Nonagenarian Siblings and Their Offspring Display Lower Risk of Mortality and Morbidity than Sporadic Nonagenarians: The Leiden Longevity Study

OBJECTIVES: To compare the risk of mortality of nonagenarian siblings with that of sporadic nonagenarians (not selected on having a nonagenarian sibling) and to compare the prevalence of morbidity in their offspring with that of the offsprings' partners.
DESIGN: Longitudinal (mortality risk) and cross-sectional (disease prevalence).
SETTING: Nationwide sample.
PARTICIPANTS: The Leiden Longevity Study consists of 991 nonagenarian siblings derived from 420 Caucasian families, 1,365 of their offspring, and 621 of the offsprings' partners. In the Leiden 85-plus Study, 599 subjects aged 85 were included, of whom 275 attained the age of 90 (sporadic nonagenarians).
MEASUREMENTS: All nonagenarian siblings and sporadic nonagenarians were followed for mortality (with a mean±standard deviation follow-up time of 2.7±1.4 years and 3.0±1.5 years, respectively). Information on medical history and medication use was collected for offspring and their partners.
RESULTS: Nonagenarian siblings had a 41% lower risk of mortality ( P <.001) than sporadic nonagenarians. The offspring of nonagenarian siblings had a lower prevalence of myocardial infarction (2.4% vs 4.1%, P =.03), hypertension (23.0% vs 27.5%, P =.01), diabetes mellitus (4.4% vs 7.6%, P =.004), and use of cardiovascular medication (23.0% vs 28.9%, P =.003) than their partners.
CONCLUSION: The lower mortality rate of nonagenarian siblings and lower prevalence of morbidity in their middle-aged offspring reinforce the notion that resilience against disease and death have similar underlying biology that is determined by genetic or familial factors.     

Cognitive vulnerability in fear of flying: the role of anxiety sensitivity

Previous research has indicated that more than 50% of air travel passengers experience hypoxia above clinical threshold. This condition produces a number of aversive somatic sensations such as difficulty breathing, elevated heart rate, dizziness, etc. Because these symptoms closely resemble the somatic symptoms of anxiety, it is interesting to look into a possible relationship between hypoxia-related symptoms and fear of flying. More specifically, the aim of this study is to clarify the role of anxiety sensitivity as a cognitive vulnerability marker in this relationship. Anxiety sensitivity is the specific tendency to interpret bodily sensations as threatening or harmful. Our hypothesis is that anxiety sensitivity moderates the relationship between hypoxia-related symptoms and fear of flying. When people with high anxiety sensitivity fly and experience somatic symptoms, they will make threatening interpretations causing fear and as a possible consequence avoidance behaviour leading to flight anxiety. About 160 participants were asked to complete the Flight Anxiety Situations Questionnaire, the Flight Anxiety Modality Questionnaire and the Anxiety Sensitivity Index. Results of a moderator analysis indicated that the relationship between somatic sensations and in-flight anxiety is stronger for people with high anxiety sensitivity than for people with low anxiety sensitivity. So it seems that anxiety sensitivity does indeed function as a moderator between the experience of somatic sensations while flying and in-flight anxiety. Clinical implications are discussed, as well as suggestions for further research.     

[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.     

EEG markers of future cognitive performance in the elderly

This exploratory follow-up study investigated whether EEG parameters can predict future cognitive performance. Forty elderly subjects, ranging from cognitively unimpaired to those with Alzheimer disease underwent EEG registration at baseline and neuropsychological examination at both baseline and follow-up. We assessed relations between EEG measures and future cognitive performance (i.e., global cognition, memory, language, and executive functioning) controlling for age, follow-up time, and baseline cognitive performance. Regression models were constructed to predict performance on the Cambridge Cognitive Examination, a widely used tool within dementia screenings. Baseline EEG measures, i.e., increased theta activity (4-8 Hz) during eyes closed and less alpha reactivity (8-13 Hz) during eyes open and memory activation, indicated lower global cognitive, language (trend significant), and executive performance at follow-up. A regression model combining baseline cognitive and EEG measures provided the best prediction of future Cambridge Cognitive Examination performance (93%). EEG and cognitive measures alone predicted, respectively, 43% and 92% of variance. EEG and cognitive measures combined provided the best prediction of future cognitive performance. Although the "cognition only" model showed similar predictive power, the EEG provided significant additional value. The added value of EEG registration in the diagnostic work-up of dementia should be further assessed in larger samples.     

Nocturnal hyperactivity, increased social novelty preference and delayed extinction of fear responses in post-weaning socially isolated mice

When rodents are reared in isolation from young age onwards, they manifest a number of behavioural alterations in adulthood. Since some of these alterations resemble symptoms of psychiatric disorders, the post-weaning social isolation (ISO) manipulation is often applied to create rodent models of these disorders. In rats, ISO effects have been thoroughly characterised, but in mice they are less well documented. Therefore, we further evaluated behaviour of adult ISO mice with a test battery that focussed on abnormalities relevant to schizophrenia. We found that ISO mice were hyperactive during the dark phase. Also, ISO mice showed alterations in magnitude, habituation and prepulse-inhibition of the acoustic startle reflex, increased anxiety, increased social preference and changes in extinction of fear responses. We did not observe increased sensitivity to locomotor-activating effects of amphetamine. It is concluded that ISO of mice might serve as a useful model to test further hypotheses regarding pathogenesis occurring at specific developmental timeframes.     

Feasibility and construct validity of a novel laparoscopic skills testing and training model

The apprentice–tutor model was useful for training surgeons for many years, but the complexity of surgical technology in the 21st century, especially endoscopic surgery, has exponentially increased the demands for surgical education. Therefore, more and more people now accept that endoscopic surgery, demanding as it requires specific skills, should also be taught outside the operating theatre. Although many systems, including animal models and simulators, have been proposed, an in-house structured and validated method for testing and training laparoscopic skills is missing in gynaecology. We have developed a laparoscopic skills testing and training (LASTT) model and performed two studies evaluating its feasibility and the construct validity of three different exercises (camera navigation, camera navigation and forceps handling, and forceps handling and bi-manual coordination), specifically selected to test and train laparoscopic psychomotor skills (LPS). In the first study, ten experts and 14 novices repeated each exercise between 20 and 30 times. The results demonstrated that the model is useful for testing and training laparoscopic skills. Clear learning curves were observed for both experts and novices, with better scores for the former at the beginning and the end of the study, proving the construct validity of the model. In the second study, 42 experts and 241 novices repeated each exercise three times during skill evaluation workshops organised by the European Academy of Gynaecological Surgery. The results confirmed the construct validity of the model. In conclusion, the LASTT model seems a cost-effective tool for providing an in-house program for continuous training and evaluation of LPS in all surgical disciplines in which laparoscopic procedures are, or might be, performed.