We found previously that the measurement of plasma levels of protein-conjugated acrolein (PC-Acro) together with IL-6 and CRP can be used to identify silent brain infarction (SBI) with high sensitivity and specificity. The aim of this study was to clarify how three biochemical markers are correlated to SBI, carotid atherosclerosis (CA) and white matter hyperintensity (WMH).
The levels of PC-Acro, IL-6 and CRP in plasma were measured by ELISA. SBI and WMH were evaluated by MRI, and CA was evaluated by duplex carotid ultrasonography.
A total of 790 apparently healthy volunteers were classified into 260 control, 214 SBI, 263 CA and 245 WMH subjects, which included 187 subjects with two or three pathologies. When the combined measurements of PC-Acro, IL-6 and CRP were evaluated together with age, using a receiver operating characteristic curve and artificial neural networks, the relative risk value (RRV), an indicator of tissue damage, was in the order SBI with CA (0.90)>SBI (0.80)>CA (0.76)>WMH with CA (0.65)>WMH (0.46)>control (0.14). RRV was also correlated with severity in each group of SBI, CA and WMH.
The RRV supports the idea that the degree of risk to develop a stroke is in the order SBI>CA>WMH.
"Our study extends this evidence by showing (1) that inflammatory markers are cross-sectionally associated with worse physical performance in late midlife and (2) that inflammatory markers explain a significant part of the association between walking speed and mortality, even in the absence of overt cardiovascular disease. Inflammatory markers may reflect subclinical cerebrovascular disease (Rosenberg 2009; Yoshida et al. 2009; Yoshida et al. 2010), which is associated with worse clinical performances (Soumaré et al. 2009) and mortality (Bokura et al. 2006; Ikram et al. 2009). Decreased muscle strength has been linked to inflammation (Degens 2010) and mortality (Landi et al. 2010; Newman et al. 2006) and may represent another possible pathway. "
[Show abstract][Hide abstract] ABSTRACT: Slow walking speed is associated with increased mortality in the elderly, but it is unknown whether a similar association is present in late midlife. Our aim was to examine walking speed in late midlife as a predictor of mortality, as well as factors that may explain this association. Data are drawn from the Whitehall II longitudinal cohort study of British civil servants. The analyses are based on 6,266 participants (29% women; mean age = 61 years, SD = 6) for whom “walking speed at usual pace” was measured over 8 ft (2.44 m) at baseline. Participants were followed for all-cause and cause-specific mortalities during a mean of 6.4 (SD = 0.8) years. During this period, 227 participants died. Participants in the bottom sex-specific third of walking speed (men, <1.26 m/s; women, <1.09 m/s) had an increased risk of death compared to those in the middle and top thirds (age- and sex-adjusted hazard ratio = 1.89, 95% confidence interval (CI) = 1.45–2.46), with no evidence of effect modification by age or sex (interactions, P ≥ 0.40). The association between walking speed and mortality was partially explained by baseline inflammatory markers (percentage reduction of the association 22.8%), height and body mass index (16.6%), chronic diseases (14.0%), and health behaviors (13.4%). Together these and other baseline factors (socioeconomic status, cardiovascular risk factors, cognitive function) explained 48.5% of the association (adjusted hazard ratio = 1.39, 95% CI = 1.04–1.84). In conclusion, walking speed measured in late midlife seems to be an important marker of mortality risk; multiple factors, in particular inflammatory markers, partially explain this association.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-012-9387-9) contains supplementary material, which is available to authorized users.
Age 06/2013; 35(3):943-52. DOI:10.1007/s11357-012-9387-9 · 3.45 Impact Factor
"Yoshida et al . , 2010 ) . SBI ( affected areas ≥3 mm diameter ) and WMH were estimated by MRI , CA by carotid ultrasound examination , and CRP and IL - 6 in plasma by ELISA . PC - Acro , IL - 6 and CRP were significantly higher in SBI and CA compared with the control . PC - Acro was most strongly correlated with CA , and IL - 6 and CRP with SBI ( Yoshida et al . , 2010 ) . Thus , CA is likely the primary risk factor related to stroke in this analysis ."
[Show abstract][Hide abstract] ABSTRACT: Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.
Biomolecules and Therapeutics 01/2013; 21(1):1-9. DOI:10.4062/biomolther.2012.097 · 1.73 Impact Factor
"They are also frequently seen in those who have suffered severe hypoxia and traumatic brain injury . Observational studies have also shown associations of higher prevalence of infarcts, white matter hyperintensities, and atrophy with inflammatory markers in older adults in the absence of overt clinical disease        . "
[Show abstract][Hide abstract] ABSTRACT: Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests that inflammation is a shared mechanism, contributing to both cognitive decline and abnormalities in brain structure and metabolism. Thus, inflammation may provide a target for intervention. Specifically, circulating inflammatory markers have been associated with declines in cognitive function and worsening of brain structural and metabolic characteristics. Additionally, it has been proposed that older brains are characterized by a sensitization to neuroinflammatory responses, even in the absence of overt disease. This increased propensity to central inflammation may contribute to poor brain health and premature brain aging. Still unknown is whether and how peripheral inflammatory factors directly contribute to decline of brain health. Human research is limited by the challenges of directly measuring neuroinflammation in vivo. This review assesses the role that inflammation may play in the brain changes that often accompany aging, focusing on relationships between peripheral inflammatory markers and brain health among well-functioning, community-dwelling adults seventy years and older. We propose that monitoring and maintaining lower levels of systemic and central inflammation among older adults could help preserve brain health and support successful aging. Hence, we also identify plausible ways and novel experimental study designs of maintaining brain health late in age through interventions that target the immune system.
Aging and Disease 02/2012; 3(1):16-33. · 3.07 Impact Factor
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