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The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) cohort study of the Canadian Consortium on Neurodegeneration in Aging (CCNA) is a national initiative to catalyze research on dementia, set up to support the research agendas of CCNA teams. This cross-country longitudinal cohort of 2310 deeply phenotyped subjects with various forms of dementia and mild memory loss or concerns, along with cognitively intact elderly subjects, will test hypotheses generated by these teams.
The COMPASS-ND protocol, initial grant proposal for funding, fifth semi-annual CCNA Progress Report submitted to the Canadian Institutes of Health Research December 2017, and other documents supplemented by modifications made and lessons learned after implementation were used by the authors to create the description of the study provided here.
The CCNA COMPASS-ND cohort includes participants from across Canada with various cognitive conditions associated with or at risk of neurodegenerative diseases. They will undergo a wide range of experimental, clinical, imaging, and genetic investigation to specifically address the causes, diagnosis, treatment, and prevention of these conditions in the aging population. Data derived from clinical and cognitive assessments, biospecimens, brain imaging, genetics, and brain donations will be used to test hypotheses generated by CCNA research teams and other Canadian researchers. The study is the most comprehensive and ambitious Canadian study of dementia. Initial data posting occurred in 2018, with the full cohort to be accrued by 2020.
Availability of data from the COMPASS-ND study will provide a major stimulus for dementia research in Canada in the coming years.
Objectives: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. Methods: Here, we used longitudinal cognitive data from 1256 late–middle aged adults from the Wisconsin Registry for Alzheimer’s Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. Results: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40–70 years). Conclusions: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119–133)
Objectives: A major challenge in cognitive aging is differentiating preclinical disease-related cognitive decline from changes associated with normal aging. Neuropsychological test authors typically publish single time-point norms, referred to here as unconditional reference values. However, detecting significant change requires longitudinal, or conditional reference values, created by modeling cognition as a function of prior performance. Our objectives were to create, depict, and examine preliminary validity of unconditional and conditional reference values for ages 40–75 years on neuropsychological tests. Method: We used quantile regression to create growth-curve–like models of performance on tests of memory and executive function using participants from the Wisconsin Registry for Alzheimer’s Prevention. Unconditional and conditional models accounted for age, sex, education, and verbal ability/literacy; conditional models also included past performance on and number of prior exposures to the test. Models were then used to estimate individuals’ unconditional and conditional percentile ranks for each test. We examined how low performance on each test (operationalized as <7th percentile) related to consensus-conference–determined cognitive statuses and subjective impairment. Results: Participants with low performance were more likely to receive an abnormal cognitive diagnosis at the current visit (but not later visits). Low performance was also linked to subjective and informant reports of worsening memory function. Conclusions: The percentile-based methods and single-test results described here show potential for detecting troublesome within-person cognitive change. Development of reference values for additional cognitive measures, investigation of alternative thresholds for abnormality (including multi-test criteria), and validation in samples with more clinical endpoints are needed. (JINS, 2019, 25, 1–14)
Dementia prevalence is rising, and it will double in the next 20 years. This study sought to understand the prevalence of dementia in hospitalized patients with ischemic stroke, and its impact on outcomes.
Using the Canadian Institute of Health Information’s (CIHI) Discharge Abstract Database (DAD), all acute ischemic stroke admissions from April 2003 to March 2015 in Canada (excluding Quebec) were analyzed. Concurrent dementia at the time of admission was assessed based on hospital diagnostic codes. Characteristics and in-hospital outcomes were compared in patients with and without dementia using χ2 and negative binomial, as well as Poisson regression analysis.
During the observed period, 313,138 people were admitted to a hospital in Canada for an ischemic stroke. Of those, 21,788 (7.0%) had a concurrent diagnosis of dementia. People with dementia had older median age (84 vs. 76 years; p<0.0001), were more often female (59.6% vs. 48.4%; p<0.0001) and more often had Charlson-Deyo Comorbidity Index ≥2 (64.5% vs. 43.5%; p<0.0001). Patients with dementia were less likely to be discharged to a rehabilitation facility (adjusted risk ratio [RR] 3.089, 95% confidence interval [CI] 2.992-3.188, p<0.0001) or home independently (adjusted RR 0.756, 95% CI 0.737-0.776, p<0.0001).
Approximately 1 in 13 hospitalized ischemic stroke patients has coded dementia. Patients with ischemic stroke and concurrent dementia have higher mortality, face significantly more dependence after stroke and utilize greater healthcare resources than stroke patients without dementia. Causative conclusions are limited by the administrative data source. Early care planning and coordination could potentially optimize outcomes.
The fragmented ecosystems along the Niagara Escarpment World Biosphere Reserve provide important habitats for biota including lichens. Nonetheless, the Reserve is disturbed by dense human populations and associated air pollution. Here we investigated patterns of lichen diversity within urban and rural sites at three different locations (Niagara, Hamilton, and Owen Sound) along the Niagara Escarpment in Ontario, Canada. Our results indicate that both lichen species richness and community composition are negatively correlated with increasing human population density and air pollution. However, our quantitative analysis of community composition using canonical correspondence analysis (CCA) indicates that human population density and air pollution is more independent than might be assumed. The CCA analysis suggests that the strongest environmental gradient (CCA1) associated with lichen community composition includes regional pollution load and climatic variables; the second gradient (CCA2) is associated with local pollution load and human population density factors. These results increase the knowledge of lichen biodiversity for the Niagara Escarpment and urban and rural fragmented ecosystems as well as along gradients of human population density and air pollution; they suggest a differential influence of regional and local pollution loads and population density factors. This study provides baseline knowledge for further research and conservation initiatives along the Niagara Escarpment World Biosphere Reserve.
Studies on the role of diet in the development of chronic diseases often rely on self-report surveys of dietary intake. Unfortunately, many validity studies have demonstrated that self-reported dietary intake is subject to systematic under-reporting, although the vast majority of such studies have been conducted in industrialised countries. The aim of the present study was to investigate whether or not systematic reporting error exists among the individuals of African ancestry (n 324) in five countries distributed across the Human Development Index (HDI) scale, a UN statistic devised to rank countries on non-income factors plus economic indicators. Using two 24 h dietary recalls to assess energy intake and the doubly labelled water method to assess total energy expenditure, we calculated the difference between these two values ((self-report − expenditure/expenditure) × 100) to identify under-reporting of habitual energy intake in selected communities in Ghana, South Africa, Seychelles, Jamaica and the USA. Under-reporting of habitual energy intake was observed in all the five countries. The South African cohort exhibited the highest mean under-reporting ( − 52·1 % of energy) compared with the cohorts of Ghana ( − 22·5 %), Jamaica ( − 17·9 %), Seychelles ( − 25·0 %) and the USA ( − 18·5 %). BMI was the most consistent predictor of under-reporting compared with other predictors. In conclusion, there is substantial under-reporting of dietary energy intake in populations across the whole range of the HDI, and this systematic reporting error increases according to the BMI of an individual.
Worry is experienced by many older adults, yet our understanding of the emotional experience of late-life worry is poor as findings regarding older adults are inferred from findings of studies conducted with young adults. In the present study, we aimed to characterize age differences in affect, self-reported arousal, and physiological arousal experienced during worry.
Fifty-three young (M = 21.4, SD = 2.6 years) and 55 older community-dwelling adults (M = 69.1, SD = 8.1 years) participated in an experimental induction of worry or pleasant/neutral recall. Measures collected included: Penn State Worry Questionnaire (PSWQ), worry intensity item, Multiple Affect Adjective Checklist-Revised (MAACL-R), Self-Assessment Maniken arousal item, and heart rate. Standardized residual scores were calculated to represent change from baseline for self-report and psychophysiological measures.
Older adults had lower trait worry and worry intensity at baseline. A significant age by induction type interaction was found for the MAACL-R subscales of anxiety, depression, hostility, and positive affect. Compared with young adults, older adults experienced smaller changes in emotions in response to the worry induction than in the recall induction. For both worry and recall inductions, older adults exhibited less change in self-reported arousal and interbeat intervals from baseline compared with young adults.
Findings from the present study illuminate both similarities and differences in the experience of worry for older and young adults. This study provides preliminary evidence for the characterization of late-life worry as generating less anxiety than worry during young adulthood.
Changing patterns of tooth wear have been used extensively to obtain information about the lifestyle and culture of pre-historic and modern humans. The assessment of tooth wear in previous anthropological studies has been largely based on quantitative analysis of wear indices and qualitative analysis of micrographs. Wear indices are simple to use and can be sensitive tools, but there is a lack of international standardization in their use. Micrographic assessment of pits and scratch marks on the worn surfaces of teeth can assist in dietary reconstruction of humans, but this approach has low reliability and high observer error. This review will provide an update on a new wear index and novel nano-techniques that hold promise for improving the analysis of tooth wear. Recently, a new wear index, termed the Basic Erosive Wear Examination index, has been proposed as a standardized universal tool for diagnosing erosive tooth wear. However, its value seems to be limited when assessing the dentitions of populations, in whom tooth wear occurs predominantly by attrition and abrasion. Optical techniques involving scanning confocal microscopy combined with fractal analysis can provide an objective assessment of the worn surface. Other nanotechnology-based methods, such as nanohardness measurements, nano-computed tomography and mass spectrometry, can be also useful in physical and chemical characterization of both sound and worn teeth, but these techniques are limited to use in vitro. A combined assessment of the worn dentition using all of these techniques promises to provide the best holistic approach to analyse tooth wear.
This paper studies the use of ion implantation and rapid thermal annealing for the fabrication of shallow junctions in sub-100 nm CMOS technology. Spike annealing recipes were optimized on the basis of delta-doping diffusion experiments and shallow junction characteristics. In addition, using GeF2 pre-amorphization implants in combination with low-energy BF2 and spike annealing, p-type junctions depths of 30 nm were obtained with sheet resistances as low as 390 Ω/sq. The combined finetuning of implantation and annealing conditions is expected to enable junction scaling into the 70-nm CMOS technology node.
The relationship between silicide thickness, sheet resistance and silicon consumption is experimentally checked for Co-disilicide and Ni-monosilicide. The reverse bias leakage current of shallow Ni-silicided and Co-silicided square diodes is compared for varying junction depth and varying silicide thickness. A lower reverse bias leakage current is obtained for a Ni-silicided shallow junction as compared to its Co-silicided counterpart. This can be attributed to the reduced silicon consumption. The Ti cap does not play an active role during the Ni-silicidation of narrow active area and poly lines. It is shown that a Ni-silicidation process is scalable without Ti cap.
Making use of SPER (Solid Phase Epitaxial Regrowth) As and B deep source/drain junctions with high activation can be obtained at temperatures below 700°C. However, higher thermal budget is required to regrow and activate the dopants in the poly gates. Low junction leakage and low contact resistance can be obtained for Ni-silicided As and B SPER junctions making use of deep As and B implants. Because of the low thermal budget source/drain junctions obtained by SPER are an attractive alternative to conventional spike annealed junctions for technologies making use of metal gates.
Silicidation of small features of various geometries and sizes using Ni-silicide was studied. Effects of dopants, surface preparation and silicidation parameters on silicide morphology were investigated. It was found that Ni silicide thickness and quality of the silicide/silicon interface (presence of NiSi2 pyramids) are dependent on the area dimensions and geometry. NiSi formed on narrow lines is thicker compared to wide areas. We found that pyramids of epitaxial NiSi2 protruding into the Si substrate are formed during the silicidation of undoped, boron-doped and BF2-doped active areas. The presence of pyramids was not observed on As-doped silicon. Rough interface due to the pyramids could be the reason for a more pronounced linewidth dependence of leakage current in the case of p+/n diodes. A higher density of pyramids was found on narrow lines (below 0.2μm) and particularly islands structures. No pyramids were found when a Ge preamorphisation implant was used.
This paper presents an overview of Ni-alloy (Ni, Ni-Pt and Ni-Ta) silicide development for the 45 nm node and beyond, including applications to self-aligned silicide (SALICIDE) processes, reaction with SiGe and strained Si on SiGe, and applications to fully silicided (FUSI) gates. Key SALICIDE issues addressed include the use of spike or low temperature rapid thermal processes (RTP) to control silicidation and junction leakage on small features, factors affecting the formation of epitaxial pyramidal NiSi2 grains, and NiSi thermal stability and agglomeration kinetics. Alloying with Pt or Ta is shown to improve thermal stability of NiSi films, although with quite different behaviors. While Pt is incorporated predominantly in solution in NiSi, Ta segregates to the surface of the films. Ni-Pt alloy silicides were also found to achieve low sheet resistance on narrow gates, low contact resistivity and low junction leakage, making them attractive for CMOS applications. For the Ni/SiGe reaction, a narrower RTP process window for low sheet resistance and a lower activation energy for agglomeration were observed when compared to the Ni/Si reaction. The lower thermal stability was correlated to Ge segregation from the Ni(SiGe) films. The Ni/doped poly-Si reaction was studied for FUSI gate applications, showing a retardation of the silicidation kinetics for high B doses and a large pile- up of dopants (for As, B or P) at the NiSi/SiO2 interface due to dopant snowplow during silicidation. The work function (WF) of NiSi was observed to shift with the addition of dopants, effect attributed to modifications of the interface dipole by the pile-up of dopants. No significant degradation was observed when comparing gate oxide breakdown statistics for Ni FUSI to conventional poly-Si gates. The process window for a FUSI gate-last process (performed after S/D Ni silicidation) was evaluated showing a potential integration problem due to possible degradation of the S/D silicide during the FUSI gate reaction.
The feasibility of the SPER junction process as a reasonable alternative to the spike anneal junction is proved in this work. Good control of the SCE and performance competitive results as compared to the spike junction are obtained. An analysis of the interaction between the halo dopant and the SPER junctions has been carried out; it is shown that the performance degrades with increasing halo dose as a consequence of an overlap resistance problem.
During spike annealing of ultra-shallow junctions, large fractions of the dopants form a partially active pile-up at the interface between silicon and the screening oxide layer. In this paper, we show results of sheet resistance, SIMS and high resolution Elastic Recoil Detection measurements to investigate the physical and electrical behaviour of B and As dopant atoms at the interface.
Our results show that the fraction of dopants segregated at the interface is as high as 30-50% for B, but is dependent on dose and the type of screening oxide. Concentrations of up to 3e20cm-3 and more of active dopants are found on the Si side of the interface. The presence of nitrogen in the oxide at the interface causes a higher and sharper pile-up. Results indicate that a similar peak is expected for As, with active concentrations above 6e20cm-3. In an HF dip, the pile-up is removed together with the oxide or deactivated during native oxide regrowth.
Further experiments show that immediately after removing the screening oxide in an HF dip the sheet resistance for B decreases sharply due to carrier accumulation, then raises to about 6-9% above the initial level depending on the oxide and dopant species. The sharp decrease in resistance is not observed for As.