Functional changes during working memory in Huntington's disease: 30-month longitudinal data from the IMAGE-HD study.

We characterized 30-month longitudinal change in functional activation and connectivity during working memory in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease (HD). In a case-control longitudinal study (baseline, 18 months, and 30 months), we compared change in fMRI activity over time during working memory in 22 pre-HD, 11 symp-HD, and 20 control participants. Outcome measures were BOLD (blood-oxygen-level-dependent) activity during 1-BACK and 2-BACK working memory and functional connectivity between dorsolateral prefrontal cortex (DLPFC) and caudate. Compared with controls, the pre-HD group showed significantly increased activation longitudinally during 1-BACK in the left DLPFC and medial frontal cortex, and further increased activation during 2-BACK in the bilateral caudate, putamen, and temporal cortex. Longitudinal change in symp-HD was not significantly different from controls. Longitudinal changes in pre-HD were associated with disease burden and years to onset. The pre-HD group showed longitudinal decreased functional connectivity between left DLPFC and caudate during both 1-BACK and 2-BACK performance. We provide an evidence for longitudinal changes in BOLD activity during working memory prior to clinical manifestations of HD. The ability to increase activation in the prefrontal cortex over time may represent an early compensatory response during the premanifest stage, which may reflect an early marker for clinically relevant functional changes in HD.

White matter connectivity reflects clinical and cognitive status in Huntington's disease.

OBJECTIVE: To investigate structural connectivity and the relationship between axonal microstructure and clinical, cognitive, and motor functions in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease. METHOD: Diffusion tensor imaging (DTI) data were acquired from 35 pre-HD, 36 symp-HD, and 35 controls. Structural connectivity was mapped between 40 brain regions of interest using tractography. Between-group differences in structural connectivity were identified using network based statistics. Radial diffusivity (RD) and fractional anisotropy (FA) were compared in the white matter tracts from aberrant networks. RD values in aberrant tracts were correlated with clinical severity, and cognitive and motor performance. RESULTS: A network connecting putamen with prefrontal and motor cortex demonstrated significantly reduced tractography streamlines in pre-HD. Symp-HD individuals showed reduced streamlines in a network connecting prefrontal, motor, and parietal cortices with both caudate and putamen. The symp-HD group, compared to controls and pre-HD, showed both increased RD and decreased FA in the fronto-parietal and caudate-paracentral tracts and increased RD in the putamen-prefrontal and putamen-motor tracts. The pre-HDclose, compared to controls, showed increased RD in the putamen-prefrontal and fronto-parietal tracts. In the pre-HD group, significant negative correlations were observed between SDMT and Stroop performance and RD in the bilateral putamen-prefrontal tract. In the symp-HD group, RD in the fronto-parietal tract was significantly positively correlated with UHDRS motor scores and significantly negatively correlated with performance on SDMT and Stroop tasks. CONCLUSIONS: We have provided evidence of aberrant connectivity and microstructural integrity in white matter networks in HD. Microstructural changes in the cortico-striatal fibers were associated with cognitive and motor performance in pre-HD, suggesting that changes in axonal integrity provide an early marker for clinically relevant impairment in HD.

Family physical activity and sedentary environments and weight change in children.

OBJECTIVE: To examine associations between family physical activity and sedentary environment and changes in body mass index (BMI) z-scores among 10-12-year-old children over three years. METHOD: Design. Longitudinal (three-year follow-up). Subjects. In total, 152 boys and 192 girls aged 10-12 years at baseline. MEASUREMENTS: Measured height and weight at baseline and follow-up (weight status, BMI z-scores); aspects of the family physical activity and sedentary environment (parental and sibling modelling, reinforcement, social support, family-related barriers, rules/restrictions, home physical environment) measured with a questionnaire completed by parents at baseline. RESULTS: At baseline, 29.6% of boys and 21.9% of girls were overweight or obese, and mean (standard deviation, SD) BMI z-scores were 0.44 (0.99) and 0.28 (0.89), respectively. There was a significant change in BMI z-score among girls (mean change = 0.19, SD = 0.55, p < 0.001), but not boys. Among boys, the number of items at home able to be used for sedentary behaviour (B = 0.11, p = 0.037) was associated with relatively greater increases in BMI z-score. Among girls, sibling engagement in physical activity at least three times/wk (B = -0.17, p = 0.010) and the number of physical activity equipment items at home (B = -0.05, p = 0.018) were associated with relatively greater decreases in BMI z-score. CONCLUSION: Sibling physical activity and environmental stimuli for sedentary behaviours and physical activity within the home may be important targets for prevention of weight gain during the transition from childhood to adolescence.

Associations among individual, social, and environmental barriers and children's walking or cycling to school.

PURPOSE: To examine associations among individual, social, and environmental barriers and children's walking or cycling to school. DESIGN: Exploratory cross-sectional study. SETTING: All eight capital cities in Australia. SUBJECTS. Parents (N=720) of school-aged children (4-13 years; 27% response rate; 49% parents of boys). MEASURES: Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for parental reporting of barriers to their children's walking or cycling to school, based on a computer-assisted telephone interview. RESULTS: Forty-one percent of children walked or cycled to school at least once per week. Multivariable analyses found inverse associations with individual ("child prefers to be driven" [OR = 0.4, 95% CI = 0.3-0.6], "no time in the mornings" [OR = 0.5, 95% CI = 0.3-0.8]); social ("worry child will take risks" [OR = 0.6, 95% CI = 0.3-0.9], "no other children to walk with" [OR = 0.7, 95% CI = 0.4-0.99], "no adults to walk with" [OR = 0.6, 95% CI = 0.4-0.9]); and environmental barriers ("too far to walk" [OR = 0.1, 95% CI = 0.0-0.1], "no direct route" [OR = 0.4, 95% CI = 0.2-0.7]) and positive associations with "concern child may be injured in a road accident" (OR = 1.9, 95% CI = 1.1-3.1) and active commuting. CONCLUSION: Working with parents, schools, and local authorities to improve pedestrian skills and environments may help to overcome barriers.