Do mobility,cognitive functioning,and depressive symptoms mediate the association between social activity and mortality risk among older men and women?

Social activity and health correlate in old age, but less is known about what explains this association. The aim of this study was to investigate whether mobility, cognitive functioning, and depressive symptoms mediate the association between social activity and mortality risk, or whether they alternatively should be considered as prerequisites for social activity in older Finnish men and women. In 1988, 406 men and 775 women aged 65–84 years took part in face-to-face interviews about their health, socioeconomic status, and social activities. Confirmatory factor analyses were used to form latent variables describing collective and productive social activity. Latent variable models were used to investigate the possible pathways among social activity, mobility, cognitive functioning, depressive symptoms, and mortality risk. In the 21-year follow-up, 89 % of men and 81 % of women had died. Collective and productive social activity correlated with a lower risk for mortality among men and women. Part of the association between social activity and mortality was mediated by mobility. Cognitive functioning and depressive symptoms were not mediators in the association. Instead, good cognitive functioning and having less depressive symptoms were prerequisites for participating in collective social activity among men and women. Among men, good cognitive functioning, and among women, good cognitive functioning and having less depressive symptoms were prerequisites for productive social activity. The health-enhancing influences of social activity may be partly explained by better mobility among persons who are socially active. Moreover, social activity may maintain mobility and thus decreases mortality risk, as many social activities also include physical activity. Better cognitive functioning and having less depressive symptoms should be considered as prerequisites for participating in social activities.     

Frontal EEG asymmetry as predictor of physiological responses to aversive memories

Evidence suggests that asymmetry in frontal electrical activity predicts responses to aversive experiences, such that higher left‐sided activity might dampen responses to trauma reminders. We measured frontal asymmetry at rest and during viewing of a trauma film, and assessed startle responses to film‐reminder images. To explore potential moderators, we compared two films (Study 1; N = 64) and modulated reappraisal (Study 2; N = 72). As expected, left frontal activation during film viewing predicted dampened responses in individuals who viewed a staged road accident. However, this effect tended to be reversed when a genocide documentary was used. In Study 2, all participants viewed the genocide film. Left frontal activity at rest again predicted higher startle responses, while reappraisal did not moderate the effects. Thus, the type of trauma film plays a crucial role in the effects of frontal asymmetry, which warrants further critical investigation.     

Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults

Aims/hypothesis

We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men.

Methods

We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17–18 years in middle-aged men.

Results

We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r?=?0.84–0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score.

Conclusions

The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.     

Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice

Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report that hypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP knockdown mice (Prep^gt/gt) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulin secretion compared with wild-type controls. Consistent with this, central infusion of a specific PREP inhibitor, {"type":"entrez-protein","attrs":{"text":"S17092","term_id":"94591","term_text":"pir||S17092"}}S17092, impaired glucose tolerance and decreased insulin levels in wild-type mice. Arguing further for a central mode of action of PREP, isolated pancreatic islets showed no difference in glucose-induced insulin release between Prep^gt/gt and wild-type mice. Furthermore, hyperinsulinemic euglycemic clamp studies showed no difference between Prep^gt/gt and wild-type control mice. Central PREP regulation of insulin and glucagon secretion appears to be mediated by the autonomic nervous system because Prep^gt/gt mice have elevated sympathetic outflow and norepinephrine levels in the pancreas, and propranolol treatment reversed glucose intolerance in these mice. Finally, re-expression of PREP by bilateral VMH injection of adeno-associated virus–PREP reversed the glucose-intolerant phenotype of the Prep^gt/gt mice. Taken together, our results unmask a previously unknown player in central regulation of glucose metabolism and pancreatic function.Prolyl endopeptidase (PREP; EC 3.4.21.26) is a highly conserved enzyme (1). In humans and rodents it is highly expressed in the brain (2), including the cortex, striatum, hypothalamus, hippocampus, and amygdala (3–6). The physiological role of PREP remains elusive (7). Many studies have focused on the putative effect of PREP on neuropeptide levels because this enzyme could function to cleave virtually all neuropeptides shorter than 30 amino acids that contain an internal proline residue (8).However, much of our understanding of this enzyme is based on in vitro data. Because PREP’s putative targets regulate a large number of signaling pathways, PREP has the capacity to regulate a variety of cellular tasks.To gain a better understanding of the role of PREP in the hypothalamus, we analyzed the effect of PREP knockdown on hypothalamic mechanisms including glucose and energy metabolism.