Multidomain intervention for the prevention of cognitive decline after stroke - a pooled patient-level data analysis.

BACKGROUND AND PURPOSE: The aim of this pooled patient-level data analysis was to test if multidomain interventions, addressing several modifiable vascular risk factors simultaneously, are more effective than usual post-stroke care for the prevention of cognitive decline after stroke. METHODS: This pooled patient-level data analysis included two randomized controlled trials using a multidomain approach to target vascular risk factors in stroke patients and cognition as primary outcome. Changes from baseline to 12 months in the trail making test (TMT)-A, TMT-B and 10-words test were analysed using stepwise backward linear mixed models with study as random factor. Two analyses were based on the intention-to-treat (ITT) principle using different imputation approaches and one was based on complete cases. RESULTS: Data from 322 patients (157 assigned to multidomain intervention and 165 to standard care) were analysed. Differences between randomization groups for TMT-A scores were found in one ITT model (P = 0.014) and approached significance in the second ITT model (P = 0.087) and for complete cases (P = 0.091). No significant intervention effects were found for any of the other cognitive variables. CONCLUSION: We found indications that multidomain interventions compared with standard care can improve the scores in TMT-A at 1 year after stroke but not those for TMT-B or the 10-words test. These results have to be interpreted with caution due to the small number of patients.

Post-stroke cognitive decline: an update and perspectives for clinical research.

The close relationship between stroke and dementia is an important health issue. Ischaemic stroke can facilitate the onset of vascular dementia as well as aggravate pre-existing cognitive decline. The onset of cognitive decline may become manifest immediately following the onset of ischaemic stroke, but often there is a delay in the development of cognitive decline after a stroke. This delay can be seen as a therapeutic time window allowing interventions to be applied to preserve cognition following stroke. Both neurodegenerative and vascular mechanisms are activated and probably result in overlapping processes within the neurovascular unit. This review focuses on the incidence and prevalence of cognitive decline following stroke, predisposing stroke aetiologies, pre-stroke decline, imaging factors and biomarkers. Outcomes are discussed in relation to timing of assessment and neuropsychological tests used for evaluation of cognitive decline in ischaemic stroke patients. Including such tests in routine evaluations of stroke patients after some weeks or months is recommended. Finally, an outlook on ongoing and planned intervention trials is added and some recommendations for future research are proposed.

Diabetes and thrombolysis for acute stroke: a clear benefit for diabetics.

BACKGROUND AND PURPOSE: Diabetes is a predictor for poor outcome after thrombolysis in stroke patients, and early post-stroke glycaemia is associated with higher rates of post-thrombolytic symptomatic intracerebral haemorrhages (SICHs). Diabetic stroke patients may nevertheless profit from thrombolysis. Here, we compared outcome data of matched thrombolysed and non-thrombolysed diabetic and non-diabetic stroke patients from a national database. METHODS: The outcomes of 1079 matched quadruples, each consisting of a thrombolysed diabetic, a non-thrombolysed diabetic, a thrombolysed non-diabetic and a non-thrombolysed non-diabetic case (a total of 4316 cases), enrolled in the Austrian Stroke Unit Registry (2004-2013), were compared. Patients were matched according to sex, age, stroke severity, pre-stroke disability and prior stroke. RESULTS: A regression model with improvement as depending variable found no effect of diabetes (P = 0.158) or the interaction diabetes × thrombolysis (P = 0.507), whereas the effect of thrombolysis itself was highly significant (P < 0.001). Functional outcome (modified Rankin Scale) was significantly better in thrombolysed than in non-thrombolysed diabetic patients at discharge from the stroke-unit (P < 0.001) and 3 months later (P = 0.006). No significant differences were found in the number of SICHs after thrombolytic treatment between diabetic (4.9%) and non-diabetic strokes (3.5%). Both groups had a higher risk of SICH compared with the non-thrombolysed groups (diabetics 2.6%, non-diabetics 2.5%). Due to lack of documentation, the effect of admission blood glucose on SICH was not investigated. CONCLUSIONS: Data from this nationwide survey show that diabetic stroke patients receive a substantial benefit from thrombolysis, and therefore diabetic strokes should not be excluded from thrombolytic treatment.

Prevention of post-stroke cognitive decline: a review focusing on lifestyle interventions.

BACKGROUND AND PURPOSE: Despite a high prevalence of post-stroke cognitive impairment, therapeutic possibilities are still limited. Stroke and dementia share the same cluster of modifiable risk factors. Thus, lifestyle interventions and strict adherence to medication may not only decrease the risk of recurrent stroke but also the risk of post-stroke cognitive decline. METHODS: We performed a systematic literature search for randomized clinical trials (RCTs) targeting modifiable risk factors for the prevention of cognitive decline following stroke. RESULTS: We identified 25 non-pharmacological interventions and eight multiple risk factor interventions in stroke patients using cognition as outcome measure. None of the published trials investigated interventions aimed at the prevention of post-stroke cognitive decline. However, a number of ongoing trials aim at risk factor reduction and include measures on cognition. CONCLUSION: Evidence for risk factor modification for the prevention of cognitive decline after stroke is scarce and comes mainly from observational studies. There is a need for more RCTs targeting the prevention of post-stroke dementia using lifestyle interventions and a multiple risk factor approach.

Is reduced female survival after mating a by-product of male-male competition in the dung fly Sepsis cynipsea?

BACKGROUND: In a number of species males damage females during copulation, but the reasons for this remain unclear. It may be that males are trying to manipulate female mating behaviour or their life histories. Alternatively, damage may be a side-effect of male-male competition. In the black scavenger or dung fly Sepsis cynipsea (Diptera: Sepsidae) mating reduces female survival, apparently because males wound females during copulation. However, this damage does not seem to relate to attempted manipulation of female reproduction by males. Here we tested the hypothesis that harming females during mating is an incidental by-product of characters favoured during pre-copulatory male-male competition. We assessed whether males and their sons vary genetically in their ability to obtain matings and harm females, and whether more successful males were also more damaging. We did this by ranking males' mating success in paired competitions across several females whose longevity under starvation was subsequently measured. RESULTS: As previously reported, our results show mating is costly for female S. cynipsea. However, variance in female longevity was not explained by male identity, family, body size, number of previous copulations, or copulation duration. Nevertheless, there was a positive correlation between the harm fathers inflicted on their mates (affecting female longevity) and the harm sons inflicted on theirs. Additionally, family identity significantly influenced male copulation success. CONCLUSION: Our results indicate a heritable component of some yet unspecified male trait(s) that influence harm and mating success. However, there was no relationship between copulation success of fathers or sons and the mean longevity of their mates. We therefore found no support for harm being a side effect of traits favoured in pre-copulatory male-male competition.

Correlated responses to artificial body size selection in growth, development, phenotypic plasticity and juvenile viability in yellow dung flies.

Most life history traits are positively influenced by body size, whereas disadvantages of large body size are poorly documented. To investigate presumed intrinsic costs of large size in the yellow dung fly (Scathophaga stercoraria; Diptera: Scathophagidae), we established two replicates each of three body size laboratory selection lines (small, control and large; selection on males only), and subjected flies of the resulting extended body size range to various abiotic stresses. Response to selection was symmetrical in the small and large lines (realized h(2) = 0.16-0.18). After 24 generations of selection body size had changed by roughly 10%. Female size showed a correlated response to selection on male size, whereas sexual size dimorphism did not change. Development time also showed a correlated response as, similar to food limited flies, small line flies emerged earlier at smaller body size. At the lowest larval food limit possible, flies of all lines emerged at the same small body size after roughly the same development time; so overall phenotypic plasticity in body size and development time strongly increased following selection. Juvenile mortality increased markedly when food was extremely limited, large line flies showing highest mortality. Winter frost disproportionately killed large (line) flies because of their longer development times. Mortality at high temperatures was high but size-selective effects were inconsistent. In all environments the larger males suffered more. Initial growth rate was higher for males and at unlimited food. Small line individuals of both sexes grew slowest at unlimited larval food but fastest at limited larval food, suggesting a physiological cost of fast growth. Overall, extension of the natural body size range by artificial selection revealed some otherwise cryptic intrinsic juvenile viability costs of large size, mediated by longer development or faster growth, but only in stressful environments.

Sexual selection on morphological and physiological traits and fluctuating asymmetry in the black scavenger fly Sepsis cynipsea.

Previous univariate studies of the fly Sepsis cynipsea (Diptera: Sepsidae) have demonstrated spatiotemporally variable and consequently overall weak sexual selection favouring large male size, which is nevertheless stronger on average than fecundity selection favouring larger females. To identify specific target(s) of selection on body size and additional traits possibly affecting mating success, two multivariate field studies of sexual selection were conducted. In one study using seasonal replicates from three populations, we assessed 15 morphological traits. No clear targets of sexual selection on male size could be detected, perhaps because spatiotemporal variation in selection was again strong. In particular, there was no (current) selection on male abdomen length or fore coxa length, the only traits for which S. cynipsea males are not smaller than females. Interestingly, copulating males had a consistently shorter fore femur base, a secondary sexual trait, and a wider clasper (hypopygium) gap, an external genital trait. In a second study using daily and seasonal replicates from one population, we included physiological measures of energy reserves (lipids, glucose, glycogen), in addition to hind tibia length and fluctuating asymmetry (FA) of all pairs of legs. This study again confirmed the mating advantage of large males, and additionally suggests independent positive influences of lipids (the long-term energy stores), with effects of glucose and glycogen (the short-term energy stores) tending to be negative. FA of paired traits was not associated with male mating success. Our study suggests that inclusion of physiological measures and genital traits in phenomenological studies of selection, which is rare, would be fruitful in other species.

How do cuckoos find their hosts? The role of habitat imprinting.

Although a number of hypotheses have been proposed for how European cuckoo, Cuculus canorus, females may find hosts belonging to their foster parents' species, clear evidence is lacking for any of them. Here, we propose 'habitat imprinting' as an alternative mechanism for host selection and provide evidence that cuckoos are able to remember acquired information about a familiar habitat. We hand-reared seven cuckoos in one of five different artificial habitats and tested them as adults in habitat choice experiments. In each test habitat, a pair of zebra finches, Taeniopygia guttuta, was presented as 'hosts'. We tested cuckoos of both sexes because the genotype of males may influence egg colour, and therefore egg mimicry; alternatively, habitat imprinting may be a general mechanism existing in both sexes but affecting egg mimicry only via females. Test cuckoos spent significantly more time looking at their respective familiar habitats than at other habitats in 1 of 2 test years. How long cuckoos were reared in the artificial habitats correlated positively with how long they spent in this habitat during the choice experiments. Additionally, test cuckoos remained longer with zebra finches that showed more nest-building behaviour but had lower levels of general activity, and they also observed these 'hosts' more frequently. If cuckoos choose to breed in habitats resembling those on which they were imprinted and search randomly for hosts in these habitats, they would increase their probability of parasitizing nests of their foster species. We propose that host specificity would be strengthened, however, if cuckoos use a sequence of several mechanisms, rather than just one, to find their hosts. (c) 1998 The Association for the Study of Animal Behaviour.