Graph Theory Analysis of Semantic Fluency in Russian-English Bilinguals.

BACKGROUND: Semantic category fluency is a widely used task involving language, memory, and executive function. Previous studies of bilingual semantic fluency have shown only small differences between languages. Graph theory analyzes complex relationships in networks, including node and edge number, clustering coefficient, average path length, average number of direct neighbors, and scale-free and small-world properties. OBJECTIVE: To shed light on whether the underlying neural processes involved in semantic category fluency testing yield substantially different networks in different languages. METHOD: We compared languages and methods using both network analysis and conventional analysis of word production. We administered the animal naming task to 51 Russian-English bilinguals in each language. We constructed network graphs using three methods: (a) simple association of unique co-occurring neighbors, (b) corrected associations between consecutive words occurring beyond chance, and (c) a network community approach using planar maximally filtered graphs. We compared the resultant network analytics as well as their scale-free and small-world properties. RESULTS: Participants produced more words in Russian than in English. Small-worldness metrics were variable between Russian and English but were consistent across the three graph theory analytical methods. CONCLUSION: The networks had similar graph theory properties in both languages. The optimal methodology for creating networks from semantic category fluency remains to be determined.

Dementia Reported Missing: Use of an Online Search Engine to Track Outcomes in Persons With Dementia Reported Missing.

BACKGROUND: Persons with dementia (PWD) reported missing are known to be at high risk for mortality. Analysis of online search engines' reports of missing PWD may show patterns in the data of this relatively common event and the broad patterns relevant to mortality risk factors. METHODS: We searched Google news for PWD reported missing for 2015. Demographics, personal details, and outcomes were recorded. RESULTS: Of 673 cases, 67 were found deceased, 525 alive, and the remainder had unknown outcomes. Mortality did not differ significantly by race/ethnicity for cases with known outcomes, but cases with unknown outcomes were significantly overrepresented among non-Caucasians (P<0.001; analysis of variance). Duration missing predicted mortality (P<0.001; χ(2)), and mortality was lower if a photograph was provided (P<0.05; χ(2)). Five states had no reports and some appeared to have fewer reports that would be expected based on estimates of dementia prevalence. CONCLUSIONS: Duration missing was the strongest predictor of mortality. Likelihood of mortality was not predicted by use of missing person alerts, and this may be a consequence of inconsistent reporting and follow-up of cases across states. Prevalence and mortality may likewise be underestimated because of the variability in usage and reporting of relevant search terms and definitions. Online resources and social media can provide information about trends and outcomes related to missing persons with dementia, but greater consistency is needed in definitions, searching, and reporting.

Rapidly progressive Alzheimer's disease features distinct structures of amyloid-ß.

Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but the cause of variable progression rates and phenotypes of sporadic Alzheimer's disease is largely unknown. We aimed to investigate the relationship between diverse structural assemblies of amyloid-ß and rates of clinical decline in Alzheimer's disease. Using novel biophysical methods, we analysed levels, particle size, and conformational characteristics of amyloid-ß in the posterior cingulate cortex, hippocampus and cerebellum of 48 cases of Alzheimer's disease with distinctly different disease durations, and correlated the data with APOE gene polymorphism. In both hippocampus and posterior cingulate cortex we identified an extensive array of distinct amyloid-ß42 particles that differ in size, display of N-terminal and C-terminal domains, and conformational stability. In contrast, amyloid-ß40 present at low levels did not form a major particle with discernible size, and both N-terminal and C- terminal domains were largely exposed. Rapidly progressive Alzheimer's disease that is associated with a low frequency of APOE e4 allele demonstrates considerably expanded conformational heterogeneity of amyloid-ß42, with higher levels of distinctly structured amyloid-ß42 particles composed of 30-100 monomers, and fewer particles composed of < 30 monomers. The link between rapid clinical decline and levels of amyloid-ß42 with distinct structural characteristics suggests that different conformers may play an important role in the pathogenesis of distinct Alzheimer's disease phenotypes. These findings indicate that Alzheimer's disease exhibits a wide spectrum of amyloid-ß42 structural states and imply the existence of prion-like conformational strains.

Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease.

Although genetic factors play a main role in determining the risk of developing Alzheimer's disease (AD), they do not explain extensive spectrum of clinicopathological phenotypes. Deposits of aggregated TAU proteins are one of the main predictors of cognitive decline in AD. We investigated the hypothesis that variabilities in AD progression could be due to diverse structural assemblies (strains) of TAU protein. Using sensitive biophysical methods in 40 patients with AD and markedly different disease durations, we identified populations of distinct TAU particles that differed in size, structural organization, and replication rate in vitro and in cell assay. The rapidly replicating, distinctly misfolded TAU conformers found in rapidly progressive AD were composed of ~80% misfolded four-repeat (4R) TAU and ~20% of misfolded 3R TAU isoform with the same conformational signatures. These biophysical observations suggest that distinctly misfolded population of 4R TAU conformers drive the rapid decline in AD and imply that effective therapeutic strategies might need to consider not a singular species but a cloud of differently misfolded TAU conformers.

Use of Appreciative Inquiry To Engage Parents as Codesigners of a Weight Management Intervention for Adolescents.

BACKGROUND: Focus groups are often used to involve families as codesigners of weight management interventions. Focus groups, however, are seldom designed to elicit families' strengths and positive experiences. The purpose of this study was to describe the use of the Appreciative Inquiry process in the conduct of focus groups to engage families in the design of a weight management intervention for adolescents. METHODS: A convenience sample of 44 parents (84% female; 82% minority) of adolescent children with a BMI ≥ 85th percentile, who were in the 6th-8th grade in a large urban school, participated in focus groups designed to elicit family-positive experiences and strengths regarding healthy living. A structured set of questions based on the Appreciative Inquiry process was used in the focus groups. Analyses consisted of the constant comparative method to generate themes. RESULTS: Parent-positive perceptions regarding their family's healthy living habits were reflected in five themes: (1) Having healthy children is a joy; (2) Becoming healthy is a process; (3) Engaging in healthy habits is a family affair; (4) Good health habits can be achieved despite obstacles; and (5) School, community, and social factors contribute to their family's health habits. Parents generated ideas to improve their families' health. CONCLUSIONS: Focus groups based on the Appreciative Inquiry process were found to be a useful approach to discover features that are important to low-income, urban-living parents to include in an adolescent weight management program. Recommendations for designing and conducting focus groups based on the Appreciative Inquiry process are provided.

Detrending Changes the Temporal Dynamics of a Semantic Fluency Task.

Objective: To study the dynamics of clustering semantic fluency responses and switching between clusters. Methods: We conducted a cross-sectional study of participants (N = 60) in a study of patient reported outcomes who were given the Saint Louis University Mental Status test. Sixty-second animal naming tests were scored for the timing of responses as well as the clustering of responses into semantic categories. Time scores were detrended to correct for exponential exhaustion and normalize the time scale across individuals. Results: Grouped by number of responses given, low performers (LP; Carter et al., 2012) switched between clusters fewer times than medium performers (MP) and high performers (HP). Prior to detrending, LP showed increased intracluster response times when compared to the other groups, but no differences were shown in intercluster response times. After detrending, however, the difference in intracluster response times disappeared and LP showed significantly faster detrended intercluster response times compared to both MP and HP. Conclusion: Prior to detrending, slower intracluster response times appear to be driving poorer performance. When time scores are detrended, our findings suggest that LP participants have quicker intercluster response times but exhaust more quickly as well. Detrending can help describe the interplay between the structure-loss and retrieval-slowing models of declining semantic fluency by isolating the component mechanisms involved in each.

From Neurodegeneration to Brain Health: An Integrated Approach.

The term "brain health" integrates general health and well-being with cognitive fitness, in the context of an environment that includes the spectrum of positive and negative factors affecting the individual. Brain health incorporates the effects of neurodegeneration in an ecological sense and the effects of environment and health practices on brain function. It also provides a framework for understanding and maximizing cognitive function across the lifespan. Despite decades of research into the pathogenesis of neurodegenerative disorders, our understanding of how to treat them is relatively rudimentary. Unidimensional approaches, such as medication monotherapies, have generally produced negative results in treatment trials. New integrative paradigms that cut across the molecular and cellular level to the individual and societal level may provide new approaches to understand and treat these disorders. This report on proceedings of a multi-disciplinary conference held in Cleveland, Ohio, in October 2013 summarizes research progress in understanding neurodegenerative disorders in a brain health context. A new "brain health" paradigm is essential to finally understand neurodegenerative disorders such as Alzheimer's disease and overcome the relative stand-still in therapeutics research that has characterized the last decade. The authors summarize progress in these emerging areas with the aim of producing new integrated scientific models for understanding brain health, potentially modifying disease course and advancing care for individuals and families affected by neurodegenerative conditions.