Dataset Information

Cognitive reserve and brain reserve in prodromal Huntington's disease.

ABSTRACT: Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Participants were genetically confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on four cognitive measures and three brain volumes over approximately 6 years. Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals.

SUBMITTER: Bonner-Jackson A

PROVIDER: S-EPMC3720793 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cognitive reserve and brain reserve in prodromal Huntington's disease.

Bonner-Jackson Aaron A Long Jeffrey D JD Westervelt Holly H Tremont Geoffrey G Aylward Elizabeth E Paulsen Jane S JS

Journal of the International Neuropsychological Society : JINS 20130523 7

Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Participants were genetically confirmed individuals with prodromal HD enrolled ...[more]

PMID: 23702309

Similar Datasets

Project description:BACKGROUND:The mechanisms underlying neurodegeneration in the striatum of Huntingon's Disease (HD) brain are currently unknown. While the striatum is massively degenerated in symptomatic individuals, which makes cellular characterization difficult, it is largely intact in asymptomatic HD gene positive (HD+) individuals. Unfortunately, as striatal tissue samples from HD+ individuals are exceedingly rare, recent focus has been on the Brodmann Area 9 (BA9), a relatively unaffected region, as a surrogate tissue. In this study, we analyze gene expression in caudate nucleus (CAU) from two HD+ individuals and compare the results with healthy and symptomatic HD brains. METHODS:High-throughput mRNA sequencing (mRNA-Seq) datasets were generated from post-mortem CAU of 2 asymptomatic HD+ individuals and compared with 26 HD and 56 neurologically normal controls. Datasets were analyzed using a custom bioinformatic analysis pipeline to identify and interpret differentially expressed (DE) genes. Results were compared to publicly available brain mRNA-Seq datasets from the Genotype-Tissue Expression (GTEx) project. The analysis employed current state of the art bioinformatics tools and tailored statistical and machine learning methods. RESULTS:The transcriptional profiles in HD+ CAU and HD BA9 samples are highly similar. Differentially expressed (DE) genes related to the heat shock response, particularly HSPA6 and HSPA1A, are common between regions. The most perturbed pathways show extensive agreement when comparing disease with control. A random forest classifier predicts that the two HD+ CAU samples strongly resemble HD BA9 and not control BA9. Nonetheless, when genes were prioritized by their specificity to HD+ CAU, pathways spanning many biological processes emerge. Comparison of HD+ BA9 with HD BA9 identified NPAS4 and REST1/2 as potential early responders to disease and reflect the active disease process. CONCLUSIONS:The caudate nucleus in HD brain is dramatically affected prior to symptom onset. Gene expression patterns observed in the HD BA9 are also present in the CAU, suggesting a common response to disease. Substantial caudate-specific differences implicate many different biological pathways including metabolism, protein folding, inflammation, and neurogenic processes. While these results are at best trends due to small sample sizes, these results nonetheless provide the most detailed insight to date into the primary HD disease process.

Dataset Information

Cognitive reserve and brain reserve in prodromal Huntington's disease.

Publications

Cognitive reserve and brain reserve in prodromal Huntington's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets