New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

A Dynamical Systems View of Psychiatric Disorders - Theory:A Review

Importance: Psychiatric disorders may come and go with symptoms changing over a lifetime. This suggests the need for a paradigm shift in diagnosis and treatment. Here we present a fresh look inspired by dynamical systems theory. This theory is used widely to explain tipping points, cycles, and chaos in complex systems ranging from the climate to ecosystems. Observations: In the dynamical systems view, we propose the healthy state has a basin of attraction representing its resilience, while disorders are alternative attractors in which the system can become trapped. Rather than an immutable trait, resilience in this approach is a dynamical property. Recent work has demonstrated the universality of generic dynamical indicators of resilience that are now employed globally to monitor the risks of collapse of complex systems, such as tropical rainforests and tipping elements of the climate system. Other dynamical systems tools are used in ecology and climate science to infer causality from time series. Moreover, experiences in ecological restoration confirm the theoretical prediction that under some conditions, short interventions may invoke long-term success when they flip the system into an alternative basin of attraction. All this implies practical applications for psychiatry, as are discussed in part 2 of this article. Conclusions and Relevance: Work in the field of dynamical systems points to novel ways of inferring causality and quantifying resilience from time series. Those approaches have now been tried and tested in a range of complex systems. The same tools may help monitoring and managing resilience of the healthy state as well as psychiatric disorders.</p

A Dynamical Systems View of Psychiatric Disorders - Practical Implications:A Review

Importance: Dynamical systems theory is widely used to explain tipping points, cycles, and chaos in complex systems ranging from the climate to ecosystems. It has been suggested that the same theory may be used to explain the nature and dynamics of psychiatric disorders, which may come and go with symptoms changing over a lifetime. Here we review evidence for the practical applicability of this theory and its quantitative tools in psychiatry. Observations: Emerging results suggest that time series of mood and behavior may be used to monitor the resilience of patients using the same generic dynamical indicators that are now employed globally to monitor the risks of collapse of complex systems, such as tropical rainforest and tipping elements of the climate system. Other dynamical systems tools used in ecology and climate science open ways to infer personalized webs of causality for patients that may be used to identify targets for intervention. Meanwhile, experiences in ecological restoration help make sense of the occasional long-term success of short interventions. Conclusions and Relevance: Those observations, while promising, evoke follow-up questions on how best to collect dynamic data, infer informative timescales, construct mechanistic models, and measure the effect of interventions on resilience. Done well, monitoring resilience to inform well-timed interventions may be integrated into approaches that give patients an active role in the lifelong challenge of managing their resilience and knowing when to seek professional help.</p

Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthritis: a literature review.

The aim of this study was to review the research literature on pain and quality of life (QoL) and the relationship between these variables among people aged 75 years and above with rheumatoid arthritis and/or osteoarthritis. A Medline and CINAHL search was carried out using MeSH terms rheumatoid arthritis, osteoarthritis, QoL and pain in various combinations. Seventeen articles were identified that met the requirements for methodological quality and inclusion criteria. No study focused only on respondents aged 75 years or over. The studies had varying representation of this age group. Pain was common in both groups and was found to increase with age and disease duration among those with rheumatoid arthritis but not among those with osteoarthritis. Increased pain could lead to depression. Pain, functional limitation and increased age were found to decrease QoL among those with rheumatoid arthritis and osteoarthritis alike. Social support was found to buffer against negative effects on QoL among those with osteoarthritis while no moderating effects were found in rheumatoid arthritis. Increased age was found to relate to pain (rheumatoid arthritis) and decrease QoL (both rheumatoid arthritis and osteoarthritis). It is, however, hard to draw any firm conclusions about older people's pain and QoL because of the lack of studies including respondents aged 75 years or over. Thus, research about pain and QoL, especially focusing on the old and the very elderly with rheumatoid arthritis/osteoarthritis, is needed. It also seems justified to say that nursing care should especially focus on older people and that these people should be assessed for their level of pain, functional limitations and QoL especially in the case of having rheumatoid arthritis and/or osteoarthritis