Langley, Christelle;
Leocadi, Michela;
Hobbs, Nicola Z;
Farag, Mena;
Murphy, Michael J;
Fayer, Kate;
Scahill, Rachael I;
... Sahakian, Barbara J; + view all
(2026)
Discovery of disrupted sustained attention and altered functional connectivity in far-from-onset Huntington's disease gene-expanded young adults.
Alzheimer's & Dementia
, 22
(1)
, Article e70944. 10.1002/alz.70944.
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Discovery of disrupted sustained attention and altered functional connectivity in far-from-onset Huntington's disease gene-expanded young adults.pdf - Published Version Download (3MB) | Preview |
Abstract
BACKGROUND: Cognitive impairments are a hallmark of Huntington's disease (HD). // METHODS: Seventy-one participants (43 HD gene-expanded [HDGE], 28 healthy controls) from the HD-Young Adult Study at two timepoints ≈ 4.7 years apart, completed the Cambridge Neuropsychological Test Automated Battery Rapid Visual Information Processing task and underwent resting-state functional magnetic resonance imaging. We focused on predefined regions of interest that are involved in sustained attention. // RESULTS: HDGE individuals showed significantly poorer sustained attention than controls (padj = 0.007), with no significant change over time. Functional connectivity (FC) analyses revealed group differences in attention-related networks, including the occipital–operculum and lentiform–orbitalis pathways. Time and group × time effects were also observed in frontal and parietal regions. // DISCUSSION: These findings demonstrate early and persistent attention deficits in HDGE, linked to altered FC in attention-related circuits. This supports the presence of early cognitive dysfunction in HD and highlights potential compensatory and pathological changes in brain networks prior to the onset of clinical motor symptoms. // Highlights: We detail the discovery of early sustained attention deficits in Huntington's disease (HD) gene-expanded (HDGE) young adults. These sustained attention deficits do not measurably decline over a 4.7-year period. Altered functional connectivity was observed in attention-related brain networks. Alterations in regions include occipital, opercular, lentiform, and frontal areas. Findings support attention as an early cognitive biomarker in HDGE young adults.
| Type: | Article |
|---|---|
| Title: | Discovery of disrupted sustained attention and altered functional connectivity in far-from-onset Huntington's disease gene-expanded young adults |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/alz.70944 |
| Publisher version: | https://doi.org/10.1002/alz.70944 |
| Language: | English |
| Additional information: | Copyright © 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Huntington's disease; sustained attention; resting-state fMRI |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10220107 |
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