pre-HD Groups Research Articles

Clinical impact of diastolic dysfunction and atrial fibrillation before and after initiating hemodialysis in patients with end-stage kidney disease

Background Diastolic dysfunction with left ventricular hypertrophy and myocardial fibrosis is an important characteristic of uremic cardiomyopathy in end-stage kidney disease (ESKD). Few studies explored the relationship between changes in diastolic dysfunction and the risk of mortality or cardiovascular outcome in patients with ESKD. We investigated the clinical impact of diastolic dysfunction and atrial fibrillation (AF) on patients starting hemodialysis (HD). Methods A total of 718 patients who started HD between 2010 and 2020 were included. We classified patients according to the pre- and post-HD diastolic dysfunction grades (DDG) evaluated by echocardiography. Patients with AF were classified separately. The primary outcome was a composite outcome of all-cause mortality and cardiac complication. Results The median age was 63 years, and 61.4% were male. Patients were divided into four groups based on pre-HD echocardiography findings. After initiating HD, the patients were classified according to changes in DDG and AF. Composite outcomes were significantly higher in the pre-HD AF groups. However, after adjusting for age and history of ischemic heart disease, pre-HD AF did not affect the composite outcomes. Patients with normal post-HD diastolic function had better outcomes than those with diastolic dysfunction or AF. Furthermore, the deterioration of diastolic dysfunction after HD was associated with an increased risk of composite outcomes. Conclusions The deterioration of diastolic dysfunction and newly development of AF after initiating HD were identified as risk factors for mortality and cardiac complications, supporting the clinical importance of the appropriate management of diastolic dysfunction and AF in patients with ESKD.

The shape of things to come. Mapping spatiotemporal progression of striatal morphology in Huntington disease: The IMAGE-HD study

Mapping the spatiotemporal progression of neuroanatomical change in Huntington's Disease (HD) is fundamental to the development of bio-measures for prognostication. Statistical shape analysis to measure the striatum has been performed in HD, however there have been a limited number of longitudinal studies. To address these limitations, we utilised the Spherical Harmonic Point Distribution Method (SPHARM-PDM) to generate point distribution models of the striatum in individuals, and used linear mixed models to test for localised shape change over time in pre-manifest HD (pre-HD), symp-HD (symp-HD) and control individuals. Longitudinal MRI scans from the IMAGE-HD study were used (baseline, 18 and 30 months). We found significant differences in the shape of the striatum between groups. Significant group-by-time interaction was observed for the putamen bilaterally, but not for caudate. A differential rate of shape change between groups over time was observed, with more significant deflation in the symp-HD group in comparison with the pre-HD and control groups. CAG repeats were correlated with bilateral striatal shape in pre-HD and symp-HD. Robust statistical analysis of the correlates of striatal shape change in HD has confirmed the suitability of striatal morphology as a potential biomarker correlated with CAG-repeat length, and potentially, an endophenotype.

Selective perforant-pathway atrophy in Huntington disease: MRI analysis of hippocampal subfields.

While individuals with Huntington disease (HD) show memory impairment that indicates hippocampal dysfunction, the available literature does not consistently identify structural evidence for involvement of the whole hippocampus but rather suggests that hippocampal atrophy may be confined to certain hippocampal subregions. We processed T1-weighted MRI from IMAGE-HD study using FreeSurfer 7.0 and compared the volumes of the hippocampal subfields among 36 early motor symptomatic (symp-HD), 40 pre-symptomatic (pre-HD), and 36 healthy control individuals across three timepoints over 36 months. Mixed-model analyses revealed significantly lower subfield volumes in symp-HD, compared with pre-HD and control groups, in the subicular regions of the perforant-pathway: presubiculum, subiculum, dentate gyrus, tail, and right molecular layer. These adjoining subfields aggregated into a single principal component, which demonstrated an accelerated rate of atrophy in the symp-HD. Volumes between pre-HD and controls did not show any significant difference. In the combined HD groups, CAG repeat length and disease burden score were associated with presubiculum, molecular layer, tail, and perforant-pathway subfield volumes. Hippocampal left tail and perforant-pathway subfields were associated with motor onset in the pre-HD group. Hippocampal subfields atrophy in early symptomatic HD affects key regions of the perforant-pathway, which may implicate the distinctive memory impairment at this stage of illness. Their volumetric associations with genetic and clinical markers suggest the selective susceptibility of these subfields to mutant Huntingtin and disease progression.

Ganglioside-focused Glycan Array Reveals Abnormal Anti-GD1b Auto-antibody in Plasma of Preclinical Huntington’s Disease

Huntington's disease (HD) is a progressive and devastating neurodegenerative disease marked by inheritable CAG nucleotide expansion. For offspring of HD patients carrying abnormal CAG expansion, biomarkers that predict disease onset are crucially important but still lacking. Alteration of brain ganglioside patterns has been observed in the pathology of patients carrying HD. Here, by using a novel and sensitive ganglioside-focused glycan array, we examined the potential of anti-glycan auto-antibodies for HD. In this study, we collected plasma from 97 participants including 42 control (NC), 16 pre-manifest HD (pre-HD), and 39 HD cases and measured the anti-glycan auto-antibodies by a novel ganglioside-focused glycan array. The association between plasma anti-glycan auto-antibodies and disease progression was analyzed using univariate and multivariate logistic regression. The disease-predictive capacity of anti-glycan auto-antibodies was further investigated by receiver operating characteristic (ROC) analysis. We found that anti-glycan auto-antibodies were generally higher in the pre-HD group when compared to the NC and HD groups. Specifically, anti-GD1b auto-antibody demonstrated the potential for distinguishing between pre-HD and control groups. Moreover, in combination with age and the number of CAG repeat, the level of anti-GD1b antibody showed excellent predictability with an area under the ROC curve (AUC) of 0.95 to discriminate between pre-HD carriers and HD patients. With glycan array technology, this study demonstrated abnormal auto-antibody responses that showed temporal changes from pre-HD to HD.

Assessment of uremic toxins in advanced chronic kidney disease patients on maintenance hemodialysis by LC-ESI-MS/MS.

In the advanced stage of chronic kidney disease (CKD), electrolytes, fluids, and metabolic wastes including various uremic toxins, accumulate at high concentrations in the patients' blood. Hemodialysis (HD) is the conventional procedure used worldwide to remove metabolic wastes. The creatinine and urea levels have been routinely monitored to estimate kidney function and effectiveness of the HD process. This study, first from in Indian perspective, aimed at the identification and quantification of major uremic toxins in CKD patients on maintenance HD (PRE-HD), and compared with the healthy controls (HC) as well as after HD (POST-HD). The study mainly focused on the identification of major uremic toxins in Indian perspective and the quantitative analysis of indoxyl sulfate and p-cresol sulfate (routinely targeted uremic toxins), and phenyl sulfate, catechol sulfate, and guaiacol sulfate (targeted for the first time), apart from creatinine and urea in PRE-HD, POST-HD, and HC groups. Blood samples were collected from 90 HD patients (both PRE-HD and POST-HD), and 74 HCs. The plasma samples were subjected to direct ESI-HRMS and LC/HRMS for untargeted metabolomics and LC-MS/MS for quantitative analysis. Various known uremic toxins, and a few new and unknown peaks were detected in PRE-HD patients. The p-cresol sulfate and indoxyl sulfate were dominant in PRE-HD, the concentrations of phenyl sulfate, catechol sulfate, and guaiacol sulfate were about 50% of that of indoxyl sulfate. Statistical evaluation on the levels of targeted uremic toxins in PRE-HD, POST-HD, and HC groups showed a significant difference among the three groups. The dialytic clearance of indoxyl sulfate and p-cresol sulfate was found to be < 35%, while that of the other three sulfates was 50-58%. LC-MS/MS method was developed and validated to evaluate five major uremic toxins in CKD patients on HD. The levels of the targeted uremic toxins could be used to assess kidney function and the effectiveness of HD.

Listener Detection of Objectively Validated Acoustic Features of Speech in Huntington’s Disease

Subtle progressive changes in speech motor function and cognition begin prior to diagnosis of Huntington's disease (HD). To determine the nature of listener-rated speech differences in premanifest and early-stage HD (i.e., PreHD and EarlyHD), compared to neurologically healthy controls. We administered a speech battery to 60 adults (16 people with PreHD, 14 with EarlyHD, and 30 neurologically healthy controls), and conducted a cognitive test of processing speed/visual attention, the Symbol Digit Modalities Test (SDMT) on participants with HD. Voice recordings were rated by expert listeners and analyzed for acoustic and perceptual speech features. Listeners perceived subtle differences in the speech of PreHD compared to controls, including abnormal pitch level and speech rate, reduced loudness and loudness inflection, altered voice quality, hypernasality, imprecise articulation, and reduced naturalness of speech. Listeners detected abnormal speech rate in PreHD compared to healthy speakers on a reading task, which correlated with slower speech rate from acoustic analysis and a lower cognitive performance score. In early-stage HD, continuous speech was characterized by longer pauses, a higher proportion of silence, and slower rate. Differences in speech and voice acoustic features are detectable in PreHD by expert listeners and align with some acoustically-derived objective speech measures. Slower speech rate in PreHD suggests altered oral motor control and/or subtle cognitive deficits that begin prior to diagnosis. Speakers with EarlyHD exhibited more silences compared to the PreHD and control groups, raising the likelihood of a link between speech and cognition that is not yet well characterized in HD.

Electrophysiological evaluation of peripheral neuropathy in chronic kidney disease patients: A study from tertiary care centre, Maharashtra

ntroduction: CKD has turned a major cause of morbidity and mortality. The prevalence of peripheral neuropathy is directly proportional to duration and severity of CKD. Peripheral neuropathy becomes evident after the patient reaches stage 4 CKD, but electrophysiological evidences occurs earlier. NCS is an important means of evaluating the functional integrity of peripheral nerves and has implications regarding clinical course and prognosis. Objectives: To study electrophysiological findings of peripheral neuropathy in CKD patients Methodology: The present study was a cross sectional; descriptive study was conducted in October 2016 to October 2018. Data analysed by using SPSS 23.0 version. Clinical and neurological examinations were done and blood investigations were performed following which NCS was done. Results: Out of 90 subjects, majority were from 45-54 years age group (26). 70% were male and 30% were females. Total 10 (11.11%) patients showed pure sensory type of PN. Total 47 (52.22%) patients showed sensory-motor type of PN. sensory-motor type of PN was the predominant type (52.22%) found in study followed by pure sensory type of PN (11.11%). Pure axonal sensory motor pattern of PN found in 15 (25%) patients in preHD group, 11 (36.66%) patients in HD group. The difference between the pre-HD and HD groups were statistically significant for the median nerve amplitude, common peroneal nerve CV, posterior tibial nerve CV, posterior tibial nerve distal latency and sural nerve distal latency (p &lt; 0.05). Conclusion:Peripheral neuropathy is very common in CKD, more common in dialysis patients as compared to predialysis patients. It’s frequency and severity increase as the duration of disease and stage of CKD increases. Sensory motor type of neuropathy is more common than pure sensory type of neuropathy.Pure axonal sensory motor and mixed (axonal + demyelinating) sensory motor neuropathy are common patterns of PN in CKD.

Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington's disease Young Adult Study (HD-YAS): a cross-sectional analysis.

SummaryBackgroundDisease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Huntington's disease gene carriers (preHD) far from predicted clinical symptom onset.MethodsWe did the Huntington's disease Young Adult Study (HD-YAS) in the UK. We recruited young adults with preHD and controls matched for age, education, and sex to ensure each group had at least 60 participants with imaging data, accounting for scan fails. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. All participants underwent detailed neuropsychiatric and cognitive assessments, including tests from the Cambridge Neuropsychological Test Automated Battery and a battery assessing emotion, motivation, impulsivity and social cognition (EMOTICOM). Imaging (done for all participants without contraindications) included volumetric MRI, diffusion imaging, and multiparametric mapping. Biofluid markers of neuronal health were examined using blood and CSF collection. We did a cross-sectional analysis using general least-squares linear models to assess group differences and associations with age and CAG length, relating to predicted years to clinical onset. Results were corrected for multiple comparisons using the false discovery rate (FDR), with FDR <0·05 deemed a significant result.FindingsData were obtained between Aug 2, 2017, and April 25, 2019. We recruited 64 young adults with preHD and 67 controls. Mean ages of participants were 29·0 years (SD 5·6) and 29·1 years (5·7) in the preHD and control groups, respectively. We noted no significant evidence of cognitive or psychiatric impairment in preHD participants 23·6 years (SD 5·8) from predicted onset (FDR 0·22–0·87 for cognitive measures, 0·31–0·91 for neuropsychiatric measures). The preHD cohort had slightly smaller putamen volumes (FDR=0·03), but this did not appear to be closely related to predicted years to onset (FDR=0·54). There were no group differences in other brain imaging measures (FDR >0·16). CSF neurofilament light protein (NfL), plasma NfL, and CSF YKL-40 were elevated in this far-from-onset preHD cohort compared with controls (FDR<0·0001, =0·01, and =0·03, respectively). CSF NfL elevations were more likely in individuals closer to expected clinical onset (FDR <0·0001).InterpretationWe report normal brain function yet a rise in sensitive measures of neurodegeneration in a preHD cohort approximately 24 years from predicted clinical onset. CSF NfL appears to be a more sensitive measure than plasma NfL to monitor disease progression. This preHD cohort is one of the earliest yet studied, and our findings could be used to inform decisions about when to initiate a potential future intervention to delay or prevent further neurodegeneration while function is intact.FundingWellcome Trust, CHDI Foundation.

Morphometric in vivo evidence of thalamic atrophy correlated with cognitive and motor dysfunction in Huntington's disease: The IMAGE-HD study

In Huntington's disease (HD), neurodegeneration causes progressive atrophy to the striatum, cortical areas, and white matter tracts - components of corticostriatal circuitry. Such processes may affect the thalamus, a key circuit node. We investigated whether differences in dorsal thalamic morphology were detectable in HD, and whether thalamic atrophy was associated with neurocognitive, neuropsychiatric and motor dysfunction.Magnetic resonance imaging scans and clinical outcome measures were obtained from 34 presymptomatic HD (pre-HD), 29 early symptomatic HD (symp-HD), and 26 healthy control individuals who participated in the IMAGE-HD study. Manual region of interest (ROI) segmentation was conducted to measure dorsal thalamic volume, and thalamic ROI underwent shape analysis using the spherical harmonic point distribution method.The symp-HD group had significant thalamic volumetric reduction and global shape deflation, indicative of atrophy, compared to pre-HD and control groups. Thalamic atrophy significantly predicted neurocognitive and motor dysfunction within the symp-HD group only.Thalamic morphology differentiates symp-HD from pre-HD and healthy individuals. Thalamic changes may be one of the structural bases (endomorphotypes), of the endophenotypic neurocognitive and motor manifestations of disease. Future research should continue to investigate the thalamus as a potential in vivo biomarker of disease progression in HD.

DNA damage signatures in peripheral blood cells as biomarkers in prodromal huntington disease.

Easily accessible biomarkers in Huntington disease (HD) are actively searched. We investigated telomere length and DNA double-strand breaks (histone variant pγ-H2AX) as predictive disease biomarkers in peripheral blood mononuclear cells (PBMC) from 25 premanifest subjects, 58 HD patients with similar CAG expansion in the huntingtin gene (HTT), and 44 healthy controls (HC). PBMC from the pre-HD and HD groups showed shorter telomeres (p < 0.0001) and a significant increase of pγ-H2AX compared to the controls (p < 0.0001). The levels of pγ-H2AX correlated robustly with the presence of the mutated gene in pre-HD and HD. The availability of a potentially reversible biomarker (pγ-H2AX) in the premanifest stage of HD, negligible in HC, provides a novel tool to monitor premanifest subjects and find patient-specific drugs. Ann Neurol 2018;00:1-6 ANN NEUROL 2019;85:296-301.

Dexmedetomidine preconditioning protects against lung injury induced by ischemia-reperfusion through inhibition of autophagy.

The present study aimed to evaluate the role of autophagy in the protective effect of dexmedetomidine in lung injury caused by ischemia-reperfusion (IR) in rats. In total 48 adult male Sprague-Dawley rats were randomly divided into 6 groups (n=8) as follows: i) Sham group; ii) the IR group; iii) IR + 1 µg/kg dexmedetomidine preconditioning group (pre-LD); iv) IR + 10 µg/kg dexmedetomidine preconditioning group (pre-HD); v) IR + 1 µg/kg dexmedetomidine postconditioning group (post-LD); and vi) IR + 10 µg/kg dexmedetomidine postconditioning group (post-HD). After the rats were anesthetized, the hilum of the left lung was occluded with a non-invasive microvascular clip for 30 min to induce ischemia. The clip was then removed and the left lung was allowed to regain ventilation and blood for 2 h. The rats were then sacrificed, the left lung removed and the wet/dry (W/D) lung weight ratio was determined. Pathological changes to the lungs were evaluated by light and transmission electron microscopy. Furthermore, the rate of lung cell apoptosis was determined by the TUNEL assay. The expression of hypoxia-inducible factor 1α (HIF-1α), Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3), BNIP3 like (BNIP3 L) and microtubule-associated protein 1A/1B light chain 3B (LC3II) was determined by western blotting. Compared with the sham group, a significant increase in the W/D lung weight ratio, and malondialdehyde (MDA), BNIP3, BNIP3 L and LC3II levels were observed in the IR group, and HIF-1α levels and superoxide dismutase (SOD) activity were decreased. Furthermore, the W/D ratio was lower in the pre-LD and pre-HD groups than in the IR group. Additionally, SOD activity was significantly higher and MDA expression was significantly lower in the pre-LD and pre-HD groups compared with the IR group. BNIP3, BNIP3 L and LC3II protein levels were significantly lower in the pre-LD and pre-HD groups compared with the IR group, while HIF-1α was notably upregulated in the pre-LD and pre-HD groups compared with the IR group. In conclusion, the results of the present study indicate that dexmedetomidine preconditioning protects against lung injury induced by IR through inhibition of autophagy and apoptosis.

Striatal hypometabolism in premanifest and manifest Huntington's disease patients.

To assess metabolic changes in cerebral 18F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate 18F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain 18F-FDG PET/CT and MRI. 18F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of 18F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50voxels). 18F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. 18F-FDG PET/CT appears as a promising method to monitor the response to disease-modifying therapies even if applied in premanifest subjects.

Abnormal Electrophysiological Motor Responses in Huntington's Disease: Evidence of Premanifest Compensation.

BackgroundHuntington's disease (HD) causes progressive motor dysfunction through characteristic atrophy. Changes to neural structure begin in premanifest stages yet individuals are able to maintain a high degree of function, suggesting involvement of supportive processing during motor performance. Electroencephalography (EEG) enables the investigation of subtle impairments at the neuronal level, and possible compensatory strategies, by examining differential activation patterns. We aimed to use EEG to investigate neural motor processing (via the Readiness Potential; RP), premotor processing and sensorimotor integration (Contingent Negative Variation; CNV) during simple motor performance in HD.MethodsWe assessed neural activity associated with motor preparation and processing in 20 premanifest (pre-HD), 14 symptomatic HD (symp-HD), and 17 healthy controls. Participants performed sequential tapping within two experimental paradigms (simple tapping; Go/No-Go). RP and CNV potentials were calculated separately for each group.ResultsMotor components and behavioural measures did not distinguish pre-HD from controls. Compared to controls and pre-HD, symp-HD demonstrated significantly reduced relative amplitude and latency of the RP, whereas controls and pre-HD did not differ. However, early CNV was found to significantly differ between control and pre-HD groups, due to enhanced early CNV in pre-HD.ConclusionsFor the first time, we provide evidence of atypical activation during preparatory processing in pre-HD. The increased activation during this early stage of the disease may reflect ancillary processing in the form of recruitment of additional neural resources for adequate motor preparation, despite atrophic disruption to structure and circuitry. We propose an early adaptive compensation mechanism in pre-HD during motor preparation.

Microstructural brain abnormalities in Huntington's disease: A two-year follow-up.

To investigate both cross-sectional and time-related changes of striatal and whole-brain microstructural properties in different stages of Huntington's disease (HD) using diffusion tensor imaging. From the TRACK-HD study, premanifest gene carriers (preHD), early manifest HD and controls were scanned at baseline and 2-year follow-up. Stratification of the preHD group into a far (preHD-A) and near (preHD-B) to predicted disease onset was performed. Age-corrected histograms of whole-brain white matter (WM), gray matter (GM) and striatal diffusion measures were computed and normalised by the number of voxels in each subject's data set. Higher cross-sectional mean, axial and radial diffusivities were found in both WM (P ≤ 0.001) and GM (P ≤ 0.001) of the manifest HD compared to the preHD and control groups. In preHD, only WM axial diffusivity (AD) was higher than in controls (P ≤ 0.01). This finding remained valid only in preHD-B (P ≤ 0.001). AD was also higher in the striatum of preHD-B compared to controls and preHD-A (P ≤ 0.01). Fractional anisotropy (FA) lacked sensitivity in differentiating between the groups. Histogram peak heights were generally lower in manifest HD compared to the preHD and control groups. No longitudinal differences were found in the degree of diffusivity change between the groups in the two year follow-up. There was a significant relationship between diffusivity and neurocognitive measures. Alterations in cross-sectional diffusion profiles between manifest HD subjects and controls were evident, both in whole-brain and striatum. In the preHD stage, only AD alterations were found, a finding suggesting that this metric is a sensitive marker for early change in HD prior to disease manifestation. The individual diffusivities were superior to FA in revealing pathologic microstructural brain alterations. Diffusion measures were well related to clinical functioning and disease stage.

Abnormal synchrony of resting state networks in premanifest and symptomatic Huntington disease: the IMAGE-HD study

Functional neural impairments have been documented in people with symptomatic Huntington disease (symp-HD) and in premanifest gene carriers (pre-HD). This study aimed to characterize synchrony in resting state cerebral networks in both pre-HD and symp-HD populations and to determine its association with disease burden and neurocognitive functions. We acquired functional magnetic resonance imaging (fMRI) data from pre-HD, symp-HD and healthy control participants. The fMRI data were analyzed using multisubject independent component analysis and dual regression. We compared networks of interest among the groups using a nonparametric permutation method and correcting for multiple comparisons. Our study included 25 people in the pre-HD, 23 in the symp-HD and 18 in the healthy control groups. Compared with the control group, the pre-HD group showed decreased synchrony in the sensorimotor and dorsal attention networks; decreased level of synchrony in the sensorimotor network was associated with poorer motor performance. Compared with the control group, the symp-HD group showed widespread reduction in synchrony in the dorsal attention network, which was associated with poorer cognitive performance. The posterior putamen and superior parietal cortex were functionally disconnected from the frontal executive network in the symp-HD compared with control and pre-HD groups. Furthermore, the left frontoparietal network showed areas of increased synchrony in the symp-HD compared with the pre-HD group. We could not directly correct for influence of autonomic changes (e.g., heart rate) and respiration on resting state synchronization. Our findings suggest that aberrant synchrony in the sensorimotor and dorsal attention networks may serve as an early signature of neural change in pre-HD individuals. The altered synchrony in dorsal attention, frontoparietal and corticostriatal networks may contribute to the development of clinical symptoms in people with Huntington disease.

Dialysis Method Alters the Expression of MicroRNA‐33a and Its Target Genes ABCA1, ABCG1 in THP‐1 Macrophages

Atherosclerosis and accompanying cardiovascular disease are the first causes of mortality in patients undergoing maintenance hemodialysis. Anti-atherosclerotic effects of hemodiafiltration (HDF) have been reported. Our study aimed to investigate the effect of serum derived from a healthy group (n = 23), before and after hemodialysis (HD) therapy (n = 23), and before and after HDF therapy (n = 17) on the expression of microRNA-33a and its target genes adenosine triphosphate-binding cassette transporter A1,G1 (ABCA1, ABCG1) in THP-1 macrophages. Meanwhile, blood lipids and high-sensitivity C-reactive protein (hs-CRP) were measured in these groups. Our data showed that the expression of miRNA-33a was lower (P < 0.05) and ABCA1 and ABCG1 were higher (P < 0.05) in the healthy group than pre-HD and pre-HDF. miR-33a was significantly decreased (P < 0.05) but ABCA1, ABCG1 was significantly increased (P < 0.05) in post-HDF compared with pre-HDF, while these parameters in pre- and post- HD groups did not show any significant change (P > 0.05). High density lipoprotein cholesterol (HDL-C) was higher and hs-CRP was lower in the healthy group than pre-HD and pre-HDF groups. Moreover, a significant increase of HDL-C (P < 0.05) and decrease (P < 0.05) of hs-CRP was shown in post-HDF compared with pre-HDF, but HD appeared to have no significant change in these subjects. HDF therapy can downregulate miR-33a expression, and then result in ABCA1, ABCG1 upregulation and an increase in circulating HDL-C, leading to a possible anti-atherosclerosis effect to some extent.

The Visual Spatial Learning Test: Differential impairment during the premanifest and manifest stages of Huntington's disease

Visual spatial memory was assessed using the Visual Spatial Learning Test (VSLT) in individuals with mild to moderate Huntington's disease (HD), pre-manifest gene carriers for HD, and demographically similar controls. The VSLT has been demonstrated to be a valid, normed measure of non-verbal memory involving minimal motoric responses. The VSLT assesses immediate and delayed memory for designs, positions of the designs, and design/position associations. The HD group was significantly impaired (p < .05) relative to both the control and Pre-HD groups on immediate and delayed memory for the designs, positions, and design/position associations. Although there were no differences between the Pre-HD and control groups on immediate or delayed memory for designs or positions, the Pre-HD group was significantly impaired (p < .05) relative to the control group on immediate and delayed memory for design/position associations. The results offer novel insight into a relatively unexamined memory deficit that may occur in gene carriers for HD prior to phenoconversion. The data indicate that the VSLT may be a useful measure of visuospatial memory during the premanifest and manifest stages of HD.

Functional magnetic resonance imaging of working memory in Huntington's disease: Cross‐sectional data from the IMAGE‐HD study

We used functional magnetic resonance imaging (fMRI) to investigate spatial working memory (WM) in an N-BACK task (0, 1, and 2-BACK) in premanifest Huntington's disease (pre-HD, n = 35), early symptomatic Huntington's disease (symp-HD, n = 23), and control (n = 32) individuals. Overall, both WM conditions (1-BACK and 2-BACK) activated a large network of regions throughout the brain, common to all groups. However, voxel-wise and time-course analyses revealed significant functional group differences, despite no significant behavioral performance differences. During 1-BACK, voxel-wise blood-oxygen-level-dependent (BOLD) signal activity was significantly reduced in a number of regions from the WM network (inferior frontal gyrus, anterior insula, caudate, putamen, and cerebellum) in pre-HD and symp-HD groups, compared with controls; however, time-course analysis of the BOLD response in the dorsolateral prefrontal cortex (DLPFC) showed increased activation in symp-HD, compared with pre-HD and controls. The pattern of reduced voxel-wise BOLD activity in pre-HD and symp-HD, relative to controls, became more pervasive during 2-BACK affecting the same structures as in 1-BACK, but also incorporated further WM regions (anterior cingulate gyrus, parietal lobe and thalamus). The DLPFC BOLD time-course for 2-BACK showed a reversed pattern to that observed in 1-BACK, with a significantly diminished signal in symp-HD, relative to pre-HD and controls. Our findings provide support for functional brain reorganisation in cortical and subcortical regions in both pre-HD and symp-HD, which are modulated by task difficulty. Moreover, the lack of a robust striatal BOLD signal in pre-HD may represent a very early signature of change observed up to 15 years prior to clinical diagnosis.

Facial Expression Recognition and Medication effects in Huntington’s disease

Facial Expression Recognition and Medication effects in Huntington’s disease

Resting-state functional connectivity in Huntington’s disease: The IMAGE-HD study

Event Abstract Back to Event Resting-state functional connectivity in Huntington’s disease: The IMAGE-HD study Govinda R. Poudel1, 2, 3*, Gary F. Egan1, 2, Andrew Churchyard4, Phyllis Chua1, Julie C. Stout1 and Nellie Georgiou-Karistianis1 1 Monash University, School of Psychology and Psychiatry, Australia 2 Monash University, Monash Biomedical Imaging, Australia 3 Monash University, Monash e-Research Centre, Australia 4 Monash Medical Centre, Department of Neurology, Australia Functional and structural neural impairments have been documented in both symptomatic Huntington’s disease (symp-HD) and premanifest gene carrier (pre-HD) individuals. The aim of this study was to characterize resting state connectivity in both pre-HD and symp-HD individuals. fMRI data was acquired via a 3 T MRI from 25 pre-HD, 23 symp-HD, and 18 healthy controls individuals. The fMRI data were pre-processed and analyzed using a data-driven method to identify several resting state networks. Voxel-wise synchronization of networks of interest were compared between groups using dual-regression and statistically tested using a permutation based non-parametric method. Nine well-established resting state networks were identified. Of the nine networks, four were significantly altered in both the pre-HD and symp-HD groups. Compared with controls, pre-HD individuals showed decreased synchrony in the sensorimotor (primary motor cortex) and dorsal attention (visual cortex) networks. Compared with controls, the symp-HD individuals showed widespread reduction in synchrony in the dorsal attention network. There was also a functional disconnection of the posterior putamen and superior parietal cortex from the frontal executive network in the symp-HD, compared with control and pre-HD individuals. Furthermore, the left fronto-parietal network showed areas of increased synchrony in symp-HD, compared with pre-HD individuals. We speculate that reduced synchrony in both the sensorimotor and dorsal attention networks may serve as an early signature of neural change in pre-HD. The widespread reduction in dorsal attention and cortico-striatal networks may contribute to the development of clinical symptoms in HD. Acknowledgements We would like to acknowledge the contribution of all the participants who took part in this study. We are also grateful to the Cure Huntington’s Disease Initiative (CHDI), Inc. (USA), for their support in funding this research. Keywords: Huntington's disease, fMRI, resting state fMRI, resting state functional connectivity, functional connectivity Conference: ACNS-2012 Australasian Cognitive Neuroscience Conference, Brisbane, Australia, 29 Nov - 2 Dec, 2012. Presentation Type: Oral Presentation Topic: Other Citation: Poudel GR, Egan GF, Churchyard A, Chua P, Stout JC and Georgiou-Karistianis N (2012). Resting-state functional connectivity in Huntington’s disease: The IMAGE-HD study. Conference Abstract: ACNS-2012 Australasian Cognitive Neuroscience Conference. doi: 10.3389/conf.fnhum.2012.208.00100 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 26 Oct 2012; Published Online: 07 Nov 2012. * Correspondence: Dr. Govinda R Poudel, Monash University, School of Psychology and Psychiatry, Clayton, VIC, 3800, Australia, govinda.poudel@monash.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Govinda R Poudel Gary F Egan Andrew Churchyard Phyllis Chua Julie C Stout Nellie Georgiou-Karistianis Google Govinda R Poudel Gary F Egan Andrew Churchyard Phyllis Chua Julie C Stout Nellie Georgiou-Karistianis Google Scholar Govinda R Poudel Gary F Egan Andrew Churchyard Phyllis Chua Julie C Stout Nellie Georgiou-Karistianis PubMed Govinda R Poudel Gary F Egan Andrew Churchyard Phyllis Chua Julie C Stout Nellie Georgiou-Karistianis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.