Dataset Information

WHODAS 2.0 in prodromal Huntington disease: measures of functioning in neuropsychiatric disease.

ABSTRACT: Clinical trials to improve day-to-day function in Huntington disease (HD) require accurate outcome measures. The DSM-5 recommends the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 for use in neuropsychiatric disorders. The DSM-5 also states proxy measures may be useful when cognitive function may be impaired. We tested WHODAS participant and companion ratings for differences in baseline and longitudinal function in three prodromal HD groups and a control group. Participants with prodromal HD were stratified by disease progression (low, medium, and high disease burden) based on their cytosine-adenine-guanine (CAG)-age product (CAP) score. Participant (N=726) and companion (N=630) WHODAS scores were examined for group differences, and for participant versus companion differences using linear mixed effects regression and Akaike's information criterion to test model fit. We also compared WHODAS with the Total Functional Capacity (TFC) scale. At baseline, functioning on the WHODAS was rated worse by participants in the high group and companions compared with controls. For longitudinal changes, companions reported functional decline over time in the medium and high groups. In simultaneous analysis, participant and companion longitudinal trajectories showed divergence in the high group, suggesting reduced validity of self-report. The WHODAS showed greater longitudinal difference than the TFC in the medium group relative to controls, whereas the TFC showed greater longitudinal difference than WHODAS in the high group. Results suggest the WHODAS can identify baseline and longitudinal differences in prodromal HD and may be useful in HD clinical trials. Companions may provide more accurate data as the disease progresses.

SUBMITTER: Downing NR

PROVIDER: S-EPMC4350592 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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WHODAS 2.0 in prodromal Huntington disease: measures of functioning in neuropsychiatric disease.

Downing Nancy R NR Kim Ji-In JI Williams Janet K JK Long Jeffrey D JD Mills James A JA Paulsen Jane S JS

European journal of human genetics : EJHG 20131211 8

Clinical trials to improve day-to-day function in Huntington disease (HD) require accurate outcome measures. The DSM-5 recommends the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 for use in neuropsychiatric disorders. The DSM-5 also states proxy measures may be useful when cognitive function may be impaired. We tested WHODAS participant and companion ratings for differences in baseline and longitudinal function in three prodromal HD groups and a control group. Participan ...[more]

PMID: 24327189

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Project description:Cognitive changes in the prodromal phase of Huntington disease (prHD) are found in multiple domains, yet their neural bases are not well understood. One component process that supports cognition is inhibitory control. In the present fMRI study, we examined brain circuits involved in response inhibition in 65 prHD participants and 36 gene-negative (NEG) controls using the stop signal task (SST). PrHD participants were subdivided into three groups (LOW, MEDIUM, HIGH) based on their CAG-Age Product (CAP) score, an index of genetic exposure and a proxy for expected time to diagnosis. Poorer response inhibition (stop signal duration) correlated with CAP scores. When response inhibition was successful, activation of the classic frontal inhibitory-network was normal in prHD, yet stepwise reductions in activation with proximity to diagnosis were found in the posterior ventral attention network (inferior parietal and temporal cortices). Failures in response inhibition in prHD were related to changes in inhibition centers (supplementary motor area (SMA)/anterior cingulate and inferior frontal cortex/insula) and ventral attention networks, where activation decreased with proximity to diagnosis. The LOW group showed evidence of early compensatory activation (hyperactivation) of right-hemisphere inhibition and attention reorienting centers, despite an absence of cortical atrophy or deficits on tests of executive functioning. Moreover, greater activation for failed than successful inhibitions in an ipsilateral motor-control network was found in the control group, whereas such differences were markedly attenuated in all prHD groups. The results were not related to changes in cortical volume and thickness, which did not differ among the groups. However, greater hypoactivation of classic right-hemisphere inhibition centers [inferior frontal gyrus (IFG)/insula, SMA/anterior cingulate cortex (ACC)] during inhibition failures correlated with greater globus pallidus atrophy. These results are the first to demonstrate that response inhibition in prHD is associated with altered functioning in brain networks that govern inhibition, attention, and motor control.

Dataset Information

WHODAS 2.0 in prodromal Huntington disease: measures of functioning in neuropsychiatric disease.

Publications

WHODAS 2.0 in prodromal Huntington disease: measures of functioning in neuropsychiatric disease.

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