Practice effects as a dynamic biomarker of early cognitive change in far-from-onset Huntington's disease.

Overview

1. Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
2. Research Institute Sant Pau (IR Sant Pau), Parkinson's disease and other Movement Disorders Research Group, 08041 Barcelona, Spain
3. European Huntington’s Disease Network (EHDN), 89081 Ulm, Germany
4. Centro de Investigación Biomédica en Red-Enfermedades Neurodegenerativas (CIBERNED), 28029 Madrid, Spain
5. Institute of Neuroscience, Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain
6. Alzheimer’s Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
7. Fundació de Recerca Clínic Barcelona – Institut D’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain

Abstract

Although cognitive performance typically appears preserved in far-from-onset Huntingtin Gene Expansion Carriers (HGECs), underlying neuropsychological mechanisms may be subtly altered and remain undetected. Practice effects from repeated task exposure provide a sensitive measure of cognitive adaptability, with early disruptions signalling reduced neural efficiency before standard deficits emerge. This study aimed to examine longitudinal practice effects across annual neuropsychological testing in far-from-onset HGECs and to identify the disease burden threshold where these patterns diverge. Data from 2777 HGECs and 2777 age-matched controls were drawn from the ENROLL-HD cohort across five annual assessments. Longitudinal cognitive trajectories were modelled using linear mixed-effects models, adjusting for demographics. Segmented regression models identified disease burden thresholds marking the onset of practice effect attenuation. Quartile-based stratification assessed the influence of genetic burden. An internet-based Practice Effects Trajectories Calculator (PE-TraC) was developed to model normative longitudinal distributions across tests and visualize individual-level trajectories. HGECs showed reduced practice effects in tasks involving processing speed and executive function, with divergence from controls emerging by Year 2. Segmented regression identified the earliest disease burden breakpoint in Stroop Word Reading Task (249.6) and the latest in the Symbol Digit Modalities Test (291.9). Quartile (Q) analyses showed that participants with the highest genetic burden (Q4) exhibited minimal or absent practice effects, Q3 showed delayed decline, and Q1–Q2 followed similar trajectories to controls. Reduced practice effects constitute a sensitive marker of early cognitive dysfunction in far-to-onset individuals. These findings support the inclusion of dynamic cognitive measures in far-from-onset HGECs trials as potential endpoints.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

• 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
• 0 scripts, each with its path and the digest of its content;
• no match between paragraphs and code yet;
• neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

The dataset used in this study was obtained from the Enroll-HD global clinical research platform (https://www.enroll-hd.org/). Enroll-HD provides de-identified clinical data to qualified researchers through periodic data sets (PDS), released every 1–2 years after extensive quality control and anonymization procedures. Access to more detailed, non-aggregated data can be requested through a specified dataset (SPS) application, subject to approval by the Scientific Review Committee of the CHDI Foundation. More information on data access procedures is available on the Enroll-HD website.

The R scripts used for data preprocessing and statistical analyses are publicly available on GitHub at: https://github.com/cfranch/R-code/.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 5 keywords, 38 references.

Cite

This paper

Franch-Marti, C., Puig-Davi, A., Rodriguez-Antiguedad, J., Perez-Perez, J., Olmedo-Saura, G., Ruiz-Barrio, I., Bojtos, L., Perez-Carasol, L., Tort-Merino, A., Pagonabarraga, J., Kulisevsky, J., & Martinez-Horta, S. (2026). Practice effects as a dynamic biomarker of early cognitive change in far-from-onset Huntington's disease. Brain communications, 8(3), fcag210. https://doi.org/10.1093/braincomms/fcag210

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.7554/elife.107661 [code]

In vivo mapping of striatal neurodegeneration in Huntington's disease with Soma and Neurite Density Imaging.

Journal: eLife

In common: clinical / translational, other condition, 5 references

[2] doi:10.1038/s41586-026-10671-9 [code]

Restoring cortical disinhibition improves Huntington's disease phenotypes.

Journal: Nature

In common: other condition, 1 reference

[3] doi:10.1038/s44321-026-00459-9

Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease.

Journal: EMBO molecular medicine

In common: other condition, 1 reference

[4] doi:10.1177/18796397261443137 [code]

Towards AI-driven prediction of <i>HTT</i> CAG size in super-expanded human spiny projection neurons from Huntington disease donors.

Journal: Journal of Huntington's disease

In common: other condition, 1 reference

[5] doi:10.1186/s13024-026-00951-3

Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.

Journal: Molecular neurodegeneration

In common: other condition, 1 reference

[6] doi:10.1186/s13024-026-00960-2 [code]

Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction.

Journal: Molecular neurodegeneration

In common: other condition, 1 reference

[7] doi:10.1186/s10020-026-01471-y

Modest rescue of RBFOX1 splicing function attenuates Huntington's disease features.

Journal: Molecular medicine (Cambridge, Mass.)

In common: other condition, 1 reference

[8] doi:10.1093/brain/awaf443 [code]

Cellular signatures underlying functional resilience in presymptomatic frontotemporal dementia.

Journal: Brain : a journal of neurology

In common: 1 reference

[9] doi:10.1162/imag.a.1306 [code]

Beneficial effects of foreign language learning and aerobic exercise on dentate gyrus volume and mnemonic discrimination in healthy older adults: Results from a randomized controlled trial.

Journal: Imaging neuroscience (Cambridge, Mass.)

In common: 1 reference

[10] doi:10.1038/s41467-026-74957-2 [code]

Joint trajectories of brain atrophy, white matter hyperintensities and cognition quantify brain maintenance.

Journal: Nature communications

In common: 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.