The COVID-19 pandemic is imposing a profound negative impact on the health and wellbeing of societies and individuals, worldwide. One concern is the effect of social isolation as a result of social ...distancing on the mental health of vulnerable populations, including older people. Within six weeks of lockdown, we initiated the CHARIOT COVID-19 Rapid Response Study, a bespoke survey of cognitively healthy older people living in London, to investigate the impact of COVID-19 and associated social isolation on mental and physical wellbeing. The sample was drawn from CHARIOT, a register of people over 50 who have consented to be contacted for aging related research. A total of 7,127 men and women (mean age=70.7 SD=7.4) participated in the baseline survey, May-July 2020. Participants were asked about changes to the 14 components of the Hospital Anxiety Depression scale (HADS) after lockdown was introduced in the UK, on 23
March. A total of 12.8% of participants reported feeling worse on the depression components of HADS (7.8% men and 17.3% women) and 12.3% reported feeling worse on the anxiety components (7.8% men and 16.5% women). Fewer participants reported feeling improved (1.5% for depression and 4.9% for anxiety). Women, younger participants, those single/widowed/divorced, reporting poor sleep, feelings of loneliness and who reported living alone were more likely to indicate feeling worse on both the depression and/or anxiety components of the HADS. There was a significant negative association between subjective loneliness and worsened components of both depression (OR 17.24, 95% CI 13.20, 22.50) and anxiety (OR 10.85, 95% CI 8.39, 14.03). Results may inform targeted interventions and help guide policy recommendations in reducing the effects of social isolation related to the pandemic, and beyond, on the mental health of older people.
Making appropriate choices often requires the ability to learn the value of available options from experience. Parkinson's disease is characterized by a loss of dopamine neurons in the substantia ...nigra, neurons hypothesized to play a role in reinforcement learning. Although previous studies have shown that Parkinson's patients are impaired in tasks involving learning from feedback, they have not directly tested the widely held hypothesis that dopamine neuron activity specifically encodes the reward prediction error signal used in reinforcement learning models. To test a key prediction of this hypothesis, we fit choice behavior from a dynamic foraging task with reinforcement learning models and show that treatment with dopaminergic drugs alters choice behavior in a manner consistent with the theory. More specifically, we found that dopaminergic drugs selectively modulate learning from positive outcomes. We observed no effect of dopaminergic drugs on learning from negative outcomes. We also found a novel dopamine-dependent effect on decision making that is not accounted for by reinforcement learning models: perseveration in choice, independent of reward history, increases with Parkinson's disease and decreases with dopamine therapy.
ObjectivesPhysical inactivity is more common in older adults, is associated with social isolation and loneliness and contributes to increased morbidity and mortality. We examined the effect of social ...restrictions to reduce COVID-19 transmission in the UK (lockdown), on physical activity (PA) levels of older adults and the social predictors of any change.DesignBaseline analysis of a survey-based prospective cohort study.SettingAdults enrolled in the Cognitive Health in Ageing Register for Investigational and Observational Trials cohort from general practitioner practices in North West London were invited to participate from April to July 2020.Participants6219 cognitively healthy adults aged 50–92 years completed the survey.Main outcome measuresSelf-reported PA before and after the introduction of lockdown, as measured by metabolic equivalent of task (MET) minutes. Associations of PA with demographic, lifestyle and social factors, mood and frailty.ResultsMean PA was significantly lower following the introduction of lockdown from 3519 to 3185 MET min/week (p<0.001). After adjustment for confounders and prelockdown PA, lower levels of PA after the introduction of lockdown were found in those who were over 85 years old (640 (95% CI 246 to 1034) MET min/week less); were divorced or single (240 (95% CI 120 to 360) MET min/week less); living alone (277 (95% CI 152 to 402) MET min/week less); reported feeling lonely often (306 (95% CI 60 to 552) MET min/week less); and showed symptoms of depression (1007 (95% CI 612 to 1401) MET min/week less) compared with those aged 50–64 years, married, cohabiting and not reporting loneliness or depression, respectively.Conclusions and implicationsMarkers of social isolation, loneliness and depression were associated with lower PA following the introduction of lockdown in the UK. Targeted interventions to increase PA in these groups should be considered.
Background
Practice effects (PE), after repeated cognitive measurements, may mask cognitive decline and represent a challenge in clinical and research settings. However, an attenuated practice effect ...may indicate the presence of brain pathologies. This study aimed to evaluate practice effects on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale, and their associations with brain amyloid status and other factors in a cohort of cognitively unimpaired older adults enrolled in the CHARIOT-PRO SubStudy.
Materials and Methods
502 cognitively unimpaired participants aged 60-85 years were assessed with RBANS in both screening and baseline clinic visits using alternate versions (median time gap of 3.5 months). We tested PE based on differences between test and retest scores in total scale and domain-specific indices. Multiple linear regressions were used to examine factors influencing PE, after adjusting for age, sex, education level,
APOE
-ε4 carriage and initial RBANS score. The latter and PE were also evaluated as predictors for amyloid positivity status based on defined thresholds, using logistic regression.
Results
Participants’ total scale, immediate memory and delayed memory indices were significantly higher in the second test than in the initial test (Cohen’s d
z
= 0.48, 0.70 and 0.35,
P
< 0.001). On the immediate memory index, the PE was significantly lower in the amyloid positive group than the amyloid negative group (
P
= 0.022). Older participants (≥70 years), women, non-
APOE
-ε4 carriers, and those with worse initial RBANS test performance had larger PE. No associations were found between brain MRI parameters and PE. In addition, attenuated practice effects in immediate or delayed memory index were independent predictors for amyloid positivity (
P
< 0.05).
Conclusion
Significant practice effects on RBANS total scale and memory indices were identified in cognitively unimpaired older adults. The association with amyloid status suggests that practice effects are not simply a source of measurement error but may be informative with regard to underlying neuropathology.
Several studies have assessed the impact of COVID-19-related lockdowns on sleep quality across global populations. However, no study to date has specifically assessed
populations, particularly those ...at highest risk of complications from coronavirus infection deemed "clinically-extremely-vulnerable-(COVID-19CEV)" (as defined by Public Health England).
In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio-demographic factors. We examined associations between these variables and sleep quality; and explored interactions of COVID-19CEV status with significant predictors of poor sleep, to identify potential moderating factors.
Thirty-seven percent of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep.
Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a "clinically-extremely-vulnerable" population and the sex differences identified within this group. Male and female older adults deemed COVID-19CEV may benefit from targeted mental health and dietary interventions, respectively. This work extends the available evidence on the notable impact of lack of social interactions during the COVID-19 pandemic on sleep, and provides recommendations toward areas for future work, including research into vulnerability factors impacting sleep disruption and COVID-19-related complications. Study results may inform tailored interventions targeted at modifiable risk factors to promote optimal sleep; additionally, providing empirical data to support health policy development in this area.
Building from the bottom up Krull, Catherine E; Krumlauf, Robb
Nature cell biology,
06/2001, Letnik:
3, Številka:
6
Journal Article
Recenzirano
Time-lapse analyses of normal cellular behaviours and signalling by fibroblast growth factor (FGF) provide new insights into the cell motions and molecules that form the posterior nervous system.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
We have investigated the pattern and regulation of Hoxa3 expression in the hindbrain and associated neural crest cells in the chick embryo, using whole mount in situ hybridization in ...conjunction with DiI labeling of neural crest cells and microsurgical manipulations. Hoxa3 is expressed in the neural plate and later in the neural tube with a rostral border of expression corresponding to the boundary between rhombomeres (r) 4 and 5. Initial expression is diffuse and becomes sharp after boundary formation. Hoxa3 exhibits uniform expression within r5 after formation of rhombomeric borders. Cell marking experiments reveal that neural crest cells migrating caudally, but not rostrally, from r5 and caudally from r6 express Hoxa3 in the normal embryo. Results from transposition experiments demonstrate that expression of Hoxa3 in r5 neural crest cells is not strictly cell-autonomous. When r5 is transposed with r4 by rostrocaudal rotation of the rhombomeres, Hoxa3 is expressed in cells migrating lateral to transposed r5 and for a short time, in condensing ganglia, but not by neural crest within the second branchial arch. Since DiI-labeled cells from transposed r5 are present in the second arch, Hoxa3-expressing neural crest cells from r5 appear to down-regulate their Hoxa3 expression in their new environment. In contrast, when r6 is transposed to the position of r4 after boundary formation, Hoxa3 is maintained in both migrating neural crest cells and those positioned within the second branchial arch and associated ganglia. These results suggest that Hoxa3 expression is cellautonomous in r6 and its associated neural crest. Our results suggest that neural crest cells expressing the same Hox gene are not equivalent; they respond differently to environmental signals and exhibit distinct degrees of cell autonomy depending upon their rhombomere of origin.
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles ...outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations.
Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required.
Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals.
Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.
Both grip strength and gait speed can be used as markers of muscle function, however, no previous study has examined them in the same population with respect to risk of falls.
In this prospective ...cohort study, utilising data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and ASPREE-Fracture substudy, we analysed the association of grip strength and gait speed and serious falls in healthy older adults. Grip strength was measured using a handheld dynamometer and gait speed from 3-metre timed walks. Serious falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations with falls.
Over an average of 4.0±1.3 years, amongst 16,445 participants, 1,533 had at least one serious fall. After adjustment for age, sex, physical activity, body mass index, Short Form 12 (state of health), chronic kidney disease, polypharmacy and aspirin, each standard deviation (SD) lower grip strength was associated with 27% (HR 1.27, 95% CI 1.17-1.38) higher risk of falls. The results remained the same for males and females. There was a dose-response relationship in the association between grip strength and falls risk. The higher risk of falls was observed in males in all body mass index (BMI) categories, but only in obese females. The association between gait speed and falls risk was weaker than the association between grip strength and falls risk.
All males and only obese females with low grip strength appear to be at the greatest risk of serious falls. These findings may assist in early identification of falls.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Polygenic risk scores (PRSs), which often aggregate results from genome-wide association studies, can bridge the gap between initial discovery efforts and clinical applications for the estimation of ...disease risk using genetics. However, there is notable heterogeneity in the application and reporting of these risk scores, which hinders the translation of PRSs into clinical care. Here, in a collaboration between the Clinical Genome Resource (ClinGen) Complex Disease Working Group and the Polygenic Score (PGS) Catalog, we present the Polygenic Risk Score Reporting Standards (PRS-RS), in which we update the Genetic Risk Prediction Studies (GRIPS) Statement to reflect the present state of the field. Drawing on the input of experts in epidemiology, statistics, disease-specific applications, implementation and policy, this comprehensive reporting framework defines the minimal information that is needed to interpret and evaluate PRSs, especially with respect to downstream clinical applications. Items span detailed descriptions of study populations, statistical methods for the development and validation of PRSs and considerations for the potential limitations of these scores. In addition, we emphasize the need for data availability and transparency, and we encourage researchers to deposit and share PRSs through the PGS Catalog to facilitate reproducibility and comparative benchmarking. By providing these criteria in a structured format that builds on existing standards and ontologies, the use of this framework in publishing PRSs will facilitate translation into clinical care and progress towards defining best practice.
PDF
