Symptoms and Treatment Needs of People with Dementia-Related Psychosis: A Mixed-Methods Study of the Patient Experience.

OBJECTIVES: This study describes the person-centered experience and impact of symptoms and the treatment needs of dementia-related psychosis (DRP) from a patient and care partner perspective. METHODS: Qualitative interviews and a quantitative survey were used to collect patient experience data from persons with DRP or their care partners. RESULTS: Sixteen participants (1 person with DRP, 15 care partners) completed the qualitative interview; 212 participants (26 persons with DRP, 186 care partners) completed the quantitative survey. The most commonly reported symptoms were visual hallucinations, auditory hallucinations, persecutory delusions, and distortion of senses. The most common impacts were difficulty differentiating what is real from what is not real, increased anxiety, and effects on personal relationships. Current treatments were less than moderately helpful, and the ability to distinguish what is real from what is not real and overall symptom improvement were described as the most important benefits of an ideal treatment. CONCLUSIONS: Patient experience data provide insights into urgent therapeutic needs of patients by describing the nature, frequency, and severity of symptoms and the impacts they have on individuals' lives. CLINICAL IMPLICATIONS: Patient experience data demonstrate an unmet need for treatments to reduce the symptoms and impacts of DRP.

Lewy Body Dementia Association's Industry Advisory Council: proceedings of the second annual meeting.

In 2019, the Lewy Body Dementia Association formed an Industry Advisory Council to bring together a collaborative group of stakeholders with the goal of accelerating clinical research into Lewy body dementia treatments. At the second annual meeting of the Industry Advisory Council, held virtually on June 18, 2020, the key members presented ongoing and planned efforts toward the council's goals. The meeting also featured a discussion about the effects of the COVID-19 pandemic on Lewy body dementia clinical research, lessons learned from that experience, and how those lessons can be applied to the design and conduct of future clinical trials. This report provides a brief summary of the meeting proceedings with a focus on efforts to improve and adapt future Lewy body dementia clinical research.

Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials.

Lewy body dementia (LBD), including dementia with Lewy bodies and Parkinson's disease dementia, affects over a million people in the USA and has a substantial impact on patients, caregivers, and society. Symptomatic treatments for LBD, which can include cognitive, neuropsychiatric, autonomic, sleep, and motor features, are limited with only two drugs (cholinesterase inhibitors) currently approved by regulatory agencies for dementia in LBD. Clinical trials represent a top research priority, but there are many challenges in the development and implementation of trials in LBD. To address these issues and advance the field of clinical trials in the LBDs, the Lewy Body Dementia Association formed an Industry Advisory Council (LBDA IAC), in addition to its Research Center of Excellence program. The LBDA IAC comprises a diverse and collaborative group of experts from academic medical centers, pharmaceutical industries, and the patient advocacy foundation. The inaugural LBDA IAC meeting, held in June 2019, aimed to bring together this group, along with representatives from regulatory agencies, to address the topic of optimizing the landscape of LBD clinical trials. This review highlights the formation of the LBDA IAC, current state of LBD clinical trials, and challenges and opportunities in the field regarding trial design, study populations, diagnostic criteria, and biomarker utilization. Current gaps include a lack of standardized clinical assessment tools and evidence-based management strategies for LBD as well as difficulty and controversy in diagnosing LBD. Challenges in LBD clinical trials include the heterogeneity of LBD pathology and symptomatology, limited understanding of the trajectory of LBD cognitive and core features, absence of LBD-specific outcome measures, and lack of established standardized biologic, imaging, or genetic biomarkers that may inform study design. Demands of study participation (e.g., travel, duration, and frequency of study visits) may also pose challenges and impact trial enrollment, retention, and outcomes. There are opportunities to improve the landscape of LBD clinical trials by harmonizing clinical assessments and biomarkers across cohorts and research studies, developing and validating outcome measures in LBD, engaging the patient community to assess research needs and priorities, and incorporating biomarker and genotype profiling in study design.

Modelling Creativity: Identifying Key Components through a Corpus-Based Approach.

Creativity is a complex, multi-faceted concept encompassing a variety of related aspects, abilities, properties and behaviours. If we wish to study creativity scientifically, then a tractable and well-articulated model of creativity is required. Such a model would be of great value to researchers investigating the nature of creativity and in particular, those concerned with the evaluation of creative practice. This paper describes a unique approach to developing a suitable model of how creative behaviour emerges that is based on the words people use to describe the concept. Using techniques from the field of statistical natural language processing, we identify a collection of fourteen key components of creativity through an analysis of a corpus of academic papers on the topic. Words are identified which appear significantly often in connection with discussions of the concept. Using a measure of lexical similarity to help cluster these words, a number of distinct themes emerge, which collectively contribute to a comprehensive and multi-perspective model of creativity. The components provide an ontology of creativity: a set of building blocks which can be used to model creative practice in a variety of domains. The components have been employed in two case studies to evaluate the creativity of computational systems and have proven useful in articulating achievements of this work and directions for further research.

Metal and proton toxicity to lake zooplankton: a chemical speciation based modelling approach.

The WHAM-FTOX model quantifies the combined toxic effects of protons and metal cations towards aquatic organisms through the toxicity function (FTOX), a linear combination of the products of organism-bound cation and a toxic potency coefficient for each cation. We describe the application of the model to predict an observable ecological field variable, species richness of pelagic lake crustacean zooplankton, studied with respect to either acidification or the impacts of metals from smelters. The fitted results give toxic potencies increasing in the order H(+) < Al < Cu < Zn < Ni. In general, observed species richness is lower than predicted, but in some instances agreement is close, and is rarely higher than predictions. The model predicts recovery in agreement with observations for three regions, namely Sudbury (Canada), Bohemian Forest (Czech Republic) and a subset of lakes across Norway, but fails to predict observed recovery from acidification in Adirondack lakes (USA).

The widespread threat of calcium decline in fresh waters.

Calcium concentrations are now commonly declining in softwater boreal lakes. Although the mechanisms leading to these declines are generally well known, the consequences for the aquatic biota have not yet been reported. By examining crustacean zooplankton remains preserved in lake sediment cores, we document near extirpations of calcium-rich Daphnia species, which are keystone herbivores in pelagic food webs, concurrent with declining lake-water calcium. A large proportion (62%, 47 to 81% by region) of the Canadian Shield lakes we examined has a calcium concentration approaching or below the threshold at which laboratory Daphnia populations suffer reduced survival and fecundity. The ecological impacts of environmental calcium loss are likely to be both widespread and pronounced.

Dissolved organic carbon trends resulting from changes in atmospheric deposition chemistry.

Several hypotheses have been proposed to explain recent, widespread increases in concentrations of dissolved organic carbon (DOC) in the surface waters of glaciated landscapes across eastern North America and northern and central Europe. Some invoke anthropogenic forcing through mechanisms related to climate change, nitrogen deposition or changes in land use, and by implication suggest that current concentrations and fluxes are without precedent. All of these hypotheses imply that DOC levels will continue to rise, with unpredictable consequences for the global carbon cycle. Alternatively, it has been proposed that DOC concentrations are returning toward pre-industrial levels as a result of a gradual decline in the sulphate content of atmospheric deposition. Here we show, through the assessment of time series data from 522 remote lakes and streams in North America and northern Europe, that rising trends in DOC between 1990 and 2004 can be concisely explained by a simple model based solely on changes in deposition chemistry and catchment acid-sensitivity. We demonstrate that DOC concentrations have increased in proportion to the rates at which atmospherically deposited anthropogenic sulphur and sea salt have declined. We conclude that acid deposition to these ecosystems has been partially buffered by changes in organic acidity and that the rise in DOC is integral to recovery from acidification. Over recent decades, deposition-driven increases in organic matter solubility may have increased the export of DOC to the oceans, a potentially important component of regional carbon balances. The increase in DOC concentrations in these regions appears unrelated to other climatic factors.

Inter- and intra-annual chemical variability during the ice-free season in lakes with different flushing rates and acid deposition histories.

Quantifying chemical variability in different lake types is important for the assessment of both chemical and biological responses to environmental change. For monitoring programs that emphasize a large number of lakes at the expense of frequent samples, high variability may influence how representative single samples are of the average conditions of individual lakes. Intensive temporal data from long-term research sites provide a unique opportunity to assess chemical variability in lakes with different characteristics. We compared the intra- and inter-annual variability of four acidification related variables (Gran alkalinity, pH, sulphate concentration, and total base cation concentration) in four lakes with different flushing rates and acid deposition histories. Variability was highest in lakes with high flushing rates and was not influenced by historic acid deposition in our study lakes. This has implications for the amount of effort required in monitoring programs. Lakes with high flushing rates will require more frequent sampling intervals than lakes with low flushing rates. Consideration of specific lake types should be included in the design of monitoring programs.

Using temporal coherence to determine the response to climate change in Boreal Shield lakes.

Climate change is expected to have important impacts on aquatic ecosystems. On the Boreal Shield, mean annual air temperatures are expected to increase 2 to 4 degrees C over the next 50 years. An important challenge is to predict how changes in climate and climate variability will impact natural systems so that sustainable management policies can be implemented. To predict responses to complex ecosystem changes associated with climate change, we used long-term biotic databases to evaluate how important elements of the biota in Boreal Shield lakes have responded to past fluctuations in climate. Our long-term records span a two decade period where there have been unusually cold years and unusually warm years. We used coherence analyses to test for regionally operating controls on climate, water temperature, pH, and plankton richness and abundance in three regions across Ontario: the Experimental Lakes Area, Sudbury, and Dorset. Inter-annual variation in air temperature was similar among regions, but there was a weak relationship among regions for precipitation. While air temperature was closely related to lake surface temperatures in each of the regions, there were weak relationships between lake surface temperature and richness or abundance of the plankton. However, inter-annual changes in lake chemistry (i.e., pH) were correlated with some biotic variables. In some lakes in Sudbury and Dorset, pH was dependent on extreme events. For example, El Nino related droughts resulted in acidification pulses in some lakes that influenced phytoplankton and zooplankton richness. These results suggest that there can be strong heterogeneity in lake ecosystem responses within and across regions.