Determinants of neurological disease: Synthesis of systematic reviews.

Systematic reviews were conducted to identify risk factors associated with the onset and progression of 14 neurological conditions, prioritized as a component of the National Population Health Study of Neurological Conditions. These systematic reviews provided a basis for evaluating the weight of evidence of evidence for risk factors for the onset and progression of the 14 individual neurological conditions considered. A number of risk factors associated with an increased risk of onset for more than one condition, including exposure to pesticides (associated with an increased risk of AD, amyotrophic lateral sclerosis, brain tumours, and PD; smoking (AD, MS); and infection (MS, Tourette syndrome). Coffee and tea intake was associated with a decreased risk of onset of both dystonia and PD. Further understanding of the etiology of priority neurological conditions will be helpful in focusing future research initiatives and in the development of interventions to reduce the burden associated with neurological conditions in Canada and internationally.

Genetic variation associated with the occurrence and progression of neurological disorders.

This paper presents an overview of genetic variation associated with the onset and progression of 14 neurological disorders, focusing primarily on association studies. The 14 disorders are heterogeneous in terms of their frequency, age of onset, etiology and progression. There is substantially less evidence on progression than onset. With regard to onset, the conditions are diverse in terms of their epidemiology and patterns of familial aggregation. While the muscular dystrophies and Huntington's disease are monogenic diseases, for the other 12 conditions only a small proportion of cases is associated with specific genetic syndromes or mutations. Excluding these, some familial aggregation remains for the majority of cases. There is considerable variation in the volume of evidence by condition, and by gene within condition. The volume of evidence is greatest for Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. As for common complex chronic diseases, genome wide association studies have found that validated genomic regions account for a low proportion of heritability. Apart from multiple sclerosis, which shares several susceptibility loci with other immune-related disorders, variation at HLA-DRB5 being associated both with Parkinson's disease and Alzheimer's disease, and the association of the C9orf72 repeat expansion with ALS and frontotemporal degeneration, there was little evidence of gene loci being consistently associated with more than one neurological condition or with other conditions. With the exception of spina bifida, for which maternal MTHFR genotype is associated with risk in the offspring, and corroborates other evidence of the importance of folate in etiology, there was little evidence that the pathways influenced by genetic variation are related to known lifestyle or environmental exposures.

The development of prospective memory in preschool children using naturalistic tasks.

The development of prospective memory (PM) in 3-, 4-, and 5-year-old children (N=123) was assessed in two experiments using several naturalistic game-like tasks that varied in the explicitness of the cues for retrieval that they provided. The goals of the study were to evaluate age differences in PM (a) with the effects of retrospective memory (RM) factored out and (b) as a function of increasing retrieval cue specificity. Results from Experiment 1 showed that there were age differences in PM on a simulated Shopping Trip task that favored older children after age differences attributable to RM were identified in a hierarchical regression. PM and RM components followed the same developmental trajectory. Because the Shopping Trip task provided a visual cue for retrieval, a second naturalistic PM task that was incidental to the Shopping Trip task (i.e., to ask for stickers at the end of the shopping trip) was included but provided no explicit cue other than the end of Shopping Trip task itself. A binary logistic regression showed that age did not predict children who succeeded and those who did not succeed. Because the end of the Shopping Trip task might have cued PM, two new tasks without any explicit cues for retrieval were examined in Experiment 2. Logistic regressions revealed that age predicted PM success on both tasks. With additional cues following failure to retrieve the PM intention, nearly all children succeeded, but the number of cues needed increased with age. The joint and separate contributions of PM and RM to successful task performance are discussed.

Diabetes and sex-specific colorectal cancer risks in Newfoundland and Labrador: a population-based retrospective cohort study.

OBJECTIVE: Studies on the relationship between diabetes and colorectal cancer (CRC) are inconsistent. It is also unclear whether CRC risk elevation for individuals with diabetes is similar for males and females. Using data from Newfoundland and Labrador (NL), the province with the highest CRC incidence and diabetes prevalence in Canada, we assessed and compared the risk elevation of CRC for males and females with diabetes, overall and by anatomic subsite. METHODS: A population-based retrospective cohort study including a study sample of 122,228 individuals aged ≥30 years was conducted using administrative health databases over a 10.5-year period (October 1, 1996 to March 31, 2007). Hazard ratios were estimated using Cox proportional hazard models. RESULTS: In comparison with non-diabetes counterparts, both males and females with diabetes were at a significantly elevated risk of overall CRC, with corresponding hazard ratios of 1.38 and 1.52, respectively. For males, diabetes significantly increased the risk of proximal and distal colon cancers, but not of rectal cancer. For females, diabetes significantly increased the risk of proximal colon and rectal cancers, but not of distal colon cancer. The results suggest that there is a stronger association between diabetes and CRC for females than for males, and the association did not change after adjusting for overweight/obesity. CONCLUSIONS: Diabetes led to a greater risk of CRC in both the male and female population in NL. Risk was subsite-specific and varied by sex. Future research should examine reasons for the observed diabetes-associated CRC risk to support CRC prevention strategies among the diabetes population.

CA1 ischemic injury does not affect the ability of Mongolian gerbils to solve response, direction, or place problems.

Open field and T-maze paradigms are used to test the effects of hippocampal lesions on spatial memory in rodents. Place cells in the dorsal CA1 region of the hippocampus are known to be responsible for the formation of global place maps, while CA3 neurons respond to changes in local contexts. It is proposed here that when dorsal CA1 is selectively destroyed, gerbils will be unable to solve direction and place problems while context-dependent representations of relative maze positions should be spared since CA3 cells are left intact. Twenty female Mongolian gerbils were subjected to 5 min of forebrain ischemia, and, along with 20 controls, were subsequently tested on a response, direction or one of two types of open field place problems. Locomotion in a circular open field was recorded as a measure of hyperactivity. Gerbils with damage restricted to dorsal CA1 were hyperactive compared to controls, but were not impaired on place, direction, or response tasks. Because gerbils solved these tasks in the absence of dorsal CA1, maze tasks which have traditionally been labeled "place" or "direction" tasks may actually be testing the animal's ability to discriminate between two relative contexts, without the need for a global place map. Our findings support recent reports that different hippocampal subfields control different aspects of spatial learning and memory. Specifically, the context-dependent representations in CA3 appear to support the learning of the "place" and, likely, "direction" solutions in current and previous open field and T-maze tasks.

Location serves as a conditional cue when harp seals (Pagophilus groenlandicus) solve object discrimination reversal problems.

We examined the capacity of harp seals (Pagophilus groenlandicus) to use spatial context (i.e., their tank) as a conditional cue to solve a two-choice visual discrimination reversal task. Seals were trained to touch one of two 3D objects. Two of four seals experienced a context shift that coincided with each of five reversals in the reward value of the two stimuli (i.e., a reversal of S+ and S-); these seals solved the six discriminations in significantly fewer trials than did seals that did not experience a context shift with the contingency reversal. Thus, harp seals use contextual cues when encoding information. The findings are discussed in terms of harp seals' adaptations to the pack-ice environment, the constraints of the learning tasks, and the nature of the subjects that were raised in captivity.