.4% women). The cognitive tests administered were A Quick Test of cognitive speed and the Mini Mental State Examination. In fully adjusted linear regressions, small but significant cross-sectional associations were found between higher BP (systolic, diastolic and pulse pressure) and worse results on both of the cognitive tests (P-values <0.05). No significant prospective associations were found. Central BP did not show a stronger association than brachial BP did. After stratification, significant results were mainly found in the group taking BP-lowering drugs at follow-up. In summary, these findings add to existing evidence on the relationship between BP and cognition, but they do not support a superior role of central compared with brachial BP in the elderly.