To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
Background Survival estimates are integral to care for patients diagnosed with dementia. Few Canadian studies have carried out long-term follow-up of well-described cohorts, analyzing survival related to multiple risk factors. Methods Survival analysis of an inception cohort enrolled at a British Columbia (BC) tertiary dementia referral clinic between 1997 and 1999 was undertaken. Vital status was completed for 168 patients diagnosed with dementia. An evaluation of the effects of demographics, vascular risk factors, cognitive and functional ratings, apolipoprotein 4-status, and cholinesterase use on survival was performed using a log-rank test and time-dependent Cox regression. Survival of this dementia cohort was compared with the age-matched life expectancy of persons in BC. Results In all, 158/168 (94.0%) subjects died over 16.6 years, with a median survival of 7.08 years. Risk factors associated with shorter survival in dementia groups included age of onset ≥80 (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.05-2.32); greater functional disability (Disability Assessment for Dementia<55% [HR 1.47, 95% CI 1.04-2.08]); and cumulative medical illness severity (Cumulative Illness Rating Scale≥7 [HR 1.51, 95% CI 1.08-2.12)]. Compared with the BC population, years of potential life lost for dementia subjects aged <65 was 15.36 years, and for dementia subjects aged ≥80 it was 1.82 years. Conclusions Survival in dementia subjects is shorter than population life expectancies for each age strata, with greatest impact on younger patients. For people diagnosed with dementia, age ≥80 years, cumulative medical illness severity, and functional disabilities are the most significant survival predictors and can be used to guide prognosis.
Excavations at the 109 hectare site of Kurd Qaburstan on the Erbil plain in the Kurdistan Region of Iraq were conducted by the Johns Hopkins University in 2013 and 2014. The Middle Bronze Age (Old Babylonian period) is the main period of occupation evident on the site, and the project therefore aims to study the character of a north Mesopotamian urban centre of the early second millennium b.c. On the high mound, excavations revealed three phases of Mittani (Late Bronze) period occupation, including evidence of elite residential architecture. On the low mound and the south slope of the high mound, Middle Bronze evidence included domestic remains with numerous ceramic vessels left in situ. Also dating to the Middle Bronze period is evidence of a city wall on the site edges. Later occupations include a cemetery, perhaps of Achaemenid date, on the south slope of the high mound and a Middle Islamic settlement on the southern lower town. Faunal and archaeobotanical analysis provide information on the plant and animal economy of the second millennium b.c. occupations, and geophysical results have documented a thirty-one hectare expanse of dense Middle Bronze Age architecture in the northern lower town.
Hand, foot, and mouth disease (HFMD) is highly prevalent in China, and more efficient methods of epidemic detection and early warning need to be developed to augment traditional surveillance systems. In this paper, a method that uses Baidu search queries to track and predict HFMD epidemics is presented, and the outbreaks of HFMD in China during the 60-month period from January 2011 to December 2015 are predicted. The Pearson correlation coefficient (R) of the predictive model and the mean absolute percentage errors between observed HFMD case counts and the predicted number show that our predictive model gives excellent fit to the data. This implies that Baidu search queries can be used in China to track and reliably predict HFMD epidemics, and can serve as a supplement to official systems for HFMD epidemic surveillance.
The main question that Firestone & Scholl (F&S) pose is whether “what and how we see is functionally independent from what and how we think, know, desire, act, and so forth” (sect. 2, para. 1). We synthesize a collection of concerns from an interdisciplinary set of coauthors regarding F&S's assumptions and appeals to intuition, resulting in their treatment of visual perception as context-free.
This chapter examines the island of Sardinia during the Iron Age to identify the types of interactions between the local Nuragic culture, which was already open to Mediterranean contacts in the Recent and Final Bronze Ages, and other populations around the Tyrrhenian Sea and in the Near East. In the Iron Age, as Sardinians managed contacts with Villanovan and Levantine peoples, they carefully selected ideological contributions and foreign materials, changing, adapting and integrating them into their own culture. Phoenicians first established themselves within Nuragic communities and later in coastal settlements, where their presence favoured the integration process. It contributed to the creation of a culture that was neither Nuragic nor Phoenician but that can define as Sardinian. The main differences between the coastal Phoenician sites and Nuragic sites of the interior consist of different proportions of handmade and domestic Phoenician pottery. Finally, the chapter discusses the variety of foreign imports in later Iron Age Sardinia.
Mutations in the progranulin gene (GRN) are a common cause of familial frontotemporal dementia. We used a comprehensive neuropsychological battery to investigate whether early cognitive changes could be detected in GRN mutation carriers before dementia onset. Twenty-four at-risk members from six families with known GRN mutations underwent detailed neuropsychological testing. Group differences were investigated by domains of attention, language, visuospatial function, verbal memory, non-verbal memory, working memory and executive function. There was a trend for mutation carriers (n=8) to perform more poorly than non-carriers (n=16) across neuropsychological domains, with significant between group differences for visuospatial function (p<.04; d=0.92) and working memory function (p<.02; d=1.10). Measurable cognitive differences exist before the development of frontotemporal dementia in subjects with GRN mutations. The neuropsychological profile of mutation carriers suggests early asymmetric, right hemisphere brain dysfunction that is consistent with recent functional imaging data from our research group and the broader literature. (JINS, 2014, 20, 1–10)
Feldman (2011) has proposed a new approach to the treatment of posttraumatic stress disorder (PTSD) in individuals at the end-of-life known as Stepwise Psychosocial Palliative Care (SPPC). This approach helps to compensate for the disadvantages of existing PTSD interventions with regard to treating patients with life-limiting and terminal illnesses by employing a palliative care philosophy. The model relies on cognitive and behavioral techniques drawn from evidence-based approaches to PTSD, deploying them in a stage-wise manner designed to allow for interventions to track with patents’ needs and prognoses. Because this model is relatively new, we seek to explore issues related to its implementation in the complex settings in which providers encounter patients at the end-of-life. We also seek to provide concrete guidance to providers regarding the management of PTSD at the end-of-life in diverse palliative care settings.
We examine three specific cases in which the SPPC model was utilized, highlighting particular treatment challenges and strategies. These case studies provide information regarding the SPPC model's application to patients in two distinct palliative care settings—a palliative care consult team and an inpatient palliative care unit.
The SPPC model's stage-wise approach allows for its flexible use given a variety of constraints related to setting and patient issues.
Significance of results:
The SPPC model provides an alternative to existing psychosocial treatments for PTSD that may be more appropriate for patients at the end of life.
We assessed serum homocysteine (tHcy) and folate concentrations among US adolescents before and after fortification of cereal-grain products with folic acid, and associations with demographic, behavioural and physiological factors.
Observational study conducted among participants of a randomized trial.
The Child and Adolescent Trial for Cardiovascular Health (CATCH) study.
Adolescents (n 2445) in grades 8 (pre-fortification, mean age 14 years) and 12 (post-fortification, mean age 18 years).
Average serum concentrations of tHcy, folate and vitamin B6 increased by 17 %, 16 % and 14 %, respectively, while serum concentrations of vitamin B12 decreased by 11 % post-fortification. Folic acid fortification provided, on average, an additional intake of 118 μg folate/d. Male sex (P < 0·0001) and white race (P = 0·0008) were associated with significantly greater increases in tHcy concentration, while increases in BMI (P = 0·006) and serum folate concentration (P < 0·0001) were associated with significant decreases in tHcy concentration. Female sex (P < 0·0001), non-smoking (P < 0·0001), use of multivitamins (P < 0·0001) and higher dietary intake of folate (P = 0·001) were associated with significantly greater increases in serum folate concentrations. From grade 8 to grade 12, the upward age trend in serum tHcy concentration was uninterrupted in its course (P > 0·50); whereas serum folic acid concentration showed a downward trend that incurred a discrete jump upward (17 % higher; P < 0·0001) with fortification. These trends differed significantly for males v. females (P < 0·001 for interaction).
Fortification had a significant impact on improving folate status but not serum tHcy concentrations among US adolescents.
There is currently little information on the genetic epidemiology of Alzheimer disease (AD) among North American Aboriginal populations. No cases of familialAD (FAD) in these populations have been published to date.
Here, we describe a large North American Aboriginal kindred with early onset FAD (EOFAD) in which genetic testing was done.
Results and Conclusions:
A novel Presenilin 1 (PS1) gene mutation (L250F) has been identified. In contrast to the three previously reported families with PS1 codon 250 mutations, affected members of this kindred demonstrate neither myoclonus nor seizures. Furthermore, the identification of a PS1 mutation in a North American Aboriginal kindred presents several unique challenges with respect to knowledge transfer and continuity of care in a geographically remote and culturally distinct community.
Heterogeneity is observed in the patterns of cognition in Alzheimer’s disease (AD). Such heterogeneity might suggest the involvement of different etiological pathways or different host responses to pathology. A total of 627 subjects with mild/moderate AD underwent cognitive assessment with the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale-2 (DRS-2). Latent class analysis (LCA) was performed on cognition subscale data to identify and characterize cognitive subgroups. Clinical, demographic, and genetic factors were explored for association with class membership. LCA suggested the existence of four subgroups; one group with mild and another with severe global impairment across the cognitive domains, one group with primary impairments in attention and construction, and another group with primary deficits in memory and orientation. Education, disease duration, age, Apolipoprotein E-ε4 (APOE ε4) status, gender, presence of grasp reflex, white matter changes, and early or prominent visuospatial impairment were all associated with class membership. Our results support the existence of heterogeneity in patterns of cognitive impairment in AD. Our observation of classes characterized by predominant deficits in attention/construction and memory respectively deserves further exploration as does the association between membership in the attention/construction class and APOE ε4 negative status. (JINS, 2010, 16, 233–243.)
Background: Home-fortification is a new strategy of adding micronutrients including zinc and iron to home-made foods. Zinc supplementation may prevent morbidity and mortality related to diarrheal illnesses, and iron supplementation may improve cognitive development, in children.
Objectives: To project clinical and economic effects of home-fortification in children in an urban slum of Karachi, Pakistan.
Methods: This is a cost benefit analysis of 5,000 simulated male and female infants (6–12 months) assigned to micronutrients or placebo for 4 months and followed for 55 years. We linked the effect of zinc on longitudinal prevalence of diarrhea to mortality, and the effect of iron on hemoglobin to IQ scores and lifetime earnings. Cost estimates were based on volumes of resource utilization from the Pakistan Sprinkles Diarrhea study. Main outcome was incremental benefit defined as the gain in lifetime earnings after accounting for the incremental costs of micronutrients over placebo (societal perspective).
Results: Our model projected that the reduction in diarrhea and improvement in hemoglobin concentrations through home-fortification was associated with reduced child mortality, higher IQ scores, and higher earnings. The present value of incremental benefit was $106 (95 percent probability interval = $17 to $193) U.S. dollars, which corresponds to $464.79 ($74.54 to $846.27) international dollars using a purchasing power parity exchange rate.
Conclusions: Home-fortification appears to improve clinical outcomes at a reasonable cost, and may actually be cost beneficial when lifetime earnings are considered.